Hypertension Drugs Flashcards
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
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!!!
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,
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
Nitroprusside (Nipride™, Nitropress™; not given chronically)
Drug class: pharmacologic class– vasodilator; therapeutic class–antihypertensive, management of severe CHF, management of pulmonary hypertension, produce controlled hypotension to reduce bleeding during surgery •
Pharmacodynamics: acts “directly” on vascular smooth muscle to cause dilatation of both veins and arterioles; metabolized to release CN- and NO, which activates guanylate cyclase, leads to production of cGMP from GTP, which then leads to vasodilation; cGMP then hydrolyzed to GMP by PDE •
Pharmacokinetics: only route is iv; rapid onset (minutes) and cessation (minutes), thereby allowing minute-by-minute titration; CN- metabolite is converted to SCN in liver, then excreted in urine; must be given by continuous infusion •
Toxicity: excessive hypotension; accumulation of CN- and thiocyanate; headache; decreased blood flow to brain •
Interactions: additive effects with most other antihypertensives •
Special considerations: monitor patient VERYclosely—must be in ICU with arterial line; avoid high infusion rates or prolonged infusions, to prevent accumulation of CN-; use with caution in patients with increased intracranial pressure •
Indications and dose/route: for treatment of hypertensive crisis, given as IV infusion at 0.3-10 mcg/kg per minute •
Monitoring: BP, HR, metabolic acidosis; most often requires arterial line
Atenolol/Tenormin™
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 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); metoprolol has hepatic metabolism (and shorter half-life) •
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; may no longer be “first line” drug for essential HTN unless other indications exist (recent data); metoprolol (needs to be taken several times per day) has more 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
Labetalol/Trandate™
• Drug class: pharmacologic class—mixed alpha- and beta-receptor blocker; therapeutic class– antihypertensive, treatment of stable CHF (Coreg™) •
Pharmacodynamics: reduces BP by blocking access of NE to beta-receptors and alpha-1 receptors, thereby lowering BP by several different mechanisms; patients differ in degree of beta-blockade vs alpha-blockade •
Pharmacokinetics: excellent absorption but high first-pass effect, leading to F~25%; onset 1-2 hours after po, 2-5 minutes when given iv; extensively metabolized in liver by 2D6 •
Toxicity: avoid in patients with bradycardia, heartblock, CHF, asthma, shock; use with caution in patients with cardiomyopathy, pheochromocytoma: Pregnancy Class D • Interactions: additive effects with most other antihypertensives •
Special considerations: use reduced doses in patients with impaired liver function; dizziness is most troubling early side effect; most often used for hypertensive crises (as with nitroprusside) •
Indications and dose/route: most commonly given iv with initial small boluses of 20 mg, followed by continuous infusion at 2 mg/min; not usually given po for chronic treatment; 80 mg thrice daily, or 240 mg SR once daily •
Monitor: BP, HR
Hydrochlorothiazide, chlorthalidone
Drug class: pharmacologic class–thiazide diuretic; therapeutic class–diuretic, antihypertensive •
Pharmacodynamics: block reuptake of Cl and Na from tubular fluid after glomerular filtration; also appears to cause decrease in SVR via unclear mechanism; will lower BP by up to 10-15 mm in many patients; useful as monotherapy or in combinations; HCTZ most commonly used, but perhaps some slight edge to chlorthalidone (duration, efficacy)(see Flack et al: Hypertension 2011; 57:665-6) •
Pharmacokinetics: F ~70%, excreted unchanged in urine; short half-life (hours); HCTZ not available in IV formulation; onset 2 h, peak 5 h, duration 10 h •
Toxicity: allergy to sulfa antibiotics (?); cause K and Mg depletion; cause Na and Cl depletion, metabolic alkalosis; volume depletion; worsen hyperuricemia •
Interactions: additive effects with most other antihypertensives •
Special considerations: more side effects in geriatric patients; Pregnancy Class D; much less effective in patients with reduced GFR •
Indications and dose/route: 12.5 mg or 25 mg po every morning; little benefit (and more toxicity) when given in higher doses •
Monitor: BP, weight, edema, K, Mg, BUN, creatinine
Clonidine
Description: synthetic and selective α2 receptor agonist • Actions:
Stimulate α2 receptors in brainstem, cause downregulation of sympathetic nervous system •
Indications: • Treat hypertension • Treat or prevent migraine •
Other facts: • May be given orally or patch • Causes sedation and dry mouth • If given intravenously or OD can cause BP
Propranolol/Inderal™
• Drug class: pharmacologic class—non-specific β-adrenoceptor blocker; 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 by hepatic metabolism (shorter half-life); metoprolol also cleared via hepatic metabolism (and shorter half-life) •
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; may no longer be “first line” drug for essential HTN unless other indications exist (recent data); metoprolol (needs to be taken several times per day) has more 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
Phentolamine mesylate/Regitine
Drug class: pharmacologic class—non-selective, competitive alpha-adrenergic receptor blocker; therapeutic class—antihypertensive drug for patients with pheochromocytoma •
Pharmacodynamics: blocks alpha-1 and alpha-2 adrenergic receptors at presynaptic and postsynaptic alpha receptors, leading to less venoconstriction and less vasoconstriction •
Pharmacokinetics: only comes in IV formulation, so F=100%; plasma half-life about 20 min after IV dose •
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: usual doses given iv have little effect on blood pressure of normal people, or those with essential hypotension (hence its early use to try to detect patients with a pheo, where the drop in BP can be 35/25 mm Hg or more) •
Indications and dose/route: Aid in Dx of pheo; treatment or prevention of intra-op HTN during pheo removal surgery; prevention of dermal sloughing after extravasation of NE infusion; hypertensive crisis from sympathomimetic amines (discuss tyramineMAO interaction); dose 5 mg IV, then titrate, repeat as needed •
Monitor: BP!!
Lisinopril, captopril, enalapril, ramipril
• Drug class: pharmacologic class–ACE inhibitor; therapeutic antihypertensive, treatment of CHF, preserving renal function, preserving LV function after MI, acute management of MI •
Pharmacodynamics: inhibits conversion of AT I to AT II by ACE; diminishes both vasocontriction and stimulation of aldosterone secretion by AT II •
Pharmacokinetics: well absorbed; onset 1 h, peak 6 h, duration 24 h; once a day is fine; excreted primarily in urine as unchanged drug •
Toxicity: orthostatic hypotension; use with caution in patients with impaired renal function, or renal artery stenosis; be careful in patients on diuretics, or those with aortic stenosis; angioedema, cough; acute renal failure •
Interactions: additive effects with most other antihypertensives; NSAIDs may reduce ability to lower BP; hyperkalemia with KCL, others •
Special considerations: often discontinue diuretics prior to beginning use to reduce hypotension; Category C/D in pregnancy, abnormal cartilage development •
Indications and dose/route: begin 10 mg per day, titrate slowly upward to 40 mg per day max •
Monitor: BP, weight, edema, K, BUN, creatinine!!!!!
