Drugs to treat HTN Flashcards
htn damages
bv in kidney, heart, and brain which leads to end organ damage- MI, stroke, renal failure, death
main risk of htn tied to
inc in systolic blood pressure- progressive stiffening of arterial circulation
htn stage 1 at
130-139 or 80-89
If 10 yr risk for HD >10%, lifestyle changes and meds
htn stage 2 at
> 140 or >90
2 medications of different classes
BP=
BP=CO x TPR
Primary agents used in tx of htn
- thiazide diuretics
- ACE inhibitors
- ARBs
- Calcium channel blockers
Thiazide diuretics
-Inhibit NaCl reabsorption in distal convoluted tubule
-low dose for htn
high dose for CHF
-Hydrochlorothiazide
-chlorthalidone, indapamide, metaolazone
-all are sulfonamides
Chlorothalidone
preferred thiazide because of long 1/2 life and research
-more effective as antihtn in AAs and elderly
AE of thiazides
- hypokalemic metabolic alkalosis
- hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia (GLUC)
If ED occurs, sildenafil can be added (PDE5 inhibitor)
Ang II causes
vasoconstriction by inc peripheral vascular resistance causing inc blood pressure
aldosterone causes
inc sodium and water retention–>inc blood pressure
ACE inhibitors
- prils
- lower bp by inhibiting ACE which conv ang I to ang II
- decreases peripheral vascular resistance and leads to increased bradykinin (AE of coughing and angioedema)
Therapeutics of ACE inhibitors
lower BP w/o compromising blood supply to brain heart or kidneys
- does not cause reflex sympathetic activation
- effective orally for monotherapy
ACE inhibitors first choice tx for htn pts with
diabetes, chronic renal disease, or lv hypertrophy
ACEI AE
hyperkalemia, cough, angioedema, anaphylaxis
- do not use in comb with ARBs
- contraindicated in pregnancy
Angiotensin Receptor Antagonists
- sartan
- more specific than ACE inhibitors because do not affect bradykinin
- more complete inhibition of angiotensin action (other enzymes than ACE can also generate ang II)
- similar AE except coughing (hyperkalemia, reduced renal fxn, contra in pregnancy)
Calcium Channel Blockers- cardiac
Verapamil (strongest cardiac effect) and diltiazem act on heart (in between nifedipine and verapamil)
- no reflex tachycardia because they depress SA and AV node
- can cause Myocardial depression- bradycarida- bad in HF
Peripheral Calcium channel blockers- Dihydropyridines
- amlodipine, nicardipine, nifedipine (strongest vasodilator), etc.
- strongest vasodilators
- most likely to produce reflex tachycardia
-can cause headache, flushing, dizziness, peripheral edema
Calcium channel blockers
-block slow calcium channels will reduce intracellular Ca–> relax arteriolar smooth muscles–> vasodilation and lower BP
-especially used in elderly and AA (along with thiazides)
-
Sympatholytic drugs
not recommended for monotherapy because of AE- postural hypotension and sodium retention
Cardioselective b blockers
atenolol, betaxolol, bisoprolol, metoprolol
cardioselective and vasodilatory b blockers
Nebivolol (NO production)
Noncardioselective b blockers
Nadolol, propranolol
b blockers- intrinsic sympathomimetic activity
b2 agonists: acebutolol, penbutolol, pindolol
w/ NO production: carteolol
b blockers- combined a and b receptors
carvedilol (a1 antagonist, blocks Ca entry) and labetalol (a1 antagonist
how do b blockers work
lower BP by blocking b-adrenergic receptors in-
heart to reduce CO
kidneys to reduce renin secretion
CNS to reduce sympathetic vasomotor tone
-used with other antihtn to counteract reflex tachycardia caused by vasodilators and increased renin secretion by thiazide and loop diuretics
AE of b blockers
- worsen symptom sin pts with reduced myocardial reserve, asthma, peripheral vascular insuff, diabetes (delays recovery of normoglycemia bc inhibits hyperglycemic responses mediated by epinephrine)
- decrease exercise tolerance in HF pts
- predispose to atherogenesis
- GI or CNS minor AE
- tachycardia with abrupt cessation
Aliskiren
orally active renin inhibitor
- dose dep reduction of blood pressure
- no generic
- avoid in pregnancy, do not combine with ACE or ARB
Drugs that block renin secretion
Clonidine- reduce renal sympathetic nerve activity
beta- blocker- block intra and extra renal receptors involved in neural control of renin secretion
Doxazosin, prazosin, terazosin
a1 adrenergic antagonist
- reduces NE induced vasoconstriction to dilate both arteries and veins
- BP falls because of decreased PR
- AE: orthostatic hypotension
Centrally acting sympatholytic drugs
Clonidine, methyldopa, guanfacine
- last line because of significant CNS adverse effects
- act in CNS as agonist on presynpatic a2 receptors and reduce peripheral vascular resistance
- withdrawal of clonidine may result in hypertensive crisis
- methyldopa limited to pregnancy
oral direct vasodilators
Hydralazine or minoxidil (K channel opener)
- both selectively dilate arteries (not venous)
IV direct vasodilators
sodium nitroprusside (NO, both arteries and veins), diazoxide (activate K channels and hyperpolarize, arteries only), fenoldopam (dopa agonist, selective for arteries), enalaprilat (ACEI), nicardipine (CCB), hydralazine (preeclampsia)
direct vasodilators
AE of vasodilators
hypotension, headaches, reflex tachycardia
- elderly with CAD- hydralazine or minoxidil may induce anginal attacks and MI
- hydralazine may cause lupus like syndrome
- minoxidil causes hypertrichosis (hair growth)
Tx in pregnancy
b- blocker (labetalol) or CCB (nifedipine); methyldopa or hydralazine may also be used
