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Pharm Exam 2

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Anti-Inflammatory drugs
Corticosteroids (steroids)
NSAIDs
Antihistamines
Leukotriene modifiers
Uses (Indications):
Reduce discomfort (palliative , symptom mgt); prevent damage (steroids); Autoimmune health problems; Prevent rejection of transplanted organs
Inflammation
Nonspecific (Normal reactions of tissues/blood vessels in response to any injury or invasion (allergy, sprained joints)
Invasion may be environmental or pathogenic microorganisms
Infection
Invading microorganisms disturb normal environment and cause harm (pathogenic invasion)
Usually accompanied by inflammation
Corticosteroids MOA
Intrinsic substance (drug): steroid hormones produced in the adrenal cortex.
MOA by subtypes:
Glucocorticoids (cortisol):
Low dose: control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing mediator production (most powerful AIDs).
High dose: suppression of inflammation
Mineralocorticoids (aldosterone): control electrolyte and water levels by promoting sodium retention in the kidney.
Corticosteroids uses
Stress, immunosuppression, allergy, asthma/COPD
Regulate inflammation (RA, SLE, IBD)
Regulate carbohydrates, protein, blood electrolyte levels,
Regulate behavior
2 types of actions:
Suppress (reduce): Inflammations
Supplement (replacement therapy): adrenal insufficiency, congenital adrenal hyperplasia
Glucocorticoids SE
GI discomfort
Water and sodium retention ->hypertension, swelling and weight gain
↑liver to generate blood glucose->hyperglycemia (fasting blood glucose = 80-120)
Elevated eye presure, clouding lens->worsen glaucoma and cataract
Fat deposit/redistribution to face, shoulder and abdomen->Buffalo hump, moon face, ↑abdominal girth
Damage capillaries->Bruises and bleeding
Growth retardation for peds
Hair redistribution->Hair loss and hairy
Mood swing (anxiety and depression)
Mood swings ->sleeping problem due to "nervous feeling"
Skin thinning, acne, stretch marks
Immune suppression ->infection WBC = 5000-10000)
Wasted muscle
↑bone loss->osteoporosis and fractures
Local deposits->fungal infection and hoarseness
Mineralocorticoid: 4H SE
hypertension (abnormally high blood pressure),
hypokalemia (low potassium levels in the blood) K = 3.5-5.5
hypernatremia (high sodium levels in the blood) and Fluid retention Na=135-145
healing impaired (immunosuppressive effects)
Corticosteroids ADE
Vision loss (cataract, glaucoma, central serous retinopathy or CSR)
Adrenal insufficiency and (Cushing's)->adrenal glands atrophy
Immune suppression
Corticosteroids Drug Names
Drug Names: -sone, -solone
Oral: Prednisone, Prednisolone
Parenteral: dexamethasone (Decadron), hydrocortisone (Solu-Cortef), methylprednisolone (Solu-Medrol)
Corticosteroids DDI
DDI:
Loop and thiazide diuretics (more potassium loss)
Hypokalemia->digoxin-induced dysrthymias if concurrent use of steroids and digoxin
Use with Nonsteroidal anti-inflammatory drugs->HTN, GI ulcer and bleeding
Counteract Insulin and oral hypoglycemics
Live vaccines
Contraindications:
Patients with systemic fungal infections
Those receiving live virus vaccines
Use with caution in pediatric patients and pregnancy/breast-feeding
Adrenal suppression and physiologic stress:
Taper the dosage overtime to prevent adrenal crisis
Switch from multiple doses to single doses
Monitor for signs of insufficiency
Corticosteroids Education
Prophylactically use H2 blockers, take with food
Assess support system
Monitor blood glucose level, adjust dose of hypoglycemic drugs
Baseline and follow up eye exams
Monitor wt, BP, lung sounds, edema
Monitor s/s bleeding buries, black emesis, stool, coffee ground emesis
Cardiac monitor, +/- supplements
Monitor s/s of infection, avoid crowds, hand washing
Monitor bone density and supplements
Monitor s/s, give NS, hydrocortisone IV, take steroids in AM, do NOT stop the meds suddenly
Corticosteroids Life Span Considerations
Pediatric:
At risk for same side effects as adults
Growth retardation
Pregnancy and breastfeeding: C
Drugs cross placenta, are excreted in breast milk (low birth wt babies, 3rd trimester)
Older adults:
Extra precautions to avoid infection
Monitor blood glucose levels
NSAIDs MOA
MOA: reduce inflammation by blocking cyclooxygenase (COX) receptor and inhibiting the COX enzymes needed for synthesis of prostaglandins production.
COX-1 receptor: GI tract, renal, blood vessels
Increase blood flow (esp. renal flow)
Form thick coating
Reduce acid production
Platelet aggregation (Aspirin)
COX-2 receptor: inflammatory cell at site, inflammatory responses (5 cardinal signs)
Action: suppress by antagonizing or blocking the COX receptors.
NSAIDs Use/EE
Therapeutic uses:
Suppress inflammation due to arthritis .
Analgesia for MILD to MODERATE pain.
Fever reduction or antipyretic.
Inhibition of platelet aggregation to prevent stroke and MI (Aspirin or ASA).
EE:
Reduced inflammation
Reduced fever
Relieved pain
Absence of injury
NSAIDs drug names
Two groups of COX inhibitors:
Nonselective COX inhibitors or 1st generation NSAIDs
aspirin (Aspirin, Ecotrin, Bayer), Ibuprofen (Advil, Motrin), Naproxen (Aleve, Anaprox, Naprosyn), Naproxen /lansoprazole (Prevacid Naprapac), Meloxicam (Mobic), Oxaprozin (Daypro), Diclofenac/misoprostol (Arthrotec), indomethacin (indocin),
Parenteral and oral: Ketorolac (Toradol)
Selective COX2 inhibitors or 2nd generation NSAIDs: celecoxib (Celebrex)
*Confusing drugs: Celebrex vs. Celexa
Nonselective COX inhibitors MOA/uses
MOA: Inhibit COX-1 and COX-2 receptors, reversible (except aspirin, 7 days)
Uses: Analgesic, antipyretic, anti-inflammatory,
ASA: MI and stroke prevention (suppression of platelet aggregation), cancer and AD prevention.
Nonselective COX inhibitors Cls
Contraindications or CIs/Precautions
Preg D for last trimester
PUD and bleeding disorders (e.g., hemophilia, vitamin K deficiency)
Children w/resent viral infection (chickenpox or influenza) NO aspirin.
Cautious use in older adults, smoker, pts with H. pylori infection, hypovolemia.
Not to use Ketorolac (Toradol) in pts w/ CHF, renal dysfunction (<5 days)
Nonselective COX inhibitors SE/ADE
SE: GI upset (N/V/D/A, abd pain, heartburn), gastric bleeding/ulcers, fluid retention->wt gain, edema, and HTN, renal impairment (↓ renal blood flow)
ADE: Kidney failure, MI and stroke for nonaspirin NSAIDS, exacerbation of asthma ,
ASA only: Salicylism or ASA poisoning, Reye's syndrome, preg anemia, postpartum hemorrhage, may prolong labor
Symptoms of aspirin overdose
Seizure, restlessness, irritability, excessive and unorganized talking, fear or nervousness, dizziness, confusion, abnormally excited mood, hallucinations, drowsiness, loss of consciousness, double vision, tinnitus, uncontrollable shaking, increased HR and RR, burning throat pain, vomiting pain, decreased urination, fever, decreased Na and K, alkalosis, death
Selective COX2 inhibitors MOA/uses/Cl/SE/ADE
MOA: Inhibit COX-2 receptors, reversible
Uses: arthritis, pain,
CI: not use celecoxib in pts w/ sulfa allergy, cautious use 2nd gen. NSAIDs in pts w/ CVD
SE: fewer than 1st generation drugs, but higher cardiovascular risks, last-choice drug for long-term management of pain, lower risk for GI side effects
ADEs: renal impairment, hypertension, and edema, increased risk for MI and stroke
NSAIDs DDI/DFI
↑ risk of bleeding when concurrent use with
Anticoagulants (Heparin and warfarin),
steroids
alcohol
Counteracting effect:
Ibuprofen reduces ASA's preventive effects on MI and stroke
↓diuretic effect of furosemide,
↓antihypertensive effect of ACE inhibitors, see AID readings for other DDIs
Additive effect: Willow bark, glucosamine chondroitin (Osteoarthritis)
Life Span Considerations for NSAIDs
Pediatric:
Only ibuprofen is recommended(>2month, by weight)
Avoid aspirin (Reye's syndrome: liver disease, coma, mental retardation and death)
Pregnancy: (pre-close ductus arteriosus)
Category C drug for first 6 months
Avoid during last 3 months (pre-close ductus arteriosus)
Older adults:
Cardiac problems (wt, swelling, SOB)
Nursing Implications for NSAIDs
Collect Hx of HTN, CHF, PUD, GERD
Monitor s/s of bruise and bleeding (black emesis, stool, Occult blood test), PTT, PT, INR
Monitor wt, VSs (T, HR, RR, BP), I &O, renal function (BUN, Cr)
Managing ASA poising or salicylism or ASA toxicity:
Give IV fluid and electrolytes
Activated charcoal and gastric lavage
Reverse acidosis
Alkalization of urine to increase ASA elimination
Hemodialysis
NSAIDs Pt Education
Take meds w/food or full glass of water
Use antiulcer and acid reduction meds to prevent ulcer
Avoid alcohol, take ibuprofen with ASA, two more NSAIDs
Stop ASA 1 wk before surgery or invasive procedures
Use Ketorolac short term (<5days) to manage post-op pain, concurrent use opioids to reduce the dosage for both drugs
Increase risk of bleeding when concurrent taking warfarin (Coumadin).
Watch for bruise and bleeding
Report OTC drugs and other herbal remedies.
Antihistamines (Histamine Blockers)
Important role in:
Allergic reaction (H1)
Regulation of gastric acid secretion (H2)
Distribution
Present in practically all tissues
Especially high in skin, lungs, and GI tract
Low content in plasma
Synthesis/storage
Mast cells and basophils
Produced by neurons
Histamine (H1) Receptors: blood vessels, respiratory mucous membranes
Vasodilation
Skin of the face and upper body
Extensive - can cause hypotension
Increased capillary permeability: Edema
Bronchoconstriction
↓ cardiac contraction->↓ cardiac output
CNS effects:
H2 Receptors: in stomach lining
Secretion of gastric acid
Act directly on parietal cells to promote acid release
Antihistamines (Histamine Blockers) MOA/uses
MOA: Block histamine from binding to its receptor s (histamine is a neurotransmitter)
Uses/Indications:
Allergic disorders (H1 blocker)
1st and 2nd generation H1 blockers
Peptic ulcer disease (H2 blocker)
Antihistamines = histamine receptor antagonists = histamine receptor blockers
Antihistamines (H1 Blockers) drug names
Two groups of H1 antagonists
First-generation H1 antagonists (older, highly sedating)
Chlorpheniramine (Chlor-Trimeton)
Clemastine (Tavist Allergy)
Cyproheptadine (generic only)
Diphenhydramine (Benadryl)
Hydroxyzine (Vistaril)
Promethazine (Phenergan)
Second-generation H1 antagonists (newer, minimal sedation, less effect on CNS, only bind to H receptor)
Fexofenadine (Allegra)
Cetirizine (Zyrtec)
Loratadine (Claritin, Tavist ND, Alavert)
Desloratadine (Clarinex)
Azelastine (Astelin)
Antihistamines (H1 Blockers) MOA/EE
MOA: ↓inflammation by blocking histamine from binding to H1 receptors and muscarinic receptors (1st generation, sedation)
EE:
Reduce vasodilation (decreased redness and flushing);
Reduce permeability of blood vessels ( decrease swelling, hive size, itchiness and pain)
Reduce mucus production (nasal, eye, airway);
Widen narrowed airways (↓ SOB) ;
CNS depression or sedation (1st generation)
CNS stimulation if overdose (seiz in peds)
Antihistamines (H1 Blockers) SE/ADE/DDI/Life span
SEs of 1st generation: Anticholinergic effects
CNS suppression: 6 Ds
PNS effects: 10 cants
GI upset (N/V/A)
ADEs of 1st generation: seizures (rare), coma
DDI of 1st gen.
Concurrent use w/ CNS depressants CNS sedation
MAOI: hypertension crisis
Life-span consideration: Peds, preg/nursing women, elderly (polypharmacy, CNS depressant user)
Leukotriene Modifier Drug names/MOA/uses/EE/SE/ADE
Drug name: -luk-, -leu-
Leukotriene-receptor antagonists (LTRA): montelukast (Singulair), zafirleukast (Accolate),
Leukotriene-receptor inhibitors: Zileuton (Zyflo)
MOA: Reduce inflammation by blocking leukotriene from binding to the receptor (LTRA) or inhibiting leukotriene production (LTRI)
Uses: allergic rhinitis
Expected effects:
reduced redness and swelling of mucous membranes due to reduced vascular permeability
Less mucus due to reduced secretions;
Improved SOB due to less bronchoconstrition
SEs/ADEs: Headache, dizziness, GI upset, liver dysfunction (zyflo and Accolate)
Leukotriene Modifier nursing implications/pt education
Nursing implication and patient education:
Monitoring: liver functioning (albumin, ALT, AST) overtime (dark urine, light stool, yellow skin)
Teach pt to report symptoms of liver problems (Jaundice, decreased appetite, tender RUQ, nausea, fatigue)
Take montelukast (Singulair) at night daily
Drugs for Rheumatoid Arthritis
Treatment Guideline
Relieve symptoms
Maintain joint function
Minimize systemic involvement
Delay progression of disease
Classes of Drugs
NSAIDs or Nonsteroidal anti-inflammatory drugs
Glucocorticoids, Adrenal corticosteroids
DMARDs, Disease-modifying anti-rheumatic drugs (know the subgroups of DMARDs from See RA_Gout drug reading)
Protocol
Start with NSAIDs If symptoms persist, add DMARDs Glucocorticoids may be added until DMARDs take effect.
Anti-gout Medications
Causes: excessive production of uric acid or impaired renal excretion of uric acid
Patho:
Hyperuricemia: Uric acid level >7 mg/dL in men or 6 mg/dL in women
Uric acid crystals deposited in joints
Prognosis: recurrent inflammatory disorder (mainly in men), episodes of severe joint pain (typically in large toe),
Treatment goal: no cure
Short-term to relieve symptoms of attack
Long-term to prevent gout attack (less than 3 times/year)
Drug Types:
NSAIDs: First-line agents: treat gout attacks
Better tolerated and more predictable than colchicine
Relief should be within 24 hours; swelling subsides over next few days
Glucocorticoids : for hypertensive patients, unresponsive to, or having contraindication to NSAIDs, not for DM pts
Uricosuric drugs: long-term to treat chronic gout
Uric Acid Inhibitor [Allopurinol (Zyloprim)]: prevent gout attacks
Types of pain
Acute: acute onset, identifiable cause, limited duration, improves with time;
Chronic: 6 months, unidentifiable cause;
Cancer : "malignant pain," both acute and chronic
Drug therapy for pain control
Non-opioid analgesics (for mild-moderate pain )
acetaminophen,
nonsteroidal anti-inflammatory drugs (NSAIDs),
Opioid analgesics (for moderate-severe pain)
Adjuvant drugs:
Anticonvulsants [carbamazepine (Tegretol)]
Antidepressants
Steroids
Non-opioids: Acetaminophen MOA/uses/SE/ADE/DDI/implication
MOA: change the perception and response to pain by Inhibiting prostaglandin synthesis in central nervous system.
Therapeutic Use/Indication:
Analgesic (alone for mild pain, combined with other opioids for moderate or above pain)
Antipyretic
SEs/ADEs:
permanent liver or kidney damage w/ overdose
Antidote: acetylcysteine (Mucomyst) , IV , < 24 hrs
DDI: Alcohol, warfarin
Implication:
Keep a total of daily intake < 4g/day,
Monitor bleeding and bruise, check INR and PT if pts taking warfarin (Coumadin)
Monitor Liver/renal function
Non-opioids: NSAIDs MOA/indication/SE/ADE
MOA:
Suppress inflammation- induced pain
act at the injury site
do not change a person's perception of pain
Indication: Mild to moderate pain @ bone, cancer, soft tissue trauma.
Side effects:
↓clot formation (aspirin) ↑ risk of bruise and bleeding
Irritation of GI tract (Peptic Ulcer Disease or PUD and gastroesophageal reflux disease or GERD)
Water and salt retention (high blood pressure or HTN and Congestive Heart failure or CHF)
Adverse effects:
Induction of asthma
ASA poisoning (aspirin only)
fever, rapid heart rate and respirations,
GI upset,
Confusion,
Tinnitus (ringing in the ears)
Acidosis, seizures, coma, and death.
Opioid Agonists (Narcotics) Drug names/MOA/indications/EE
Drug names: Morphine sulfate, fentanyl (Duragesic), Meperidine (Demerol), oxycodine (OxyContin), Hydromorphone (Dilaudid)
MOA:
Reduce pain by binding to opioid receptors in brain, altering perception and respponse to pain and reducing anxiety (opioid receptor agonist)
do nothing at the injured site
Types: agonists, agonist-antagonists and antagonist
Indications: moderate to severe pain
EE: reduce pain
Opioid Agonists (Narcotics) Cl
CI/Precautions
Not to use Meperidine in renal failure pts, causing seizures and neurotoxicity.
Cautious use in pts with:
Asthma, emphysema, head injuries, very young and old (resp. depression)
Pregnant and women in labor (dependence, resp. depression, prolonged labor)
Extremely obese (prolonged SEs/ADEs sequestration)
Inflammatory bowel disease (megacolon or paralytic ileus)
BPH (urinary retention)
Liver and renal disease
Opioid Agonists (Narcotics) SE/ADE
Constipation (↓ GI motility), GI upset
drowsiness, sedation (mental clouding)
Dizziness (orthostatic hypotension)
Skin pruritus (itchiness), urticaria (hive)
Urinary retention
Miosis
Cough suppression -> mucus accumulation
Adverse effects
respiratory depression (opioid blocker, Narcan)
Overdose triad: coma, resp. depression and pinpoint pupils
Addiction: psychological needs
Dependence: physical needs
Tolerance (Pharmacodynamics)<-receptor exhaustion
withdrawal : Nausea, vomiting, abdominal cramping, sweating, delirium, seizures
** withdrawal occurs when suddenly quitting the drug after long-term use
Opioid agonists (narcotics) DDI
↑ CNS sedation: other CNS depressants and alcohol
Additive anticholinergic effects of 10cants and 6Ds: concurrent use anticholinergic, 1st gen. antihistamine, tricyclic antidepressants
Hyperpyrexic coma: concurrent use MAOI or monoamine oxidase inhibitors (MAOIs), causing excitation, seizures, respiratory depression
Additive hypotensive effects: concurrent use anti-hypertensives.
Opioid Agonists (Narcotics) Nursing implications
Nursing Implications:
Monitor VSs, I&O, vision, fall risks, lung sounds,
Naloxone (Narcan) or nalmefene (Revex) and resuscitation equipment available
Monitor patient controlled analgesia (PCA) pump settings and assess pain before and 30min after meds given
Encourage pulmonary toileting: DBC, IS
Prophylactic use antiemetic meds,
Provide assistance with ambulation (belt and walker)
Scheduled toilet time and check PVR
Taper dosage slowly in pts w/ addiction.
Concurrent use short-acting opioids with transdermal patch until onset of therapeutic effects
Opioid Agonists (Narcotics) pt education
Patient Education:
Avoid to use CNS depressants (alcohol and Benzo) with opioids
Avoid driving or operating heavy machinery
Increase fluid intake and physical activity
Use stool softener and laxative to prevent constipation
Change position slowly (dangle and rise slowly)
Avoid use opioid with MAOI antidepressants
Avoid use opioid with anti-hypertensive drugs together
Take pain pills on a regular schedule (ATC) rather than PRN
Life Span Considerations for Opioids
Pediatric:
Newborn addiction/withdrawal can occur (Heroin)
Monitor newborns with apnea monitor and/or pulse oximetry (Narcan for resp. depression)
Pregnancy and breastfeeding:
No breastfeeding if taking opioids
Older adults:
Mental status
Visual impairment (smaller pupil)
Orthostatic hypotension, risk for falls
Avoid meperidine (Demerol)
Opioid Agonist-Antagonist Drug names/MOA/uses
Drug names: Butorphanol (Stadol), Nalbuphine (Nubain), Buprenorphine hydrochloride (Buprenex)
MOA: Reduce pain by acting as antagonist on mu receptor and agonists on Kappa receptors
Low abuse potential due to little euphoria (high dose can cause anxiety, restless, mental confusion)
Less repiratory depression
Less analgesic effect
Uses/Indications:
moderate to severe pain
Treat opioid dependence [Buprenorphine (Buprenex)]
migraine with the intranasal spray
adjunct drug during anesthesia for surgery, labor and delivery
manage labor pain in women [Butorphanol (Stadol)]
NO narcotic antagonist activity in nondependent patients
Opioid Agonist-Antagonist Cl/SE/ADE/DDI
CI/precaution:
Not to give pts with physical dependence on opioids
Not to give pts w/ angina, MI, renal/liver disease, respiratory depression, head injury
Not to give to pts taking opioid agonist
SE/ADE:
Abstinence syndrome (cramping, HTN, N/V)
Sedation respiratory depression
Dizziness
Increased intracranial pressure headache
Increased cardiac workload
DDI
Additive sedation: co-adm with CNS depressants
Counteractive effects: co-adm with opioid agonists
Opioid Agonist-Antagonist implications/education
Implication and Educations:
Monitor VSs, LOC, headache
Advise pt abstinence syndrome may be precipitated if he/she is physically dependent on opioids.
Advise pt to stop opioid agonists before using opioid agonist-antagonist
Narcan and resuscitation kit ready to use
Change position slowly
Avoid driving or operating machine
Opioid Antagonists drug name/MOA/uses/Cl/SE/ADE/implication/education
Drug name: Naloxone (Narcan), Naltrexone (ReVia), Nalmefene (Revex)
MOA: Reverse opioid effect by competing for opioid receptors (affinity) and have no opioid effect (NO intrinsic activity).
Uses/Indications:
Treat opioid overdose
Reverse respiratory depression induced by opioids
CI/Precautions: not to use in pts w/ opioid dependency.
SE/ADE: tachycardia, tachypnea, HTN, abstinence syndrome, pulmonary edema
Implication and Educations:
Monitor VSs, cardiac rhythm, respiratory functions, withdrawal s/s
Assess pain and provide pain control
Resuscitation equipment ready to use
Assess pts substance use history
Significant first pass loss: NO ENTERAL or ORAL route
Need for repeat dosage (shorter half-life compared to opioids)
Adjuvant Drugs for Pain overview/types
Overview:
Always used with primary pain meds (opioid agonist) to increase pain relief but with lower dosage requirement for opioids -> less SE/ADE
Types:
Anticonvulsants: carbamazepine (Tegretol), gabapentin (Neurontin), phenytoin (Dilantin)
Antidepressants: tricyclics, amitriptyline (Elavil)
CNS stimulants: methylphenidate (Ritalin)
Antihistamines: hydroxyzine (Vistaril)
Steroids: dexamethasone (Decadron)
Bisphosphonates: etidronate (Didronel)
NSAIDS: ibuprofen (Motrin), ketorolac (Toradol)
Adjuvant drugs for pain uses/EE
Therapeutic Uses/Indications:
Concurrent use with opioids, NOT to use alone
NSAIDs inflammation.
Tricyclic antidepressants depression and neuropathic pain (cramping, aching, burning, darting, and lancinating pain)
Anticonvulsants CHRONIC neuropathic pain (DM, CA), migraines, fibromyalgia, and neuralgia
CNS stimulants enhance analgesia and reduce sedation.
Antihistamines relieve pain associated anxiety, prevent insomnia and relieve nausea.
Glucocorticoids pain induced by intracranial pressure and spinal cord compression.
Bisphosphonates manage hypercalcemia induced bone pain due to cancer
EE: enhance the effects of opioids, relieve depression, seizures and other symptoms aggravating pain, reduce opioid SE/ADE, reduce neuropathic and CA bone pain
Adjuvant Drugs for Pain: SEs/ADEs
Antidepressants:
orthostatic hypotension,
Sedation,
other anticholinergic effects (10cants and 6 Ds)
Anticonvulsants: CNS depression, bone marrow suppression, GI distress
CNS stimulants: wt loss, insomnia,
Antihistamines: sedation, dry mouth
Steroids: adrenal insufficiency, Osteoporosis, hypokalemia, hypernatremia, hyperglycemia, peptic ulcer disease (PUD),
Bisphosphonate: transient flu-like s/s, irritation of injection site, renal failure/UTI
NSAIDs: bone marrow suppression, GI distress
Adjuvant Drugs for Pain: CI/Pr
Antidepressants:
Not for pts w/ recent MI and taking MAOI within 2week,
Cautious use in pts w/ seizure, urinary retention, BPH, close-angle glaucoma, hyperthyroidism, liver/renal disease
Anticonvulsants:
Not for pts w/ bone marrow suppression and taking MAOI within 2-wk,
Cautious use in pts w/ seizure
CNS stimulants:
Not for pts w/ hyperthyroidism, HTN, taking MAOI within 2-wk,
Cautious use in pts w/ agitation or tics
Antihistamines: (1st generation)
Cautious use in elderly due to CNS sedation
Steroids:
Not for pts w/ fungal infection
Cautious use in pts w/ seizure disorder, peptic ulcer disease or PUD, hypertension, hypothyroidism, DM, or liver disease.
Bisphosphonate: Cautious use in pts w/ kidney disease
NSAIDs:
Not for pt w/ history of bronchospasm induced by NSAIDs
Cautious use in pts w/ PUD, hypertension, and liver/ kidney disease.
Adjuvant Drugs for Pain: DDI/DFI
Antidepressants and antihistamines: additive CNS depression if concurrent use other CNS depressants (alcohol)
Anticonvulsants:
They are liver enzyme inducers reduce OC and warfarin (Coumadin) levels if taking together
Grapefruit juice is liver enzyme inhibitor prolong anticonvulsants' effects
Phenytoin and phenobarbital, liver enzyme inducers reduce carbamazepine levels
NSAIDs:
Counteractive with antihypertensive, diuretics
Additive with steroids GI bleed
NSAIDs increase anticoagulants and lithium levels
CNS stimulants:
Taking with other basic drugs increase reabsorption
Taking with other acidic drugs increase elimination
Insulin and hypoglycemic drugs reduce glucose.
Taking with MAOI severe hypertension
Taking with caffeine and OTC sympathomimetic CNS overstimulation
Steroids
Taking with hypoglycemic drugs counteractive
Taking with NSAIDs risk for GI bleed
Steroids↓K+↑risk of digoxin-induced dysrhythmias
Bot steroids and diuretics promote K+ loss
Nursing Implications and Educations for adjuvant drugs for pain
Antidepressants:
change position slowly, assist ambulation, monitor orthostatic BP
Avoid driving and operating heavy machinery
Other anticholinergic effects: increase fluid intake, chew gum/candy, physical active, laxative/stool softener, check bladder, vision, I/O
Not to use with other CNS depressants (alcohol)
Anticonvulsants:
Monitor CBC and platelets count, PT and INR when taking with warfarin
Instruct to watch bruising and bleeding, infection and anemic s/s
Take with food, but avoid grape fruit juice
Increase OC dose when taking together
CNS stimulants:
monitor wt, VSs, drug and glucose level
take last dose no later than 4pm,
monitor Avoid caffeine, OTC sympathomimetic
Antihistamines: avoid driving and operating machine, increase fluid intake, suck on candy, chew gum, not to use with other CNS depressants (alcohol)
Steroids:
Monitor s/s adrenal insufficiency, cardiac rhythm, K+ , Na+, glucose levels, GI bleed
Take with food, use acid reduction meds
Increase hypoglycemic agents
take pill in AM
Bisphosphonate: Monitor fever, injection site, Cr, BUN, s/s UTI
NSAIDs: monitor bruise and bleeding.
Adjuvant drugs: Anticonvulsants MOA/SE/ADE/life span
Common drugs
Gabapentin (Neurontin) (1st choice, but 4 wks to work)
Pregabalin (Lyrica) (1 wk to work)
MOA: change the way sodium and calcium travel across the surface of sensory nerve cells in the brain. The nerve cells send fewer pain signals to the brain.
SE/ADEs - CNS depression, bone marrow suppression, GI distress
Special population consideration:
Pediatric: Causing aggressive behavior (Paradoxical effect)
Pregnancy and breastfeeding: Category C, Avoid breastfeeding
Elderly: Start low dose and increase dose slowly, not stop suddenly.
Adjuvant drugs: Antidepressants MOA/uses/SE/ADE
TCAs and SNRIs
Tricyclic (TCAs): amitriptyline (Elavil), nortriptyline (Pamelor),
serotonin-norepinephrine reuptake inhibitor (SNRI): duloxetine (Cymbalta), venlafaxine(Effexor)
MOA: reduce pain signals transmitted to brain
Indications: (Take 1-2 weeks to work)
SE/ADEs: (Anticholinergic effect, 10cants 6Ds)
**Cyclobenzaprine (flexeril), is a muscle relaxant medication used to relieve skeletal muscle spasms, causing heavy sedation.
CNS depressants: Sedative-hypnotics
Definitions:
Sedatives: induce a sense of calm and reduce anxiety
Hypnotics: induce sleep.
Types:
Benzodiazepines,
Barbiturates,
Benzodiazepine-like medications or Benzodiazepine receptor agonists (first line drugs), or non-Benzodiazepines, or atypical benzo-receptor ligands
Antihistamines
Antidepressants
Non-Benzodiazepines names/MOA/uses/Cl
Drug names: zolpidem (Ambien), eszopiclone (Lunesta), Zaleplon (Sonata), Trazodone (Desyrel)
MOA:
Prolong sleep duration and reduce awakenings by ehancing the action of neurotransmitter gamma-aminobutyric acid (GABA-A) in the CNS.
Have NO antianxiety, muscle relaxant, antiepileptic effects
Low risk of tolerance, abuse and dependence.
Indication:
insomnia, help improve both sleep maintenance and daytime alertness
short-acting, short-term use (7-10 days), < 4 weeks.
CI/Pr: Preg B. not for nursing mother, cautious use in elderly and pts w/ renal/liver/respiratory dysfunction.
Non-Benzodiazepines SE/ADE/DDI/pt education
Non-Benzodiazepines (Benzodiazepine receptor agonists )
SE/ADEs: lightheadedness, drowsiness, daytime sleepiness, dizziness, fatigue, headache, GI upset, sleep-related behavior (sleep-driving, phone calling, eating, sleepwalking)
DDI: additive CNS depression when concurrent use with other CNS depressants (alcohol)
Patient education:
Take zolpidem immediately before going to sleep
Take zolpidem only when able to get a full night' s sleep (7 - 8 hours)
Not drink alcohol the same evening
Benzodiazepine Hypnotics names/MOA/uses/Cl/SE
Drug names: "-pam" or "-lam"clonazepam (Klonopin), lorazepam (Ativan), alprazolam (Xanax), temazepam (Restoril), diazepam (Valium)
MOA: reduce anxiety and induce sleep by increasing action of GABA in CNS
Uses: anxiety, seizure, insomnia, muscle spasm, alcohol withdrawal, Panic disorder, induce anesthesia
CI/Pr:
preg. D,
Not for pts w/ sleep apnea, respiratory depression, organic brain disease or lactation
Cautious use in pts w/ hx of substance abuse, liver/renal failure
SE: CNS depression, respiratory depression, daytime sleepiness, anterograde amnesia, sleep-related behaviors, falls and urinary incontinence in elderly patients.
Benzodiazepine Hypnotics ADE/DDI
ADEs: Often occur with abrupt discontinuation
Physical dependence withdrawal Symptoms
Short-term therapy: GI distress, sweating, dysrhythmia, anxiety, insomnia, tremor and dizziness
Long-term therapy: delirium, paranoia, panic, HTN, seizures,
paradoxical response (rebound insomnia, excitation, euphoria, anxiety and rage)
Acute toxicity
Oral toxicity: drowsiness, lethargy, confusion
IV toxicity: respiratory depression
DDI: additive sedation with concurrent use with other CNS depressants (alcohol)
Benzodiazepine Hypnotics implications/education
Avoid driving and operating machine
Monitory VSs
Resuscitation equipment available at bedside
For oral toxicity:
Gastric lavage followed by activated charcoal or saline cathartics
For IV toxicity:
Administer Flumazenil (Romazicon ) to counteract sedation and reverse side effects
Monitor the client's VSs, maintain patent airway and IV fluids to keep BP
Resuscitation equipment available
Advise pts to avoid alcohol and other CNS depressants.
Advise pts to avoid abrupt discontinuation of treatment to prevent withdrawal symptoms
Benzodiazepines must be tapered over several weeks.
The elderly should not take long-acting forms.
Melatonin Agonist names/MOA/uses/Cl/SE/ADE/DDI/pt education
Drug names: ramelteon (Rozerem)
MOA: Induce sleep by activating melatonin receptors
Uses: management of insomnia
CI/Pr: not use in pregnant and nursing women, cautious use in pts w/ liver disease
SE/ADE: sleepiness, dizziness, fatigue, hormonal imbalance (amenorrhea, decreased libido, difficulty with fertility, galactorrhea)
DDI
Taking with high fat food reduced drug absorption
Additive sedation when taking with CNS depressants.
Teaching:
Take meds on empty stomach
Take meds 30 min before bedtime
Other Drugs for Insomnia
Antidepressants (i.e., Cymbalta)
Used for secondary insomnia caused by depression
Not recommended to give the elderly patients due to the risk for side effects (daytime sleepiness, dizziness) and drug interactions.
Pain Relievers.
Tylenol PM can help mild insomnia without causing any daytime sleepiness.
Herbs and Supplements
Melatonin: the most studied dietary supplement for insomnia. It reduces the time to fall asleep (sleep onset) and the time spent asleep (sleep duration).
Life Span Considerations for Drugs for Insomnia
Pediatric:
Antihistamines may cause increased excitement
Pregnancy and breastfeeding:
Benzodiazepines - categories D and X
Zolpidem (Ambien) - categories B and C
Most cross placenta, enter breast milk
Older adults:
Lower doses because of increased sensitivity
More likely to experience side effects
Increased risk for falls
Alzheimer's disease
Devastating illness
Gradually progressive neurologic disorders
Neuropsychiatric symptoms:
memory loss -> Impaired thinking ->Inability to perform ADLs -> death
Incurable, degenerative, irreversible and terminal disease
AD Pathophysiology
Reduced Levels of acetylcholine (ACh)
Beta-amyloid and neuritic plaques
Form outside of neurons
Spherical bodies composed of beta-amyloid core
Neurofibrillary tangles and tau
Degeneration of neurons caused by the accumulation of toxins aforementioned
Early in hippocampus: Memory (short-term)
Later in cerebral cortex: Speech, perception, reasoning, and other higher functions
Risk Factors of AD
Known risk factors
Advancing age
Family history (genetics)
Possible risk factors
Female
Head injury (TBI)
Low educational level
Production of Apolipoprotein E4 (apoE4)
High levels of homocysteine
Nicotine in cigarette smoke
Herpes simplex virus type 1 (HSV1)
Down syndrome
HTN and high cholesterol
Symptoms of AD
Memory loss
Confusion
Feeling disoriented
Impaired judgment
Personality changes
Difficulty with self-care
Behavior problems (wandering, pacing, agitation, screaming)
Inability to recognize family members
Inability to communicate
Diagnosis of AD
Age
Clinical manifestation
Diagnostic testing:
MRI - atrophy of brain areas
PET - altered patterns in the brain
Cerebrospinal fluid analysis, presence of abnormal proteins
Drug therapy of AD
Goal: improve symptoms or palliative care, no cure
Five drugs are approved for AD dementia (not effective).
Cholinesterase inhibitors
Donepezil (Aricept)
Galantamine (Razadyne)
Rivastigmine (Exelon): pill or patch
Tacrine (Cognex): liver damage
NMDA receptor antagonist
Memantine (Namenda)
Cholinesterase inhibitors names/MOA/uses
Drug names: -stigmine or -onium
MOA: Prevent cholinesterase (ChE) from inactivating acetylcholine (ACh) and increase available ACh
Use:
mild to moderate AD Only donepezil is approved for treatment of advanced AD
Treat and Dx of myasthenia gravis,
Reversal of Nondepolarizing neuromuscular blocking agents used for general anesthesia
Cholinesterase inhibitors EE/SE/ADE
Expected Effects or EE
Slow progression of symptoms, improved cognitive function, control behavior and live independent life
Side effects:
SLUDGE:
DUMBBELSS:
Adverse effects:
"killer B's": bronchorrhea and bronchospasm (leading cause of death)
Cholinergic crisis: excessive muscarinic stimulation block NMJ or neuromuscular junction resp.depression
dysrhythmia, GI bleeding, seizures, liver damage
Cholinesterase inhibitors Cl/DDI
Contraindications/Precautions:
Not use in pt w/ obstructive GI and GU problems
Cautiously in pt w/seizure disorders, hyperthyroidism, peptic ulcer disease, asthma, bradycardia, and hypotension.
Preg. Categ. C
DDI:
Succinylcholine (neuromuscular blocker used for intubation)
Reduced effects when using with 1st generation antihistamines, TCAs, traditional antipsychotics
Cholinesterase inhibitors nursing implications/pt education
Nursing Implications:
Safe administration:
Starts low go slow
Notify the provider if observing SE/ADEs
Treat SE and ADE w/ antidote (atropine)
Monitor closely and Provide oxygen, mechanical ventilation until full muscle function return
Patient education:
Encourage safety tips of self-dosage adjustments
Wear a medical alert bracelet.
NMDA receptor antagonist MOA
NMDA (N-Methyl-D-aspartate ): neuroprotective agent
MOA:
Glutamate: amino acid (excitatory neurotransmitter).
Glutamate is released excessively when brain cells are damaged by AD, and causes further brain cell damage.
NMDA blocker improves the symptom by blocking NMDA receptors, inhibiting glutamate release , and helping protect brain cells.
NMDA receptor antagonist names/use/EE/SE/ADE
Drug names: Memantine (Namenda)
Use: moderate to severe AD
Expected Effects:
Maintain ability to perform ADL's
Fewer behavioral changes
Slow cognitive decline
Slow functional deterioration
SE: GI upset, dizziness, headache, fatigue, restlessness, confusion, constipation
ADE: hallucinations, confusion, cerebrovascular events, movement difficulties or cognitive decline
Other Treatments of AD
-Management of Neuropsychiatric S/S
Prevalence: 80%, agitation, aggression, delusions, hallucinations
1st line therapy: non-pharmacologic method
Atypical antipsychotics are preferred. (less SE and tardive dyskinesia), Risperidone (Risperdal) and Olanzapine (Zyprexa), reduce rate of psychosis and agitation
Traditional antipyschotic: Haloperidol (Haldol) helps with agitation, not for long-term use
-Vitamin E and selegiline (MAO-B Iinhibitor): Studies inconclusive to support effectiveness
-NSAIDs: prevention
-Ginkgo biloba: About equal benefits of tacrine without liver damage
-SSRIs for depression (not AD symptoms)
Overall Drug Therapy for AD
Monitoring:
Baseline cognitive and physical status and function
Swallowing ability, seizures, fall risk
Patient teaching (include caregiver):
Goal is temporary improvement
May be effective for 6months-3 years
Combination Therapy (cholinesterase inhibitors and Namenda) more effective than one alone
Life Span Considerations for Drugs for AD
Older adults:
Use cautiously with GI bleeding; liver, kidney, heart disease
Use rivastigmine (Exelon) cautiously with asthma, COPD
Older, frail females should not take >5 mg/day of donepezil (Aricept)
Tacrine (Cognex) should not be given to elderly due to hepatotoxicity
START LOW, GO SLOW
Parkinson's Disease
The second most common neurodegenerative disorder after Alzheimer's disease
Slow, progressive, degenerative CNS disorder, and unknown cause
Patho:
Death of dopamine-containing cells in the substantia nigra (midbrain)
Decreased dopamine level in CNS
Imbalance between dopamine and acetylcholine (ACh)
Begins subtly; progresses gradually Symptoms:
Motor -related, including resting tremor, rigidity, bradykinesia (slow movement), postural instability and rapid shuffling gait
Non-motor: cognitive and behavioral, dementia
neuropsychiatric problems , dementia
mood, depression, behavior or thought alterations
sensory and sleep difficulties
Risk factors - age (> 50), genetics, environment
Reduced risk in tobacco smokers.
Parkinson's Disease goals/SE/ADE/options
PD treatment outcome: No CURE, palliative care
Goals: NO CURE, Do not stop progression of PD
decrease severity of symptoms, disability, drug SEs/ADEs
Improve and prolong normal function, achieve an acceptable quality of life.
Dosage determined by degree of impairment in ADLs
Options:
Use combination therapy to delay motor complications
Deep brain stimulation can improve symptoms
Pacemaker, used in advanced stages
Drugs for PD
Drugs increase dopamine action ↓ rigidity
Dopaminergic: levodopa, Levodopa/carbidopa (Sinemet)
Dopamine agonists: Pramipexole (Mirapex)
COMT inhibitors - allow more levodopa to reach brain
MAO-B inhibitors - inhibit monoamine oxidase B that breaks down dopamine in brain
Dopamine releaser (antiviral)
Drug reduce acetylcholine action ↓ tremor
Centrally acting anticholinergics - block cholinergic nerve impulses that help control muscles, benztropine (Cogentin), trihexyphenidyl (Artane)
Dopaminergics: Levodopa MOA/uses/treatment
MOA: Dopamine precursor crosses BBB and is converted to doamine (DA), stimulates DA receptors improvement of PD symptoms
Indication: GOLD STANDARD!! First line to treat PD
early stage of motor symptoms
More severe symptoms
Treatment outcomes
more effective than dopamine agonists, but long-term use carries a higher risk for disabling dyskinesias
Highly effective in first 2 years, then diminish over time, relapse be end of 5 years
Dopaminergics: Levodopa SE/ADE/Cl
SEs/AEDs:
GI upset, Cardiovascular effects, OH, Psychosis, discolorate sweat and urine,
Activate malignant melanoma
depression with suicidal tendencies
neutropenia,
neuroleptic malignant syndrome.
dopamine dysregulation syndrome due to compulsive drug overuse , manifested as "punding"
CI/Precaustions:
Preg. C,
not for pt w/ maligant melanoma,
not use within 2 weeks of MAOI use,
Cautious in pt w/ heart disease, psychiatric disorders, and elderly
Dopaminergic: Levodopa complications/DDI/DFI
Long term complications:
Dyskinesias: involuntary movements
fluctuations in the response to medication.
"on" state: good response to medication and few symptoms
"off "state: no response to medication and significant motor symptoms
Acute loss of effect and on-off phenomenon
DDI/DFI:
Food delays absorption
High-protein foods will reduce therapeutic effects
pyridoxine (vitamin B6) reduce the drug effects
first-generation antipsychotics, MAOIs (hypertensive crisis)
Dopaminergics: Levodopa/Carbidopa MOA/names
MOA of Carbidopa
90-95% levodopa is metabolized in peripheral ,
Add peripheral dopa decarboxylase inhibitors (Carbidopa and benserazide) to prevent the metabolism of L-DOPA before reaching CNS
Increases the available levodopa in the CNS and allows for 75% decrease of levodopa dosage
Reduces cardiovascular and GI adverse effects
Drug name: levodopa/carbidopa (Sinemet), levodopa/benserazide (co-beneldopa).
Nursing Implications for Dopaminergics: Levodopa/carbidopa
Interventions:
Baseline VSs, neurologic, mental status
Baseline dyskinesia, rigidity, tremors, gait, swallowing ability
Reduce dose if dyskinesia worsen (expect resumption of PD)
Antipsychotic meds for psychosis
Patient teaching (include caregiver):
Instruct the drugs are for symptom improvement NOT cure.
Start small dose to avoid GI and problem and drowsiness
Take pills same time each day
Prevent falls (OH),
START LOW, GO SLOW
Dopamine agonists names/MOA/uses
Drug names: Pramipexole (Mirapex), Ropinirole (Requip), Piribedil (Trivastan), bromocriptine (Parlodel)
MOA: Bind and activate dopamine (DA) receptors in the brain
USE:
Initial therapy for motor symptoms and used to delay motor complications.
Use alone in early PD, then with Levodopa in advancing PD
Complement therapy for patients with on-off fluctuations and dyskinesias from levodopa;
Late PD stage: Shorten Levodopa's off periods
used in younger pts who tolerate better daytime drowsiness and postural hypotension.
**Travoprost (travatan) vs. Piribedil (Trivastan)
Dopamine agonists SE/ADE/Cl/DDI
SE: day-time sleepiness and drowsiness, nausea and constipation, water retention, Orthostatic HYPOTENSION,
ADE: impulse control disorders (such as compulsive sexual activity and eating, and pathological gambling and shopping, stronger than levodopa), psychosis (visual hallucinations, nightmares), and dyskinesias
CI/precaustions:
Preg C
Cautious in pts w/ liver and kidney impairment.
DDI: concurrent use with levodopa OH, dyskinesias (monitor closely)
COMT Inhibitor names/MOA/SE/ADE
Catechol-O-methyltransferase (COMT) is the enzymes that degrade catecholamines such as dopamine, epinephrine, and norepinephrine.
MOA: Increase L-DOPA bioavailability and prolong its effects in brain by inhibiting catechol-O-methyl transferase (COMT) from metabolizing L-DOPA into 3-methoxy-dopa (3-O-methyldopa) in the periphery that can NOT cross the blood brain barrier (BBB).
SE/AE: Muscle aches and rhabdomylosis, neuroleptic malignant syndrome, liver damage.
MAO-B inhibitors names/MOA/uses/disadvantages
Drug names: Lazabemide (Pakio, Tempium), Pargyline (Eutonyl), Rasagiline (Azilect), Selegiline (Deprenyl, Eldepryl, Emsam)
MOA: Increase the level of dopamine in CNS by inhibiting dopamine being metabolized by monoamine oxidase-B (MAO-B)
USE: 2nd and 3rd line
monotherapy to improve mild motor symptoms
delay the need for levodopa in early disease,
Combined with levodopa to reduce wearing-off effect
Disadvantages:
produce more adverse effects
less effective than levodopa.
Monoamine Oxidase Inhibitors (MAOIs)
No MAOIs in the top 100
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Tranylcypromine (Parnate)
Selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A.
Selegiline (Eldepryl, Emsam)
MAOIs
MAO-A inhibition reduces the breakdown of primarily serotonin, norepinephrine, and dopamine.
Diet must be monitored for tyramine intake.
MAO-B inhibition reduces the breakdown mainly of dopamine and phenethylamine.
No dietary restrictions associated (although not true in larger doses).
SE:
CNS Stimulation
Orthostatic hypotension
Hypertensive crisis
Local rash
MAOIs nursing implications/pt education
Interventions:
Baseline VSs, neurologic, mental status, liver/kidney function
Baseline dyskinesia, rigidity, tremors, gait, swallowing ability
Give antipsychotic meds for psychosis
Patient teaching (include caregiver):
Avoid using other CNS depressants
Avoid driving and operating machine
Avoid sudden position change, rise slow and dangle before standing
Take with food if GI upset
Watch s/s liver/renal dysfunction
Instruct slow onset (wks-mos) and sudden loss of drug effect, indication of drug holiday (IP setting)
Life Span Considerations for PD Drugs
Patient teaching (include caregiver):
Elderly more sensitive to AE: confusion, hallucinations, uncontrolled body movements possible
Keep levodopa doses as low as possible while maintaining functionality, or Drug Holiday
Delay the initiation of therapy with levodopa by using alternatives (dopamine agonists and MAO-B inhibitors)
Don't suddenly quit L-DOPA
Pregnancy and breastfeeding:
Not been tested; use only when benefits outweigh risks
Bromocriptine (Parlodel) - not recommended during pregnancy; stops production of breast milk
Other Drugs for PD
Centrally acting anticholinergics
Drug name: Benzatropine (Cogentin), trihexyphenidyl (Artane)
MOA: Block acetylcholine at muscarinic receptors -> keep balance between dopamine and acetylcholine in the brain.
SE/ADEs: N/V, anticholinergic SEs (10cants and 6Ds), antihistamine SE (sedation and drowsiness)
CI: narrow-angle glaucoma, elderly (BPH and urinary retention)
Antiviral
Drug name: amantadine (Symmetrel)
MOA: stimulate DA release, prevent dopamine reuptake, and block cholinergic and glutamate receptors
SE/ADEs: CNS effects (confusion, dizziness, restlessness), anticholinergic SE , and discoloration of skin
90% of patients develop non-motor symptoms (autonomic disturbances, depression, dementia, and psychosis)
Anticholinergic (Cogentin, Artane) exacerbates dementia
Antidepressants: Amitriptyline (TCA), only effective drug
Cholinesterase inhibitors: dementia,
Psychosis: Clozapine (Clozaril), only use antipycal antipsychotic drug
Modafinil (Provigil ): daytime sleepiness
Fetal Tissue Transplantation
Antidepressant drugs
Selective serotonin reuptake inhibitors (SSRIs)
Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
Tricyclic antidepressants (TCAs)
Monoamine oxidase inhibitors (MAOIs)
Other atypical antidepressants
SSRIs
Four SSRIs are in the top 100:
escitalopram (Lexapro)
fluoxetine (Prozac, Sarafem, Symbyax)
paroxetine (Paxil)
sertraline (Zoloft)
Other SSRIs:
citalopram (Celexa)
fluvoxamine (Luvox)
Serotonin Syndrome
The symptoms are often described as a clinical triad of abnormalities:
Cognitive effects: mental confusion, hypomania, hallucinations, agitation, headache, coma.
Autonomic effects: shivering, sweating, fever, hypertension, tachycardia, nausea, diarrhea.
Somatic effects: myoclonus/clonus (muscle twitching), hyperreflexia, tremor.
Have to have all 3
SSRIs SE
Sexual dysfunction
CNS stimulation
Weight loss
Withdrawal syndrome
Hyponatremia
Rash
Sleepiness, faintness, lightheadedness
GI Bleeding
Bruxism
Drug Interactions with SSRIs
Herbs: St John's Wort, Yohimbe
Antidepressants: Monoamine oxidase inhibitors (MAOs), TCAs, SSRIs, SNRIs, mirtazapine, venlafaxine
Opioids: tramadol, pethidine, oxycodone, morphine, meperidine
CNS stimulants: phentermine, diethylpropion, amphetamines, sibutramine, methylphenidate
Illicit drugs: methylenedioxymethamphetamine (MDMA or ecstasy), lysergic acid diethylamide (LSD), cocaine, PMA
Others: selegiline, tryptophan, buspirone, kanna, lithium, linezolid, dextromethorphan (DXM), 5-Hydroxytryptophan, chlorpheniramine, bupropion, risperidone
SNRIs
Three SNRIs in the top 100
venlafaxine (Effexor)
duloxetine (Cymbalta) #10!
desvenlafaxine (Pristiq)
TCAs SE
Orthostatic hypotension
Anticholinergic effects
Sedation
Cardiac toxicity
Tricyclic Antidepressants (TCAs)
One TCA is in the top 100
Amitriptyline (Elavil)
Other TCAs
Clomipramine (Anafranil)
Doxepin (Sinequan)
Imipramine (Tofranil)
Trimipramine (Surmontil)
Desipramine (Norpramin)
Nortriptyline (Pamelor)
Protriptyline (Vivactil)
Amoxapine (Asendin)
Tetracyclic:
Maprotiline (Ludiomil)
Other atypical antidepressants SE
Anticholinergic effects
Suppress appetite
Seizures
Atypical Antidepressants
amoxapine (Asendin)
bupropion (Wellbutrin)
maprotiline (Remeron)
Serotonin antagonist & reuptake inhibitors (SARIs)
nefazodone (Formerly Serzone)
trazadone (Desyrel) (sedating)
Selective norepinephrine reuptake inhibitor
reboxetine (Vestra)
Mood Stabilizers
Mood Stabilizers
Antimania
Anticonvulsants
Atypical antipsychotics
Antidepressants
Benzodiazapines
Calcium Channel blockers
Antimania - Lithium SE/toxicity
Need a pre-lithium work up
Renal, thyroid, ECG, CBC, fasting BS
Side effects and toxicity
Weight gain
Cardiac changes
Tremors, fatigue, HA, mental dullness, lethargy
Acnes, rash
Thyroid Dysfunction
GI
Renal (including micro structural changes which are not a contributor to morbidity)
Warning signs of lithium toxicity
Anorexia
Nausea and vomiting
Hand tremor
Muscle twitching
Hyperactive deep tendon reflexes
Ataxia
Vertigo
Weakness, drowsiness
Signs of lithium intoxication
Fever
Decreased urine output
Decreased blood pressure
Irregular pulse
ECG changes
Altered level of consciousness
Seizures
Coma
Death
Anticonvulsants names/SE
Probably work by enhancing the effects of the inhibitory neurotransmitter GABA (Gamma-aminobutyric acid) and desenstatizing the kindling effect of stress and trauma (and street drugs)
valproic acid (Depakote)
carbamazepame (Tegretol)
lamotrigine (Lamictal)
SE:
GI effects
Hepatotoxicity
Pancreatitis
Thrombocytopenia
Teratogenesis
Calcium Channel Blockers
Modulate mood by inhibiting calcium channels in the postsynaptic neuron; an action similar to Lithium
If pt did not respond to Lithium, will not likely respond to these drugs
Can use in pts with HTN, supraventricular arrhythmias, and pregnancy
Top 100:
verapamil (Calan)
Other CCBs:
nifedipine (Adalat, Procardia)
nimodipine (Nimotop)
Antipsychotics
Five of the six atypical neuroleptics are approved for Bipolar I and II
olanzapine (zyprexa)
olanzapine / fluoxetine (Symbyax)
quetiapine (Seroquel)
apriprazole (Abilify)
ziprasidone (Geodone)
Antianxiety and Sedative-Hypnotic Drugs
Benzodiazepines (BZs) and several nonbenzodiazepine antianxiety drugs
BZs most widely prescribed drugs in the world
Benzodiazepine Drugs names
Antianxiety drugs
Top 100: lorazepam (Ativan), diazepam (Valium)
Others: alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), clorazepate (Tranxene), halazepam (Paxipam), oxazepam (Serax)
Sedative-hypnotic drugs
Top 100: temazepam (Restoril)
Others: Estazolam (ProSom), flurazepam (Dalmane), triazolam (Halcion), quazepam (Doral)
Benzodiazepine Drugs implications
When used as hypnotics, they induce sleep rapidly, and effect should be gone by morning
Because they are in same class as alcohol, can be used to suppress alcohol withdrawal syndrome; treatment of choice for this
Potential for OD
Benzodiazepine drug SE/ADE
Side effects of BZs are common, dose related, usually short term and harmless
Drowsiness, sedation, ataxia, dizziness
Feelings of detachment, irritability or hostility
Anterograde amnesia
Cognitive effects with long-term use
Tolerance, dependency, rebound insomnia/anxiety
Rarely nausea, headache, confusion, depression
Benzodiazepine drug withdrawal symptoms
Agitation, Anorexia, Hyperactivity, Insomnia, Irritability, Nausea, vomiting, Sensitivity to light, sounds, Tinnitus, Tremulousness, Anxiety, Autonomic arousal, Dizziness, Generalized seizures, Hallucinations, Headache
Benzodiazepine drug use during pregnancy
Rare with palate malformations and intrauterine growth retardation, especially when used in first trimester
When used late in pregnancy or breast-feeding, BZs associated with floppy infant syndrome, neonatal withdrawal symptoms, poor sucking reflex
Nonbenzodiazepines drug names
Antihistamines (also used for sleep): diphenhydramine (Benadryl), hydroxyzine (Atarax, Vistaril)
Antidepressants: sertraline (Zoloft), paroxetine (Paxil), fluoxetine (Prozac), venlafaxine (Effexor), trazodone (Desyrel), other selective serotonin reuptake inhibitors (SSRIs)
Uses for Nonbenzodiazepines
Propranolol (beta-blocker), clonidine (top 100) (alpha2-receptor agonist) for off-label treatment of anxiety
Block peripheral or central noradrenergic (norepinephrine) activity, anxiety (tremor, palpitations, tachycardia, sweating)
Buspirone (BuSpar)
Does not exhibit muscle-relaxant or anticonvulsant activity, interaction with CNS depressants, sedative-hypnotic properties
Sedative-Hypnotic Agents uses/SE
Generally well tolerated
Few antianxiety, anticonvulsant, or muscle-relaxant properties
Side effects: daytime drowsiness, dizziness, GI upset
Difference between these drugs is their half-life and subsequent length of action
Antihistamines
Sometimes used as sedative-hypnotic agents for sedating effects
Not usually as effective as BZs but do not cause physical dependence or abuse
Trazodone (Desyrel)
Antidepressant; significant sedating effects
Preferred antidepressant for insomnia
Offers sedation with few cholinergic effects
Much greater safety profile in overdose compared with tricyclic antidepressants
Nonbenzodiazepine Sedative-Hypnotic Agents
Zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta): new class of compounds for insomnia
Bind more selectively to neuronal receptors involved in inducing sleep (benzodiazepine-1 receptors on BZ/GABA receptor complex)
Ramelteon (Rozerem)
New, nonscheduled sleep aid
Specific melatonin agonist
Barbiturates
Secobarbital, pentobarbital, and other older nonbenzodiazepine antianxiety and sedative-hypnotic agents (meprobamate, alcohols, chloral hydrate) rarely used
Uses for Selective Serotonin Reuptake Inhibitors
Many SSRIs (antidepressants) effective in treating anxiety disorders
Generalized anxiety disorder
Obsessive-compulsive disorder
Panic disorder
Bulimia
Seasonal affective disorder
Posttraumatic stress disorder
Premenstrual dysphoric disorder
Traditional Antipsychotics
Dopamine antagonists (D2 receptor antagonists)
Target positive symptoms of schizophrenia
Advantage
Less expensive than atypical antipsychotics
Disadvantages
Do not treat negative symptoms
Extrapyramidal side effects (EPS)
Tardive dyskinesia
Anticholinergic effects (ACH)
Lower seizure threshold
Atypical Antipsychotics (First-Line Antipsychotics)
Serotonin-dopamine antagonists
(5-HT2A receptor antagonists)
Advantages
Diminishes negative as well as positive symptoms of schizophrenia
Less side effects encourages medication compliance
Improves symptoms of depression and anxiety
Decreases suicidal behavior
Disadvantages
Weight gain
Metabolic abnormalities
Typical Antipsychotics drug names
Phenothiazines
Chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), perphenazine (Trilafon), trifluoperazine (Stelazine), fluphenazine (Prolixin)
Thiothixene (Navane)
Butyrophenone: haloperidol (Haldol)
Dibenzoxazepine: loxapine (Loxitane)
Dihydroindolone: molindone (Moban)
Diphenylbutylpiperidine: pimozide (Orap)
Atypical Antipsychotic drug names
Aripiprazole (Abilify) (# 6 in the top 100)
Clozapine (Clozaril)
Paliperidone (Invega)
Risperidone (Risperdal, Consta, M-Tabs)
Olanzapine (Zyprexa, Zydis)
Quetiapine (Seroquel) (#8 in the top 100)
Ziprasidone (Geodon)
Extrapyramidal Side Effects
Pseudoparkinsonism
Acute dystonic reactions
Opisthotonos
Oculogyric crisis
Akathisia
Tardive dyskinesia (AIMS test)
Facial
Limbs
-Choreic
-Athetoid
Trunk
Side Effects: α2 Block: Cardiovascular Effects
Hypotension
Postural hypotension
Tachycardia
Side Effects: Rare and Toxic Effects
Agranulocytosis
Cholestatic jaundice
Neuroleptic malignant syndrome (NMS)
Severe extrapyramidal
Hyperpyrexia
Autonomic dysfunction
Nicotine MOA/SE/ADE/Drugs
MOA:
In low doses nicotine activates nicotinic receptors. Most effects occur from activated receptors in autonomic ganglia and the adrenal medulla. In the CNS, nicotine rapidly acts on the mesolimbic reward system of the brain, promoting the release of dopamine and mimicking the effects of cocaine and other highly addictive substances
SE/ADE:
Cardiovascular stimulation, increased myocardial oxygen consumption, CNS stimulation, increased RR and tremors, increased alertness and arousal, increased GI secretions and smooth-muscle tone, relaxation/relief of anxiety.
Abstinence syndrome is evidenced by irritability, nervousness, restlessness, insomnia, and difficulty concentrating.
Very strong psychological dependence.
Treatment:
nicotine replacement therapy (NRT)
nicotine patch, lozenges, nasal spray, and inhalers.
Bupropion (Zyban) - can cause dry mouth
Varenicline (Chantix)
Nortriptyline (Aventyl, Pamelor)
For Nicotine gum, use of chewing gum is not recommended for longer than 6 months, advise clients to chew gum slowly and intermittently over 30 min. Advise clients to avoid eating or drinking 15 minutes prior to and while chewing the gum. For Nicotine patch, clients should apply a nicotine patch to an area of clean, dry skin each day. Advise clients to avoid using any nicotine products while the patch is on. Patch should be removed prior to MRI scan and replaced when the scan is completed
Cocaine MOA/SE/ADE
Cocaine is the most potent of the abused stimulants.
MOA:
Cocaine inhibits the neuronal uptake of dopamine in the brain and increases the activation of dopamine receptors in the brain reward system. This action magnifies pleasures and leads to rapid dependence. Cocaine also increases norepinephrine at postsynaptic receptor sites, producing intense vasoconstriction and cardiovascular stimulation.
SE/ADE:
stimulation of CNS, increased energy/alertness, impairment of concentration and memory, irritability and mood swings, paranoia, and depression.
paranoid delusions to visual hallucinations, tactile hallucinations, skin excoriations from scratching, needle marks, and increased BP, HR, and temp.
Acute cocaine toxicity may be manifested by cardiac palpitations, tachycardia, increased respiratory rate, and fever. At high levels of overdose, grand mal seizures, hypertension, and dysrhythmias or myocardial ischemia can occur. The client experiences restlessness, paranoia, agitated delirium, and confusion. Bizarre, erratic, and violent behavior may occur. Death is often related to a cerebrovascular accident, fatal dysrhythmias, or myocardial infarction
Cocaine treatment
Emergency management. Treatment may be complicated by the possibility that the client has combined the use of cocaine with heroin, alcohol, or PCP. There is no specific antidote for cocaine toxicity, but during an overdose most symptoms can be controlled with a variety of drugs.
Cognitive-behavioral therapies
However, recent studies indicate that disulfiram (Antabuse), a well-established medication for the treatment of alcoholism, has helped nonalcoholic people addicted to cocaine reduce drug use from 2.5 days a week to 0.5 days a week on average. It has also been found that when modafinil (Provigil), a CNS stimulant used for treatment of narcolepsy, is combined with behavioral therapy the likelihood of cocaine abstinence is increased. Under study as potential cocaine treatment agents are the anticonvulsant topiramate (Topamax) and the antiemetic ondansetron (Zofran)
Amphetamines MOA/SE/ADE/Treatment
MOA:
Amphetamines act similarly to cocaine, stimulating the release of dopamine and norepinephrine in the brain and the sympathetic nervous system. The dopamine release in the brain reward system produces euphoria and an increase in self-confidence.
SE/ADE:
increased alertness, improved performance, relief of fatigue, and anorexia, cardiovascular stimulation with increased HR and BP, irritability, anxiety, paranoia, and hostile and violent behaviors,
in tooth decay and dermatologic deterioration.
"overamping," may result in amphetamine psychosis, paranoia, seizures, and death.
Withdrawal symptoms of amphetamines are similar to those of cocaine use.
Treatment:
Patients often seek treatment for complications of amphetamine abuse such as panic reactions, psychosis, or depression. Emergency management of amphetamine toxicity is the same as that for cocaine. Elevated blood pressure and tachycardia can be controlled with vasodilators and adrenergic β-blockers. Drug elimination can be enhanced by administering agents such as ammonium chloride that acidify the urine. Cessation and maintenance of abstinence are difficult in amphetamine abuse. Depression can last for months.
Caffeine MOA/SE/ADE/Treatment
MOA:
Caffeine is a methylxanthine that stimulates the CNS, especially the medullary respiratory center. It also is a diuretic and myocardial stimulant. Caffeine relaxes smooth muscle and promotes peripheral vasodilation and cerebral vasoconstriction.
SE/ADE:
Oral doses of 200 mg (two cups of coffee) can elevate mood, produce insomnia, increase irritability, cause anxiety, and offset fatigue. Heavy intake of 500 mg or more per day is known to cause intoxication with symptoms of nervousness, insomnia, gastric hyperacidity, muscle twitching, confusion, chest pain, tachycardia, and cardiac dysrhythmias. In toxic doses, caffeine influences behavior patterns and may precipitate states of panic. Until the advent of caffeine pills and highly caffeinated energy drinks, caffeine overdoses were very rare because people developed undesirable symptoms before they could ingest enough.
Physical and psychological dependence on caffeine have been found with chronic use of more than 500 mg/day.
withdrawal symptoms are headache, irritability, drowsiness, and fatigue occurring within 12 to 24 hours.
Treatment:
Attention is given to controlling hypertension, dysrhythmias, and seizures as with other CNS stimulants. Gradually reduce daily intake.
Alcohol MOA/SE/ADE/Treatment
MOA:
Alcohol affects almost all cells of the body and has complex effects on the neurons in the CNS. Alcohol is a general CNS depressant. Additionally, alcohol binds with receptors in the brain reward system resulting in the release of dopamine and promoting the addictive process.
SE/ADE:
The symptoms of alcohol use include nausea; vomiting; tremors; restlessness and inability to sleep; depressed mood or irritability; increased heart rate, blood pressure, respiratory rate, and temperature; and tonic-clonic seizures. Illusions are also common. Acute overdose produces vomiting, coma, and respiratory depression. Alcohol-induced hypotension may lead to renal failure and cardiogenic shock, common causes of alcohol-related death.
hangovers manifested by malaise, nausea, headache, thirst, and a general feeling of fatigue. In alcoholics, sudden withdrawal may have life-threatening effects such as severe disorientation, psychotic symptoms (hallucinations), severe hypertension, and cardiac dysrhythmias that may progress to death.
Treatment:
Acute Phase--Detoxification
Initial treatment of acute alcohol intoxication or overdose requires implementation of the basic principles of airway, breathing, and circulation (ABCs). No antidote for alcohol is available, and stimulants should not be given.
thiamine should be started before treatment with IV glucose solution in all patients with alcoholism and continued until the client resumes a normal diet.
Abstinence Maintenance Phase—Following Detoxification
These include disulfiram (Antabuse), a daily oral medication that is a type of aversion (behavioral) therapy and prevents drinking by causing an unpleasant reaction if alcohol is consumed, and naltrexone, which blocks the desired effects of alcohol
Naltrexone (ReVia, Depade) is a pure opioid antagonist that decreases craving and pleasurable effects of alcohol and blocks the "high" of alcohol use.
Acamprosate (Campral) is used to decrease unpleasant feelings such as tension, dysphoria, anxiety, restlessness and cravings brought about by abstinence from alcohol
Ondansetron (Zofran), an antagonist of receptors in the brain reward system, decreases motivation for drinking in early onset alcoholism; and topiramate (Topamax), an anticonvulsant, may be helpful in decreasing craving for alcohol as well as cocaine.
Sedative-hypnotics MOA/SE/ADE/Treatment
MOA:
Sedative-hypnotic drugs act primarily on the CNS. Benzodiazepines enhance the effects of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain. Barbiturates not only enhance the inhibitory effect of GABA, but they can directly mimic the actions of GABA. Barbiturates are powerful respiratory depressants and can readily cause death by overdose.
SE/ADE:
initial euphoria and intoxication similar to that of alcohol.
Withdrawal from sedative-hypnotics can be very serious. In the first 12 to 16 hours following the last dose, the client may develop anxiety, tremors, weakness, nausea, vomiting, muscle cramps, and increased reflexes. After 24 hours, the client craves the drug and may experience delirium, grand mal seizures, and respiratory and cardiac arrest. Symptoms of withdrawal peak on the second or third day for short-acting (shorter half-life) drugs (e.g., alprazolam, secobarbital, pentobarbital) and on the seventh or eighth day for long-acting (longer half-life) drugs (e.g., diazepam, chlordiazepoxide, phenobarbital).
Treatment:
Overdoses of benzodiazepines are treated with flumazenil (Romazicon), a specific benzodiazepine antagonist
Gastric lavage may be used if the drug was taken orally within 4 to 6 hours. Dialysis may be required to decrease the drug level. Gradual withdrawal of the drug is required during withdrawal syndrome. Phenobarbital, a long-acting barbiturate, may be used to control withdrawal symptoms in a client dependent on barbiturates. Phenobarbital is then gradually withdrawn when the client is stable. To manage their symptoms safely, hospitalization is recommended during drug withdrawal for individuals who have been abusing large amounts of barbiturates.
Opioids MOA/SE/ADE/Treatment
MOA:
Important to the abuse potential of opioids is their ability to activate the brain reward system, reinforcing their addictive effect
SE/ADE:
The primary effects of opioids include analgesia, drowsiness, slurred speech, and detachment from the environment. IV use usually causes a "rush" of feelings in the lower abdomen, along with warm skin flushing and a strong sense of euphoria. Cross-tolerance among the opioids is common, but cross-tolerance to other CNS depressants does not occur. However, additive effects of other CNS depressants may lead to increased CNS depression.
Although opioid withdrawal is acutely uncomfortable, it is not usually life threatening, as is withdrawal from other CNS depressants. However, suicidal ideation may occur.
Treatment:
A narcotic antagonist such as naloxone (Narcan) should be used to reverse respiratory depression and coma induce by opioids overdose. Treatment of withdrawal syndrome is symptom-based and does not always require the use of medication. Methadone (Dolophine) in decreasing doses over 10 to 14 days is the drug most often used to decrease symptoms during opioid detoxification. Methadone is an oral opioid agonist that replaces the opioid to which the patient is addicted. Some patients obtain relief from withdrawal symptoms with the use of clonidine (Catapres), a centrally acting alpha2-adrenergic agonist that may also be used for nicotine addiction. It is most effective against autonomic GI hyperactivity (diarrhea, nausea, vomiting), but it does not decrease craving. The action of clonidine in nicotine and opioid addiction is not fully understood. Buprenorphine (Subutex) is an agonist-antagonist opioid that may be used for detoxification and maintenance therapy. Because of its action on specific opiate receptors, it can decrease the symptoms of withdrawal and suppress drug craving, yet it has a low potential for abuse.
Naltrexone (oral ReVia, injectable Vivitrol) is an opioid antagonist that blocks euphoria and all other opioid effects. It is used for abstinence maintenance therapy. Like naloxone, it will precipitate withdrawal symptoms when administered to opioid-dependent individuals.
Marijuana MOA/SE/ADE/Treatment
MOA:
THC affects cannabinoid receptors in the brain and may act in part through the same reward system as opioids and cocaine.
SE/ADE:
euphoria, sedation, and hallucinations, relaxation, enhanced sensory perception, and distortion of time perception, short-term memory loss, decreased ability to perform multistep tasks, and temporal disintegration, Intense anxiety, delusions, paranoia, and a state of toxic psychosis can occur. Decreased sperm production and decreased reproductive hormones in both men and women. Decreased motor coordination, tremors, and increased heart and respiratory rates. A condition known as amotivational syndrome, characterized by apathy, dullness, and disinterest, may also occur.
Treatment:
Treatment is directed toward relief of symptoms
Multiple sclerosis immunomodulators (interferon beta) MOA/SE/ADE
MOA:
Interferon beta is a naturally occurring glycoprotein with antiviral, antiproliferative, and immunomodulatory actions. Natural interferon beta is produced in response to viral invasion and other biologic inducers. In patients with MS, benefits are thought to derive primarily from inhibiting the migration of proinflammatory leukocytes across the blood-brain barrier, thereby preventing these cells from reaching neurons of the CNS.
SE/ADE:
flu-like reactions, hepatotoxicity, myelosuppression or bone marrow suppression, injection-site reactions, depression, neutralizing antibodies, and drug interactions (Exercise caution when combining interferon beta with other drugs that can suppress the bone marrow or cause liver injury.)
Multiple sclerosis immunomodulators (Glatiramer Acetate) MOA/SE/ADE
MOA:
In patients with MS, the drug promotes a "T-cell shift." That is, it decreases production of proinflammatory TH1 cells and increases production of anti-inflammatory TH2 cells. The anti-inflammatory cells migrate across the blood-brain barrier at sites of inflammation, and then suppress the inflammatory attack on myelin
SE/ADE:
Injection-site reactions—pain, erythema, pruritus (itching), induration (pitting)—are most common.
About 10% of patients experience a self-limited postinjection reaction—characterized by flushing, palpitations, severe chest pain, anxiety, laryngeal constriction, and urticaria—that typically lasts 15 to 20 minutes.
Multiple sclerosis immunomodulators (Natalizumab) MOA/SE/ADE
MOA:
In patients with MS and Crohn's disease, natalizumab prevents circulating leukocytes (T cells and monocytes) from leaving the vasculature, and thereby prevents these cells from migrating to sites where they can do harm. In order to exit the vasculature, activated leukocytes must first adhere to the vascular endothelium, a process that requires the interaction of two types of molecules: (1) integrins (adhesion molecules) expressed on the surface of leukocytes and (2) integrin receptors expressed on cells of the vascular epithelium. Natalizumab binds with integrin molecules on leukocytes, and thereby renders these cells unable to bind with integrin receptors on the capillary wall. As a result, the leukocytes cannot cross the capillary wall, and hence are unable to exit the vasculature to reach their sites of inflammatory action. In patients with MS, natalizumab prevents activated leukocytes from crossing the blood-brain barrier. In patients with Crohn's disease, the drug prevents leukocytes from crossing capillaries that deliver blood to the GI tract.
SE/ADE:
headache, fatigue, abdominal discomfort, arthralgia, depression, diarrhea, gastroenteritis, UTI, and lower respiratory tract infections. The most serious effects are PML, liver injury, and hypersensitivity reactions.
MS immunosuppressants (Mitoxantrone) MOA/SE/ADE
MOA:
). In patients with MS, mitoxantrone suppresses production of immune system cells (B lymphocytes, T lymphocytes, and macrophages), and thereby decreases autoimmune destruction of myelin. Additional protection may derive from reducing antigen presentation and reducing production of cytokines (eg, interleukin-2, TNF-alpha, interferon gamma) that participate in the immune response.
SE/ADE:
Mitoxantrone can cause a variety of adverse effects. Myelosuppression, cardiotoxicity, and fetal injury are the greatest concerns. Hepatotoxicity, hair loss and injury to the GI mucosa, resulting in stomatitis and GI distress.nausea, vomiting, menstrual irregularities (eg, amenorrhea), and symptoms of allergy (itching, rash, hypotension, shortness of breath). blue-green tint to the urine, skin, and sclera.
Myasthenia gravis MOA/SE/ADE
MOA:
Cholinesterase inhibitors prevent the degradation of acetylcholine (ACh) by acetylcholinesterase (also known simply as cholinesterase [ChE]). By preventing ACh inactivation, anticholinesterase agents can intensify the effects of ACh released from motor neurons, and can thereby increase muscle strength. Cholinesterase inhibitors do not cure MG. Rather, they only produce symptomatic relief, and hence patients usually need therapy lifelong.
SE/ADE:
Excessive muscarinic stimulation and neuromuscular blockade.
Acute Toxicity (AKA Cholinergic crisis) S/S treatment
S/S:
Overdose with cholinesterase inhibitors causes excessive muscarinic stimulation and respiratory depression. It is characterized by depolarizing neuromuscular blockade plus signs of excessive muscarinic stimulation (hypersalivation, tearing, sweating, bradycardia, involuntary urination and defecation, miosis, and spasm of accommodation). Death results from respiratory depression. Respiratory depression results from a combination of depolarizing neuromuscular blockade and CNS depression.
Treatment:
Intravenous atropine can alleviate the muscarinic effects of cholinesterase inhibition. Respiratory depression from cholinesterase inhibitors cannot be managed with drugs. Rather, treatment consists of mechanical ventilation with oxygen. Suctioning may be necessary if atropine fails to suppress bronchial secretions.
Myasthenic crisis
Patients who are inadequately medicated may experience myasthenic crisis, a state characterized by extreme muscle weakness (caused by insufficient ACh at the NMJ). Left untreated, myasthenic crisis can result in death from paralysis of the muscles of respiration. A cholinesterase inhibitor (eg, neostigmine) is used to relieve the crisis.
Cholinergic crisis
As noted, overdose with a cholinesterase inhibitor can produce cholinergic crisis. Like myasthenic crisis, cholinergic crisis is characterized by extreme muscle weakness or frank paralysis. In addition, cholinergic crisis is accompanied by signs of excessive muscarinic stimulation. Treatment consists of respiratory support plus atropine. The offending cholinesterase inhibitor should be withheld until muscle strength has returned.
Distinguishing Myasthenic Crisis from Cholinergic Crisis.
Because myasthenic crisis and cholinergic crisis share similar symptoms (muscle weakness or paralysis), but are treated very differently, it is essential to distinguish between them. A history of medication use or signs of excessive muscarinic stimulation are usually sufficient to permit a differential diagnosis. If these clues are inadequate, the differential diagnosis can be made by administering a challenging dose of edrophonium, an ultrashort-acting cholinesterase inhibitor. If edrophonium-induced elevation of ACh levels alleviates symptoms, the crisis is myasthenic. Conversely, if edrophonium intensifies symptoms, the crisis is cholinergic. Since the symptoms of cholinergic crisis will be made even worse by edrophonium, atropine and oxygen should be immediately available whenever edrophonium is used for this test
Centrally acting muscle relaxants MOA/SE/ADE
Carisoprodol (Soma), Cyclobenzaprine (Flexeril), Metaxalone (Skelaxin), Tizanidine (Zanaflex)
MOA:
relax muscle spasm and dpress muscle spasticity by enhancing GABA and primarily causing CNS sedation. It has NOT direct effects on skeletal muscle
SE/ADE:
CNS depression (drowsiness, dizziness, lightheadedness, sleepiness, fatigue). dry mouth, blurred vision, photophobia, urinary retention, and constipation.
Hepatic toxicity (anorexia, nausea, vomiting, abdominal pain, jaundice) and physical dependence, life threatening abstinence syndrome if abruptly withdrawn.
baclofen (Lioresal)
MOA:
Suppress hyperactive reflexes by mimicking the inhibitory neurotransmitter, GABA, on spinal neurons (CNS). It is centrally acting drug, having no direct effects on skeletal muscle
SE/ADE:
GI discomfort(Nausea, constipation), urinary retention, CNS depression (drowsiness, dizziness, lightheadedness, sleepiness, fatigue), weakness.
Abrupt stop can cause withdrawal symptoms: visual hallucinations, paranoid ideation, and seizures.
Diazepam (Valium), benzodiazepine
MOA:
Acts in the CNS to suppress spasticity by mimicking GABA at receptors in the spinal cord and brain to produce sedation. Does not affect skeletal muscle directly.
SE/ADE:
CNS depression (drowsiness, dizziness, lightheadedness, sleepiness, fatigue). GI discomfort
Sedation
Peripherally acting muscle relaxant MOA/SE/ADE
dantrolene (Dantrium)
MOA:
Acts directly on spastic muscles and inhibits muscle contraction by suppressing release of calcium in skeletal muscles.
SE/ADE:
GI discomfort, muscle weakness, CNS depression (drowsiness, dizziness, lightheadedness, sleepiness, fatigue).
Hepatic toxicity (anorexia, nausea, vomiting, abdominal pain, jaundice)
Neuromuscular blockers (NMB) MOA/EE/SE/ADE/Cl/DDI/nursing implications
succinylcholine (Anectine), pancuronium (Pavulon), atracurium (Tracrium), vecuronium (Norcuron)
MOA:
Block acetylcholine (ACh) at the neuromuscular junction or NMJ to promote muscle relaxation and paralysis.
EE:
relaxed muscle during surgery and ventilation and intubation, no seizure during ECT
SE/ADE:
muscle ache, apnea, hypotension, hyperkalemia, malignant hyperthermia
Cl:
pts with myasthenia gravis (MG), respiratory dysfunctions, fluid and electrolyte imbalance
DDI:
general anesthetics, antibiotics, cholinesterase inhibitors for succinylcholine
implications:
pseudocholinesterase for succinylcholine, electrolytes like potassium
report family and history of malignant hyperthermia, using antibiotics, low level of pseudocholinesterase if applicable
Drugs for Local Anesthetics
Drug names: -caine or -cain
MOA: ↓pain by blocking conduction of pain impulses in local area, no loss of consciousness.
Uses: dental, minor surgical/procedures, diagnostics, L/D
SE/ADE: CNS excitations (seizures), hypotension, cardio-suppression (e.g., bradycardia/heart block, cardiac arrest), prolonged labor, fetal CNS and cardio-suppression, spinal HA due to hypotension, urinary retention
Nursing implications and patient educations
Vasoconstrictors, epi to keep and prolong local anesthetic effects and decreases the risk of systemic toxicity.
Protect numb area from injury
Monitor complications
Resuscitation kits available
Instruct patient monitoring and reporting complications.
Opioid Analgesics for women in labor
Locoreginal: Epidural, spinal, and combined spinal-epidurals
The only consistently effective means of relieving the pain of labor and delivery
Drug of choices: bupivacaine, ropivacaine, fentanyl and morphine
Uses: anticipated difficulty with intubation, hx of malignant hyperthermia, cardiopulmonary disorders, high spinal cord lesion, preeclampsia
Contraindications: patient refusal, risk for bleeding, lower back infection, unstable hypovolemia, increased intracranial pressure,
Systemic Drugs: IV, PCA , IM, and inhalation routes
Uses:
prefers less invasive techniques
Regional techniques are contraindicated
Lack of availability of skilled providers
DOC: morphine, fentanyl, Remifentanil, Meperidine (Demerol), opioid agonists-antagonists (Nalbuphine [Nubain] and butorphanol [Stadol])
Not as effective as regional analgesia, more for sedation less analgesic
CI: delivery within 4 hrs of administration
SE/ADE: GI upset, sedation, maternal aspiration, maternal and neonatal respiratory depression, reduce fetal heart rate variability
Drugs for Acute Migraine Attacks
Mild analgesics: aspirin or ASA, NSAIDs, acetaminophen (Tylenol)
Triptans:
serotonin agonists for acute migraine,
MOA: reduce pain by inhibiting vasoactive peptides release vasoconstriction, blocking pain pathways
Oral preparations are available
NOT concurrent use of Ergots
Ergots or ergotamine (DHE or dihydroergotamine)
Poor oral and rectal absorptions
SE/ADE: N/V, rebound headaches, cardiovascular complications, Ergotism , physical dependence, and abortion
Antiemetics: metoclopramide (Reglan), chlorpromazine (Thorazine) and prochlorperazine (Compazine)
Adjunct therapy for acute migraine headache
IV and IM preferred
Other medications:
Benzodiazepines, anticonvulsants, TCA, CCB, opioids and barbiturates
ONLY used for intractable migraine HA, NEVER for chronic management or FIRST line treatment
Staged approach per setting:
Outpatient setting: triptans for moderate to severe migraine
Emergency department:
Severe migraine with severe N/V:
IV antiemetic + diphenhydramine or DHE + corticosteroid (dexamethasone)
Early treat and large single dose preferred.
Prophylactic therapy for migraine: propranolol (Inderal)