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Pharmacotherapeutics for Podiatrists

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What are the NPS competencies?
5 sequential competencies and 2 core competencies.
1.Understands the person and their clinical needs
2.Understands the treatment options and how they support the person's clinical needs
3.Works in partnership with the person to develop a treatment and implement a treatment plan
4.Communicates the treatment plan clearly to other health professionals
5. Monitors and reviews the person's response to treatment
What is meant by competency 1. Understands the treatment options and how they support the person's clinical needs?
-Establish a therapeutic partnership with the person
-Have a collaborative relationship with other health professionals
-Perform a comprehensive assessment to assist in understanding the person's clinical needs and context
-Generate and explores possible DDx
How to develop a therapeutic partnership?
A therapeutic partnership is developed by:
-demonstrating interest and empathy
-establishing rapport
-using appropriate communication techniques
-encouraging information sharing; listen; ask open ended questions.
-tailor information to the person's needs
What is mean by competency 2; understands the RX options and how they support the person's clinical needs?
- consider all your treatment options; consider what is most appropriate for the individual treatment and their presenting complaint
-consider conservative Rx options and identify appropriate pharmacological treatment options
What is meant by competency 3; works in partnership with the person to develop and implement a Rx plan?
-Negotiates therapeutic goals with the patient
-Works in partnership with the patient and other health professionals to select medications and tailor a Rx plan
-Develops a R/V plan tailored to the patient's needs
What is meant by competency 4; communicates the Rx plan clearly to other health professionals?
- provides clear instructions to those who dispense, supply or administer medications prescribed to the patient
-provides information about medications and the Rx plan; with the patient's consent; to other health professionals who provide care to the patient.
What is meant by competency 5; monitors and reviews the patient's response to Rx?
-Obtains information to assess the patient's response to treatment; and works in partnership with them and other health professionals to address issue arsing from the review
What are the 2 core competencies of the NPS framework?
1. Practices professionally
2. Communicates and collaborates effectively with the patient and other health professionals
What does core competency 1; practices professionally mean?
-practices within the law
-practices according to professional standards, codes of conduct and within own scope of practice
-practices the principles of quality use of medicines
-demonstrates commitment to continual quality improvement of the health professional's own prescribing
-address the potential for bias in prescribing decisions
What does core competency 2; communicates and collaborates effectively with the patient and other health professionals mean?
-obtains consent to provide clinical services
-acknowledges the patient; their family and carers as integral to care and collaborates to achieve optimal health outcomes
-respects the patient
-communicates effectively to ensure safe use of medications
-collaborates with other health professionals to achieve optimal health outcomes
Pain Medications
...
Neural mechanisms of pain
-pain is a subjective experience
-typically it is a direct response to an event associated with tissue damage
-severe pain can arise independantly of any obvious cause and may persist long after the precipitating injury has healed
Treating pain: assess the pain severity
Before starting treatment you should always assess the type and severity of pain.

Use one of many pain scales available to allow the patient to communicate the severity of their pain with you.

-numerical pain scales
-verbal scales: none, mild, moderate, severe, worst imaginable pain
-visual analogue scales
-wong-baker FACES pain scale useful in paediatrics

using a scale provides a consistant way to monitor pain intensity and treatment response
Pain may be classified clinically as
-noiceptive
-neuropathic or;
-mixed noiceptive/neuropathic

Pain is sometimes described as acute or chronic
Noiceptive: due to activation of normal pain fibres in response to noxious stimuli: may be somatic (involving skin/muscle/superficial structures) or visceral (deep structures i.e. organs)
Neuropathic: pain resulting from injury, disease or dysfunction that affects the peripheral, central or both nervous systems.
The two pains respond differently to treatment and the type of pain should be identified before commencing treatment.
Starting treatment: pain is best treated early because once established it is harder to treat; early management of acute pain may minimise the transition to chronic pain.
What are your drug choices?
-paracetamol, NSAIDs, opiods, LA, and adjuvant agents including antidepressants, antiepileptics and corticosteroids. The analgesic should be tailored to the patient and their type and severity of pain.
What is the WHO analgesic ladder?
The WHO analgesic ladder is often used for acute and chronic pain. Treatment starts at the step appropriate for pain severity and is adjusted according to pain severity.
Rungs on the WHO analgesic ladder:
Mild pain: regular paracetamol or NSAID
Moderate pain: weak opioid tramadol, codeine, low does oxycodone with a non opioid (usually paracetamol); use seperate products to allow individual dose titration
Severe pain: potent opioid (morphine) with a non-opiod
Consider the need for co-analgesics, laxatives, non-drug treatments at every step.
What are the routes of administration for pain medication?
Oral: use where possible is as effecyive as parenteral administration in most cases. Use a conventional release product for acute pain, dose titration (initial treatment or unstable phases) and for breakthrough and incident pain. Use controlled release products for stable chronic pain; slow onset makes then unsuitable for acute pain.
Parenteral: IV administration is preferred for acute, severe pain i.e. post-operatively. Not appropriate for chronic pain.
Transdermal: patches containing opioids are appropriate for stable chronic pain although the dose is relatively inflexiable.
Methoxyflurane: may be useful short term; inhaled pain relief; can be used during ambulance transportation to hospital
Rectal: an alternative to parenteral highly vascular area; rapidly absorbed.
REMEMBER: non-drug treatments
-heat or cold applications
-massage
-exercise
-immobilisation
-TENS
-cognitive behavioural therapies
-surgery i.e neural blockade or spinal cord stimulation
What is acute pain?
Acute pain has a defined pattern of onset, site, character, and duration; the cause is often identifiable e.g. disease, trauma

Rationale for drug use:
-relieve suffering
-reduce or prevent harmful physiological and psychological effects
-reduce transition to chronic pain
-assist rehabilitation by physical therapy and mobilisation

Before commencing treatment identify the precipitating cause if possible; this must not delay administration of adequate analgesia
When to start treatment of acute pain?
As soon as possible. When pain is predictable i.e. post-op prophylaxis is appropriate
Treating post-op pain
-Aim for early control and regular assessment; as post-op pain tends to change with time. Even minor surgery can be associated with substantial pain; which can last up to a week and interfere with activity of daily lifestyle (ADL's).
-An as required (PRN) regimen where the does of analgesic is titrated to the patient's response is often appropriate. Where pain is predicatble regular anlagesics e.g. paracetamol and or NSAIDs may also be used
-NSAIDs and/or paracetamol may be adequate after minor and day case procedures. Codeine 60mg added to paracetamol produces additional pain relief even as a single dose
-Opioids are the mainstay for relief of moderate-severe post-op pain
Things to remember when treating acute pain.
Consider the possibility of undetected pathology or the development of other problems if pain
-responds poorly to appropriate management
-changes in patter
-increases in severity
-is becoming chronic

N/B patients on chronic opioid treatment may require higher doses of opioids for relief of acute pain (e.g. post-op)
What is chronic pain?
Chronic pain is pain persisting for more then 3 months or persisting after healing is expected to complete. Often acute exacerbations of chronic pain may occur.

Rationale for drug use:
-provide symtpom relief
-maintain or restore function
-improve quality of life

Before commencing treatment:
-treat identifiable pathology if possible
-discuss and agree on realistic treatment goals with the patient/ carer. It is not usually possible to eliminate pain completely but it should be possible to reduce symptoms to a tolerable level.

Minimising adverse drug effects and maintaining or restoring function are also important considerations
Things to remember in the treatment of chronic pain.
-Titrate analgesic dosage against patient response and AEs and RV regularly; after titration an dstabilisation give regular analgesics for continous pain relief
-Ensure eraly referral of patients whose pain relief is inadequate to a multidisciplinary pain clinic or palliative care service
Non-opioid analgesics
-paracetamol
-aspirin
-NSAIDs
Paracetamol
Paracetamol has an antipyretic action, minimal anti-inflammatory effects and no effect on platelets; it can be used in all ages and is preffered to NSAIDs for fever and mild to moderate pain as it has fewer AE. In OA its use alone is preferred but under-used.

MOA: not fully determined. The antipyretic effect is probably due to reduced production of prostaglandins in the hypothalmus. Paracetamol has negligible anti-inflammatory effects.

OOA: onset of pain relief approx 30 mins post oral administration

Pregnancy: CAT A. Breastfeeding: Safe to use

Indications:
-mild to moderate pain (includes combination with codeine)
-fever
-migraine (with metoclopramide for N and V)

Precautions:
-sodium restriction: soluble paracetamol can contain large amounts of sodium
-hepatic: patients with chronic liver disease may be at increased risk of liver damage following therapeutic dose or overdose of paracetamol

Adverse effects:
Common: increase of aminotranferases
Hepatotoxicity: a trial has found that 4mg daily of paracteamol for 4 or more days commonly caused an increase in aminotransferase levels; the clinical significance of this is unclear

Dose:
Adult, child >12 years
Oral/rectal, 0.5-1 g every 4-6 hours; maximum 4 g daily
Oral controlled release (665 mg), 2 tablets every 6-8 hours swallowed whole. Maximum 6 tablets (3990 mg) daily
Maximum dose
Usual maximum dose in adults is 4 g daily
Combination with codeine
1-2 tablets (of paracetamol 500 mg and codeine 8, 15 or 30 mg) every 4-6 hours if needed, up to a max 8/day

Counselling
There are many brands of paracetamol. It is also contained in many cough and cold products. Prevent overdosing by checking carefully which strength product is being used, and the correct dose for that product. Avoid using more than one product containing paracetamol at the same time. Too much paracetamol can cause liver damage
Aspirin
MOA: Aspirin has analgesic, antipyretic, anti-inflammatory and antiplatelet actions. It is a nonselective NSAID, preventing synthesis of prostaglandins by noncompetitively inhibiting both forms of cyclo-oxygenase (COX), COX-1 and COX-2.

Pregnancy: CAT C Breastfeeding: Avoid


Indications
-Inhibition of platelet aggregation
-Mild-to-moderate pain
-Fever

Dose:

Analgesic, anti-inflammatory, antipyretic, 300-900 mg every 4-6 hours when necessary

Precautions:

-Allergic reaction to aspirin or other NSAID—contraindicated.
-Heart failure, uncontrolled hypertension—may be exacerbated by sodium and fluid retention caused by aspirin-induced reduction in GFR
-Asthma—risk of bronchospasm is increased
-Gout—avoid aspirin during an acute attack as plasma urate conc may change
-History of peptic ulcer—increases risk of GI ulceration
-Risk of bleeding: Contraindicated in severe active bleeding or disease states with an increased risk of severe bleeding, eg bleeding disorders, PUD
-Renal: Renal impairment increases risk of bleeding
-Surgery: If possible, stop aspirin (analgesic or anti-inflammatory doses) at least 7 days before surgery, especially if there is a significant risk of perioperative bleeding, and in people requiring critical haemostasis
-Elderly: Increased risk of AEs, in particular GI ulceration and renal impairment
-Children: Avoid use for analgesia or fever in children <12 years

Adverse effects
Common: nausea, dyspepsia, vomiting, GI ulceration or bleeding, asymptomatic blood loss, increased bleeding time, headache, dizziness
Rare: major haemorrhage (GI or other), blood dyscrasias
Allergy: Bronchospasm, angioedema, urticaria and rhinitis have been precipitated by aspirin, particularly in people with asthma

Counselling
If you develop swollen ankles, difficulty in breathing, black stools or vomit that looks like coffee grounds, stop taking the medicine and contact your doctor without delay.
It may be advisable to stop taking aspirin 7 days before planned surgery
NSAIDs
NSAIDs have anti-inflammatory and antipyretic properties and some have anti-platelet effects

Nonselective NSAIDs (COX-1 and COX-2 inhibitors)
-Aspirin
-Diclofenac
-Ibuprofen
-Indomethacin
-Ketorolac
-Naproxen

Selective NSAIDs (COX-2 inhibitors)
-Celecoxib
-Meloxicam
NSAIDs MOA and indications for use.
Have analgesic, antipyretic and anti-inflammatory actions. They inhibit synthesis of prostaglandins by inhibiting cyclo-oxygenase (COX) present as COX-1 and COX-2:
inhibition of COX-1 results in impaired gastric cytoprotection and antiplatelet effects
inhibition of COX-2 results in anti-inflammatory and analgesic action
reduction in glomerular filtration rate and renal blood flow occurs with both COX-1 and COX-2 inhibition
Most NSAIDs are nonselective, inhibiting both COX-1 and COX-2. Although selective COX-2 inhibitors have little or no effect on COX-1 at therapeutic doses, they are still associated with GI adverse effects

Indications for use:
-RA including JRA
-OA
-inflammatory arthropathies including ankolysingspondolisis, psoriatic arthritis
-acute gout
-pain especially due to inflammation and tissue injury e.g. post op
-fever
NSAIDs precautions
-Allergic reactions to NSAIDs, including aspirin
-Asthma —NSAIDs may increase risk of bronchospasm
-Coagulation disorders—nonselective NSAIDs increase bleed risk
-Cardio- or cerebrovascular: NSAIDs increase risk of cardiovascular events, eg MI and stroke.
-Heart failure and hypertension may worsen due to sodium and fluid retention
-Gastrointestinal: CI in active or Hx of PUD/ GI bleeding
-Renal: Pre-existing renal impairment increases the risk of NSAID-induced impairment; nonselective NSAIDs increase risk of bleeding
-Surgery: Risk of renal impairment or increased blood loss in major sxs, cease few days prior
-Elderly: Increased risk of adverse effects, in particular heart failure, GI ulceration and renal impairment.

Pregnancy: CAT C Breastfeeding: safe
AEs NSAIDS
Common: nausea, dyspepsia, GI ulceration or bleeding, raised liver enzymes, diarrhoea,
headache, dizziness, salt and fluid retention, hypertension
Infrequent: oesophageal ulceration, heart failure, hyperkalaemia, renal impairment, confusion, bronchospasm, rash

Cardiovascular effects: All NSAIDs can worsen existing CVDz

Gastrointestinal effects
All NSAIDs can cause serious GI adverse effects
Selective NSAIDs (COX-2 inhibitors) are generally associated with a lower risk
Nonselective NSAIDs: ketoprofen and piroxicam appear to have the highest risk of GI complications while diclofenac and ibuprofen appear to have the lowest
NSAIDs counselling; practice points
Counselling
If you develop swollen ankles, difficulty in breathing, black stools or dark coffee-coloured vomit, stop taking the medicine and seek medical advice.

Do not take aspirin for pain relief as it will increase the risk of side effects with this medicine

Practice points
about 60% of patients will respond to any NSAID; those who do not respond to one may respond to another
in osteoarthritis, maximal analgesic and anti-inflammatory effects are usually seen within 2 weeks; if appropriate responses are not observed within 3 weeks, try a different NSAID
there is no rationale for using >1 NSAID at a time (excluding low-dose aspirin)
for extra pain relief NSAIDs may be used with paracetamol and, if pain is severe, an opioid
seek specialist advice if a patient has aspirin-induced asthma and great need for an NSAID
To reduce complications:
use the lowest effective dose for the shortest period of time
use paracetamol to enable lower doses of NSAID
use one of the proton pump inhibitors with an NSAID in patients who must have an NSAID and are at high risk of GI adverse effects
Ibuprofen
Non-selective NSAID.
Topical or Oral.
Dose:
Adults: 200-400mg 3 or 4 times a day. Maximum of 2400mg daily.
Topical: Adults. Children >12 years; 4-10cm rubbed into affected area if needed; up to 4 times daily.

Counselling: Take oral doses with or shortly after food. PLUS counselling for NSAIDS

Practice points
Ibuprofen can reduce the antiplatelet activity of low-dose aspirin and potentially reduce or negates its cardioprotective effect.
It is unlikely that an occasional dose would have a clinically important effect; if regular use is anticipated choose an alternative NSAID
Naproxen
Non-selective NSAID
Indications for use: RA, OA, ankylosing spondylitis, pain (especially due to inflammation)
Dose:
maximum: 1250 mg daily
conventional product: 250-500 mg twice daily
controlled release: 750-100mg once daily
Controlled release products can be taken at night to relieve nocturnal and morning symptoms
Practice points: naproxen can reduce the antiplatelt activity of low dose aspirin and potentially reduce or negate its cardioprtective effect
Ketorolac
Non-selective NSAID
Indications: mild to moderate post operative pain.
Contraindications
Conditions where risk of bleeding is increased or haemostasis is critical
Dehydration or hypovolaemia
Treatment with probenecid, aspirin, lithium or oxpentifylline
Moderate to severe renal impairment
Precautions
Reduce dose in mild renal impairment (renal impairment increases the half life of the drug)
Elderly: the half life of Ketorolac may be greater in older people and thus increase the risk of AE; a reduced dose should be used to avoid this
Dose: oral; 10 mg every 6-8 hrs (maximum 30-40mg daily)
Diclofenac (Voltaren)
Non-selective NSAID
MOA, Indications, precautions, AE and counselling as per NSAIDs

Precautions: increased cardiovascular risk-avoid diclofenac as it may increase the risk of a cardiovascular event.

Dose:
Oral/rectal: 75-150mg daily in 2 or 3 doses. Maximum 200mg daily
Topical: 1% gel, rub into the affceted area 3 or 4 times daily
Indomethacin
Non-selective NSAID
MOA, Indications, precautions, AE and counselling as per NSAIDs

Additional indication: Acute GOUT.

Dose:
Oral 25-50mg 2-4 times daily
Rectal 100mg once or twice daily
Meloxicam
Selective NSAID
MOA, Indications, precautions, AE and counselling as per NSAIDs
Very good for Rx of OA
Dose:
Adult 7.5 -15mg once daily; if required
Practice points:
-use the lowest effective dose, as the COX-2 selectivity of meloxicam is dose-dependent
-15mg provides greater pain relief than 7.5mg but also a higher frequency of GI adverse effects
-it is not indicated for relief of pain unrelated to arthritis
Celecoxib
Selective NSAID
MOA, Indications, precautions, AE and counselling as per NSAIDs
Contraindications
Allergy to sulfonamides- may increase the risk of allergy to celecoxib
Heart failure, angina, peripheral arterial disease or cerebrovascular disease
Use is contarindicated in severe hepatic impairement; reduced dose is reccomended in moderate impairment
Dose:
Risk of cardiovascular adverse events is dose related; do not use >200mg daily long term.
ankylosing spondylitis; OA: Adult up to 200mg daily in 1 or 2 doses
RA: Adult 100mg twice daily; may be increased to 200mg twice daily (short term)
Pain (post op, MSK, soft tissue) Adult 400mg single dose on the first day then 200mg once or twice daily if need; maximum 5 days of treatment
Moderate hepatic impairment: start at half the recommended dose
Practice points:
similar risk of ulcer-related complications to non-selective NSAIDS
Combination products
Problems with combination products include:
-fixed combinations do not allow titartion of doses of components
-accumulation of the drug with the longer half-life where the combination contains drugs with different half lives
-increased likelihood of adverse effects including analgesic nephropathy
-potential misuse of opioid-containing combinations
-often more expensive
Opioids
MOA: opioid analgesics mimic endogenous opioids by activating opiod receptors in the central nervous systems to produce
-analgesia
-respiratory depression
-sedation
-constipation
They reduce transmission of the pain impulse by acting pre and post synaptically in the spinal cord, and by modulating the descending inhibitory pathways from the brain.

Indications for use: Acute or chronic pain
Opioid precautions
Epilepsy or seizure risk.
Respiratory: use with extreme caution in patients with respiratory depression, severe obstructive airways disease, asthma or decreased respiratory reserve as opioids may further depress respiration, decrease the cough reflex and dry secretions
Renal: use with caution. The continued use of codeine, morphine, pethidine and tramadol in renally impaired persons may cause an accumulation of active/toxic metabolites.
Hepatic: May require a dose adjustment
Elderly: opioid dose requirement decreases progressively with age. There is an increased risk of AE including cognitive impairment, sedation and falls. Use a lower initial dose and titrate to effect.
Pregnancy: CAT C. Do not breastfeed.
Opioids: Adverse Effects
Common: Nausea and vomiting, dyspepsia, drowsiness, dizziness, headache, orthostatic hypotension, itch, dry mouth, miosis, urinary retention, constipation.
CONSTIPATION: tolerance develops slowly if at all. Attention to fluid intake, diet and mobility plus regular laxative use (eg Senna, sorbitol) is essential as soon as chronic opioid treatment is started.
RESPIRATORY DEPRESSION THE MOST SERIOUS ADVERSE EFFECT OF OPIOIDS.
DEPENDENCE:physical dependance is common: withdrawal symptoms (nausea, vomiting, diarrhoea, sweating, anxiety) occur if chronic treatment is stopped suddenly or an antagonist is given.
The risk of psychological dependance (compulsion to use the drug) and addiction (compulsive use to the detriment of physical and/or psychological and/or social function) develpoing in patients iwthout a substance misuse is unknown, but probably rare.
Opioids: Counselling
This medication may make you feel drowsy and may increase the effects of alcohol. If you are effected do not drive or operate heavy machinery. Be careful when you stand up as this medication may make you dizzy if you stand up too quickly.
Opioids: Practice points
-Morphine is the preferred opioid analgesic for moderate to severe pain because of familiarity, availabilty, and cost (rather than superior efficacy)
-Always use a laxative for people requiring regular opiods long term
-Nalooxne is used to reverse opiod related sedation and respiratory depression
Codeine
Opioid analgesic.
Indications: mild to moderate pain (includes combinations with aspirin, ibuprofen, paracetamol); cough supression, diarrhoea
Dose: Oral, SC or IM 30-60mg every 4 hrs, maximum 240mg in 24 hrs. Consider alternative opiod if this dose is reached.
Codeine: Practice points
-Codeine may be used for moderate pain not controlled by non-opioid analgesics; it is frequently used with paracetamol or aspirin.
-Codeine is metabolised to morphine by CYP2D6.
-Some people are unlikely to obtain analgesia with codeine due to a genetic lack of CYP2D6 eg 6-10% of caucasians and 1-2% of Asians
-Some people are ultra-rapid metabolisers, eg up to 10% of caucasians , 1-2% of Asians and 29% of Ethiopians, and may achieve higher morphine concentrations, increasing their risk of toxicity.
-Beware of potential misuse as a street drug
Codeine: combination products
-Combinations of codeine 60mg and paracetamol 100mg are more effective for acute pain than paracetamol 1000mg alone, although the incidence of drowsiness is increased
-There is no evidence that combination analgesics containing lower doses of codeine with paracetamol, apsirin or ibuprofen have any benefit over these non-opioids alone.
-Use a laxative with long term use of codeine
Oxycodone
MOA, indications, percautions, AEs and counselling as per opioids.
Equivalence: 15-20mg oral oxycodone is approximately equianalgesic to 20-30mg oral morphine or 10mg IM morphine. When changing drugs; start at half of the calculated equianalgesic dose and titrate to response.
Practice points:
-oxycodone may be tried as an alternative opioid for patients intolerant of morphine
-do not use controlled release tablets for acute pain as slow onset and offset make rapid, safe titration impossible; their onset of action is up to 1 hour and duration of effect is about 12 hours.
Other pain meds: Methoxyflurane
MOA: basically an inhaled anaesthetic. Thought to enhance inhibitory ion channel activity and inhibit excitatory activity in the brain to induce hypnosis and amnesia, and in the spinal cord to cause immobility in response to painful stimuli.
Indications: analgesia (in subanaesthetic concentrations)
Precautions:
-contraindicated in renal impairment
-CAT A, Breastfeeding OK
AE: ucommon and usually mild in analgesic doses e.g nausea, vomiting, headache, drowsiness
Rarely: arrhytmias, malignant hyperthermia, hepatotoxicity (volatile agents)
Methoxyflurane: Dose and practice points
Dose: adult 0.2-0.7%; up to 6mL/day. Maximum 15mL/week. Do not use on consecutive days.
Practice points:
-mainly used for immediate, short-term pain relief in the pre-hospital setting e.g QAS
-onset of pain relief after 6-8 breaths; continues for several minutes after use
-3mL of methoxyflurane used intermittently provides analgesia for approximately 20-30 minutes.
Treatment of Gout
Rationale for drug use:
Acute gout: provide symptom relief
Chronic gout: prevent acute attacks, joint destruction, disability, nephrolithiasis and renal disease, and resolve tophi.
Before starting treatment: minimise exacerbating factors e.g. obesity, alcohol consumption, diuretic use; particularly in tophaceous gout.
Acute gout: consider diagnosis and exclude infective cause, especially for acute monoarthritis (spetic and crystal arthritis may occur together)
Urate-lowering treatment: many patient will not have recurrent acut gout and long term treatment exposes them to the risk of drug toxicity, which may be severe; consider the need for urate-lowering treatment carefully
Treatment of Gout: When to start treatment
Asymptomatic hyperuricaemia: treatment is not indicated
Acute gout: treat early to limit morbidity and possibly shorten the duration of attack. Diagnosis may be confirmed by arthrocentesis before or after starting treatment with and NSAID, corticosteroid or colchicine
Urate lowering treatment: consider the need for urate lowering treatment carefully. If attacks are infrequent, early treatment of acute attacks and risk factor management may be sufficient and will avoid toxicity associated with this long term treatment.
Allopurinol and probenecid are indicated in tophaceous gout, urate nephrolithiasis, and nephropathy. They may be used in non-tophaceous gout if acute attacks are frequent.
Ensure acute attack is resolved before starting urate-lowering treatment, as changes in plasma uric acid concentartion may exacerbate and prolong acute attacks.
Consider prophylaxis, with colchicine or NSAID, for the first 3-6 months of treatment to reduce risk of an acute attack
Treatment of Acute Gout: Drug choice
Acute gout
NSAIDs (except aspirin) treatment of choice for acute gout if not contraindicated. All NSAIDs appear to be equally effective. Use full dose and continue treatment for a week after acute attack has settled.
Corticosteroids are often the preferred treatment for acute gout in patients with complex medical problems where NSAIDs are contraindicated. They may be given IV or orally or by intra-articular injection when 1 or 2 joints are involved.
Colchicine is reserved for acute gout when NSAIDs and corticosteroids (systemic or intra-articular) are contraindicated or inappropriate
Urate-lowering treatment
-Start with a low dose and increase slowly to minimise risk of precipitating acute gout
-Allopurinol lowers plasma urate by inhibiting its production; it is commonly used in long term treatment of gout.
-Probenecid reduces plasma urate by increasing renal excretion of uric acid; it is infrequently used for long-term treatment of gout. Sometimes specialists use it with allopurinol for tophaceous disease when allopurinol alone is inadequate. Renal impairment reduces its effectiveness.
Prevention of acute attacks during urate-lowering treatment
Treatment with low-dose colchicine or NSAID may be used to prevent acute gout (affects about 25% of patients) during the first 3-6 months of urate lowering treatment, however, longer treatment may be needed if attacks continue or if large tophi are present.
Colchicine is preferred treatment; it has been shown to reduce the frequency and severity of acute attacks.
NSAIDs (except aspirin): use the lowest effective dose (trial evidence to guide use is lacking)
Treatment of Gout: Factors influencing drug selection
Renal impairment
-Gout is common in renal impairment due to reduced clearance of uric acid. Renal impairment also has consequences for many drugs used for gout:
-Corticosteroids are preferred in acute gout
-NSAIDs may worsen renal function and are associated with an increased risk of GI toxicity; avoid use
-Allopurinol has a renally excreted metabolite; reduce dose to avoid toxicity
Anticoagulant treatment
Systemic corticosteroids are often the treatment of choice in anticoagulant patients with acute gout. Colchicine can be used; avoid NSAIDs due to risk of GI bleeding. Intra-articular corticosteroids are generally not reccomended.
Treatment of Gout: practice points
-although gout is more likely in people with hyperuricaemia, some people with gout have normal urate concentrations and may people with hyperuricaemia never develop gout
-instruct patients with recurrent acute attacks to take an NSAID or colchicine at the earliest sign of an attack (most attacks resolve in 7-10 days)
-there is a delay before colchicine's onset of effect in an acute attack, advise use of an analgesic e.g. paracetamol during this time
-avoid aspirin as an analgesic during an acute attack; in such doses aspirin may change plasma urate concentration, which may worsen and prolong an attack
-do not stop low dose aspirin in coronary or cerebrovascular disease, although these doses increase urate concentrations
Colchicine
MOA: inhibits neutrophil migartion, chemotaxis, adhesions and phagocytosis in the inflammed area; reduces the inflammatory reaction to urate crystals but has no effect on uric acid production or excretion.
Indications: relief of pain in acute gout; prophylaxis of recurrent gout attacks including when starting urate-lowering treatment
Precautions:
-history of blood dyscrasias
-severe GI disease-colchicine may exacerbate symptoms
-other drugs-contraindicated in renal or hepatic impairment if used with strong inhibitors of CYP3A4 or P-glycoprotein inhibitors due to possible toxicity due to increased colchicine concentration.
-Renal impairment-reduces elimination of colchicine, increases risk of AE. Lower dose may be needed.
-Hepatic impairment-reduces elimination of colchicine, increases risk of AE. May need to use lower dose. in acute gout increase the time between courses for severe hepatic impairment. Do not use for acute attack in patients with hepatic impairment who are taking prophylactic colchicine.
CAT B2. Breastfeeding NO
AE:
Common: diarrhoea, nausea, abdominal discomfort, vomiting
Infrequent: GI haemorrhage, rash
Dose
Acute gout attack
Adult, 1 mg as soon as possible, then 500 micrograms 1 hour later (maximum 1.5 mg per course). Do not repeat the course within 3 days (wait at least 12 hours before resuming prophylactic colchicine).
CrCl <80 mL/minute or hepatic impairment, do not use for acute attack if using colchicine for prophylaxis.
CrCl <30 mL/minute or severe hepatic impairment, dosage as above; do not repeat the course within 2 weeks.

Prophylaxis, including when starting urate-lowering treatment
Adult, 500 micrograms once or twice daily, according to response and GI symptoms.
Colchicine: counselling
-do not take more than 3 tablets (1.5mg) in a course to treat acute gout or repeat the course within 3 days
-tell all health professionals that you are taking colchicine so that they can choose medicines appropriately
-avoid grapefruit juice as it may increase rge amount of colchicine in your bloodstream and could increase the chances of side effects occuring
-stop taking this medicine, and tell your prescriber or doctor if you develop severe diarrhoea or vomiting, muscle pain, tenderness or weakness, numbness or tingling in your fingers or toes, unusual bleeding, brusing or an infection
Colchicine: practice points
Accumulation and toxicity may occur if
-acute course is repeated too quickly
-colchicine is continued when GI effects occur (elimination can take >10days)
-colchicine is used with a drug that inhibits its metabolism e.g. clarithromycin
-Measure complete blood count before using long term; repeat after 1 and 6 months then annually
-consider for acute gout only when NSAIDs and corticosteroids are contraindicated or inappropriate
-in an acute attack start colchicine as soon as possible (most effective if started within 24hr of the onset of symptoms)
-joint inflammation subsides within 48 hours in 75-80% of patients
-colchicine is used to prevent attacks during the first 3-6 months of urate-lowering treatment (longer if attacks continue or large tophi are present)
-colchicine may be used instead of NSAIDs in heart failure as it does not cause fluid retention
OA
Rationale for drug use
-relieve symptoms (pain/stiffness) and improve joint function to enable the patient to exercise and increase strength and mobility
Before starting treatment
-advise on non-drug measures such as weight loss, activity (use it or loss it), physical therapy, devices eg walking stick and arthritis self management courses.
When to start drug treatment
-consider drug treatment when patient requests symptom relief
OA Drugs
Paracetamol is the preffered drug. It is better tolerated then an NSAID and may be as effective, especially if OA is mild to moderate in severity.
Topical NSAIDS, capsaicin and rubefacients can be used but may be expensive. Local application has the advantage of lower systemic absorption and less frequent serious adverse effects. Topcal NSAIDs may be sufficient if symptoms are mild or can be added to regular paracetamol.
NSAIDs
-serious adverse effects are associated with all NSAIDs
-no difference in efficacy has been demonstrated between different NSAIDs in the treatment of OA
-addition of an NSAID ri regular paracetamol may produce adidtive benefit and limit the dose of NSAID required
-If NSAIDs are ineffective, contraindicated or not tolerated, consider intra-articular or peri-articular corticosteroids, opioid analgesics or surgery
OA: Glucosamine
Commonly used to relieve OA pain, however data regarding its efficacy are mixed and benefits appear modest. Available from pharmacies and health food shops in a variety of salt forms, products and strengths. Some products are extracted from shellfish ad contain traces of animal prteins; they should not be taken by people allergic to shellfish.
OA: treatment summary
-encourage regular exercise and non-drug measures to reduce pain, increase strength and mobility.
-start drug treatment with regular paracetamol; continue non-drug measures
-if more analgesia is required consider adding a topical NSAID
-if further analgesia is needed add a low dose of a short acting NSAID to be used only when needed (i.e. 30-60 minutes before painful acivity), consider intra-articular corticosteroid
-if further analgesia is required use a higher dose of NSAID
-if this is inadequate consider orthopaedic review and oral opiod analgesics
Practice points
-clinical signs of inflammation may not predict a better response to an NSAID than to paracetamol
-many patients on a long-term NSAID can be switched to paracetamol without an increase in symptoms
Acute soft tissue injuries
Bursitis and tendonitis
-RICES and use of pasisve motion to maintain mobility, local heat
-analgesics reduce pain and mobilisation (NSAIDs)
-Topical NSAIDs and rubefacients may be considered

Strains and sprains
-reduce pain and swelling with rest, ice, compression and elevation ofthe injured limb for the firts 1-2 days
-early mobilisation aids recovery
-use analgesics (paracetamol) to reduce pain and assist mobilisation
-topical NSAIDs or rubefacients can also be considered
Practical points in pain medication prescription
-an integrated multidisciplinary approach to pain management is often required for both acute and chronic pain; patient involvment in the initial and ocntinuing assessment of their pain and their response to treatment is essential
-people with a history of substance misuse may require higher dose of analgesics to manage their pain effectively; liase with local drug and alcohol services regarding their care
-fear of adverse effects of analgesics is often disproportionate to actual risk and should not result in undertreatment; however long term use of NSAIDs is associated with a significant incidence of serious problems especially in the elderly
- children and adults experience similar types of pain and the principles of pain management, including drug treatment, apply to all individuals
Prescribing for the elderly
Pharmacokinetics
The most important effect of ageing is reduction in renal function, resulting in reduced elimination of renally excreted drugs and active drug metabolites >> Dosages of these drugs should be reduced in the elderly>> Failure to make appropriate dose alterations probably explains, in part, the increased incidence of adverse drug reactions in the elderly
Acute illness (eg MI, UTI) can lead to a rapid decrease in renal function and renal clearance of drugs, and a person stabilised on a renally cleared drug with a narrow therapeutic range may rapidly develop toxicity>> Monitor renal function and adjust chronic drug treatment appropriately in elderly patients with acute disease
Pharmacodynamics
Age-related changes in drug receptors and target organ responses can alter sensitivity to the effect of drugs (eg increased CNS effects of opioids)
Impairment of secondary compensatory mechanisms may predispose to adverse effects (eg orthostatic hypotension with diuretics)
Polypharmacy
The higher prevalence of disease in the elderly means that they often take many drugs >>risk of adverse drug effects and interactions is higher
Be aware that patients may be prescribed drugs from several sources (different doctors and hospitals). This is further complicated by the possibility of the person taking self-prescribed OTC medications, drugs for a previous illness, or even drugs prescribed for another person; the elderly are well known as hoarders of medicines.
Noncompliance
This can be unintentional, eg as a result of confusion or forgetfulness, or intentional, eg as an attempt to minimise adverse effects or to save money
Prescribing for the elderly
Practice points
whenever possible, use non-pharmacological treatments
prescribe the lowest feasible dose
prescribe the smallest number of medications, with the simplest dose regimens
prescribe from a limited range of drugs, and be familiar with their effects in the elderly
if there is difficulty in swallowing, prescribe liquid medications if available
provide simple verbal and written instructions for every medication, including repeat prescriptions, to improve compliance
be aware that presenting symptoms may be a result of existing medications; do not assume they are symptoms of old age
child-proof containers should be avoided where possible, as manual dexterity is often impaired in older people
regularly review chronic treatment; it may be possible to stop medications, or necessary to reduce the dose if renal function declines
most older people cope with their own medications when treatment regimens are simple; if necessary, make sure the carer understands the treatment regimen
Polypharmacy
Def: use of multiple medications by a patient. The precise minimum number of medications used to define "polypharmacy" is variable, but generally ranges from 5 to 10. While polypharmacy most commonly refers to prescribed medications, it is important to also consider the number of over-the-counter and herbal/supplements used.
The issue of polypharmacy is of particular concern in older people who, compared to younger individuals, tend to have more disease conditions for which therapies are prescribed. It has been estimated that 20% of Medicare beneficiaries have ≥5 chronic conditions and 50% receive ≥ 5 medications
The use of greater numbers of drug therapies has been independently associated with an increased risk for an adverse drug event, irrespective of age. There are multiple reasons why older adults are especially impacted by polypharmacy:
Older individuals are at greater risk for adverse drug events due to metabolic changes and decreased drug clearance associated with aging; this risk is compounded by increasing numbers of drugs used.
Polypharmacy increases the potential for drug-drug interactions
Polypharmacy increases the possibility of "prescribing cascades". A prescribing cascade develops when an adverse drug event is misinterpreted as a new medical condition and additional drug therapy is then prescribed to treat this medical condition
Use of multiple medications can lead to problems with medication adherence, compounded by visual or cognitive compromise in many older adults.
Antihistamines
Histamine release causes vasodilation and increases capillary permeability >> Antihistamines selectively antagonise the action of histamine at H1 receptors

Indications:
Allergic rhinitis and conjunctivitis
Chronic urticaria

Non-sedating-
Desloratadine: 5mg OD (Aerius, Claramax)
Fexofenadine:180 mg OD (Fexal, Fexotabs, Telfast)
Loratadine: 10mg OD (Allereze, Claratyne, Lorano)

Sedating-
Promethazine

Response to a specific antihistamine varies widely, and it may be necessary to try a number of agents to determine which is best tolerated and most effective; response to one member of a class does not predict response to another member of that class
Promethazine
MOA:Antagonise the action of histamine at H1 receptors, reducing histamine-related vasodilation and increased capillary permeability.
They also have anticholinergic activity, some have alpha-blocking activity and some have antiserotonin activity, eg cyproheptadine.

Indications
Allergic conditions, eg rhinitis, conjunctivitis, urticaria, contact dermatitis
Pruritus
Nausea and vomiting, including motion sickness
Sedation, eg for cases of burns, measles, chickenpox
Premedication
Precautions
Epilepsy—promethazine lowers the seizure threshold.
Pregnancy: Category C, Breastfeeding: Limited data but short-term use appears safe. Sedation of mother is main concern
Closed-angle glaucoma, increased intraocular pressure, pyloroduodenal obstruction, bladder neck obstruction, hyperthyroidism—may be worsened by the anticholinergic effects of antihistamines.
Elderly: Avoid use (less sedating antihistamines preferred for allergic conditions) or use a lower dose; increased risk of adverse effects, eg dizziness, sedation, confusion, hypotension, falls, anticholinergic effects
Children: Avoid use, particularly in children <2 years (less sedating antihistamines preferred for allergic conditions); increased risk of adverse effects, eg sedation, paradoxical stimulation, anticholinergic effects
Adverse effects
Common: sedation, dizziness, tinnitus, blurred vision, euphoria, incoordination, anxiety, insomnia, tremor, nausea, vomiting, constipation, diarrhoea, epigastric discomfort, dry mouth, cough
Paradoxical stimulation: CNS stimulation (excitation, hallucinations, ataxia, seizures) may occur rarely, especially in children, rather than sedation.
Promethazine: dosage and counselling
Dose
Allergy
Adult, child >12 years, oral 25-75 mg once daily, or 10-25 mg 2-3 times daily or IM 25-50 mg single dose.
Child >2 years, IM/oral 0.125 mg/kg 3 times daily, and 0.5 mg/kg at night.

Nausea and vomiting
Adult, child >12 years, oral 25 mg or IM 12.5-25 mg every 4-6 hours as needed, maximum 100 mg daily.

Sedation
Adult, child >12 years, oral 25-75 mg once daily or IM 25-50 mg single dose.

Counselling
This medication may make you sleepy; don't drive or operate machinery if this happens.
Avoid alcohol and other medication that may cause sedation.
Corticosteroids
MOA: anti-inflammatory, immunosuppressive and antimitotic activity against cutaneous fibroblasts and epidermal cells. They are also vasoconstrictive.

Products:
Desonide (Desowen)
Betamethasone (Diprosone)
Hydrocortisone (DermAid Soft Cream)
Methylprednisolone (Advantan)
Triamcinolone (Aristocort, Tricortone)
Dexamethasone

Indications
Relief of inflammation and itch in conditions such as eczema and psoriasis

Precautions
Diabetes—avoid extensive use as systemic absorption can increase blood glucose concentration.
Immunocompromised patients—avoid extensive use as systemic absorption can result in further immunosuppression.
Skin
Contraindicated for application to ulcerative skin conditions, untreated skin infections, rosacea, acne vulgaris or areas with impaired circulation.
Skin atrophy (eg in the elderly) can be potentiated by topical corticosteroids and can increase their systemic absorption.
Pregnancy: Use the lowest appropriate potency of topical corticosteroid for the shortest time necessary where emollients and other simple measures are inadequate; betamethasone, clobetasone, hydrocortisone, methylprednisolone and triamcinolone Australian category A; desonide and mometasone Australian category B3
Breastfeeding: Safe to use

Adverse effects
Relative potency, patient age, site and extent of disease, product type, method of application and length of treatment determine the incidence and severity of adverse effects.
Common: folliculitis, steroid rosacea, perioral dermatitis, skin atrophy, delayed wound healing, striae, purpura, depigmentation, telangiectasia, acneiform eruptions
Infrequent: allergic contact dermatitis

Comparative information
Potency: determined by vasoconstrictive ability, inhibition of inflammation, potential for causing adverse effects and formulation (for the same concentration of corticosteroid, ointments are more potent than creams)
Both absorption-enhancing ingredients (eg urea, salicylic acid) and occlusion will increase relative potency
Site: use hydrocortisone on face and flexures; avoid using more potent corticosteroids on these areas. However, methylprednisolone may be used in unresponsive cases under close supervision for 2-3 days (maximum 7 days). More potent products may be used on palms, soles and lichenified areas.
Application: topical corticosteroids are usually applied twice a day, except for mometasone and methylprednisolone, which are applied once a day. There is no benefit from more frequent application; in some cases less frequent application may be adequate (eg eczema).
Corticosteroids: practice points
use an appropriately potent product for the shortest time necessary to control skin disorder
potential for systemic absorption increases with extent and activity of disease; monitor strength and amount being used
to reduce adverse effects of topical corticosteroids during treatment of chronic dermatoses, they may be used:
to treat exacerbations only
on 2 consecutive days/week to maintain remission
in combination with other agents
continuously, after initial response, using a low-potency product
allow sufficient time for absorption between application of a topical corticosteroid and a moisturiser; it is not clear which to apply first
wet wrap treatment may be useful in acute eczema
occlusion with polythene films may be used on a short-term basis on the palms and soles or on limited areas of lichenification (use vinyl gloves for hands)
BEWARE; the triple whammy
'triple whammy' - the combination of an ACE inhibitor (ACEI) or an angiotensin II receptor antagonist (A2RA), a diuretic and an NSAID (including a COX-2 selective NSAID), which may predispose vulnerable patients to renal failure

Risk factors include:
advanced age,
pre-existing renal impairment and
dehydration

There are now many combination products available that contain both an ACEI or an A2RA and a diuretic
ANTIFUNGALS
Fungal infections are common and often seen in podiatry.
Fungi are present in our environment an may co-exist with humans as commensals without causing pathological conditions
Mycoses have a much higher prevalence amongst the immunosuppressed population>> usually commensal mycoses causing opportunistic infections
Older people, diabetics, pregnant women
What fungal infections can we treat?
Superficial fungal infections >> 2 types
-Dermatomycoses
Infections of the skin, hair and nails, most commonly caused by Trichophyton, Epidermophyton and Microsporum
-Candidiasis
Mucous membranes (mouth/vagina) and skin
Why treat fungal infections?
-Cosmetic reasons
-Comfort reasons
-If left untreated fungal infections can become widespread and predispose patients to secondary bacterial infections
Antifungal drugs
-Topical and Systemic preparations
-Many antifungal agents are quite toxic >> If systemic therapy is indicated their use must be under strict supervision
Podiatry prescribed anti-fungals
1. Azoles
-clotrimazole, econazole, miconazole, ketoconazole, bifonazole
2.Fines
-terbinafine, amorolfine
3.Nystatin
Azoles
A group of synthetic fungistatic agents with broad spectrum activity
Dermatomycoses:
-Azoles inhibit the steroid that converts lanosterol to ergosterol
Ergosterol is the main sterol in the fungal cell membrane
Lack of egosterol > change in fluidity of membrane > inhibition of membrane-associated enzymes >> replication inhibition
Candida
-Inhibit the transformation of candial yeast cells into hyphae (the invasive and pathogenic form of the MO)
Ketoconazole
MOA: Impair biosynthesis of ergosterol for cyoplasmic membrane >> Inhibiting fungal growth (FUNGISTATIC)
Indication: Tinea, cutaneous candidiasis (Paronychia)
Topical Ketoconazole
CAT B3; Breastfeeding: safe
AE: Infrequent, usually well tolerated - burning, stinging, itch, erythema (Rare: allergic Rxn)
Oral Ketoconazole
Indication>> Recalcitrant cases of superficial mycoses where other antifunal Rx have failed

Pharmacokinetics: Well absorbed in the GIT, metabolised by the liver, excreted in the bile and urine (t ½ 8hrs)

Dose: 200mg OD for 2-3/52 Should be taken with food >> May increase dose to 400mg OD if inadequate response after reasonable trial
Pregnancy: B3, NOT for use if breastfeeding

AE:
LIVER TOXICITY >> Can be FATAL
Inhibition of testosterone synthesis >> gynacomastia
Infrequently: h'ache, dizziness, N/V, abdo px, itch, rash, allergic Rxn

Contraindications
Liver Disease (Acute or chronic)
Pregnancy
Concurrent use with ciclosporin, terfenadine or aztemizole inhibit the metabolism of Ketoconazole >> Increase plasma concentrations>> Increased SE >>>> MUST CHECK MIMS

Products:
Nizoral
Ketoconazole (NIZORAL)
MPORTANT**
>> Because of the risk of serious hepatotoxicity, Nizoral tablets should only be used when the potential benefits outweigh the potential risks (Consider other Rx first!!)
Must assess liver function prior to Rx to rule our chronic liver disease and monitor at frequent and regular intervals during Rx and at the first signs of hepatotoxicity
Pts should be be instructed to seek prompt medical advice if signs/symptoms of hepatitis >> N/V, fatigue, jaundice, abdo px, dark urine >>>>>> STOP RX IMMEDIATELY!!
Miconazole
MOA: Impair biosynthesis of ergosterol for cyoplasmic membrane >> Inhibiting fungal growth (FUNGISTATIC)
Pharmacokinetics: Well absorbed in the GIT, has a short plasma t ½ and needs to be given every 8 hrs. Inactivated by the liver
Indication: Tinea, cutaneous candidiasis (Paronychia)
Dose: Topical application twice daily
Pregnancy: A, Safe for breast feeding pts
AE: Relatively infrequent, usually well tolerated - burning, stinging, itch, erythema (Rare: allergic Rxn)
Can cause GIT upset
Rare: pruritis, blood dyscrasia, low sodium
Isolated reports of liver dysfunction: avoid use in pts with liver disease
Preparations:
Cream/liquid/spray/powder 2% 15g > Daktarin
Econazole
MOA: Impair biosynthesis of ergosterol for cyoplasmic membrane >> Inhibiting fungal growth (FUNGISTATIC)
Pharmacokinetics: Used only for TOPICAL application
Indication: Tinea, cutaneous candidiasis (Paronychia)
Dose: Topical application two-three times daily
Pregnancy: A, Safe for breast feeding pts
AE: Infrequent, usually well tolerated - burning, stinging, itch, erythema (Rare: allergic Rxn)
Products:
Cream 1%, 20g >> Pevaryl
Clotrimazole
MOA: Impair biosynthesis of ergosterol for cyoplasmic membrane >> Inhibiting fungal growth (FUNGISTATIC)
Pharmacokinetics: Used only for TOPICAL application
Indication: Tinea, cutaneous candidiasis (Paronychia)
Dose: Topical appliaction two or three times daily for 2-4/52
Pregnancy: A, Safe for breast feeding pts
AE: Infrequent, usually well tolerated - burning, stinging, itch, erythema (Rare: allergic Rxn)
Products:
Cream 1% 20g/ 50g > Canesten, Chemists Own Clozole Broard spectrum antifungal, Clozole, Clonea
Liquid 1% 20ml > Canesten
Bifonazole
MOA: Impair biosynthesis of ergosterol for cyoplasmic membrane >> Inhibiting fungal growth (FUNGISTATIC)
Pharmacokinetics: Used only for TOPICAL application
Indication: Tinea, cutaneous candidiasis (Paronychia)
Dose: Topical application once daily, continue use until 2/52 post symptom resolution
AE: Infrequent, usually well tolerated - burning, stinging, itch, erythema (Rare: allergic Rxn)
Pregnancy: B3, Safe for breast feeding pts
Preparations:
Cream 1% 20g - Canesten Once Daily
Cream 1% 15g - Mycospor
Terbinafine
MOA: Inhibition of the enzyme involved that converts squalene to ergosterol - the sterol necessary for cell wall synthesis. Build-up of squalene is TOXIC to the organism (FUNGACIDIAL). Only fungistatic against C.albicans
Pharmacokinetics: Used for oral therapy and topical application.
Topical: Rapidly absorbed by skin, nails and fat, penetrates skin and mucous membranes
Metabolised by liver, metabolites excreted in urine
Indication: Especially useful in onychomycosis, used in tinea pedis
Topical Terbinafine
Topical: Rapidly absorbed by skin, nails and fat, penetrates skin and mucous membranes
Rapid action of topical preparations usually allows shorter duration of treatment than with topical azoles, but is more expensive >> may be useful when pt compliance is an issue
Dose: Topical application once or twice daily for 1-2/52 (Rx course should not exceed 4/52)
Symptoms are usually relieved within a few days>> need to R/V DX if no signs of improvement after 2/52
TOPICAL: CAT B1, Breastfeeding: unlikely to be a concern
AE:
Infrequent: erythema, itch, stinging.
Rare: allergic Rxn
Preparations:
Cream 1% 15g/30g: Chemists own Tamsil, Lamisil
Gel 1% 15g: Lamisil DermGel
Liquid 1%: Lamisil Once
Note: liquid forms a film on the skin; for treatment of interdigital tinea pedis > a single application appears to be as effective as 1/52 Rx with cream prep. Liquid is not recommended for plantar tinea pedis
Oral Terbinafine
Metabolised by liver, metabolites excreted in urine
AE: Infrequent: Occur in 10% - usually self-limiting
GIT disturbance/ Rash/ Pruritis/ Headache/ dizziness
Indication>> Recalcitrant cases of superficial mycoses where other antifunal Rx have failed
Dose: 250mg OD for 6/52 if tinea pedis, up to 3/12 for OM
CAT B1, NOT for use if breastfeeding
AE: Generally well tolerated
Most commonly GIT upset
Infrequently: h'ache, dizziness, N/V, abdo px, itch, rash, allergic Rxn
Contraindications
Liver Disease (Acute or chronic)
Preparation:
Lamisil
Amorolfine
MOA: Inhibition of the enzyme involved that converts squalene to ergosterol - the sterol necessary for cell wall synthesis. Build-up of squalene is TOXIC to the organism (FUNGICIDAL)
Pharmacokinetics: TOPICAL only (Nail Lacquer)
Indication: Especially useful in onychomycosis
Used for superficial and distal OM >> not effective when nail matrix is involved
CAT B3, Breastfeeding: unlikely to be a concern
Dose: Top to nail 1-2/week until nail regrows
AE: Infrequent - erythema, itch, burning. Rare - allergic Rxn
Preparations:
Liquid 5% 5ml: Loceryl Nail Lacquer
Nystatin
MOA: Intereferes with membrane permeability and transport functions
Indication: Candidal infections of the skin, mucous membranes and GIT
Dose: Topical twice daily until healing complete
AE: Nausea, vomiting and diarrhoea
Preparation:
Cream 15g: Mycostatin
Prescribing Rationale: Antifungals
Define the patient's problem?
Specify the therapeutic objective?
What do you want to achieve with the treatment?
Verify whether your drug is suitable for this patient?
Check effectiveness and safety
Start the treatment
Give information, instructions and warnings
Monitor (stop) the treatment
Define the Pt's Problem
Diagnosis, diagnosis, diagnosis!!
Detailed history
Physical examination
X-rays and investigations

Disease/disorder
Extrinsic vs Intrinsic Factors

Sign of underlying disease
Remember your HIGH RISK groups!
Pregnancy
Lactation
Children
Elderly
Renal failure
Hepatic failure
History of drug allergy
Other diseases
Other medication
Immunocompromised/ immunosuppressed
Onychomycosis eTGA
-Because many disorders can mimic OM, eTGA recommend the establishment of a microbiological diagnosis prior to Rx commencement >> MCS +ve in ≈ 80 % of cases
-eTGA advise careful consideration of all treatment options especially if treatment is for cosmetic reasons only >> these drugs can be expensive for the pt and have SERIOUS AEs. However the toenails can be reservoir of infn and precipitate recurrent cellulitis in association with tinea of the feet.
Different Rx recommended depending on type of OM
>> DSO & TDO require ORAL antifungal Rx
>> Early, mild DSO has limited response to topical preparations and can be considered when oral antifungal meds are contraindicated
>> WSO is responsive to topical azoles
eTGA: OM Rx with Topical Antifungal
Amorolfine 5% nail lacquer topically once/ week
>> May require up to 12 months Rx!!
eTGA: OM Rx with Oral Antifungal
Terbinafine
ADULT: 250mg, once daily for 12 weeks
CHILD: < 20kg - 62.5mg, 20 - 40kg - 125mg
OR Itraconazole OR Fluconazole

Terbinafine has a cure rate of up to 80%
Itraconazole and fluconazole have been used extensively overseas and as a 3 month course have cure rates of up to 70%
Terbinafine is currently the drug of choice
eTGA: Tinea Pedis: Topical Rx
Topical Rx appropriate when localised infection.
Options
Terbinafine 1% cream/gel Top OD 1/52
Bifonazole 1% cream Top OD 2-3/52
Clotrimazole 1% cream/sol Top BD 2-4/52 and continued for 2/52 post symptom resolution
Econazole 1% cream Top BD continued for 1/52 post symptom resolution
Ketoconazole 2% cream Top OD continued for 2/52 post symptom resolution
Miconazole 2% cream/spray/powder Top BD 4/52
eTGA: Tinea Pedis: Oral Rx
Oral Rx appropriate for Rx of tinea in hair-bearing areas and on the palms/soles,
widespread tinea, tinea unresponsive to topical Rx and recurrent tinea.
Options:
Terbinafine 250mg PO OD 2-6/52 >> Treatment to continue until clinical resolution is achieved (Most cases 4/52 course is optimal)
Fluconazole, Iraconazole
eTGA: Paronychia
CP may be aggravated by secondary infection i.e Candida >>> antifungal managment

Miconazole 2% tincture topically BD for 5-7/7
eTGA: Onycholysis
Onycholysis: separation of nail plate from nail bed most commonly secondary to trauma or psoriasis
MOI: Space under nail plate > accumulation of moisture and debris > secondary infection with pseudomonas can occur >> olive green discolouration of nail plate
Rx: Vinegar soaks for 5-10 min twice daily
CAMs: what is a CAM?
Complementary and alternative therapies, including:
-acupuncture
-herbs
-reiki
-folk medicine
-massage
-naturopathy
-special diets
-yoga
-tai chi
-relaxation techiques
-homeopathy
-high dose viatmins
-hypnosis
-chiropractic
History of herbal medicine.
Plants have been used for medicinal purposes thorughout history.
today .120 conventionally used pharmaceuticals are derived from plant species
After about 1920, standardised pharmaceutical drugs increasingly replaced herbal therapies in the US--> synthetic drgs had larger pharmacological effects and greater profitability
Why do people use herbal medicines?
CAMs are used by people as way of:
-enhancing health
-helping with common chronic symptoms or diseases where conventional medicine may not offer a cure
-the belief that nature is healing is the mistaken perception that a naturally-derived product is always safe
Why is it important to ask our patients about herbal medicines?
Herbs are pharmacologically active and therefore can positively and negatively impact patient health
Positive effects >> improvement of symptoms
Negative effects >> AEs and drug-herb interactions (YES, they are dangerous)
Providers may need to consider herb-drug interactions when prescribing conventional medications
Regulation of herbal medicine
-There is substantial variation in the quality of commercially available products
-Variability in product quality can impact the product's efficacy, safety, and clinical usefulness
Product Variation
-plant species used
-plants parts used
-harvesting and storage conditions
-processing
-accuracy of labelling
-purity
Where to source further information:
Natural Medicines Comprehensive Database
(www.naturaldatabase.com)
Natural Standard
(www.naturalstandard.com)
Consumer Lab
(www.consumerlab.com)
What is an Adeverse Effect?
Adverse effects are noxious and/or undesirable effects associated with the use of a drug at doses normally used. They may occur as part of the drug's pharmacologic action, or may be unpredictable. The risk of a serious adverse effect may be acceptable if the disease being treated is also serious.
Classification
Predictable: Includes adverse effects predictable from knowledge of specific drug pharmacology and pharmacokinetics. Often related temporally to initiation of a drug or to dose increase.
Unpredictable: Includes immunologically mediated adverse effects, effects due to genetic differences in drug metabolism, and other effects where the underlying mechanism is not understood. Onset of effect may be less clearly related to initiation of the drug, and is often delayed.

Talk to your patients about AEs
-educate about possible AE, follow up, and notify other health professionals if they occur.
What factors predispose to AE occurring?
AGE: very young and very old increased risk of AE
GENDER: F>M (relatively smaller size for given doses)
DOSE: many AEs are dose related
POLYPHARMACY: incidence of AE increases with the number of drugs a patient is taking
HISTORY: patients with a history of AEs seem to be at higher risk of AEs with subsequent medications
GENETIC FACTORS: relative deficiency of enzymes involved in rge metabolisms of some drugs increases the risk of AE
LIVER
The liver secretes bile, which aids digestion by emulsifying lipids, and has a central role in metabolism of
bilirubin, from haem;
bile salts, the principal mechanism for clearance of cholesterol;
carbohydrates, e.g. maintenance of blood glucose within a narrow range;
amino acids and ammonia, e.g. control of the plasma concentration of amino acids, and clearing portal venous ammonia generated within the gut lumen;
proteins, most circulating plasma proteins being produced by hepatocytes; and
lipid and lipoproteins
Interruption to these processes results in the major metabolic consequences of acute and chronic liver disease
Synthetic role: Manufactures our clotting factors 2,7,9,10
Liver failure:
Hepatocellular failure occurs when loss of liver parenchymal cell function exceeds the capacity of hepatocytes to regenerate or repair liver injury
Acute hepatocellular failure is characterized by hepatocellular jaundice, elevated serum aminotransferase levels, and prolongation of the prothrombin time associated with an acute liver disease/insult
Fulminant hepatic failure is the syndrome of acute hepatocellular failure complicated by hepatic encephalopathy, occurring within 8 weeks of the onset of clinical liver disease
Chronic hepatocellular failure is characterized by a chronic hepatocellular disease and one or more features of hepatocellular failure
The most common causes of fulminant hepatic failure are acute viral hepatitis and DRUGS
SIGNS OF LIVER TOXICITY
Jaundice: skin and sclera get a yellowish pigmentation
Ascites: build up of fluid in the peritoneal cavity
Bruising/ bleeding: -->hamatemesis (vomiting blood)
Caput medusae: distended, engorged umbilical veins
Hepatic flap: tremor of the hands with the wrists extended; said to resemble a bird flapping its wings
Steatorrhoea: excess fat in the faeces
Dark urine
Fatigue
Drug induced liver injury (DILI)
Liver injury can develop following the use of many drugs, both prescription and over-the-counter, through a variety of mechanisms
DILI accounts for up to 10 percent of all adverse drug reactions
DILI is the cause of acute jaundice in up to 50 percent of patients presenting with jaundice
Over 1000 medications and herbal products have been implicated in the development of DILI
Herbal remedies may be associated with hepatotoxicity, making it important to discuss the use of herbal and dietary supplements (HDS) and complementary and alternative medical (CAM) therapies in an attempt to prevent potential complications, such as herb-drug interactions
DILI presentation
Acute presentations can range from mild asymptomatic biochemical abnormalities to an acute illness with jaundice that resembles viral hepatitis to acute liver failure
The presence of jaundice (serum bilirubin >2 times the upper limit of normal) in association with an elevation in serum aminotransferases (>3 times the upper limit of normal) is associated with a worse prognosis than that seen in the setting of isolated aminotransferase abnormalities
Subclinical — Many drugs can induce asymptomatic elevations in liver enzymes without producing overt clinical disease. Drug-induced liver injury (DILI) is generally considered subclinical or insignificant if the serum alanine aminotransferase (ALT) is <3 times the upper limit of normal
Most subclinical ALT elevations are benign and resolve once the offending agent has been discontinued. The time course of resolution can be variable but generally occurs over weeks to months
Acute DILI
Acute DILI is the most common form of liver injury caused by drugs, accounting for approximately 10 percent of all cases of acute hepatitis
The patterns of acute injury may present as cholestasis, hepatocellular (cytotoxic) damage, a mixed pattern of cytotoxic and cholestatic injury, or, less commonly, steatosis
Discontinuation of the offending agent usually results in complete recovery, although the prognosis is generally worse in patients with hepatocellular injury presenting with jaundice
In the setting of cholestatic injury, jaundice can take months to resolve. DILI is probably the most common cause of cholestatic hepatitis
Diagnosing DILI
The diagnosis of DILI can be difficult >> the relationship between exposure to the drug and hepatic toxicity is not always clear. Patients may be taking multiple meds and they may have concomitant liver diseases (such as alcoholism or NASH), which can produce similar clinical and laboratory features
Key elements for attributing liver injury to a drug include:
-Exposure must precede the onset of liver injury (although the latent period is highly variable)
-Underlying liver disease should be excluded
-Injury may improve when the drug is stopped (although in some cases injury may initially worsen for days or weeks, while in fulminant cases, declining liver biochemical tests may indicate deterioration rather than improvement)
-Liver injury may have recurred more rapidly and severely after repeated exposure
DILI: Treatment
-The main treatment for DILI is withdrawal of the offending drug
-Early recognition of drug toxicity is important to permit assessment of severity and monitoring for acute liver failure
Recreational drug use: dependance criteria for diagnosis
A maladaptive pattern of substance use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period:
Tolerance, as defined by either of the following: (a) A need for markedly increased amounts of the substance to achieve intoxication or desired effect (b) Markedly diminished effect with continued use of the same amount of the substance
Withdrawal, as manifested by either of the following: (a) The characteristic withdrawal syndrome for the substance (b) The same (or closely related) substance is taken to relieve or avoid withdrawal symptoms
The substance is often taken in larger amounts or over a longer period than was intended.
There is a persistent desire or unsuccessful effort to cut down or control substance use.
A great deal of time is spent in activities necessary to obtain the substance (e.g., visiting multiple doctors or driving long distances), use the substance (e.g., chain smoking), or recover from its effects.
Important social, occupational, or recreational activities are given up or reduced because of substance use.
The substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance (e.g., current cocaine use despite recognition of cocaine-induced depression or continued drinking despite recognition that an ulcer was made worse by alcohol consumption).
Specify if: With physiological dependence: evidence of tolerance or withdrawal (i.e., either item 1 or 2 is present) Without physiological dependence: no evidence of tolerance or withdrawal (i.e., neither item 1 nor 2 is present)

After long-term use, most drugs of abuse produce adaptive changes in the brain that are manifested as acute and chronic withdrawal syndromes when drug use ceases
Other drug-induced changes in the brain appear to be related to the processes by which the memories of drug action are stored and by which drug-related stimuli acquire and retain salience
Alcohol
Alcoholism: (i.e., alcohol abuse and dependence) Evidence of repeated impairments from alcohol in multiple areas of life functioning, despite which the person returns to drinking
Tolerance: With repeated administration of alcohol, larger and larger doses of the drug are required to produce the desired effect
Craving: The state of motivation to seek out alcohol is an important component of drinking behaviour

AEs
Blackout (anterograde amnesia)
Sleep impairment
Cerebellar degeneration
Peripheral neuropathy
GI effects; inflammation of the stomach, oesophagus, with vomiting/ bleeding. Liver toxicity. Pancreatitis

Withdrawl
In people who have been drinking heavily over a prolonged period, a rapid decrease in blood alcohol levels might produce a variety of physical symptoms that are the opposite of what was initially experienced with intoxication.
These include a coarse tremor of the hands, insomnia, anxiety, and increased blood pressure, heart rate, body temperature, and respiratory rate
For some the symptoms include convulsions or delirium
Cannabis
-The main reason why most people use cannabis is to experience a "high": mild euphoria; relaxation and perceptual alterations, including time distortion; and the intensification of ordinary experiences such as eating, watching films, listening to music
-High doses have been reported to produce visual and auditory hallucinations, delusional ideas, and thought disorder in normal volunteers.
-There is clinical and epidemiological evidence of an association between schizophrenia and cannabis use that suggests that cannabis use can precipitate schizophrenia or exacerbate its symptoms
AE of cannabis use:
CVS: increased heart rate. BP increases while siiting and decreases with standing.
Resp:Regular cannabis smoking impairs the functioning of the large airways and causes symptoms of chronic bronchitis such as coughing, sputum, and wheezing. May be carcinogenic
Immunity: may impair cell-mediated and humoral immunity and reduce resistance to infection by bacteria and viruses
Reproductive effects: Chronic administration may disrupt male and female reproductive systems in reducing testosterone secretion and sperm production, motility, and viability in males and disrupting the ovulatory cycle in females.
Methaemoglobinemia.
Methemoglobin is an altered state of hemoglobin in which the ferrous (Fe2+) irons of heme are oxidized to the ferric (Fe3+) state. The ferric hemes of methemoglobin are UNABLE to bind oxygen. In addition, the oxygen affinity of any remaining ferrous hemes in the hemoglobin tetramer is increased. As a result, the oxygen dissociation curve is "left-shifted
The net effect is that the patient with increased concentrations of methemoglobin has a greater functional anemia than suggested by the laboratory data. The circulating methemoglobin-containing hemoglobin molecules are unable to carry oxygen and the remaining oxyhemoglobin has increased oxygen affinity, resulting in impaired oxygen delivery to the tissues

There are two types of methaemoglobinaemia.
1.congenital methaemoglobinaemia -characterized by diminished enzymatic reduction of methemoglobin (ie, hemoglobin with its iron in the ferric state) back to functional hemoglobin (ie, hemoglobin with its iron in the ferrous state). Affected patients appear cyanotic but are generally asymptomatic >> Autosomal recessive
2.acquired methaemoglobinaemia- typically results from ingestion of specific drugs or agents that cause an increase in the production of methemoglobin. It can be a fatal disease. Most cases are acquired; major drugs implicated include benzocaine spray for topical anaesthesia and inhaled nitric oxide and LAs

Signs and symptoms:

Symptoms in patients with acquired methaemoglobinemia result from an acute impairment in oxygen delivery to tissues that does not allow sufficient time for compensatory mechanisms to take place
-Early symptoms include headache, fatigue, dyspnea, and lethargy
-At higher methaemoglobin levels, respiratory depression, altered consciousness, shock, seizures, and death may occur
-The presence of methaemoglobin is suspected when there is clinical "cyanosis" in the presence of normal arterial pO2
-The blood in methaemoglobinemia has been variously described as dark-red, chocolate, or brownish to blue in colour, which, if noted during a procedure associated with the use of a topical anesthetic agent, is a valuable clue for making this diagnosis

Treatment:
Search for the offending agent, if identified remove and discontinue use
Refer to hospital
Patient groups and safe prescribing: Who are our HIGH risk groups?
-Pregnant and Lactating women
-Children
-Elderly
-Renal failure
-Hepatic failure
-History of drug allergy
-Other medication
-Immunodeficient/ Immunosuppressed
-Patients with problems with compliance and or poor insight into their condition
The immune system.
The immune system is made up of lymphoid tissue in the body, which includes:
-bone marrow
-lymph nodes
-parts of the spleen and GI tract
-thymus
-tonsils
-proteins and cells in the blood

The immune system helps protecte the body from harmful substances called antigens: including bacteria, viruses, toxins, cancer cells and foreign blood or tissues.

Sequence: immune system detects antigen>production of antibodies>antibodies destroy harmful substance via phagocytosis

Immune system disorders occur when the immune system does not fight tumors or harmful substances as it should >> immune response may be overactive / underactive
What does it mean to be immunodeficinet?
Immunodeficiency disorders occur when the body's immune response is reduced or absent.

Immunodeficiency disorders may affect any part of the immune system >> Most commonly, these conditions occur when special white blood cells called T or B lymphocytes (or both) do not work as well as they should, or when your body doesn't produce enough antibodies
What does it mean to be immunosuppressed?
-People are said to be immunosuppressed when they have an immunodeficiency disorder due to treatment with a medication that weakens the immune system
-Immunosuppressive therapies are critical to the treatment of autoimmune disorders and malignant disease, the maintenance of transplanted tissues, and the prevention of graft-versus-host disease

Drugs and biologics that suppress immune function have the potential to cause serious unintended immunologic effects including:
-Increased risk of infection or
-The development of malignant or autoimmune diseases
The risk of these complications is influenced by:
-The specific agent used and its dose and duration,
-Patient-specific factors including: the nature of the underlying disease, the patient's functional status and medical fragility
-Use of combinations of immunosuppressive agents
Immunosuppressed populations
Arthritis: Rheumatoid, Psoariatic, Reactive, SLE, Ank Spond
Cancer patients: Chemo, BMT
Respiratory disease: COPD, asthma
Dermatological disorgers: SLE, Scleroderma, Psoriasis
Which drugs cause immunosuppression?
Anti-inflammatory agents
-Glucocorticoids: prednisone, methylprednisolone, triamcinolone, dexamethasone, and betamethasone
-Cyclosporin & Tacrolimus: potent imm'supp action on functioning of T lymphocytes
Antimetabolities
-Methotrexate: inhibition of dihydrofolate reductase > decresed synthesis of nucleotides and amino acids, & inhibiting cell division. Selectively targets rapidly dividing cells
-Azathioprine:inhibit the biosynthesis of nucleotides required for DNA replication in dividing cells
Alkylating Agents
-Cyclophosphomide: chemically modify nucleotides > DNA breakage & errors in DNA replication and transcription > apoptosis
Glucocorticoids (steroids)
Pharmacologic doses of glucocorticoids are used to treat patients with inflammatory, allergic, immunological disorders. If chronic, this supra-physiologic therapy has many adverse effects, including: Cushing's syndrome, infections and changes in mental status

Action:
-inhibitory effects on a broad range of T cells and B cell responses >> neutrophilic leukocytosis, accompanied by dramatic reductions in circulating eosinophils, monocytes, and lymphocytes
-Effects on the innate immune system include dose-dependent impaired phagocyte function and attenuated production of proinflammatory mediators
-Glucocorticoids impair a variety of T cell functions and induce T cell apoptosis. B cells are less affected and antibody production is largely preserved

Doses of < 40 mg per day in adults can be considered low to moderate. Systemic glucocorticoid therapy is associated with a dose-dependent increase in the risk of infection. Patients are most often affected by common viral, bacterial, and fungal pathogens.

The goal of glucocorticoid therapy, as with any therapy, is to obtain maximum benefit with minimum adverse side effects. Potent synthetic glucocorticoids (eg, prednisone, methylprednisolone, triamcinolone, dexamethasone, and betamethasone) have little mineralocorticoid, androgenic, or estrogenic activity >> the major systemic side effects are those of suppression of hypothalamic-pituitary-adrenal function and Cushing's syndrome

The most common side effects of oral steroids include:
Weight gain
Changes in mood and thinking
Trouble sleeping
Thin skin
Eye problems
Heart problems
Osteoporosis and other bone problems
Growth problems in children
High blood sugar
Higher chance of getting infections
What is cortisol?
Cortisol is a streoid hormone made in the adrenal glands in response to signalling from the pituitry gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are the increase blood sugar through glucogenesis; suppress the imune system; and aid in fat, protein and carbohydrate metabolism. It also decrease bone formation.
Cushing's Syndrome
Cushing's syndrome occurs when a person has an excess of cortisol.
Causes:
-medications that act like cortisol i.e steroids-people may take high doses of these medications for conditions such as asthma or arthritis
-abnormal growth in the pituitry gland or other parts of the body can signal the adrenal glands to make too much cortisol
-problems in the adrenal glands that may cause an over production of cortisol

Symptoms:
Symptoms:
-Weight gain in the face, neck, back, or belly
-Thin skin that bruises easily. People can also have reddish-purple stretch marks
-Absent or irregular monthly periods
-Increased hair growth, oily skin, or acne
-Proximal muscle weakness
-Osteoporosis
-Diabetes (high blood sugar levels)
-High blood pressure and heart problems
-Changes in mood, such as feeling depressed, worried, or angry
-Getting infections more easily
-DVT
Antipsychotics
Antipsychotics are used primarily to treat psychotic disorders >> Including:Acute and chronic psychoses (eg schizophrenia) and Bipolar disorder

Rationale for use includes relief from symptoms such as hallucinations, delusions or abnormal behaviour/thought, and for their sedative and tranquillising effects in very disturbed or aggressive patients

MOA: Antipsychotic actions are thought to be mediated (at least in part) by blockade of dopaminergic transmission in various parts of the brain (in particular the limbic system)

AEs:
-Adverse effects traditionally associated with older agents appear to be less common or less severe with some of the newer antipsychotics

Common: sedation, anxiety, agitation, EPSE (below), orthostatic hypotension, tachycardia, blurred vision, mydriasis, constipation, nausea, dry mouth, urinary retention, sexual adverse effects, weight gain, hyperprolactinaemia (may result in galactorrhoea, gynaecomastia, amenorrhoea or infertility)

Extrapyramidal side effects:
-Dystonias
-Akathisia
-Parkinsonism
-Tardive dyskinesia

Metabolic effects
-People with schizophrenia have an increased risk of cardiovascular disease. Clozapine, olanzapine and quetiapine, in particular, have been associated with increased blood glucose, weight gain and dyslipidaemia.
-Some agents (particularly clozapine and olanzapine) are associated with an increased risk of type 2 diabetes
Peripheral Oedema
What is oedema?- a palpable swelling produced by expansion of the interstitial fluid volume. An increase in interstiial fluid volume that could lead to oedema is prevented in normal subjects because of the tight balance of haemodynamic forces along the capillary wall and adequate functioning of the lymphatic vessels.

For generalised oedema to occur, two factors must be present:
-altered capillary hameodynamics that favor the movement of fluid from the vascular space into the interstitium. such movement requires either an increased capillary hydrostatic pressure, decreased capillary oncotic pressure abd/or increased capillary permeability.
-the retention of dietary or intravenously administered sodium and water by the kidneys.

Oedema is not clinically apparent until the interstitial volum has increased 2.5 to 3 L; an amount almost equal to the plasma volume.

Causes of peripheral oedema include:
-heart failure
-renal disease
-lymphatic obstruction/disease
-venous insufficiency
-DRUGS
Drug-induced oedema
The diagnosis is suspected from the combination of the use of one of drugs and no other apparent cause for the oedema
Among the most predictable causes of drug-induced oedema are:
-Direct vasodilators, such as minoxidil and nifedipine in which the fall in blood pressure itself probably plays an important role both directly and by activating the renin-angiotensin-aldosterone and sympathetic NS,>> both stimulate sodium retention
-NSAIDs can exacerbate oedema in patients with underlying heart failure or cirrhosis
Pitting vs non-pitting oedema
Pitting reflects movement of the excess interstitial water in response to pressure. Non-pitting oedema suggest lymphatic obstruction or hypothyroidism,
Peripheral oedema is located in dependant area; primaroly in the lower extremities in ambulatory patient or over the sacrum in patient confined to bed rest.
What about unilateral oedema?
-much less common then bilateral oedema
It is associated with: venous insufficiency, thrombosis or lymphedema.

DVT should alway be excluded in patients with acute onset of otherwise unexplained unilateral leg oedema.
Fibromyalgia
-common cause of chronic MSK pain
-a soft tissue pain disorder that affects muscles and soft tisuses such as tendons and ligaments
-there is no inflammation of the tissue and the etiology of fibromyalgia pain is unknown
-has been a controversial illness as the patient looks well, no abnormlities are present on physical examination
-often considered psychogenic or psychosomatic
-current pathophysiological concepts focus on alterations in CNS pain processing

Symptoms:
-widespread MSK pain
-paraesthesias
-fatigue
-cognitive and mood disturbances
-headaches
Safe and Effective prescribing
The process is seen as relatively low risk; simply an instruction to a pharmacist to dispense a medication. However it is a core competency which requires a careful balance of benefits versus risks and rational medication use to minimise the risk of harm.
Approx 2% of IP are harmed by medication errors (greater in the community)- 50% result from the prescribing process

Prescribing mistakes
-lack of patient knowledge, including patients awareness of ADR (prescriber has to educate the patient)
-Prescriber lacks drug knowledge; interactions and indications
-The medication order is unclear or ambiguous

-Know your patients
-Know your medicines: limited number, P-drugs, prescribing formularies
-Use your resources
Four stages of learning- Maslow
Unconsciously incompetent ✗ dangerous

Consciously incompetent - starting point, anxious

Unconsciously competent - advancing, bored

Consciously competent ✓
Conservative prescribing
Principles: try not to start one
Choose wisely: become familiar with a limited number of drugs; one's knowledge and experience with those drugs increases dramtically and can predict outcomes.
Follow-up: efficacy and ADRs
Factors influencing safe prescribing
The patient: diagnosis, patient history, rneal function etc, medication history, allergies
Pharnacology: knowledge of therapeutics, AEs and interactions
Practical: handwriting, time, prescriber number, notification of AE
Resources: MIMS, AMH, eTG, iPhone, protocols or guidelines within the practice, supervision and experience
Medication history
-what you need to know?
-why you need to know it?
-where to source your information?
Need to know:
-current medication: dose, form, strength, frequency, indication
-past medication and treatment failures
-over the counter medications
-recreational drugs
-adverse reactions
-allergies and sensitivities-with clinical detail i.e. morphine and vomiting, penicillin rash vs anaphylaxis
-estimate of patient adherance with their medicines
Medication history
-what you need to know?
-why you need to know it?
-where to source your information?
WHY?
-dangers of over-prescribing
-exposure to side effects
-risk of AEs
-interactions with other medications
-renal/liver function
-microbial resistance
-cost
Medication history
-what you need to know?
-why you need to know it?
-where to source your information?
Where to source your information:
-GP letter or records
-patients own tablets-webster pack, pharmacy sachets
-written list from patient or carer
-nursing home form
-pharmacist patient records
-recent discharge letters
Beaware that there can be errors, that not all medications may be disclosed, some medication may have been ceased etc
Thorough Medication History
Verification:
Collection of the medication history
Obtaining a complete and accurate list of each patient's current medications (medication history) including name, dosage, frequency and route

Clarification:
Ensuring that the medications and doses are appropriate

Reconciliation:
Documentation of changes in the prescriptions
Resolving any discrepancies that may exist between the medication history list and prescribed medicines before an adverse drug reaction (ADR) can occur
ADRs can result from omitted drugs or doses
Remember the GP
- There a point of care for the patient
Communication between health profesisonals is key:
-What has been done and what medications
-Why they have been commenced and for how long
-What are the treatment goals
-Ongoing care/who should follow-up
Help update the patients records
Medication can be stopped as GP and patient unsure why it has been started
Australian podiatry board: before prescribing
Endorsed podiatrists must take all resonable steps to ensure that
-a therapeutic need exists and,
-to prescribe/supply only for the treatment of patients under their care for conditions of the foot

N/B prescriptions written by endorsed podiatrists are not covered under the PBS; make sure to get informed financial consent.
The Prescription
The prescripton must:
-be written only for the person named on the prescription
-not include any particular that is false or misleading
-not be written in a scret code or cipher

Prescriptions must be handwritten legibly and include the following
-name, address, prescriber number, and telephone numbe of the podiatrist
-name, address, DOB of the patient
-date the prescription was written
-podiatrist's signature
-quantity to be supplied
-direction for the precise dose or use and frequency of administration
Things to DO
and things NOT TO DO
DO -write quantities smaller than 1 gram as milligrams
-write quantities less than 1 milligram as micrograms
-use mL not cubic centimetres
-write in English, read and check the prescription before isssuing it to your patient
-keep a copy of all prescriptions
-store prescription pads in a safe, secure place
DONT
-abbreviate drug names, abbreviate the words nanogram, microgram
-omit directions for use
-write as directed or PRN (write as necessary)
Drug Schedules
S2 - Pharmacy Medicine
S3 - Pharmacist only medicine
S4 - Prescription only medicine
S8 - Controlled drug

We can prescribe from the above drug schedules.

S5 Caution S6Poison S7Dangerous Poison, S9 Prohibited substance

S4 drugs must be kept in a lockable storage facility to which only the endorsed podiatrist has access
Antimicrobials
Antibiotic Stewardship
-optimise use of antimicrobials
-reduce inappropraite antimicrobial use
-improve patient outcomes
-reduce adverse consequences i.e. antimicrobial resistance, toxicity and unnecessary costs
-antibiotics should ony be used when appropriate and then the right drug should be employed for the diagnosis
-sometimes infections are not infections and antibiotics are not necessary
Antibiotic Stewardship
Hospital programs
-decrease antimicrobial use and imporve patient care
-key to prevent the emergence of antimicrobial resistance; reduce institutional resistance rates, morbidity, mortality and healthcare costs
-Decrease preventable health care associated infection
Antibiotic Stewardship: strategies for effective AMS
-therapeutic guidelines
-prescribing restrictions
-feedback
-audit
-using microbiology
How is this implemented?
-ongoing training and education
Why is this so important?
The introduction of antimicrobial agents has been one of the most significant developments in medicine. It has contributed to the reduction of infectious diseases . Previously feared and often fatal infections became 'miraculously' curable.
Treatment with antimicrobial agents seemed so effective and safe that doctors often prescribed antimicrobials for dubious indications and for longer than necessary with little concern of AE. The emergence of antimicrobial resistance caused little alarm, because new and more effective agents with broader abtibacterial spectra were being developed.Today the prevalence of multi-drug resistant bacterial pathogens is a major concern with the emergence of super bugs such as VRE and MRSA.
Why have we seen an emergence of super-bugs?
Unnecessary antimicrobial use for:
self-limiting or noninfective illness with
inappropriate antimicrobial choice, dose or duration of therapy

Drive the selection of resistant bacteria, disrupt normal microbial flora, and increase the risk of colonisation with resistant organisms and subsequent transmission to others.
What the bugs are doing?
Inappropriate antimicrobial use increases morbidity and mortality due to avoidable
drug toxicity,
suboptimal treatment of the original infection, or
subsequent infection with multiresistant bacteria, fungi or Clostridium difficile.

Patients with antimicrobial resistant infections are more likely to experience ineffective treatment, recurrent infection, delayed recovery or even death.

A two-fold higher death rate has been reported among patients with antimicrobial-resistant infections.
How to treat when super-bugs are present?
When multiresistant pathogens are prevalent, clinicians are forced to use broader spectrum and (usually) more expensive agents for empirical therapy for seriously ill patients with sepsis.
What should we do?
-minimise the use of broad-spectrum antimicrobials
-avoid the widespread use of cephalosporins, quinolones, broad-spectrum penicillins and clindamycin unless there are clear indications for their use.
-broad spectrum antimicrobials should be restricted to the treatment of serious infections when the pathogen is unknown or when other effective agents are unavailable
Surgical Prophylaxis
Use of single dose for surgical prophylaxis

However, a key principle is to have a high concentration of the antimicrobial agent(s) in the relevant tissues at the time of the operation, when microbes may contaminate the tissues.

Usually a single dose at induction of anaesthesia.
Only in lengthy operations (i.e. over four hours) may a second intraoperative dose be considered necessary.

Policies for the prophylactic use of antimicrobials should state that the single dose is the preferred option.
timing the first dose to be 30-60 minutes pre-incision
The antimicrobial creed: MINDME
M microbiology: guides therapy wherever possible

I indications: should be evidence based

N narrowest spectrum required

D dosage: appropriate to the site and type of infection

M minimise duration of therapy

E ensure monotherapy in most cases
Initiating antibiotic therapy
At initiation of treatment, the prescriber should
-provide a clinical rationale for antimicrobial initiation
-send the appropriate sepcimens to a diagnostic microbiology laboratory
-select the antimicrobial according to local policy and having considered the patient risk group (including their drug allergy profile)
-considre removal of any foreign body, drainage of pus or other surgical intervention as apporpriate
Available antibiotics for podiatrists
Amoxycillin - B lactam
Augmentin - B lactam
Cephalexin - Cephalosporin
Ciprofloxacin (SA) - Quinolone
Clindamycin - Lincosamide
Cotrimoxazole - TMP, Folate synthesis
Fluclox/Dicloxacillin - B lactam
Metronidazole - Nitroimidazole
Mupirocin - Bactroban, topical
Roxithromycin - Macrolide
Silver Sulfadiazine - Flamazine, topical
ABs: Flucloxacillin and Dicloxacillin
-Antistaphylococcal and also have antistreptococcal activity.
-Reliably absorbed by the oral route
Food reduces absorption and they are best taken half to one hour before food.
- Ideally, dosed at 6-hourly intervals
Flucloxacillin
-Generally well tolerated
-Rarely associated with cholestatic jaundice, (older patients on prolonged therapy)
Dicloxacillin
-Less irreversible hepatotoxicity but results in more infusion phlebitis and interstitial nephritis.
Dicloxacillin may be preferable to flucloxacillin for oral therapy or in patients requiring prolonged therapy.
B1 (Fluclox), B2 (Diclox)
AE: diarrhoea, nausea, rash, urticaria, fungal infection, transient increase in liver enzymes and bilirubin, cholestatic jaundice
ABs: Clindamycin
-Lincosamide
-Oral doses have a high bioavailability
-Up to 20% of patients will experience diarrhoea
-Reversible subclinical transaminitis is not uncommon with parenteral clindamycin
-Acute symptomatic hepatotoxicity with oral clindamycin is rare
-Clinicians should have a low threshold for checking liver function in their patients, particularly if they become unwell while taking clindamycin.
-CAT A, compatible
Concerns as podiatrist
...
Foot infection
Soft Tissue
Bone
Diabetic
Vascular

Simple
Moderate
Severe - immunocompromised patient, PVD, emergency soft tissue infections, and infections associated with trauma

Can affect skin, subcutaneous tissue, adipose tissue, superficial or deep fascia, ligaments, tendons, tendon sheaths, joints and/or joint capsules.

Normal foot
>20joints, 44 tendons, ~100 ligaments, 4 major compartments, numerous fascial planes
Diabetic foot
Often worse than they appear

Should always be regarded as serious.

Acute infections usually due to Staphylococcus aureus and streptococci

Chronic infections are often polymicrobial
Gram-positive and Gram-negative aerobes and anaerobes.

Culture of tissue specimens obtained by biopsy or aspiration may guide therapy.
Why are diabetes difficult to treat?
Poor wound healing:
-Decreased vessel permeability - endothelial cell dysfunction
-Amplification of the atherosclerotic process
-Neuropathy
-Immune dysfunction - reduced chemotaxis and impaired phagocytosis
Leg ulcers
Most commonly result from underlying pathology, which has secondary deleterious effects on the skin.
-Venous,
-Arterial
-Mixed venous and arterial
-Pressure,
-Neuropathic
-Traumatic and
-Diabetic
Some ulcers may be caused by multiple factors,
Diabetic ulcers (vascular insufficiency, infection, neuropathic pressure)
Rheumatoid ulcers (vasculitis, atrophic skin, trauma, infection, calf muscle pump failure).
Ulcer examination
-Site, size, shape, edges.
-Floor :"Black, Yellow or Red"
-Base : skin, fat,tendon or bone
-?any pus beneath floor
-Surrounding skin : temp, colour , ? cellulitis,
-Dermatitis, pigmentation, exudate.
-? allergy to current dressing
-Arterial: pulses +/- ABI's
-Venous
-Neurological
-Joints
-Exclude Diabetes and blood disorder
-Vascular Lab
Diabetic ulcer
-Assess vascular supply and consider underlying osteomyelitis or septic arthritis.
-Surgical debridement is often necessary
-Antibiotic therapy should be effective against the mixed aerobic and anaerobic organisms frequently responsible.
-Multifactorial and may result from infection, neurological disease or vascular insufficiency.
-Correct them where possible
-Treat infection vigorously!
-Refer patients with vascular insufficiency to a vascular surgeon for assessment.
-Prevention is the key to management of the diabetic foot and good foot care is essential.
-Encourage patients to inspect their feet frequently, to treat coincidental infections such as tinea, pay attention to small injuries and abrasions, and look after their footwear.

For mild to moderate infection with no evidence of osteomyelitis or septic arthritis, use:
amoxycillin+clavulanate 875+125 mg orally, 12-hourly
OR
cephalexin 500 mg orally, 6-hourly
PLUS
metronidazole 400 mg orally, 12-hourly.
For patients with penicillin hypersensitivity use:
ciprofloxacin 500 mg orally, 12-hourly
PLUS
clindamycin 600 mg orally, 8-hourly.
Continue antibiotic therapy for at least 5 days.

For severe limb- or life-threatening infection (systemic toxicity/septic shock, bacteraemia, marked necrosis/gangrene, ulceration to deep tissues, severe cellulitis, presence of osteomyelitis), use
piperacillin+tazobactam 4+0.5 g IV, 8-hourly
OR
ticarcillin+clavulanate 3+0.1 g IV, 6-hourly.

For patients with penicillin hypersensitivity (see Table 2.2), use initially:
ciprofloxacin 400 mg IV, 12-hourly
or
ciprofloxacin 750 mg orally, 12-hourly
PLUS EITHER
clindamycin 900 mg IV, 8-hourly (slow infusion required)
OR
lincomycin 900 mg IV, 8-hourly (slow infusion required).
Venous ulcer
-Leg is warm and may be oedematous
-Ulcer is usually situated on the medial aspect of the leg
-Surrounding evidence of venous insufficiency including presence of:
haemosiderin pigmentation,
lipodermatosclerosis (firm, sometimes tender red-to-brown induration), and
atrophie blanche (pale scarring with stippled telangiectasia).
-Ulcers usually contain yellowish slough in the base and are moderately to highly exudative.

Management:
-Compression:mainstay of therapy for venous leg ulcers. Assists in healing by reducing venous hypertension, enhancing venous return by improving calf muscle pump function, and reducing peripheral oedema.
Compression bandaging is suitable for patients with an ankle-brachial index of 0.8 or greater. Lighter compression may still be appropriate for ratios between 0.6 and 0.8.
-Exercise: encourage regular exercise such as walking or dorsiflexing the foot to maintain calf muscle pump function.
-Surgery and sclerotherapy: appropriate if venous incompetence is limited to the superficial or perforator system, which can be determined by duplex ultrasound scanning. The aim is to eliminate areas of incompetence and therefore reduce venous hypertension. Usually performed once the ulcer has healed but they can sometimes be done to enhance healing of a resistant ulcer
Surgical approaches include junctional ligation, and stripping or stab phlebectomy
Arterial ulcer
-Leg is cold and often pale or cyanotic
-Reduced sweating and hair growth.
-Toenails are often dystrophic
-The ulcers are most frequently in the pretibial area or on the feet or toes.
-Usually have a deep, have a punched-out appearance and are painful
-Necrotic eschar may be present and tendons may be visible in the base of the ulcer
-Tend to be relatively dry with low levels of exudate.

If arterial insufficiency is suspected clinically or proven by performing an ankle-brachial index (ABI)
-Refer to a vascular surgeon to establish if corrective surgery is appropriate.
-Compression therapy is contraindicated in arterial ulcers if ABI is less than 0.6, due to exacerbation of ischaemia and ulceration!!
Pressure/ Neuropathic ulcer
-Occur on pressure-bearing areas and are generally easy to diagnose on clinical grounds.
-May also result from friction or shearing forces
-Pressure ulcers occurring on the legs or feet are usually dry and are surrounded by thick hyperkeratotic skin.
-Risk factors for pressure ulcers include
neurological disease, spinal cord injury, debilitation and surgical procedures requiring prolonged bed rest.

Management:
-Pressure avoidance is critical
-Debride necrotic debris and surrounding hyperkeratotic tissue as an important initial step.
-Address general medical issues
malnutrition, cardiac failure, anaemia and diabetes mellitus.
-Implement pressure avoidance measures
Investigations
-All legs are colonised by bacteria (eg staphylococcus, pseudomonas).
-Swabs are rarely helpful
-Should be considered in ulcers complicated by recurrent episodes of cellulitis
Resistant or painful ulcers
Systemic symptoms - fever
-Group A beta-haemolytic streptococci (Streptococcus pyogenes) are pathogenic and require treatment.
-Biopsy can be useful to investigate specific skin pathology. Consider biopsy if aetiologies such as vasculitis, neoplasia or atypical infection are suspected, or if the ulcer shows no response to appropriate treatment over several months.
-Culture of biopsy tissue is necessary to identify ulcers due to atypical mycobacterial infection or other rare infective aetiologies.
ABI: the ankle brachial index
-Assess arterial perfusion by comparing the systolic pressure at the ankle to that of the upper arm.
-It is performed using a simple handheld continuous wave Doppler as a stethoscope and a standard sphygmomanometer.
-A ratio for the ankle to brachial systolic pressure of less than 0.8 suggests a significant component of arterial insufficiency.
-Mild compression may be used if the ratio is between 0.6 and 0.8
-If the index is below 0.6 avoid compression and refer to a vascular surgeon.
-Interpret Doppler pressures in patients with diabetes mellitus and arterial calcification with care, as they can have falsely high readings.
Osteomyelitis
-Bony inflammation
-Almost always due to infection
-Without specific risk factors, it is particularly common between the ages of 2-12 (M>F)
-May arise from haematogenous spread (Monomicrobial)
-Direct inoculation following trauma or surgery
-Spread from a contiguous structure such as a joint (Polymicrobial)
-Staphylococcus aureus accounts for more than 80% of disease. Swab - M/C/S prior to Ab's

-Initial stage, bacteria multiply setting up localised inflammatory reaction
-Localised cell death
-With time, infection becomes demarcated by a rim of granulation tissue and new bone deposition

Complications
-Sequestration
-Sinus Formation
-Septic Arthritis
-Necrosis
-Sepsis

Clinical Manifestations

Local findings
-Tenderness
-Warmth
-Erythema
-Swelling
Systemic Symptoms
-Fever
-Rigors
-Hypotension
-Tachycardia
Often only pain though

Chronic osteomyelitis
-Presence of a sinus tract is pathognomic of chronic osteomyelitis
-Bone exposed + DM is diagnostic
-Lesions overlying bony prominences
-Diabetics who develop cutaneous ulcers oftern develop OM before bone exposed

Investigations
-bone biopsy
-imaging
-bloods

In chronic infections, sinus cultures may be misleading. If cultures are negative and alternative pathology is ruled out, treat as S. aureus infection.
Chronic infections are more difficult to treat and often require prolonged therapy.

Sequestra, dead bone or foreign material requires surgical removal in chronic infection, or in acute infection which fails to resolve
Septic arthritis
-Inflammation of a joint secondary to bacterial or fungal infection
-Septic arthritis generally presents as a monoarticular arthritis, either spontaneously or following penetrating trauma
-Pathogens involved are generally similar to those that cause acute osteomyelitis.
Bacteria spread through the bloodstream to a joint
-Joint is directly infected from an injury or during surgery
-The most common sites for this type of infection are the knee and hip.
-Most cases of acute septic arthritis are caused by bacteria such as staphylococcus or streptococcus.
-Chronic septic arthritis (which is less common) is caused by organisms such as Mycobacterium tuberculosis and Candida albicans

Risk factors:
-Artificial joint implants
-Bacterial infection somewhere else in your body
-Chronic illness or disease
diabetes, rheumatoid arthritis, and sickle cell disease
-Intravenous (IV) or injection drug use
-Medications that suppress your immune system
-Recent joint injury
-Recent joint arthroscopy or other surgery

Symptoms:

Usually come on quickly
-Fever
-Joint swelling that is usually in just one joint
-Joint pain, which gets worse with movement.

Symptoms in newborns or infants:
-Cries when infected joint is moved
-Fever
-Inability to move the limb with the infected joint (pseudoparalysis)
-Irritability

Symptoms in children and adults:
-Inability to move the limb with the infected joint (pseudoparalysis)
-Intense joint pain
-Joint swelling
-Joint redness
-Low fever

Investigations
-Aspiration of joint fluid
-Cell count,
-Crystals
-M/C/S
-Blood culture
-X-ray of affected joint

Treatment and prognosis
-Antibiotics
-Resting, keeping the joint still, raising the joint, and using cool compresses may help relieve pain
-Aspirate synovial fluid.
-Severe cases - washout
-Recovery is good with prompt antibiotic treatment
-If treatment is delayed, permanent joint damage may result.

Complications
-Joint degeneration (arthritis)
-Sepsis
-Necrosis of bone
Cellulitis and erysipelas
-Skin infections that develop as a result of bacterial entry via breaches in the skin barrier. Often Staph or Strept infection. characterised by a sharply demarcated, red, tender plaque. With malaise and fever; and lymphatic streaking sometimes being involved.
-May also complicate wounds (eg cuts, abrasions), insect bites or scabies.
-Lower extremeties are the most common site of infection.
-Both are diffuse, spreading skin infections
excluding infections associated with underlying suppurative foci, such as cutaneous abscesses, necrotizing fasciitis, septic arthritis, and osteomyelitis.

-Erysipelas - involves the upper dermis and superficial lymphatics

-Cellulitis - deeper dermis and subcutaneous fat

In practice, however, distinguishing between cellulitis and erysipelas is clinically difficult

Ddx:
-acute contact dermatitis
-septic bursitis
-gout
-acute lipodermatosclerosis
-necrotizing fasciitis
-bursitis
-osteomyelitis
-herpes
-DVT
-malignancy
-drug reaction
-insect sting

Preventive measures
-Examine patient for tinea of the feet
If present treat aggressively
-Leg oedema or venous insufficiency or ulcers, use compression stockings.
-In patients with predisposing conditions (eg lymphoedema), recurrent cellulitis is predominantly caused by Streptococcus pyogenes. Patients can be provided with phenoxymethylpenicillin as for mild early cellulitis so they may initiate therapy as soon as symptoms of infection begin.
-In cases of frequent recurrence, continuous prophylaxis may be considered
phenoxymethylpenicillin 250 mg orally, twice daily for up to 6 months initially.

N/B bilateral cellulitis is very uncommon

Worrying signs
Signs and symptoms of systemic toxicity:
-Fever, hypothermia,rigors
-Tachycardia [heart rate, >100 beats/min]
-Hypotension [systolic blood pressure, <90 mm Hg or 20 mm Hg below baseline])
-Cellulitis with soft, fluctuant areas suggestive of abscess formation
-A red streak from an area of cellulitis or a fast-spreading area of redness
-Significant pain not relieved by simple analgesics
-Inability to move an extremity or joint because of pain
-Patients with diabetes, cancer, or immunosuppression should be made aware that localized cellulitis may become serious
Features of cellulitis
-Skin erythema (Rubor)
-Oedema (Tumor)
-Warmth (Calor)
-Tender (Dolor)
-Functio Laesa
-?Fever

-Extends more deeply than erysipelas, and involves the subcutaneous tissues.
-In children is often periorbital and in adults most often affects the lower legs
-Spontaneous rapidly spreading cellulitis is most commonly due to S. pyogenes, or other streptococci (eg group B, C or G).
-Staphylococcus aureus causes cellulitis less frequently and is often associated with penetrating trauma or ulceration.
-other organisms can cause cellulitis but usually only in certain circumstances
(eg Aeromonas following fresh water exposure and Vibrio species following an injury in salt water).
-In immunosuppressed patients, a wide variety of organisms including
-Gram-negative bacteria
-Fungi
-Mycobacteria may also be responsible.

Investigations
-Swab if purulent - M/C/S
-Xray - IF worried about underlying osteomyelitis or septic arthritis
-Bloods and culture - M/C/S, FBC, ESR, CRP
Erysipelas
Erysipelas is distinguished clinically from other forms of cutaneous infection by the following 2 features:
-Lesions are raised above the level of the surrounding skin
-A clear line of demarcation between involved and uninvolved tissue.

It is almost always caused by Streptococcus pyogenesIt is more common among infants, young children and older adults. Erysipelas classically involves the face with a butterfly pattern, but also commonly affects the lower legs

Signs and symptoms
-Blisters
-Fever, shaking, and chills
-Painful, very red, swollen, and warm skin underneath the sore (lesion)
-Skin lesion with a raised border
-Sores (erysipelas lesions) on the cheeks and bridge of the nose
-Essentially diagnosed on how the skin looks
-With treatment, the outcome is good
It may take a few weeks for the skin to return to normal. Peeling is common
Risk factors for cellulitis/erysipelas
-Known injury :any cut, fracture, burn or even a scrape increases your risk of cellulitis because the injury gives bacteria an entry point.
-Weakened immune system: conditions that weaken your immune system leave you more susceptible to infections such as cellulitis.
Possible conditions that can weaken your immune system include diabetes, chronic leukaemias, HIV/AIDS, chronic kidney disease, liver disease, circulation disorders and the use of certain medications, such as corticosteroids.
Skin conditions: certain skin disorders, such as eczema, athlete's foot, chickenpox and shingles, cause breaks in the skin and increase your risk of cellulitis.
-Chronic swelling of your arms or legs (lymphedema): swollen tissue may crack, leaving your skin vulnerable to bacterial infection.
Intravenous drug use: people who inject illicit drugs have a higher risk of developing cellulitis.
Treatment
Nonantibiotic therapy
-Elevation
-Treat underlying cause
-Rest is advisable and elevation of the affected area hastens clinical improvement. If the skin has eroded, use nonstick dressings.

Mild early cellulitis and erysipelas

If Staphylococcus aureus and Streptococcus pyogenes, use:
di/flucloxacillin 500 mg (child: 12.5 mg/kg up to 500 mg) orally, 6-hourly for 7 to 10 days.

If S. pyogenes is confirmed, or suspected due to clinical presentation or local disease patterns (eg in Indigenous communities in central and northern Australia), use:
phenoxymethylpenicillin 500 mg (child: 10 mg/kg up to 500 mg) orally, 6-hourly for 10 days
OR
procaine penicillin 1.5 g (child: 50 mg/kg up to 1.5 g) IM, daily for at least 3 days.


Cephalexin can be used for patients with penicillin hypersensitivity. Use:
cephalexin 500 mg (child: 12.5 mg/kg up to 500 mg) orally, 6-hourly for 7 to 10 days.

For patients with immediate penicillin use:
Clindamycin 450 mg (child: 10 mg/kg up to 450 mg) orally, 8-hourly for 7 to 10 days

Severe cellulitis

If patient has significant systemic features or is not responding to oral therapy after 48 hours, commence IV therapy.

To treat infection with either streptococci or staphylococci, use initially:
di/flucloxacillin 2 g (child: 50 mg/kg up to 2 g) IV, 6-hourly.

For patients hypersensitive to penicillin use initially:
cephazolin 2 g (child: 50 mg/kg up to 2 g) IV, 8-hourly.

For patients with immediate penicillin hypersensitivity, use initially:
clindamycin 450 mg (child: 10 mg/kg up to 450 mg) IV or orally, 8-hourly
OR
lincomycin 600 mg (child: 15 mg/kg up to 600 mg) IV, 8-hourly
OR
vancomycin 1.5 g (child less than 12 years: 30 mg/kg up to 1.5 g) IV, 12-hourly

IV antibiotics may be more appropriate in patients with
-Immunosuppression
-Facial cellulitis
-Significant concurrent condition, including lymphoedema and cardiac, hepatic, or renal failure

Other antibiotic options:
Rifampicin- used to treat MRSA unfections; poor activity against streptococci
Ciprofloxacin-active against all strains of s.aureus; borderline activity against s.pyogenes. Emergence of resistance in MRSA developing. Expensive. AE: achilles tendon rupture.
tetracyclines: could be used but resistance is prevalent in both s.aureus and s.pyogenes.
Follow- up
-Reassess with short-interval follow-up, ideally within 48-72 hours, to ensure improvement
-In patients who respond slowly to therapy, antibiotics may need to be continued until inflammation resolves
-A transient increase in erythema over the first day of treatment is common
Represents an inflammatory reaction to cell lysis caused by antibiotics.
Outcome
-The vast majority of cellulitis and soft-tissue infections can be treated on an outpatient basis with oral antibiotics and do not result in lasting sequelae!
-Most conditions respond well to standard oral antibiotics.
-When outpatient therapy is unsuccessful and for patients who require admission initially, IV antibiotics are usually effective.
Cellulitis may progress to serious illness by
-uncontrolled contiguous spread
-lymphatic
-circulatory systems
Complications include
-Lymphangitis,
-Abscess formation
-Gangrenous cellulitis
-Necrotizing fasciitis, myonecrosis
-Sepsis
-Death
Certain strains of bacteria, most notably group A beta-hemolytic Streptococcus (GABHS) and S aureus, produce toxins that may mediate a more severe systemic infection, leading to septic shock and death.
Local Anaesthetics
Two types of LA: amino amides and amino esters.

MOA: reversibly bind to and inactivate sodium channels; sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. When a nerve loses depolarisation and capacity to propagate an impulse, the individual lose sensation in the area supplied by the nerve.

Acidosis in the environment into which the local anesthetic is injected (as is present in an infected, pus tissue) further increases the ionized fraction of drug. This is consistent with slower onset and poor quality of local anesthesia when a local anesthetic is injected into an acidic infected area.

Local anesthetics with a higher degree of protein binding have a prolonged duration of action. Increased dose increases the duration of the block

The half-life of esters is only a few minutes due to their rapid hydrolysis in the plasma and liver, whereas the half-life of amides is a few hours

Metabolism
Pregnancy and Newborns
-Patients with reduced cholinesterase activity (new born, pregnant) may have an increased potential for toxicity from ester local anesthetics
-Lignocaine, bupivacaine and ropivacaine have metabolites that can contribute to activity and toxicity
-Prilocaine is metabolised to ortho-toluidine (o-toluidine), which can oxidise haemoglobin to methaemoglobin
-Amides are mainly metabolized by the liver
Patient with severe hepatic disease may be more susceptible to adverse reactions from amide local anesthetics
-Thin nerve fibers are more easily blocked than thick ones.
-Myelinated fibers are more readily blocked than unmyelinated ones.

Adjuncts:
Bicarbonate to lower pH decrease burning sensation upon injection
Adrenaline: increases half life, decreases bleeding; should never be used in end arteries: fingers, toes, penis, nose and ears

Injection technique: aspirate before injecting, IV injection of LA increase toxicity risk. Use the smallest needle possible to decrease the pain of injection. Warming the LA and injecting slowly may ease patient discomfort.

Administration speed is important because toxicity develops as a result of peak serum concentration; if doing multiple area spread the toatl dose over a longer period to achieve lower peak serum levels of LA.

Toxicity: LA is relatively safe, low incidence of AE. Different drugs have different complications. Always have resuscitation equipment available.
AE: CNS, respiratory, CVS, allergy, methaemoglobinaemia

Dose: use the lowest dose and concentration required to produce effective anaesthesia. Depends on the patients weight, the drug and its concentration.
The process of rational prescribing
-Define the patient's problem?
-Specify the therapeutic objective? (what do you want to achieve with the treatment?)
-Verify whether your drug is suitable for this patient? (check effectiveness and safety)
-Start the treatment
-Give information, instructions and warnings
-Monitor (stop) the treatment