Antihypertensives Flashcards
What types of drugs can be used to treat HTN?
Diuretics Alpha-2 stimulants Vasodilators --hydralazine --minoxidil ACE inhibitors Angiotensin receptor blockers
What are the limits to HTN therapy?
What factors affect HTN?
Limits: kidney and blood flow
Factors: age, genetics, race
What diuretics are used to tx HTN?
Hydochlorothiazide
Chlorthalidone
Why do diuretics work for treating HTN?
with increased BP, Na accumulates in vascular smooth mm and then exchanges for Ca which increases the tone
–causes blood vessel constriction which gives high BP
Diuretics increase Na loss
Use of diuretics in pts with HTN
Lower BP when used alone
Prevent “false tolerance” (inc BP which occurs with other antiHTNive drugs)
–prevent sodium accumulation
Good for elderly and African Americas
What are things to be careful of with diuretics?
- High blood lipids
- Increased glucose b/c blocks insulin release
- K+ depletion b/c high Na in collecting duct
- DONT USE WITH ASPIRIN
- –part of diuretic effect is production of prostaglandins
- –aspirin blocks this
Alpha-2 adrenergic receptors are found where? Do what?
Found mainly on nerve ends
Inhibit release of neurotransmitter
Decrease sympathetic outflow from brainstem by acting on alpha2a receptors
- -dec NE release
- -baroreceptors still fxn
What drugs are alpha-2 stimulants?
Alpha methyl DOPA
Clonidine
What side effects can be seen with alpha-2 stimulant use?
Decreased mental acuity
Nightmares
CNS depression
Dry mouth
Rebound inc BP on abrupt cessation
Hydralazine
- what does it do?
- what can they cause (in terms of side effect)?
- how can we minimize this?
Releases NO to increase cyclic GMP and dilate ARTERIES
can cause reflex tachycardia
–combine with B-blockers to minimize
Why is the difference between slow and fast acetylators important for hydralazine use?
People that are slow acetylators tend to the patients that develop lupus like syndrome with drug use
- -this is not lupus
- -it will stop with cessation of the drug
Contrast alpha blockers and hydralazine
Alpha blockers work on arteries and veins
Hydralazine works on arteries only
Less postural hypotension occurs with hydralazine
Minoxidil
- -what does it do? how?
- -what can it cause? how do we prevent this?
- -what are other side effects?
Dilates arteries (skin, sk mm, heart, GI tract) --opens ATP-sensitive K+ channels --> causes hyper polarization
Can cause severe reflex tachycardia
-have to use with B-blocker to prevent
Sodium retention due to increased renin
-have to use with diuretics to prevent
Can cause hair growth - Hirsutism
What drug is Rogaine?
Minoxidil
This does not work via hormonal influence, but via direct stimulation of the hair follicle
What drugs are ACE inhibitors?
Captopril (8 hr duration)
Enalapril (24 hr duration)
Look for “PRIL”
How do ACE inhibitors work?
Block formation of angiotensin II
–end product inhibition by analogues of 2aa fragment
Less angio II means less vasoconstriction
Less aldosterone means Na loss
Block bradykinin metabolism
–vasodilation
Advantage of ACE inhibitor therapy
Increased kidney blood flow
- -release of PGE2
- -syngergistic with diuretics
Good in elderly
Like Beta blockers, prevent 2nd heart attack
No reflex tachycardia
No CNS depression
Abrupt withdrawal is not a problem
Precautions for use of ACE inhibitors
Chronic non-productive cough --bradykinin? Bad in pregnancy --oligohydramnios (dec amniotic fluid) --fetal BP dec; renal failure in 2nd, 3rd trimester Prodrugs don't work in patients with bad livers --have to be converted there Loss of taste with captopril Severe allergic rxn to first dose
Angiontensin II receptor blockers (ARBs)
- how do they work?
- examples?
Competitive block of angiotensin II-1 (AT1) receptor
(little block of AT2)
Losartan
Valsartan
“SARTAN”
Advantages and disadvantes of ARBs
Advantages
- less cough
- less angioedema
Disadvantages
- oligohydramnios
- less effective in African Americans
- slow acting
- –full effect in ~3 weeks
What agents can be used in hypertensive emergencies?
Whats considered to be a hypertensive emergency?
Unstable angina, internal blooding, hypertensive encephalopathy
Nitroprusside
Fenoldopam
Diazoxide
Nitroprusside
NO generator
Can cause nausea, disorientation, mm cramps
Also releases cyanide (but not a lot is produced and its converted quickly)
Fenoldopam
D1 agonist like dopamine
Diazoxide
Like minoxidil but weaker
Duration 12 hrs
What is pre-eclampsia?
What is the effective treatment
HTN in pregnancy
(also called “toxemia of pregnancy”)
MgSO4 treats it
–offsets Mg++ loss which occurs in pregnancy
