ATI pharmacology Set 5

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Drugs affecting nervous system

• Muscarinic agonists (parasympathomimetic)  Bethanechol
• Muscarinic antagonists  Atropine
• Ganglionic-stimulating agents  Nicotine
• Cholinesterase inhibitors (ChE)  Physostigmine or neostigmine
• Neuromuscular-blocking agents  Tubocurarine
• Adrenergic agonists (sympathomimetic)  Epinephrine
• Adrenergic antagonists block α & β receptors.  Prazosin  α adrenergic antagonist
 Propanolol  β adrenergic antagonist

Nicotine n Receptors

Release of epinephrine from adrenal medulla

Nicotine m receptors

• Located at neuromuscular junction of skeletal muscle
• Causes skeletal muscle contraction

Muscarinic Receptors

• Decreased secretions from lungs, stomach, intestines, sweat glands
• Decrease in HR
• Smooth muscle contraction in bronchi and GI tract
• Miosis (sphincter contraction) and accommodation (ciliary contraction)
• Voiding due to contraction of detrusor muscle and relaxation of trigone and sphincter muscles

Alpha 1 receptors

• Mydriasis d/t radial muscle contraction
• Veins and arterioles are activated to constrict
• increased peripheral resistance, increased blood pressure
• Male sex organs are activated to promote ejaculation
• Contraction of prostatic capsule, trigone, and sphincter muscles

Dopamine receptors

• Dilates blood vessels in the kidneys

Beta 1 receptors

• Predominant receptor found on the heart
• increased HR, increased Contraction Force, increased Conduction through AV node
• increased lipolysis
• Release of Renin by the kidneys

Beta 2 receptors

• Dilates bronchi
• Relaxes uterine smooth muscle
• Vasodilation of arterioles in heart, lungs, and skeletal muscle
• Slightly decreased peripheral resistance
• Increased glycogenolysis in the liver and muscles
• Skeletal muscle contraction

Medications affecting nervous system

• Adaptive changes within brain with prolonged exposure
• Increased therapeutic effect
• Decreased side effects
• Tolerance, physical dependence
• Do not stop abruptly
• Highly variable individual response to mediations

Parkinson's Disease

• Treatment uses two main classes:
• Meds that activate dopamine receptors (directly or indirectly)
• Meds that block acetylcholine receptors

Seizure Disorder

• Change in types of seizures respond to change in medications
• Usually require life-long management
• Meds must be discontinued slowly over 6 weeks to several months

Schizophrenia

• Clinical course includes semi-remission punctuated by acute exacerbations
• Positive symptoms (Agitation, delusions)
• Conventional antipsychotic  Thorazine
• Atypical antipsychotic  Clozapine
• Negative symptoms (Social withdrawal, poor self-care)
• Atypical antipsychotic  Clozapine
• Cognitive symptoms (Difficulties with memory and learning)
• Initial doses are high and given throughout day; maintenance doses given at bedtime.

Depression

• Symptom relief can take 1-3 weeks and possibly 2-3 months
• Three main groups:
• Tricyclic antidepressants (TCAs)
• Selective serotonin reuptake inhibitors (SSRIs)
• Monamine oxidase inhibitors (MAOIs)

Bipolar disorders

• Typically managed with mood stabilizers. Antipsychotics and antidepressants may be used during acute episodes of mania or depression.
• Lithium
• Valproic acid (Depakote)
• Carbamazepine (Tegretol)

Cholinesterase Inhibitor

Proto: Neostigmine, Physostigmine
Expected Action: Prevents ACh degradation leads to increased transmission of nerve impulses by increased [ACh]
Therapeutic Uses:
• increased muscle strength by increased [ACh] at neuromuscular junction in myasthenia gravis
• Reversal of nondepolarizing neuromuscular blocking agents (tubocurarine)
Adverse Effects:
• Excessive muscarinic stimulation: Increased GI motility & secretions, bradycardia, urinary urgency (side effect can be treated with atropine)
• Cholinergic crisis: Above plus resp. depression from neuromuscular blockade.
Contraindications/Precautions: • Pregnancy (C)
• CI in obstruction of GI/GU systems / caution with seizures, asthma, bradycardia, hypotension, peptic ulcer disease
Interactions: Tubocurarine - Neostigmine reverses blockade
• Atropine - counteracts • Succinylcholine - increased neuromuscular blockade
Education: Wear medic-alert bracelet

Neuromuscular Blocking Agents

Proto: Nondepolarizing: tubocurarine, pancuronium Depolarizing: succinylcholine
Expected Action: Block ACh at neuromuscular junction - don't cross blood-brain barrier
Therapeutic Uses: Control spontaneous respiration in ventilated pts.
• Adjuncts to general anesthesia • Diagnose myasthenia gravis
• Succinylcholine for: electroconvulsive therapy, intubation, endoscopy
Adverse Effects: • Hypotension from histamine release & ganglionic blockade
• Respiratory arrest • Bradycardia, dysrhythmias
Succinylcholine: • Low pseudocholinesterase activity  apnea
• Malignant hyperthermia (dantrolene) • Pain • Hyperkalemia
Contraindications/Precautions: • Pregnancy (C) •
• SCh: CI for hyperkalemia (trauma, burns) •
Interactions: • General anesthetics
• Aminoglycosides/tetracyclines -  NM blockade
• Neostigmine/ChE inhibitors: decreased η nondepolarizing / increased η depolarizing

Dopaminergics

Proto: Levodopa, carbidopa, Sinemet
Expected Action: Levodopa taken up and converted to dopamine. Carbidopa augments levodopa by preventing conversion to dopamine in intestine and periphery (increased [DA] in CNS).
Therapeutic Use: Symptomatic relief from dyskinesias
AE: • Dyskinesias • Discoloration of sweat & urine
• Nausea / drowsiness • Orthostatic hypotension
• Psychosis (clozapine) • Activation of malignant melanoma
Contraindications/Precautions: • !! ĉ cardiac or psychiatric disorders
• CI ĉ melanoma • 2 weeks from MAOI • Pregnancy (C)
Interactions
Proteins interfere with absorption and transport
• Conventional antipsychotics (haldol, compazine) decreased η
• MAOI leads to hypertension
• Carbidopa, dopamine agonists, anticholinergics, COMT inhibitors and dopamine releasers increased therapeutic effects.
• Pyridoxine decreased η

COMT

• Catechol O-Methyltransferase
• Deactivates catecholamines (dopamine, norepinephrine, acetylcholine, epinephrine, serotonin, histamine, etc)
• Found in post-synaptic cell membranes of adrenergic neurons where it degrades norepinephrine.
• Also found in gut

Dopamine Agonists (Anti-Parkinson's)

Proto: Pramipexole, ropinirole, bromocryptine
Expected Action: Act directly on dopamine receptors
Therapeutic Uses:
• Monotherapy early / combined with levodopa in later stages
Adverse Effects: • Orthostatic hypotension • Psychosis
• Sleep attacks • Daytime sleepiness • Dyskinesias • Nausea
Contraindications/Precautions: • Pregnancy (C)
• Caution ĉ liver & kidney impairment
Interactions:
• Levodopa: Can  motor-control fluctuations permitting lower dose
• Levodopa: Also  risk of orthostatic hypotension and dyskinesias

Centrally Acting Anticholinergics (Anti-Parkinson's)

Proto: Benztropine (Cogentin), trihexyphenidyl (Artane)
Expected Action: Block ACh at muscarinic receptors which helps maintain ACh, dopamine balance
Adverse Effects: • Nausea (take ĉ food) •
• Atropine-like effects (dry mouth, blurred vision, mydriasis, constipation)
• Antihistamine effects (sedation, drowsiness)
Contraindications/Precautions: CI in narrow-angle glaucoma

Antivirals

Proto: Amantadine
Expected Action: Stimulate dopamine release, prevent dopamine reuptake, and may block cholinergic and glutamate receptors
Therapeutic Uses: • Parkinson's Disease
• CNS Effects
• Atropine-like effects

Antiepileptics

• Barbiturates phenobarbital (Luminal)
• Hydantoins phenytoin (Dilantin)
• Benzodiazepines diazepam (Valium)
• Lorazepam (Ativan)
• Carbamazepine (Tegretol)
• Ethosuximide (Zarontin)
• Valproic acid (Depakote)
• Gabapentin (Neurontin)
• Other meds lamotrigine (Lamictal)
• oxcarbazepine (Trileptal)
• clonazepam (Klonopin)
• Mechanisms:
• Slow Ca2+ and Na+ reentry to neuron
• Suppress neuron firing

Barbiturates (Antileptics)

• Partial seizures and generalized tonic-clonic seizures
• Not effective against absence seizures
Adverse Effects:
• CNS effects: Adults as sedation and anxiety, kids as irritability and hyperactivity
• Toxicity: Nystagmus, ataxia, respiratory depression, pinpoint pupils
Contraindications/Precautions: • Pregnancy (D)
• CI ĉ intermittent porphyria

Hydantoins (Antiepileptic)

Proto: Phenytoin (Dilantin)
Therapeutic use: Effective against all major forms except absence seizures
Adverse Effects:
• CNS effects • Skin rash • Teratogenic • Gingival hyperplasia
• Cardiovascular • Endocrine effects • Vitamin D metabolism
Contraindications/Precautions:
• CI: sinus bradycardia, SA blocks, 2nd & 3rd degree AV blocks
Interactions: • Oral contraceptives, warfarin, glucocorticoids: η of these
• EtOH, diazepam, cimetidine, valproic acid: increased phenytoin levels
• Carbamazepine, phenobarbital, chronic EtOH: decreased phenytoin levels
• CNS depressants (e.g. barbiturates/EtOH): Additive effects with concurrent use
Education: • Use IV route for status epilepticus • Antidysrhythmics

Carbmazepine (Antiepileptic)

Prototype: Tegretol
Therapeutic use: • Partial seizures, tonic-clonic seizures, bipolar disorder, trigeminal neuralgia
Adverse Effects: • Skin disorders
• Cognitive function is minimally affected but CNS effects can occur
• Blood dyscrasias • Teratogenic • Hypo-osmolarity (increased ADH secretion)
Contraindications/Precautions:
• CI: marrow suppression / bleeding disorders
Interactions: • Grapefruit juice: inhibits metabolism  [carbamazepine]
• Phenytoin & phenobarbital: decreased η carbamazepine
• Oral contraceptives and warfarin: Carbamazepine stimulates hepatic enzymes which decrease levels of these medications

Ethosuximide (Antiepileptic)

Proto: Zarontin
Therapeutic Use: Indicated ONLY for absence seizures
AE
• GI effects (take ĉ food)
• CNS effects (fatigue, dizziness)

Valproic Acid (Antiepileptic)

Proto: Depakote
Therapeutic use: Partial, generalized, and absence seizures, bipolar disorder, and migraines
Adverse Effects:
• GI effects (take ĉ food) • Hepatotoxicity • Thrombocytopenia
• Pancreatitis as evidenced by nausea, vomiting, and abdominal pain
Contraindications/Precautions:
• Avoid in children younger than 3 (hepatotoxicity) • Liver disorders
Interactions: Phenytoin and phenobarbital: Concurrent use increase these medications

Gabapentin (Antiepileptic)

Proto: Neurontin
Therapeutic Use: Single agent used for partial seizures • Neuropathic pain • Migraine prev.
Adverse Effects: CNS effects (drowsiness, nystagmus)

Benzodiazepines (antiepileptics)

Proto: Diazepam (Valium)
Therapeutic Use: Used in status epilepticus
Adverse Effects:
• Respiratory depression
• Anterograde amnesia
• Teratogenic

Muscle Relaxants / Antispasmodics

Centrally Acting Muscle Relaxants
• Diazepam (valium) • Baclofen (Lioresal)
• Cyclobenzaprine (Flexeril) • Metaxalone (Skelaxin)
Peripherally Acting Muscle Relaxants
• Dantrolene (Dantrium)

Diazepam (Valium)

Expected Action
• Acts in CNS to enhance GABA and produce sedation
• Acts in CNS to depress spasticity of muscles
Therapeutic Uses: • Relief of spasticity d/t Cerebral Palsy or MS
• Anxiety & panic disorders • EtOH withdrawal • Insomnia
• Status epilepticus • Anesthesia induction • Relief of spasm d/t injury
Adverse Effects: •
• CNS depression • Physical dependence from long-term use
Contraindications/Precautions:
• Pregnancy (D) • Caution ĉ impaired liver or renal function
Interactions
• CNS depressants (EtOH, opioids, antihistamines, barbiturates): Additive CNS depressive effects with concurrent use.

Centrally Acting (Muscle Relaxant, Antispasmodic)

Proto: Baclofen, cyclobenzaprine, metaxalone
Expected Action
• Acts in CNS to depress spasticity of muscles
Therapeutic Uses: • Relief of muscle spasm d/t injury
• Relief of spasticity r/t cerebral palsy or multiple sclerosis
Adverse Effects:
• CNS depression • Physical dependence from long-term use
• Metaxalone: hepatotoxicity • Baclofen: nausea, urinary retention, constipation
Contraindications/Precautions: • Caution in patients with impaired liver or renal function.
• Baclofen: Pregnancy (C)
Interactions: • CNS depressants (EtOH, opioids, antihistamines) - additive CNS depressant effects with concurrent use.

Peripherally Acting (Muscle Relaxant, Antispasmodic)

Name: Dantrolene (Dantrium)
Expected Action: Only peripherally acting muscle relaxant. Inhibits muscle contraction by preventing release of calcium in skeletal muscles.
Therapeutic Uses:
• Relief of spasticity d/t cerebral palsy or multiple sclerosis
• Treatment of malignant hyperthermia
Adverse Effects:
• CNS depression • Hepatic toxicity
Contraindications/Precautions:
• Pregnancy (C) • Caution with impaired liver & renal function
Interactions: CNS depressants - additive effects

Local Anesthetics

Amide type: Lidocaine - Ester type: tetracaine, procaine
Expected Action: decreased pain by blocking local conduction of pain impulses
Adverse Effects: • CNS excitation -- treat ĉ midazolam (Versed) or diazepam
• Hypotension, bradycardia, heart block, cardiac arrest
• Allergic reactions (more likely ĉ esters)
• decreased uterine contractility. • Freely cross placenta
• Spinal headache (lay flat for 12 hrs) • Urinary retention (call after 8 hrs)
Contraindications/Precautions: • CI in dysrhythmias and/or heart block
• Caution with liver/kidney dysfunction, heart failure, myasthenia gravis

General Inhalation Anesthetics

Proto: Halothane (Fluothane), isoflurane (Forane), nitrous oxide
Expected Action: Loss of consciousness, loss of sensation, relaxation of muscles, amnesia
Adverse Effects: • Hepatotoxicity • Gastric aspiration
• Hypotension • Respiratory & cardiovascular depression
• Malignant hyperthermia (d/c med, ice or ice saline infusion, dantrolene)
Interactions: •
• CNS depressants: Additive effect • Opioids: constipation & urinary retention

Education: • Succinylcholine - used as a muscle relaxant
• Encourage early ambulation • Assist with lung expansion

IV Anesthetics

• Barbiturates: Thiopental (Pentothal) • Ketamine (Ketalar)
• Benzodiazepines: Diazepam (Valium), midazolam (Versed), lorazepam (Ativan)
• Propofol (Diprivan)
Therapeutic Uses:
• Adjunct to inhalation anesthesia
• Induction & maintenance of anesthesia • Amnesia
• Midazolam & an opioid result in conscious sedation
• Ketamine can be used with children

IV Anesthetics (Effects and interactions)

Prototype: Thiopental, Diazepam, Ketamine, Propofol, Midazolam
Adverse Effects: •
• Respiratory and cardiovascular depression
• Propofol: Bacterial infection (use opened vial within 6 hrs)
• Ketamine: Psychologic reaction (premedicate with diazepam to decreased risk)
Contraindications/Precautions: •
• Ketamine should be avoided with psychiatric disorders
Interactions: •
• CNS depressants and stimulants: Additive effects
• Opioid analgesics: Constipation and urinary retention
Education: •
• Midazolam (Versed): inject over >2 minutes
• Propofol (Diprivan): inject into large vein; prep site with lidocaine.

Typical Antipsychotics

Proto: decreased η: chlorpromazine (Thorazine), increased η: haloperidol (Haldol)
Others: fluphenazine, molindone, perphenazine, thiothixene
Expected Action• Dopamine, acetylcholine, histamine, & norepinephrine receptors in brain and periphery are blocked. Symptom inhibition d/t dopamine2 blockade in brain.
Therapeutic Uses: • Delusional disorder • Bipolar disorder
• Tourette's Syndrome • • Schizoaffective disorder
• Dementia • Schizophrenia • Huntington's chorea
Adverse Effects: • Agranulocytosis • Sedation • Photosensitivity
• Anticholinergic effects • Ortho hypotension • Neuroendocrine effects
• Seizures • Parkinsonism • Sexual dysfunction • Dysrhythmias
• Dystonia • Akathisia • Tardive dyskinesia •
• Neuroleptic malignant syndrome
Interactions: • Anticholinergics: increased η • CNS depressants: Additive effects
• Levodopa: Counteracts antipsychotics by stimulating dopamine receptors
Education: • Consider depot preparations • Protect liquid prep from ☼
• Early EPS symptoms with anticholinergics, β-blockers, benzodiazepines

Atypical Antipsychotics

Proto: clozapine - Others: risperidone, olanzapine, quetiapine
Expected Action: Action results from blocking serotonin and dopamine receptors (block other receptors, too) --  Pr developing EPS or tardive dyskinesia
Therapeutic Uses: • Severe schizophrenia
• Psychosis induced by levodopa therapy
Adverse Effects: • Agranulocytosis (WBC<3000/cc, Neu<1500/cc)
• Weight gain • New onset diabetes • Seizures
• Myocarditis (dyspnea, increased RR, lethargy, chest pain, palpitations)
Interaction: Immunosuppressive medications: Avoid

Normal Lab Values

• RBC=4.7-6.1 x 1012/L • WBC = 5-10 x 109/L • PLT = 150-400 x 109/L
• PO2=75-100 mm Hg • PCO2=34-45 mm Hg • pH = 7.35-7.45
• Hgb=14-18 g/dL • Hct=42-52% • PT=11-12.5 s • PTT=60-70 s
• Na+=135-145 mEq/L • Cl-=100-108 mEq/L • Ca2+=9-10.5 mEq/L
• K+=3.5-5 mEq/L • PO43-=3-4.5 mg/dL • Mg2+=1.3-2.1 mEq/L
• Prot=6-8 g/dL • • BUN=8-25 mg/dL
• Alb=3.5-5 g/dL • Osm=275-295 mOsm/kg • Creatinine=0.6-1.5 mg/dL
Neu=55-70%
(2,500-8,000) Lym=20-40%
(1,000-4,000) Mon=2-8%
(100-700) Eos=1-4%
(50-500)

Tricyclic Antidepressants

Proto: amitriptyline (Elavil), Others: imipramine (Tofranil), doxepin (Sinequan)
Expected Action: Block reuptake of norepinephrine and serotonin in synaptic space
Therapeutic Uses: • Depression & bipolar disorders
Adverse Effects: • Orthostatic hypotension • Sedation
• Anticholinergic effects • Cardiac toxicity @ mega doses
• Toxicity evidenced by dysrhythmias, confusion, & agitation followed by seizures
Contraindications/Precautions: • Pregnancy (C)
Interactions: • MAOIs  hypertension
• Antihistamine & anticholinergicsadditive effects
• Epi/Norepi leads to increased amounts of adrenergics because reuptake is blocked by TCA
• Ephedrine/amphetamine leads to decreased responses to these d/t uptake inhibition keeps them from reaching site of action in nerve terminal
• EtOH, benzodiazepines, opioids, antihistamines leads to Additive CNS depression

SSRIs

Proto: fluoxetine (Prozac) - Others: citalopram (Celexa), escitalopram (Lexapro), paroxetine (Paxil), sertraline (Zoloft)
Expected Action: Block reuptake of serotonin in synaptic space
Therapeutic Uses: • Major depression • Panic disorders • Bulimia
• OCD • PTSD • PMDD
Adverse Effects: • Sexual dysfunction • Weight gain • Rash
• Withdrawal syndrome • Sleepiness, faintness • Hyponatremia
• Serotonin syndrome 2-72 hrs (confusion, anxiety, agitation, hallucinations)
Contraindications/Precautions: • Pregnancy (C)
• CI: MAOIs
Interactions: • MAOIs   risk of serotonin syndrome
• Warfarin leads to increased warfarin levels • TCA & Lithium leads to levels of these
• NSAIDs & anticoagulants  fluoxetine suppresses platelets increased bleeding risk

MAOIs

Proto: phenelzine (Nardil) - Others: isocarboxazide
Expected Action: Block MAO in brain leads to inceased norepinephrine and serotonin available for impulses
Therapeutic Uses: • Atypical depression • OCD • Bulimia nervosa
Adverse Effects: • Orthostatic hypotension • CNS stimulation
• Hypertensive crisis from dietary tyramine (increased HR, increased BP): Induce vasodilation with IV phentolamine (α-blocker) or sublingual nifedipine.
Contraindications/Precautions: •
• CI: SSRIs, pheochromocytoma, cardiovascular disease & renal insufficiency
Interactions: • Indirect sympathomimetic leads to release NE causing hypertensive crisis
• TCA leads to hypertensive crisis • SSRIs leads to serotonin syndrome
• Antihypertensives leads to additive hypotensive effect • Meperidine leads to hyperpyrexia
• Tyramine-rich foods lead to hypertensive crisis (aged cheese, salami, avocados, bananas, protein, & red wine)
• Vasopressors (phenylethylamine, caffeine) lead to hypertension

Atypical Antidepressants

Proto: bupropion (Wellbutrin) - Others: mirtazapine (Remeron), venlafaxine (Effexor), reboxetine (Vestra), trazodone
Expected Action: Inhibit dopamine uptake
Therapeutic Uses: • Depression • Aid to quit smoking
Adverse Effects: • Seizures
• Headache, dry mouth, constipation, increased HR, restlessness, weight loss
Contraindications/Precautions: • Pregnancy - B
• CI: Seizure disorders, MAOIs
Interactions: • MAOIs (e.g. phenelzine) leads to increased risk of toxicity

Mood Stabilizer

Proto: Lithium, mood-stabilizing anticonvulsants:
valproic acid (Depakote), carbamazepine (Tegretol)
Expeced Action
• Lithium causes serotonin receptor blockade
• Lithium use will evidence decrease in neuronal apathy and/or increase in neuronal growth.
Therapeutic Uses: • Bipolar / alcoholism / bulimia / schizophrenia
Adverse Effects: • GI effects, usually transient (give ĉ milk)
• Tremors (give β-blocker like propanolol) • Polyuria • Renal toxicity
• Goiter/hypothyroidism • Teratogenic
Contraindications/Precautions: • Pregnancy - D • No lactation
• Caution ĉ renal dysfunction, heart disease, Na+ depletion & dehydration
Interactions: •
• Diuretics lead to decreased Na+ which leads o decreased lithium excretion which will lead to toxicity
• NSAIDs lead to increased renal absorption lithium which leads to toxicity (aspirin OK)
• Anticholinergics lead to abdominal discomfort from urinary retention & polyuria
Education
• Maintain adequate sodium intake and 8-12 glasses of H2O
• Plasma lithium levels must be monitored (> 1.5 mEq/L is toxic)

Sedative-Hypnotics -- Benzodiazepines

Proto: diazepam (Valium) - Others: alprazolam (Xanax), lorazepam (Ativan), chlordiazepoxide (Librium)
Expected Action: Enhance the action of gamma-aminobutyric acid (GABA)
Therapeutic Uses: • Anxiety • Seizures • Panic disorder
• Muscle spasms • Anesthesia • EtOH w/d • Insomnia
Adverse Effects: • CNS depression • Anterograde amnesia
• Paradoxical response • Respiratory depression •
• Acute toxicity (treat oral ĉ charcoal, treat IV ĉ flumazenil)
Contraindications/Precautions: Teratogenic
Interactions: CNS depressants lead to additive effects

Sedative-Hypnotic Nonbenzodiazepines

Proto: zolpidem (Ambien) - Others: zaleplon (Sonata), eszopiclone (Lunesta) , trazodone (Desyrel)
Expected Action: Enhance action of GABA in CNS leading to prolonged sleep duration. They do not function as antianxiety, muscle relaxant, or antiepileptic agents.
Therapeutic Uses: Management of insomnia
Adverse Effects: Daytime sleepiness and lightheadedness
Interactions
• CNS depressants lead to additive effects
• Food leads to decreased absorption when taken with food

Anxiolytics (Non Barbiturate)

Proto: Buspirone (BuSpar)
Expected Action: Uncertain - it does bind to serotonin and dopamine receptors.
Therapeutic Uses: Treatment of Generalized Anxiety Disorder
Adverse Effects: CNS effects and NO SEDATION
Contraindications/Precautions: Erythromycin, ketoconazole, and grapefruit juice leads to increased effects of buspirone
• Does NOT potentiate CNS depressants
Education: Take with meals to prevent gastric irritation

CNS Stimulants

Proto: methylphenidate (Ritalin) - Others: amphetamine, dextroamphetamine (Dexedrine), Adderall, caffeine
Expected Action: Release norepinephrine and dopamine and prevent their reuptake in CNS.
Therapeutic Uses: • ADHD • Obesity • Narcolepsy
Adverse Effects: • CNS stimulation • Weight loss
• Cardiovascular effects (dysrhythmias, chest pain, increased BP)
Caution: hyperthyroidism, heart disease, glaucoma, Hx of drug abuse, MAOIs
Interactions: •
• MAOIs leads to hypertensive crisis • Caffeine leads to increased CNS stimulant effects
• Phenytoin, warfarin, phenobarbital  Inhibited metabolism of these leads to increased levels
• OTC cold & decongestants leads to increased CNS stimulant effects

Alcohol Abuse Drugs

Withdrawal Symptoms • Usually start within 12-72 hours / Persist 5-7 days
• Can be mild: nausea, anxiety, tremors
• Can be life-threatening: hallucinations, cramps, tremors, seizures, increased HR, increased BP, increased T
Support Meds:
• Benzodiazepines (chlordiazepoxide, diazepam, lorazepam) leads to decreased DT and risk of seizures, decreased intensity of symptoms
• Adjuncts (carbamazepine, clonidine, propanolol) leads to decreased seizure, decreased craving, depress autonomic response (decreased HR, decreased BP, decreased T)
Maintenance Meds:
• Disulfiram (Antabuse) --> ĉ EtOH, aldehyde syndrome occurs (nausea, extreme vomiting, hypotension) --> Can progress to respiratory and cardiac depression, seizures, and death.
• Naltrexone (ReVia) --> Opioid antagonist that decrease craving and pleasurable effects
• Acamprosate (Campral) leads to decreased pleasant effects of abstinence (anxiety, etc)

Drugs of Abuse of Opiates

Withdrawal Symptoms • Self-limiting in 7-10 days
• Begins with sweating and rhinorrhea, progressing from tremors and irritability to weakness, nausea, vomiting, muscle/bone pain, and spasticity.
• NOT life-threatening.
Detox Meds:
• Methadone substitution --> Prevents withdrawal syndrome.
Maintenance Meds:
• Methadone --> Long-term maintenance. Dependence is transferred to methadone.
• Clonidine (Catapres) --> Control autonomic hyperactivity (nausea, vomiting)
• Buprenorphine (Subutex) --> Opioid agonist/antagonist
• Naloxone (Suboxone) --> Opioid agonist/antagonist

Drugs of Abuse of Nicotine

Withdrawal Symptoms: Abstinence syndrome is evidenced by irritability, nervousness, restlessness
Support Meds:
• Bupropion (Zyban)’  craving and symptoms of withdrawal.
• Nicotine ’ Pharmaceutical replacement to alleviate symptoms
Education
• Chew gum over 30 minutes; avoid eating and drinking within 15 minutes of gum
• Gum not recommended for use longer than 6 months
• Avoid use of all nicotine products while pregnant or breastfeeding.

Vasopressin (Pitressin) + Desmopressin (DDAVP)

Expected Action: Promote H2O reabsorption in kidneys (desmopressin preferred)
• Vasoconstriction due to smooth muscle contraction (vasopressin)
Therapeutic Uses: • Diabetes insipidus • Cardiac arrest
Adverse Effects: • Overhydration (sleepiness, pounding headache)
Contraindications/Precautions: ♀ (X) • Pregnancy
• CAD or decreased peripheral circulation (risk for gangrene)
Education: • Monitor site carefully; extravasation can cause gangrene.

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