2013-09-16 Anti-Hypertensive II Flashcards
- Clonidine/Catapres™ (also methyldopa; drug costs $4 to $37 to $108 (Catapress™ patches) per month)
Class? PD? PK? Toxicity? Interactions? Special considerations? Monitor?
Drug class: pharmacologic class–central alpha-2 agonist; therapeutic class–antihypertensive, adjunct to Rx of opioid withdrawal, prophylaxis of migraine
Pharmacodynamics: stimulates alpha-2 adrenoceptors in brainstem, thereby leading to down-regulation of sympathetic output
Pharmacokinetics: Onset 1 h, duration 8 h, F~85%, also avalable as cutaneous patch
Toxicity: withdraw gradually because of risk of rebound HTN; risk of bradycardia in sinus node disease; letharagy, fatigue, depression
Interactions: additive effects with most other antihypertensives; additive sedation with other CNS drugs
Special considerations: Pregnancy class C; avoid in patients with renal insufficiency
Indications and dose/route: begin with 0.1 mg po bid, up to 1.2 mg per day; transdermal begin with 0.1 mg per 24 h as a 7-day patch
Monitor: follow BP and HR, fatigue, also consider baseline EKG
Methyldopa
[See Rang card]
- Trimethaphan/Arfonad™ (no others in class; for brief use as IV infusion only, in OR or ICU; no cost info)
Class? PD? PK? Toxicity? Interactions? Special considerations? Monitor?
Notes from class: like the old gangliectomy procedure!
Drug class: pharmacologic class—ganglionic transmission blocker; therapeutic class– antihypertensive
Pharmacodynamics: blocks nicotinic transmission with both sympathetic and parasympathetic ganglia (NN receptors); produces veno- and vaso-dilatation
Pharmacokinetics: useful only when given iv; produces fall in BP within minutes; partly metabolized, and partly excreted by kidneys
Toxicity: watch out for sudden, severe drop in BP; also fall in HR; also, reduction in just about any sympathetic or parasympathetic response
Interactions: additive effects with most other antihypertensives;
Special considerations: patients are quite miserable, hence only used during general anesthesia; also, helps to tilt patient to help control BP
Indications and dose/route: given by iv infusion, and only to treat HTN crisis, or for controlled hypotension during surgery
Monitor: minute to minute monitoring of BP (and HR)
Note: I include this drug to show that this mechanism does work!! This drug is not used in the long-term management of HTN!!
- Reserpine (cheap!, no brand name found; 2000 years old!)
Class? PD? PK? Toxicity? Interactions? Special considerations? Monitor?
Drug class: pharmacologic class–Rauwolfia alkaloid; therapeutic class–antihypertensive
Pharmacodynamics: binds to vesicles that contain NE or serotonin, preventing their uptake, and ultimately depleting the neuron of NE (or serotonin); this effect takes 2-3 weeks to develop, and including neurons and also the adrenal medulla
Pharmacokinetics: good oral bioavailability, but biologic effects take 2-3 weeks to develop (via slow depletion of NE from vesicles)
Toxicity: dizziness; orthostatic hypotension; depression (particularly bad!)
Interactions: additive effects with most other antihypertensives
Special considerations: approved by the FDA in 1953!!! First antihypertensive drug approved, and first sympatholytic drug approved by the FDA (remember that in 1960’s, drugs included only reserpine, HCTZ, and hydralazine)
Indications and dose/route: For HTN, 0.1-0.2 mg po q day
Monitor: BP, sympathetic tone, depression!!!!
Note: I include this drug to show that this mechanism does work, and for historical interest!! This drug is not used in the long-term management of HTN today in the US, but it is of great historical importance!!
- Atenolol/Tenormin™ (also propranolol, metoprolol,Toprol XL™, many others; class runs $4/$52 for atenolol to $108 for Inderal LA per month)
Class? PD? PK? Toxicity? Interactions? Special considerations? Monitor?
[see rang card, too]
Notes from class: recall that beta2 blockade can worsen asthma
Drug class: pharmacologic class–beta-adrenoceptor blocker (beta-1 specific); therapeutic class–antihypertensive, antiarrhythmic, primary and secondary prevention of MI, anti-anginal
Pharmacodynamics: binds directly to beta-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
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)
Toxicity: excessive hypotension; bradycardia; heart block can worsen severe CHF (but indicated for mild to moderate CHF); worsen bronchospasm in severe asthmatics; can also cause nightmares
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 unless other indications exist (recent data)
Indications and dose/route: for treatment of hypertension, 25-100 mg per day, in one or two doses
Monitoring: BP, HR, exercise tolerance
- Prazosin/Minipress™ (also Terazosin, doxazosin; tamsulosin; class costs range from $4/$21 to $71 per month )
Class? PD? PK? Toxicity? Interactions? Special considerations? Monitor?
[see Rang card, too]
Drug class: pharmacologic class–alpha-1 adrenoceptor blocker; therapeutic class– antihypertensive, treatment of BPH (alpha-1 receptors), treatment of Raynaud’s syndrome (alpha-1 causes vasospasm), treatment for kidney stones (alpha-1 blockade relaxes SMM in ureters)
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 with 1 mg tid, advance to 20 mg per day divided tid
Monitor: BP, weight, edema
- Labetalol/Trandate™ (also Carvedilol/Coreg™; class cost $4 (carvedilol generic) to $26 per month)
Class? PD? PK? Toxicity? Interactions? Special considerations? Monitor?
Drug class: pharmacologic class–alpha- and beta-receptor blocker; therapeutic class– antihypertensive, treatment of 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 IID6
Toxicity: avoid in patient with bradycardia, heartblock, CHF, asthma, shock; use with caution in patients with cardiomyopathy, pheochromocytoma: Pregnancy Class D (but may be better in pregnancy??)
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
Should beta-blockers be used as first line for HTN?
Not unless you are using it to treat other co-morbidities shown to respond to beta-blockade. Recent studies suggest increased stroke risk.
