Antihypertensives Flashcards
evidence based tx of systemic arterial HTN
Treat with the intent of reducing risk of CV events and thereby reducing CV morbidity and mortality.
BP goal (controversial)
< 150/90 mmHg for patients > 60 y.o. (<140/90? controversial)
< 140/90mmHg for most patients < 60 years of age
strategies for antihypertensive therapy
Reduce TPR
Reduce CO
Reduce body fluid volume (salt & water)
Adjust homeostatic regulatory reflexes
- reflex tachycardia (increased SANS)
- edema (increased renin activity)
MOA of clonidine and role in therapy?
increase a2 activity - alter SANS activity
Most commonly prescribed central alpha2-agonist
SE of clonidine
Can cause rebound hypertension if stopped abruptly
Optimally used with a diuretic to diminish fluid retention
Overdose can cause paradoxical hypertension
MOA of a-methyldopa
Stimulate central alpha2 receptors –> decreased release of NE
role of a methyldopa in therapy
gestational hypertension
chronic hypertension in pregnancy
MOA of reserpine
blocks transport of NE into storage granules
role of reserpine in therapy
the most effective use of reserpine is in combination with a thiazide diuretic, which can mitigate related sodium and water retention.
SE of resserpine
- *strong sympatholytic effect results in increased parasympathetic activity:**
- nasal stuffiness, increased gastric acid secretion, diarrhea, and bradycardia.
MOA of guanethidine
affect vesicle storage:
- Transported across the sympathetic nerve membrane via NET1 –> concentrated in transmitter vesicles & replaces NE –> gradual depletion of NE stores
name the ACE inhibitors
Captopril, Lisinopril, Fosinopril
role of ACE inhibitors in therapy (Captopril, Lisinopril, Fosinopril)
First-line or add-on therapy for uncomplicated HTN
First-line therapy for compelling indications of:
- diabetes
- chronic kidney disease
- coronary artery disease
- left ventricular dysfunction
- previous ischemic stroke
ACE inhibitors are cleared mostly by what?
when would you reduce the dose?
Cleared mostly by the kidney –> reduce dose in kidney failure
Elevated plasma renin activity causes hyperresponsive to ACEIs reduce doses in pts with high plasma renin levels (e.g., heart failure, Na+-depleted patients)
action of ACE?
Angiotensin I –> angiotensin II
SE of ACEI
coughing
who should avoid use of ACEI
pregnancy
what are the angiotensin receptor blockers (ARBs)
receptor = AT1
Losartan, Valsartan, Candesartan
effects of ARBs (Losartan, Valsartan, Candesartan)
- *Inhibit Ang II-induced:**
1) contraction of vascular smooth muscle
2) thirst
3) vasopressinrelease
4) aldosterone secretion
5) release of adrenal catecholamines
6) enhancement of noradrenergic neurotransmission
7) increases in sympathetic tone
8) changes in renal function
9) cellular hypertrophy and hyperplasia
role of ARBs (losartan, valsartan, candesartan) in therapy
First-line or add-on therapy for uncomplicated hypertension – as effective as ACEIs
First-line therapy for compelling indications of
- Diabetes
- Chronic kidney disease
- Coronary artery disease
- Left ventricular dysfunction
Commonly used as an alternative for patients with intolerance to ACE inhibitors
when should ARBs not be used
pregnancy
what is a direct renin inhibitor?
what is it preventing?
Aliskiren
Binds directly to the catalytic site of renin –> prevents it from cleaving angiotensinogen to generate angiotensin I
role of aliskiren in therapy
Approved as monotherapy or in combination therapy for HTN
Demonstrated efficacy in lowering BP when used in combination with a thiazide, ACE inhibitor, ARB, or CCB
SE of aliskiren
Can cause hyperkalemia in patients with CKD and diabetes or in those receiving a potassium-sparing diuretic, aldosterone antagonist, ACE inhibitor, or ARB
when should aliskiren not be used
pregnancy
what antihypertensive therapies should not be used in pregnancy
Angiotensin Receptor Blockers (Losartan, Valsartan, Candesartan)
ACE inhibitors (Captopril, Lisinopril, Fosinopril)
Aliskiren
what are the Dihydropyridine Calcium Channel Blockers for HTN
Amlodipine, Clevidipine, Nicardipine, Nifedipine, Nimodipine, Felodipine
role of Dihydropyridine Calcium Channel Blockers for HTN (“-dipine”) in HTN therapy
First-line or add-on therapy for uncomplicated hypertension
Add-on therapy for
- Diabetes
- Coronary artery disease
when should you avoid use of Dihydropyridine Calcium Channel Blockers for HTN (“-dipine”) in HTN therapy
left ventricular dysfunction (all except amlodipine and felodipine)
what are the Non-dihydropyridine Calcium Channel Blockers for HTN
Verapamil
Diltiazem
role of Non-dihydropyridine Calcium Channel Blockers for HTN therapy (verapamil, diltiazem)
Alternative to β-blockers in coronary artery disease
when should verapamil and diltiazem be avoided
left ventricular dysfunction
Verapamil, Diltiazem:
situation with potentially favorable effects?
- Migraine headache
- Arrhythmias
- High-normal heart rate or tachycardia
Verapamil, Diltiazem:
situation with potentially unfavorable effects?
Low-normal HR
what drug - direct acting vasodilators –> opening K+ channels
decrease IP3-induced Ca2+ release from smooth muscle SR –> decrease contraction
Opens Ca2+-activated K+ channels in smooth muscle –> relaxation
Relaxes arterioles; little/no effect on veins;
Hydralazine
role of hydralazine for therapy
- often used as ADD ON (often with diuretic) therapy to manage resistant HTN, particularly in patients with severe chronic kidney disease
- Safe in pregnant women –> used for gestational HTN
SE of hydralazine
Drug-induced lupus with long-term use
compensatory tachycardia and Na+ retention
when using hydralzaine for chronic HTN what should you do to mitigate SE of compensatory tachycardia and Na+ retention
used in combination with both a diuretic and β-blocker or NDHP CCB
MOA of minoxidil
direct-acting vasodilator –> opening K+ channels
relaxes arteriolar VSMCs (no effects on veins)
role of minoxidil in therapy
Oral use only for severe, refractory hypertension
Use in combination with β-blockers and diuretics
SE of minoxidil
Reflex increase in myocardial contractility
what is minoxiil used in combination with
Use in combination with β-blockers and diuretics
MOA of sodium nitroprusside
direct-acting vasodilator - via NO
donates NO ⇒ cGMP-mediated Ca2+ sequestration
- decreases both afterload and preload (venodilation)
how is sodium nitroprusside administered
IV
use for sodium nitroprusside
Intravenous agent used in hypertensive emergencies and the rapid management of CHF
- very rapid onset of action
how can the diuretics - Chlorthalidone, Hydrochlorothiazide, Indapamide - be used for HTN
First-line or add-on therapy for uncomplicated HTN
First-line therapy for compelling indications of
- left ventricular dysfunction
- previous ischemic stroke
how can spironolactone or eplerenone (aldosterone antagonist - diuretic) be used for HTN
Add-on therapy for resistant hypertension
Add-on therapy for:
- coronary artery disease
- left ventricular dysfunction
what drugs can be used for hypertension in pregnancy
methyldopa - extensive safety data
labetalol
long-acting nifedipine
hydralazone
metoprolol
advantage and disadvantage of hydralazine in tx for HTN in pregnancy
Ad. = extensive clinical experience
Disad = increased risk of maternal hypotension
why is labetalol preferred over other beta blockers for HTN in pregnancy
because of a theoretical beneficial effect of α-blockade on uteroplacental blood flow
what drugs should be avoided if pregnant?
what drugs are contraindicated?
Avoid:
- diuretics
- atenolol
- nitroprusside
Contraindicated:
- ACE inhibitors
- Angiotensin receptor antagonists
