Antihypertensives Flashcards
discuss the role of diuretics in management of hypertension
- what effects do they have?
- initial effect: volume depletion
- long term effects: decrease PVR of by reducing sodium content/and decreasing senstivity of smooth muscle cells
what are the thiazides and and how can they be used to treat HTN
hydrochlorothiazide, chlorthoalidone, polythiazide, metolzode, indapamide
- monotherapy:
- thiazed can used as an initial therapy for patients with mild/moderate HTN and normal renal function
- (if renal function is impaired or the patient has heart failure, loop diuretics are better)
- thiazed can used as an initial therapy for patients with mild/moderate HTN and normal renal function
- in combination with other drugs:
- for counteracting fluid retention
what are the loop durietcs and how are they used to treat HTN?
= furosemide
- used hypertensive patients with for patients with renal dysfunction or CHF
K+ sparing diruetics
what are they and what is their role in the management of hypertension?
= spironlactone, eplerenone
- these are weaker diuretics that can can be used to counter the hypokalemic effects of other diuretics.
- (they block aldosterone and limit K+ secretion)
AES of thiazide and loop diuretics
- hyponatremia
- hypokalemia
- hypomagnesia
may increase plasma lipid, uric acid and gucose levels
what are the ACE inhibitors and ARBs
what is their role in management of hypertension?
what are their limitations?
ACE inhibitors: - prils
ARBs (AT1 receptor blockers): - sartans
-
benefitial in patients with:
- diabetes
- chronic renal disease
- HF
- patients with hyperuricemia due to diuretics
- less effective in African American patients
AEs of ACE inhibitors/ARBs
- both
- hypotension
- hypoglycemia
- hyperkalemia
- impaired renal function
- angioedema (mostly ACE inhibitors)
- just ACE inhibitors: persistent dry cough
contraindications of ACE inhibitors/ARBs
- pregnancy
- bilateral renal artery stenosis
major drug drug interactions of ACE/inhibitors & ARBS
- NSAIDS: counter their anti-hypertensive effects
- potassium sparing diuretics: together, there drugs put the patient at high risk of hyperkalemia
- lithium
MOA of calcium channel blockers
-
block smooth muscle contraction
- block Ca++ influx –> no ca++-calmodulin formation –> no myoskin light chain kinase phosphorylation –> inactivate myosin light chain
what are the two classes of calcium channel blockers used to treat HTN?
- non-dihydropyridines
- dihydropyridines
non-dydropyramids
- MOA
- list the drugs
- MOA: block contraction of cardiac muscle
- reduce SA influx into cardiac muscle, SA nodes, AV nodes
- lower CO –> lower blood pressure
- drugs:
- verapamil
- diltiazem
dihydropyridines (DHPs)
- MOA
- drugs in this class
- MOA: reduce vascular smooth muscle contraction
- reduce Ca++ influx into vascular smooth muscle cells –> lower peripheal resistance –> lower BP
- drugs: - dipines
-
long acting:
- more commonly used
- ex: amlodipine
- short acting:
- no commonly used for HTN (too many AEs)
-
long acting:
indication (s) for DHPs
hypertension in pregnant women (they are safe during pregnancy)
AES of both long and short acting DHPs
- flushing
- dizziness
- headache
- periphal edema in lower legs/hands
AEs specific to short acting DHPs
tachycardia - hence, short acting DHP rarely used to treat HTN
drug drug interactions of DHPS
- CYP - 3A4 inhibitors
- these will increase plasma concentration of DHPs – > can cause hypotension
MAO of B1 receptor blockers in treatment of HTN
- in the heart: reduce HR and contracility
- in the kidney: inhibit renin release
what drugs are non selective B1, B2 blockers?
propanolol
what are the cardioselective (B1) blockers
- metoprolol
- atenolol
what drugs are a1 and non- selective beta blockers
- labetalol
- carvedilol
when are beta-blockers a top choice for hypertension?
- in patients with other indications:
- MI
- angina
- migraine
- arythmias
- HF
caution when giving beta blockers for HTN
Abrupt discontinuation of beta blockers can lead to withdrawal hypertension and ischemia
- must taper the dose
drug drug interactions of beta blockers
NSAIDS (reduce B blocker anti-hypertensive effects)
what are the non-selective alpha antagonists and what are their primary uses?
- block both a1 and a2
- phenoxybenzmine: treats pheochromocytoma
- phentolamine: treats hypertensive crisis
what are the selective a1 antagonists and what is their primary use
-
- zosins
- prazosin
- terazosin
- ect.
- used to treat chronic hypertension
what are the a2 receptor antagonists and their primary use?
- methyldopa:
- prodrug that is safe during pregnancy
- used to treat HTN during pregnancy
- clonidine: not a first line HTN drug
list the alpha blockers that are used to treat HTN and what type of HTN they treat
- phentolamine (non-selective): for hypertensive crisis
- -zosins (a1 blockers): for chronic hypertension
- methyldopa (a2 blocker): for hypertension in pregnancy
hydralazine
- what kind of drug?
- MOA
- route of administration
- pharmokinetics
- therapuetic uses
-
an arterial vasodilator
- (MOA not understood)
- administration: oral or parentral
- pharmokinetics
- metabolized via acetylation
- therapuetic uses:
-
moderate to severe hypertension
- given with a diuretic and a sympatholytic
- safe during pregnancy
-
chronic heart failure:
- when combined with a nitrate
-
moderate to severe hypertension
minoxidil
- what kind of drug?
- MOA
- route of adminsitration
- therapuetic uses
- an arterial vasodilator
- MOA
- opens K+ channels, which hyperpolarizes the arterial cell membrane and directly inhibits Ca++ influx
- MOA
- route of adminsitration: oral
- therapuetic uses: for severe, refractory hypertension
- like hydralazine, combined sympatholytic + a diruetic
what are the arterial vasodilatrors and what adverse effects do they share?
(hyralazine and minoxidil)
- excessive vasodilation
- fluid retention
- hypotension
- reflex tachycardia
adverse effects of minoxidil
- excessive vasodilation, fluid retension, hypotension, reflex tachycardia
- stimulates hair growth
AEs of hydralazine
- excessive vasodilation, fluid retention, hypotention, reflex tachycardia
-
lupus erythematous like syndrome
- especially in patients that are slow acetylators
what are the top drugs for initial treatment of hypertension?
“ACT-B”
ACE Inhibitors & Ang-receptor Blockers
Ca++ channel blockers
Thiazide diuretics
B-receptor antagonists
what are the types of combination therapy that can be done with anti-hypertensives?
- Combination therapy (i.e. drugs with complementary mechanisms).
- Thiazide diuretic + most other drugs
- ACE inhibitor or ARB + Ca2+ channel blocker
what blood pressure constitutes a hypertensive crisis?
what cardiovascular emergencies and neurovascular emergencies can can cause a hypertensive crisis?
- Sudden, life-threatening elevation of BP accompanied by acute end-organ damage (systolic >180 mmHg and diastolic BP usually > 120 mm Hg).
- cardiovascular emergencies: aortic dissection, acute coronary syndrome, and acute heart failure.
- neurologic emergencies: hypertensive encephalopathy, acute ischemic stroke, acute intracerebral hemorrhage, and subarachnoid hemorrhage.
what parenteral drugs can be used for hypertensive emergencies?
D1 dopamine receptor agonist: fenoldopam
β-blocker: Esmolol
α1- and β-blocker: Labetalol
Calcium channel blockers: nicardipine, clevidipine
α-blocker: Phentolamine
ACE inhibitor: Enalaprilat
nitroprusside
- MOA
- effects
- pharmokinetics
- nitroprusside is an NO donor
- pharmokinetics:
- administered IV
- rapid onset of action (< 1 min) and short duration of action (<10 min)
- MOA:
- relaxes veins an arteries
- reduces preload and afterload
- immediate onset and allows rapid BP control
adverse effects of nitroprusside
- excessive vasodilation
- hypotension
- cyanide toxicity
contraindications of nitroprusside?
- patients with leber’s optic atrophy and tobacco ambyopia:
- these patients are rhonadese deficient
- impaired renal function
- patients treated with other NO donotrs
- hypertension caused by:
- aortic coarctation
- ateriovenous shunting
- acute HF with systemic vascular resistance
- septic shock
nitrates
- list the drugs in this class
- MOA
- pharmokinetics
- clinical uses
- nitrates
- nitroglycerin
- isorbide
- dinitrate
- pharmokinetics: like nitroprusside, administered IV, rapid onset of action
- clinical uses: like nitroprusside, these drugs are used in hypertensive crisis
- MOA:
- similar to nitroprusside
- cause both arterial and venous dilation, but venodilation > arteriol dilation
- clinical uses:
- beneficial to treating hypertensive crisis due to coronary heart disease and coronary bypass
AES of nitrates
nitroglycerin, isorbide, dinitrate
- headache
- tolerance
- tachycardia
