Antihypertensives Flashcards
diuretics in hypertension
- most popular anti-hypertensives
- hydrochlorothiazide, chlorthalidone
- increase in BP-> sodium accumulates in vascular smooth muscle and then exchanges for Ca which increase tone
- diuretics increase Na loss
- replace fluid-> no changes in BP
- replace salt-> increase BP
use of diuretics in increase BP
- lower BP when used alone
- prevent false tolerance (increase BP which occurs with other anti-hypertensive drugs)
- prevent sodium accumulation
- good for elderly
- beta-blockers for young caucasian
want to watch out for when using diuretics in increased BP
-beware of high blood lipids, increase glucose can block insulin release, potassium depletion due to high sodium in collecting duct and don’t give aspirin
alpha-2 stimulants in HTN
alpha-2 adrenergic receptors
- mainly on nerve ends
- inhibits release of NT
- decrease sympathetic outflow from brainstem by acting on alpha-2 receptors
- decrease NE release heart and blood vessels
- baroreceptors still functional
alpha-2 stimulant drugs
- alpha methyl DOPA
2. clonidine
alpha methyl DOPA
- first on market
- irregular absorption
clonidine
- good bioavailability but complex CNS effects
- also used in opiate withdrawal
side effects of alpha-2 stimulants
- decrease mental acuity
- nightmares
- CNS depression
- dry mouth in 50%
- rebound increase BP on abrupt cessation of therapy
vasodilators nin HTN
- hydralazine release NO to increase cyclic GMP and dilate arteries
- reflex tachycardia (desirable in pregnancy)
- some nausea, lupus in 15% (in slow acetylators)
- slow and fast acetylators
- contrast with alpha-blockers (which dilate arteries and veins, less postural hypotension)
minoxidol in HTN
- dilates arteries (skin, sk. mm, heart, GI)
- use with beta-blocker, and diuretic
- opens ATP-sensitive potassium channels-> hyperpolization
- severe reflex tachycardia
- sodium retention (increase renin), also increase Na reabsorption in proximal tubule
- powerful, resistant in increase BP
- hair growth (hirsutism) (rogaine)
ACE inhibitors
well tolerated
- captopril (8 hr duration)
- enalapril (24 hr duration)
MOA of ACE inhibitors
- block formation of angiotensin II
- end product inhibition by analogs of 2aa fragment
- less angio II-> less vasoconstriction
- less aldosterone-> sodium loss
- block bradykinin metabolism-> vasodilation
advantages in ACE inhibitors
- increase kidney blood flow: release PGE2, synergistic with diuretics
- good in elderly
- like beta-blockers, prevent 2nd heart attack
- no reflex tachycardia
- no CNS depression
- abrupt withdrawal no problem
precautions with ACE inhibitors
- Chronic non-productive cough, ACE high in lungs
- Bad in pregnancy
- oligohydramnios (decrease amniotic fluid): fetal decrease in BP, and renal failure in 2nd/3rd trimester
- face/limb deformities in 1st trimester - prodrugs don’t work in patients with bad liver
- loss of taste with captopril
- severe allergic reactions 1st dose
angiotensin II receptor blockers (ARB’s)
- competitive block of angiotensin II-1 receptor, little block of AT 2 receptor
- less cough, less angioedema
ARB’s drugs
-Isoartan, Valsartan
how are ARB’s like ACE inhibitors?
- oligohydramnios still a problem
- less effective in AA
- full BP effect in 3 weeks
what is goal of HTN therapy
decrease risk of cardiovascular disease
-beta-block/diuretics decrease incidence stroke but NOT MI
why do beta-block/diuretics decrease incidence of stroke but not MI?
can’t prevent angio II changes in heart of blood vessels
-need ACE inhibitors
agents in HTN emergencies
- unstable angina, internal bleeding or HTN encephalopathy
1. nitroprusside
2. fenoldopam
3. diazoxide
nitroprusside
NO generator
-nausea, disorientation, muscle cramps
fenoldopam
D1 agonist like dopamine
diazoxide
like minoxidil but weaker, duration 12 hours
preclampsia
- HTN in pregnancy
- called toxemia or pregnancy, or if convulsions occur “eclampsia”
- involves 5-10% of pregnancies especially primigravida
treatment of preclampsia
MgSO4
-offets Mg loss which occurs in pregnancy
combination therapy for HTN
ACE inhibitor, diuretic, beta-blocker, minoxidil
- not just one drug effective
- “Mosaic theory”
