Flashcards in Antihypertensives Deck (39):
What is the BP range for pre-hypertension?
What is stage 1 hypertension?
What is stage 2 hypertension?
What is heart or pump-based hypertension?
more common in young with hyperkinetic circulation (increased sympathetic nervous system) with increased CO and normal peripheral resistance.
What is vascular-based hypertension?
increased peripheral resistance with age, vasoconstriction, and normal CO
What is renal/volume-based hypertension?
increased Na+/H2O/fluid retention and increased RAAS/CO/peripheral resistance
What are some other causes of hypertension (HTN)?
hyperthyroidism, pheochromocytoma, hyperaldosteronism
How does increased Na+ concentration lead to hypertension?
increased Na+ inside sm. muscle leads to increased Ca++ (due to Na+/Ca++ exchanger), increasing sensitivity to NE/EPI/Ang II, thus increasing vasoconstriction and peripheral resistance
*Thus using Na+ restriction/ diuretics will lower these effects :)
What is the non-drug approach to reducing HTN?
reduce Na+ intake, weight loss, exercise, and eliminate smoking, caffeine, and stress.
What do the baroreceptors do when BP increases?
they stretch, sending afferent signal to the nucleus of the tractus solitarius in the brainstem, synapsing on inhibitory interneurons in the vasomotor center, inhibiting the sympathetics, and augmenting the parasympathetics.
What is the "Stepped Care" Method to treating HTN?
using drugs in combinations so that the compensatory mechanisms are neutralized and have an additive hypotensive effect.
What are the 3 steps in the Stepped Care method?
Step 1= diuretic, beta blocker or ACE inhibitor
Step 2= other sympathoplegic agents
Step 3= vasodilators
*What diuretics are preferred for mild to moderate HTN?
thiazides (ex. hydrochlorothiazide)
*What diuretics are preferred for severe HTN with significant renal impairment?
loop diuretics (ex. furosimide)
What is the CHRONIC effect of diuretics on HTN?
decreased peripheral resistance due to reduction in intracellular Na+ and Ca++, and thus less vasoconstricting action to NE/EPI and Ang II.
Would thiazides or loop diuretics help protect against osteoporosis?
thiazides because they retain calcium, rather than lose it.
Why are beta blockers useful for HTN?
they interfere with both compensatory reflexes (inotropy and chronotropy). Are more useful in younger pts with hyperkinetic circulation and high sympathetic tone.
They also reduce left ventricular hypertrophy
What makes Lebetaolol and Carvedilol useful?
they block both alpha 1 and beta 1 and 2 receptors, thus significantly lowering BP and CO. They are used IV in hypertensive emergencies or pheochromocytoma.
Why is prazosin helpful?
it is a selective alpha 1 blocker which will promote vasodilation to decrease peripheral resistance, increase CO in CHF pts, and decrease left ventricular hypertrophy.
What is unique about prazosin?
it may cause Na/H2O retention, and can cause postural hypotension (1st dose).
How do the presynaptic and postsynaptic alpha 2 receptors work?
- presynaptic= negative feedback and decreases NE release.
- postsynaptic= inhibits SNS outflow from vasomotor/cardiac centers to decrease vasomotor tone (BP and HR)
*What is methyldopa?
alpha-2 agonist at receptors in the brainstem and is SAFE in PREGNANCY.
Can cause HEMOLYTIC ANEMIA with + Coombs test.
*What is hydralazine?
arteriolar vasodilator, that usually requires triple therapy with diuretic and beta blocker due to baroreceptor reflex tachycardia.
It also has a high first pass acetylation.
*What is Minoxidil (Rogaine)?
arteriolar dilator that works by opening K+ channels and hyperpolarization of smooth muscle membrane. Used only in hypertensive emergencies, but not first line.
ADRs= reflex tachycardia and Na+/H2O retention resulting in edema/CHF/pericardial tamponade. Also HIRSUTISM (actually used for this as it helps with hair loss).
What is Nitroprusside?
potent nitrate given IV and used for hypertensive crisis usually caused by malignant hypertension. It is both a veno- and vasodilator, that works by dephosphorylate myosin light chain kinase (MLCK).
ADR= conversion to thiocyanate, which is toxic if it accumulates causing spasms and convulsions.
What is a new drug used for hypertensive crisis?
Fenolopam= dopamine-1 agonist that dilates renal/mesenterics
What is the antidote for nitroprusside's conversion to thiocyanate, if it accumulates?
What is Diazoxide?
thiazide-like drug with no diuretic activity, but rather activates/opens K+ channels, hyperpolarizing arterial smooth muscle. Used for hypertensive crisis.
This requires the use of a beta blocker also to reduce the reflex tachycardia.
What are verapamil/diltiazem?
non-dihydropyridine Ca++ channel blockers that decrease HR, AV conduction (hence increasing PR interval) and decrease contractility.
Will decrease BP via vasodilation (less than Nifedipine).
CAUTION with use of BETA BLOCKERS as these can reduce contractility too much causing CHF or decrease HR causing heart block :(
- They will also stimulate sympathetics reflexively.
- Verapamil will cause constipation.
What is Nifedipine (dihydropyradine)?
dihydropyridine Ca++ channel blocker that will cause arteriolar dilation only, and no direct cardiac effects.
Can cause reflex tachycardia and exacerbate ischemia in unstable angina or MI. Thus, use of a nondihydropyradine for unstable angina would be better. For stable angina, nifedipine and amlodopine are still recommended to use first, due to their affects of decreased afterload and coronary artery dilation :)
**What are angiotensin converting enzyme (ACE) inhibitors?
decrease angiotensin II, decreasing vasoconstriction and thus peripheral resistance and BP (decreasing pre/afterload).
They also increase bradykinin= vasodilator (also coughing) and will increase prostaglandins and NO as a result.
They will also increase CO in CHF and decrease GFR in the kidney; useful in diabetic nephropathy.
What are the ADRs of ACE inhibitors?
cough/wheezing/angioedema, and are contraindicated in 2nd and 3rd trimester of pregnanacy
What are some of the ACE inhibitors?
Captopril= rapid onset and short duration (3 hr half-life)
Lisinopril= slow onset, taken once a day (12 hr half-life)
What are the Angiotensin Receptor Blockers (ARBs)?
competitive angiotensin I (AT-1) receptor blocker (AT-1 is the same receptor for angiotensin II). This has a similar action as ACE inhibitors, except it does not increase bradykinin and subsequent prostaglandin synthesis.
* Less cough and angioedema than ACE inhibitors :)
Can you use ARBs during pregnancy?
*How do we treat African Americans differently with HTN?
Use MORE diuretics and Ca++ channel blockers
Use LESS beta blockers and ACE inhibitors
**If patient has edema/CHF with HTN what drugs are preferred?
diuretics and ACE inhibitors
**If patient has CHF, diabetes, or is post MI with HTN, what should be used?
ACE inhibitors or ARBs.