Term 1 Drugs Flashcards
Pseudoephedrine
Description: Synthetic derivative of ephedrine •
Actions: Acts indirectly to release NE from adrenergic nerve endings, also some direct agonism at alpha- and beta-adrenergic receptors •
Indications: • Nasal and sinus decongestant • Less ability to dilate bronchioles than ephedrine •
Other facts: • FDA approval in 1959 • 1996 need to report bulk sales • 2005 stored behind counter or locked cabinet, need photo ID, need to maintain purchaser log, risk of diversion to produce methamphetamine (Breaking Bad) • 2008 labeled as risk of injury or death, no cold products for kids <2 yo
Ezetimibe (Zetia™)
- Drug class: Pharm class–2-azetidinone compound; Therapeutic class–cholesterol absorption inhibitor
- Pharmacodynamics: Selectively blocks the intestinal absorption of cholesterol and related phytosterols, by acting at the level of the small bowel brush border; causes reduction of hepatic cholesterol stores, and an increase in the blood clearance of cholesterol; when used as monotherapy, can lower LDL-chol by up to 18%; often used with a statin; recent work suggests that while it can lower LDL-chol, it may not add to overall clinical efficacy (clinical endpoints)
- Pharmacokinetics: Given orally; Tmax 4-12h; extensively metabolized to the glucoronide; F 35-60%; t 1/2 = 22 h
- Toxicity: HA in about 8%, diarrhea in about 4%
- Interactions with other drugs: Use in combination with dietary therapy, as monotherapy, or in combination with a statin (is available as Vitorin™, ezetimibe + simvastatin); bile acid sequestrants may decrease F
- Special considerations: Use with caution in patients with hepatic or renal impairment
- Indications and dose/route: 10 mg po daily
Scopolamine hydrobromide (Transderm Scop™)
Class: Alkaloid derived from plant, muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors throughout body Indications: prevention of nausea and vomiting caused by motion sickness; for prolonged use, usually given as a transdermal patch; can also be given as oral tablet
PK: when given as a patch (1.5 mg), onset is in 4 h, peak 24 h, duration 72 h (apply new patch every 3 days)
Contraindications and ADRs: avoid in patients with acute angle-closure glaucoma, urinary or GI tract obstruction, ileus, toxic megacolon, or ophthalmic prep in patients with eye adhesions between iris and lens; can cause wide range of anticholinergic side effects, including agitation, confusion, delirium, blurred vision; avoid also in patients with BPH, in patients in hot or humid environments
Other facts: overdose can cause delirium and tachycardia; physostigmine is occasionally given for severe overdose
Dose: apply transdermal patch (1.5 mg) behind ear 4 hours before anticipated trip, apply new patch every 3 days
Tiotropium
Class: Synthetic, inhaled muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors in the respiratory tract, thus leading to bronchodilatation
Indications: bronchospasm in chronic bronchitis and emphysema; bronchospasm in asthma; rhinorrhea in allergic rhinitis or with common cold
PK: much of an inhaled dose is actually swallowed (only 10% gets to lungs); not well absorbed from the resp tract; drug is metabolized in liver, or excreted unchanged in feces
Duration: 6-8 hours
Contraindications and ADRs: avoid in patients with problems with atropine or similar drugs; use cautiously in patients with angle-closure glaucoma, BPH, bladder neck obstruction;
ADRs include bitter taste, blurred vision, dry moiuth, nausea, bronchospasm (perhaps from propellant)
Other facts: close relative is tiotropium (Spiriva™)
Dose: for bronchospasm, usual dose is 2 puffs (36 mcg per puff) qid not to exceed 12 puffs per 24h
Rocuronium Bromide (Zemuron™)
Class: Neuromuscular blocker; approved by FDA in 1994
MOA: Bind to and block NMJ cholinergic receptors (NM), denying access to ACh, and producing a flaccid paralysis; developed to have rapid onset of action, relatively short duration of action, and minimal release of histamine; sequence of paralysis begins with small muscles (eyes, face, neck), then large muscles (limbs, chest, abd wall) and finally diaphragm Indications: to facilitate routine or rapid-sequence intubation; to produce NM blockade during surgery or ventilation
PK: has a half-life of rapid distribution (1-2 min), slower distribution phase (14-18 min), and terminal half-life (2.4 h); cleared mostly via hepatic metabolism
Contraindications and ADRs: never give to patient allergic to bromide; can cause hypo- or hypertension, tachycardia
Other facts: Other than succinylcholine, has the most rapid onset of any neuromuscular blocker, so useful when you wish to avoid sux, but need a rapid induction and rapid paralysis; little histamine release, no ganglionic blocking effects (both of which minimize hypotension)
Dose: always given iv; varies with indication, and with which inhalational agent is being used
Atropine
Class: Alkaloid derived from belladonna, muscarinic receptor blocker
MOA: blocks the ability of acetylcholine to bind to and stimulate muscarinic receptors throughout body
Indications: symptomatic bradycardia; pre-op patients to reduce bronchial secretions and to block vagal reflexes (e.g. during intubation); to block muscarinic effects of anticholinesterases given to reverse effects of neuromuscular blockers; antidote for poisoning by anticholinesterase insecticides or poisons (e.g. Sarin); to manage pupil size in patients with acute iritis or uveitis
PK: most commonly given iv, but also topically to eye; >50% metabolized in liver; after iv dose, onset immediate, peak 2-4 min, duration 4 h
Contraindications and ADRs: avoid in patients with acute angle-closure glaucoma, urinary or GI tract obstruction, ileus, toxic megacolon, or ophthalmic prep in patients with eye adhesions between iris and lens; can cause wide range of anticholinergic side effects, including agitation, confusion, delirium, blurred vision
Other facts: overdose can cause delirium and tachycardia; physostigmine is occasionally given for severe overdose
Dose: for bradycardia, 0.5 -1 mg iv push; for pre-op use, 0.4 mg IM 3o minutes before anesthesia; for insecticide poisoning, may need 2-6 mg iv, repeated every 5 minutes
Prazosin
• Drug class: pharmacologic class—selective alpha-1 adrenoceptor blocker; therapeutic class– antihypertensive, treatment of BPH •
Pharmacodynamics: blocks alpha-1 receptors on arterioles and veins, thereby inhibiting NE-mediated vasoconstriction and venoconstriction •
Pharmacokinetics: available po or transdermal; variable oral bioavailability (~60%), onset 2 h, duration 12-24 h; extensively metabolized in liver •
Toxicity: excessive hypotension with passing out, especially orthostatic, especially in patients on diuretics •
Interactions: additive effects with most other antihypertensives, especially diuretics •
Special considerations: start gradually, and at bedtime, to avoid first-time passing out ; male patients with BPH? •
Indications and dose/route: as monotherapy, begin with1 mg tid, advance to 20 mg per day divided tid •
Monitor: BP, weight, edema,
Hydralazine (Apresoline™; rarely given chronically
• Drug class: pharmacologic class–peripheral vasodilator; therapeutic class– antihypertensive, treatment of CHF, vasodilator •
Pharmacodynamics: “direct” acting vasodilator; seems to act by inducing endothelium to produce NO, which then passes to SM cells and induces production of cGMP, minimal venodilating effect •
Pharmacokinetics: given po, im, iv; metabolized extensively in GI mucosa and in liver, eventually excreted as metabolites in urine; F ~40%; onset 30 after po dose, 10 min after iv dose; persist for 2-6 hours •
Toxicity: more dangerous in patients with renal disease, prior stroke, angina; watch for hypotension, edema, occasionally drug-induced lupus •
Interactions: additive effects with most other antihypertensives •
Special considerations: never use as chronic oral monotherapy for treatment of hypertension, since edema and reflex tachycardia will result; concern giving to patients with CAD •
Indications and dose/route: dose 10-50 mg po four times daily •
Monitor: BP, weight, edema, BUN, creatinine, symptoms of lupus or angina
Bethanechol
Class: Synthetic cholinergic muscarinic receptor agonist
MOA: Direct agonist at muscarinic receptors, especially those of the detrusor muscle of the bladder (but not highly specific); stimulation enhances the tone of that muscle, encouraging bladder wall contraction and urination; Quaternary ammonium structure prevents CNS action; not degraded by AChE, which prolongs half-life and occupancy at receptor;
Indications: used to treat urinary retention associated with neurogenic bladder; also used in past to treat ileus of GI tract (not terribly helpful!)
PK: older drug, not well absorbed; F not known; effects last about 1 hour
ADRs, contraindications: avoid in patients with asthma, bladder outlet obstruction, bradycardia, CAD, GI obstruction, parkinsonism; ADRs include abd pain, diarrhea, flushing, HA, lacrimation, salivation, N, V, wheezing
Other facts: Not used much today, but of historical interest, and also illustrates clinical problems with such non-specific muscarinic receptor agonists
Dose: Oral tablets need to be taken every few hours
Propranolol
- Drug class: pharmacologic class—non-specific β-adrenoceptor blocker (able to block both beta-1 and beta-2 receptors equally well); therapeutic class–antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti-anginal
- Pharmacodynamics: binds directly to β1-receptors and β2 receptors, leading to lower blood pressure via several potential mechanisms (less cardiac output, less activation of the RAA system); recent evidence suggests less effective in preventing strokes than other drugs;
- Pharmacokinetics: available po or iv; variable oral F; onset 1-2 hours h, duration 12-24 h; can be given once per day as LA formulation; cleared primarily by hepatic metabolism (shorter half-life); (Note: a longer-acting drug of this class is called nadolol, and is cleared primarily by renal excretion)
- Toxicity: excessive hypotension; bradycardia; heart block can worsen severe CHF (but indicated for mild to moderate and stable CHF); worsen bronchospasm in severe asthmatics
- Interactions: additive effects with most other antihypertensives, additive AV block with CEB’s
- Special considerations: may be especially useful in HTN patients with exertional angina, MI, atrial fibrillation; watch out for abrupt withdrawal; beta-blockers are no longer considered “first line” drugs for essential HTN unless other indications exist (recent data);
- Indications and dose/route: for treatment of hypertension, 80 to 640 mg per day, in two to four divided doses; or one dose in sustained release formulation
- Monitoring: BP, HR, exercise tolerance
Nicotine (NicoDerm™, Nicorette™, Nicotrol™)
Drug class: Direct-acting nicotinic cholinergic receptor agonist (primarily at NN receptors)
MOA: potent ganglionic and CNS stimulant; in small doses, stimulates all ganglionic transmission; in larger doses, can actually block ganglionic transmission (think of succinylcholine); CNS stimulation and convulsions may occur at higher doses
Indications: Treatment to aid smoking cessation, and for the relief of nicotine withdrawal symptoms
PK: different kinetics for transdermal systems, chewing gum, lozenges
ADRs, contraindications: avoid in patients with angina, post-MI, arrhythmias; can cause tachycardia, N,V, salivation, insomnia, chest pain, atrial fibrillation
Other info: Patients usually advised to stop smoking completely upon initiation
Dose: Often start with new transdermal patch every day (21 mg/24 hours), along with gum 2-4 mg per square as needed for urge to smoke; counseling program also helpful
Aliroc’umab (Praluent™)
- Drug class: PCSK9 inhibitor (proprotein convertase subtilisin kexin type 9 inhibitor)
- Pharmacodynamics: PCSK9 normally binds to LDL receptors on hepatocytes, promoting receptor degradation; this human monoclonal Ab targets PCSK9, prevents it from binding to LDL receptors, and thereby increases LDL receptor lifetime on hepatocyte surface, and thus increasing hepatic uptake of LDL-Chol from blood
- PK: given SC injection every 2 weeks; half-life 12 days; clearance by proteolysis
- Toxicity: injection site reactions (5%) and myalgias (5%); rare hypersensitivity reactions
- Interactions: not reported
- Special issues: not yet approved for use on its own; given to high risk patients as an adjunct to diet, inadequate response to statins; not tested yet in pregnant women, or patients who cannot tolerate statin
- Dose: 75-150 mg SC injection every 2 weeks
- Note: little data yet about long-term efficacy and safety; it is very expensive
Salmeterol
Description: synthetic selective β2 (β2>>β1) receptor agonist (with relatively little β1 stimulation at normal doses) •
Actions: Potent agonist at β2 receptors on smooth muscle cells in airways (e.g. bronchioles) • increased mucociliary clearance, decrease vascular permeability, decrease mediator release
Metabolism: COMT/MAO,
Pharmacokinetics: F 15-75, 1/2 life is 6-8 hours. only 8-15% reaches systemic circulation
Pharmacodynamics: duration is 12 hours
Indications: • Prompt-acting rescue inhaler for asthma, COPD (bronchodilator) • Inhibit premature labor (relaxes smooth muscle cells in uterus as well) •
Other facts: • Most often given as MDI (metered dose inhaler) • Can be given via nebulizer • Rarely given any more as iv infusion • Side effects include CVS: tachycardia, palpitations, tremor, angina, arrhythmias, vasodilate pulm arterioles CNS: anxiety, headache and tremor. Metabolic- hypokalemia, hyperglycemia can develop tolerance.
Pilocarpine HCl
Class: Alkaloid derived from plant (1875), with particular affinity for sweat glands and eye receptors, approved by FDA in 19745, as antiglaucoma agent; also used for xerostomia
MOA: Stimulates muscarinic receptors of the sphincter muscles in the iris, producing miosis; also, produces vasodilation of conjunctival vessels of the outflow tract and contraction of ciliary muscles, resulting in deepening of the anterior chamber; both actions help to lower ocular pressure through enhanced clearance of aqueous humor in anterior chamber of eye
Indications: emergency treatment of acute narrow-angle glaucoma; chronic management of open-angle glaucoma; to counteract effect of mydriatic eyedrops
PK: reduction in eye pressure reaches maximum in 75 min; is eventually absorbed from tears, nose, stomach; metabolic pathway not clear; when taken by mouth, half-life around 1 h
ADRs, contraindications: do not use in acute iritis, inflammatory disease of anterior chamber, or asthma; can cause blurred vision, N,V, salivation, , excessive sweating
Other facts: Oral formulation (Salagen™) given to treat xerostomia from salivary gland hypofunction, usually caused by radiotherapy to head and neck cancers
Dose: Instill 1-2 drops into affected eye (various concentrations) q4-12 h
Tamsulosinn/Flomax™
Drug class: pharmacologic class—selective alpha-1 adrenoceptor blocker; therapeutic class– treatment of obstructive symptoms of BPH •
Pharmacodynamics: selectively blocks alpha-1 receptors, but preferentially (seen clinically) in the prostate, leading to relaxation of smooth muscles in the bladder neck and prostate, improving urine flow, and reducing obstructive symptoms of BPH •
Pharmacokinetics: completely absorbed after oral ingestion; >90% metabolized by CYP 450 enzymes; half-life about 6 hours, but duration of action up to 15 hours due to slow absorption •
Toxicity: excessive hypotension with syncope, especially orthostatic, especially in patients on diuretics, allergic reactions, decreased libido •
Interactions: additive effects with most other antihypertensives, especially diuretics •
Special considerations: rule out carcinoma of prostate before beginning treatment; do not crush or chew tablets, as that will speed up absorption; can also be used to treat spasm of ureter in patients passing kidney stones •
Indications and dose/route: for symptoms of BPH, 0.4 mg po qd or bid; similar doses for renal colic •
Monitor: BP
diphenhydramine
H1 inhibitor
mechanism: competitive inhibtor of H1 receptor (histamine release)
indications: allergic rhintis
PK- oral, hepatic metabolism, gets to CNS
ADRs: sedation, headache, constipation, prolonged QT interval
Succinylcholine (Anectine™)
Drug class: Neuromuscular blocking agent, of the depolarizing type (only member of this class); approved by the FDA in 1952
MOA: binds to NM receptors (specifically) and causes inward Na current and depolarization of the muscle cell; this leads to influx of calcium and contraction, visible as muscle fasciculations; tight binding to receptor prevents Ach from binding to receptor; drug itself is not cleaved by AChE; eventually the cell extrudes calcium, and the fasciculations and contraction ceases, leading to a flaccid paralysis (remember, Ach can’t access the nicotinic receptor, it is blocked
Indications: to produce muscle paralysis quickly and briefly, as needed for emergency intubations, or for brief procedures such as ECT
PK: when given iv 90% of drug is eventually metabolized pseudocholinesterase, but not by the actual synaptic AChE; complete relaxation is produced within 30-60 sec, and lasts 2-10 minutes, with gradual recovery of muscle strength and ability to contract
Contraindications, ADRs: previous malignant hyperthermia, or prolonged paralysis (due to deficiency in pseudocholinesterase); avoid in patients with burns, trauma, or renal disease (prolonged half-life of succinylmonocholine); ADR’s include apnea, bradycardia, cardiac arrest, asystole, bronchospasm, malignant hyperthermia, salivation, hypotension
Other info: quickest onset of all muscle relaxants (makes intubation easier, more quickly); known to release histamine in some patients; reserved now for use in emergencies that require “crash intubation”
Dose and route: for iv route in adults, 1.0-1.5 mg/kg, up to 150 mg total dose
disodium cromoglycate
unknown MOA- decreases chloride channels and Ca flux, decreases eosinophil cytokine release
indications: allergic rihintis
ADRS. nasal stinging, headache, nausea
Norepinephrine
• Drug class: pharmacologic class—direct-acting adrenergic agonist; therapeutic class— vasopressor, vasoconstrictor •
Pharmacodynamics/MOA: major action is to stimulate peripheral alpha-1 adrenoceptors, thereby leading to vasoconstriction (resistance arterioles, increase SVR) and venoconstriction (in capacitance vessels, increase preload). This increases CO, SVR, and MAP, but decreases blood flow to vulnerable tissues like skin, muscle, and kidney. Also, stimulates beta-1 receptors in the heart, increasing HR and contractility. Main effects are vasoconstriction and cardiac stimulation. •
Pharmacokinetics: F ~100% (given IV only!) Metabolized by COMT and MAO, mostly in liver. Metabolites are excreted in urine. Half-life 1-2 minutes (e.g. can be titrated quickly IV). Can cross the placenta, but not the blood/brain barrier. •
Toxicity: excessive vasoconstriction in mesenteric vessels, peripheral arterioles causing ischemia, infarction, digital gangrene; reflex bradycardia •
Interactions: use cautiously in patients taking an MAO inhibitor such as phenelzine (use lower doses); risk of excessive hypertension in patients taking propranolol •
Special considerations: correct volume depletion with IV fluids BEFORE giving NE infusion; select infusion site carefully—extravasation is a major problem; monitor patient and BP continuously in ICU setting; use cautiously in pediatric and geriatric patients •
Indications and dose/route: for adults with acute hypotension and shock (related to low SVR) infuse 2-12 mcg/min •
Monitor: BP, HR, infusion site, evidence of extravasation
Losartan
Drug class: pharmacologic class–angiotensin-1 receptor blocker (ARB); therapeutic class—antihypertensive, preserve renal function, treatment of CHF •
Pharmacodynamics: block stimulation of AT I receptor by angiotensin II, thereby reducing vasoconstriction and production of aldosterone •
Pharmacokinetics: F ~30%; onset 6 h; extensive first pass effect; active metabolite is 40x more potent, much longer half-life •
Toxicity: dizziness; orthostatic hypotension; worsening of renal failure •
Interactions: additive effects with most other antihypertensives •
Special considerations: Pregnancy class C/D; use care in patients on diuretics, those with renal artery stenosis, those with mitral or aortic stenosis •
Indications and dose/route: For HTN, daily doses 25-100 mg q day •
Monitor: BP, weight, edema, lytes, BUN, creatinine!!!
Atenolol, metoprolol
Drug class: pharmacologic class— “specific” β1-adrenoceptor blocker; therapeutic class–antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti-anginal
- Pharmacodynamics: binds directly to β1-receptors, with a preference for beta-1 over beta-2, leading to lower blood pressure via several potential mechanisms (less cardiac output, less activation of the RAA system); recent evidence suggests all beta-blockers are less effective in preventing strokes than other drugs used as monotherapy for HTN
- Pharmacokinetics: available po or iv; variable oral F; onset 1-2 hours h, duration 12-24 h; can be given once per day; renally excreted (longer half-life); (Note: metoprolol has hepatic metabolism, not renal clearance, and has a shorter half-life than atenolol)
- Toxicity: excessive hypotension; bradycardia; heart block; can worsen severe CHF (but indicated for mild to moderate and stable CHF); worsen bronchospasm in severe asthmatics
- Interactions: additive effects with most other anti-hypertensives; additive AV block with CEB’s
- Special considerations: may be especially useful in HTN patients with exertional angina, MI, atrial fibrillation; watch out for abrupt withdrawal; beta blockers are no longer “first line” drugs for essential HTN unless other indications exist (recent data); (Note: metoprolol needs to be taken several times per day, but has more clinical research data for use in patients s/p MI)
- Indications and dose/route: for treatment of hypertension, 25-100 mg per day, in one or two doses
- Monitoring: BP, HR, exercise tolerance
Trimethaphan (Arfonad)
Drug class: Ganglionic blocker (NN cholinergic receptor blocker)
MOA: binds to NN receptors (specifically) and prevents action of locally released ACh, thereby blocking neurotransmission in both parasympathetic and sympathetic ganglia; since usually the SNS has greater tone, this results primarily in drop in HR and BP; dose can be titrated to produce desired reduction in BP; drop is greater if patients is placed in head-up tilt (pooling of blood in leg veins)
Indications: to produce deliberate hypotension during some operative procedures; not used very often, as more precise blood pressure-lowering agents are now available
PK:
Contraindications, ADRs: should not be given to patients who are hemodynamically unstable, or who are already hypotensive; since there are many side effects, only given to anesthetized patients
Other info: oral formulation not available; harder to titrate than drugs such as nitroprusside
Dose and route: for iv route only,
Varenicline (Chantix™)
Drug class: Very selective and potent competitive partial agonist of α4-β2 nicotinic (NN) receptors, for smoking cessation; approved by FDA in 2006
MOA: By binding to nicotinic (NN) receptors in the brain, increases mesolimbic dopamine, preventing drop in dopamine levels and craving the next cigarette Indications: to help with smoking cessation programs, in conjunction with counseling
PK: well absorbed po; Tmax 4 h, t1/2 = 24 h; excreted primarily in urine as unchanged drug
Contraindications, ADRs: use cautiously in patients with severe renal impairment; Contraindicated in pregnancy/lactation. May produce abnormal dreams, anxiety, depression, irritability, insomnia, diarrhea, N, V, Causes drowsiness, caution operating machinery
Other info: Reports of suicidal thoughts and aggressive and erratic behavior → patients and caregivers should be instructed about the importance of monitoring for neuropsychiatric symptoms, and to communicate immediately with the prescriber the emergence of agitation, depression, unusual changes in behavior, or suicidality. Psychiatric patients – use extreme caution.
Dose and route: 1 mg po BID for healthy adults, 0.5 mg po BID fo patients with renal impairment CrCl < 50 ml/min; begin treatment 1 week before stop date
Nicotinic Acid (niacin)
- Drug class: pharmacologic class–vitamin; therapeutic class–cholesterol-lowering agent
- Pharmacodynamics: lowers BOTH TG and LDL-chol; decreased production of VLDL > decreased production of LDL > increase in LDL receptor expression in liver; modestly effective as single agent, usually used in combination; can also raise HDL; Note: recent study NEJM 2011 showed that while adding niacin to a statin can further reduce TG and raise HDL, these changes were NOT associated with improved clinical outcomes
- PK: well absorbed, large first pass effect (to nicotinamide); Tmax 45 min; half-life 45 min; urinary excretion of unchanged drug and metabolite
- Toxicity: many patients develop skin flushing, which can be lessened by taking aspirin; some patients develop hepatitis
- Interactions: absorption decreased by cholestyramine
- Special issues: in 1930s found to be a vitamin (B3) that cured pellagra; renamed niacin in 1940s; partially converted in the body to nicotinamide, which is NOT active in lowering lipids, but is active in forming NAD; avoid in patients with CAD, heavy ethanol use
- Dose: pellagra 100 mg tid; hyperlipidemia 0.5-2 gm tid after meals
Benztropine mesylate (Cogentin™)
Class: Synthetic muscarinic receptor blocker
MOA: Tertiary amine, therefore able to penetrate blood brain barrier to reach and block muscarinic receptors located in the CNS; changes the balance of CNS dopaminergic tone to cholinergic tone (reduced)
Indications: parkinsonism; to treat some drug (neuroleptic)-induced extrapyramidal reactions, including acute dystonic reactions
PK: absorbed from GI tract, metabolism unknown; excreted in urine as unchanged drug; with po use, onset 1-2 h, duration 24 h; with iv use, onset 15 min, duration 24 h
Contraindications and ADRs: avoid in patients with acute angleclosure glaucoma; in children < 3 yo; in hot weather; ADRs include confusion, psychosis, tachycardia, blurred vision, dilated pupils, constipation, dry mouth, ileus, urine retention nausea, bronchospasm (perhaps from propellant)
Other facts: avoid use in breast-feeding women
Dose: for parkinsonism, 0.5 to 6 mg po daily; for drug-induced extrapyramidal reactions, 1-4 mg po per day; for acute dystonic reaction, 1-23 mg iv, followed by 1-2 mg po bid to prevent recurrence
Amlodipine besylate
Drug class: pharmacologic class—dihydropyridine calcium entry blocker; therapeutic class– antihypertensive, antianginal (classical and variant) •
Pharmacodynamics: reduces BP by inhibiting influx of calcium through “slow channels”, thereby dilating peripheral arterioles; also, produces negative inotropic effect as well in myocardial cells; for angina, reduces afterload, thus decreasing oxygen consumption; also, inhibits spasm of coronary arteries in vasospastic angina •
Pharmacokinetics: F 64-90%; peak effects 6-12 hours post dose; duration 24 hours; extensively metabolized in liver 90% excreted in urine as inactive metabolites •
Toxicity: hypotension, AV block, worsening of CHF, bradycardia, headache, edema; watch out in patients with aortic stenosis, heart failure, severe liver disease •
Interactions: additive effects with most other antihypertensives; additive toxic effects on heart when given with beta-blockers (negative inotropic and dromotropic effects) •
Special considerations: shorter-acting nifedipine (and similar CEBs) can increase risk of MI (unclear why); Pregnancy C; less cardiac impact than older verapamil and diltiazem •
Indications and dose/route: 2.5 up to 10 mg daily •
Monitor: weight, edema, BP
