yang Flashcards
what drugs are alpha-1 antagonists?
prazosin
terazosin
doxazosin
what is the pk of alpha-1 antagonists?
prazosin –> 3 hours
terazosin –> 12 hours
doxazosin –> 20 hours
what is the metabolism of alpha-1 antagonists?
extensive metabolism that is excreted in the bile
what is the MOA of prazosin?
Alpha-1 antagonism decreases TPR –> activates the baroreceptor reflex —-> increases NE release into the myocardium –> increase in HR via beta-1 receptors.
Negative feedback via alpha-2 receptors in the myocardium mitigates NE release
what are alpha-1 antagonists?
quinazolines that produce vasodilation via alpha-1 antagonism in arterioles and venules without causing reflex tachycardia or increased CO (presynaptic alpha-2 effect)
what are the effects of alpha-1 antagonists?
decrease TPR with less reflex tachycardia than nonselective antagonists (phentolamine)
what are the compensatory effects of alpha-1 antagonists?
reflex tachycardia
renin release
co-administer diuretic to decrease retention of salt and water
what are the clinical use of alpha-1 antagonists?
BPH
HTN (not first line)
reynaud’s disease
what is reynaud’s disease
numbness due to cold or stress producing vasconstriction in hands/feet
what are the problems with alpha-1 antagonists?
first dose phenomenon (most common with prazosin)
what is the first dose phenomenon?
orthostatic hypotension and syncope particularly with first dose
what are the effects of direct-acting alpha-2 agonists?
inhibit NE release and decrease sympathetic tone in CNS –> resulting in decreased HR, contractility, and renin release, and less vasoconstriction
what is clonidine?
alpha-2 agonist and imidazoline receptor
activates the presynaptic alpha-2 receptor in the CNS to decrease SNS activity to the heart and blood vessels
how is clonidine administered?
oral
parenteral
transdermal
what is the half life of clonidine?
8-12 hours
is clonidine lipophilic or hydrophilic?
lipophilic
what are the clinical uses of clonidine?
HTN
ADHD
neuropathic pain/opiate withdrawal
restless leg syndrome
what are the SE of clonidine?
hypotension
sedation
dry mouth
withdrawal syndrome after prolonged use –> HTN tachycardia, angina, MI so taper dose
what are guanabenz and guanfacine?
oral direct acting alpha-2 agonists and open ring imidazolidines that are mostly non-ionized at physiological pH
what is the half life of guanabenz?
6 hours
what is the half life of guanfacine?
12-16 hours
what is the clinical usage of guanabenz and guanfacine?
HTN
ADHD
what is methyldopa?
oral direct-acting alpha-2 agonist and prodrug that reduces sympathetic outflow
what is the metabolic pathway of methyldopate
methyldopate –> methylopa (via esterase) –> alpha-methyldopamine (via L-aromatic amino acid decarboxylase) –> (IR,2S)-alpha-methylnorepineprhine (via dopamine beta-hydroxylase)
what is methyldopate?
ester hydrochloride salt that is water soluble and used parenterally
what is the clinical use of methyldopa?
HTN especially in pregnancy
what drugs are central acting alpha-2 agonists?
clonidine
methyldopa
guanabenz
guanfacine
what is the action of methyldopa?
false transmitter that displaced NE from vesicle
what are the effects of alpha-2 agonists?
decrease TPR, HR, and renin activity
what are the SE of methylopa?
sedation
sodium/water retention (combine with diuretic)
what is the impact of beta blockers on angina?
reduce myocardial oxygen demand via reduced HR and contractility
what is the impact of beta-blockers on cardiac arrhythmia?
slows AV nodal conduction
what is the impact of beta blockers in post-MI?
reduce myocardial oxygen demand and slows AV nodal conduction
what is the impact of beta-blockers in HTN?
decrease CO and inhibit renin secretion
what is the role of beta blockers in congestive HF?
decrease chronic overstimualtion/toxicity of compensatory catecholamines
what drugs are non-selective beta blockers?
propranolol
timolol
nadolol
pindolol
carteolol
what are the indications for propranolol?
HTN (no effect on BP in normotensive individuals)
angina
cardiac arrhythmias
ischemic heart disease
prophylaxis for migraines
what are the indications of timolol?
open-angle glaucoma
HTN
angina
migraine
what are the problems with beta-blockers?
use caution asthmatic due to beta-2 receptor blockade
rebound HTN if abrupt d/c so taper dose
what are the pharmacologic effects of propranolol?
decreased CO, HR, renin release, and LDL
increase VLDL and bronchial airway resistance
inhibits lipolysis, compensatory glycogenolysis, and glucose release in response to hypoglycemia
what is the metabolism of propranolol?
extensive first-pass hepatic metabolism
lipophilic
what is the half life of propranolol?
3-4 hours
what is nadolol?
non selective beta blocker that is less lipophilic and mostly excreted unchanged in the urine
what is the half life of nadolol?
20 hours
what are the clinical uses of nadolol?
HTN
angina
migraine
what is pindolol?
non selective beta blocker with intrinsic sympathomimetic activity that is less likely to cause bradycardia or lipid abnormalities
what is the indication of pindolol?
HTN
angina
migraine
best for patients who have severe bradycardia (under 40 BPM) or little cardiac reserve
what drugs are non selective beta blockers with intrinsic sympathomimetic activity?
carteolol
pindolol
what is carteolol
non selective beta blocker with ISA that is less likely to cause bradycardia or lipid abnormalities
what is the indication of carteolol?
HTN
glaucoma
what drugs are beta-1 selective antagonists?
metoprolol
bisoprolol
atenolol
esmolol
what are the indications of metoprolol?
HTN
angina
cardiac arrhythmias
ischemic heart disease
congestive HF
what are the problems associated with metoprolol?
rebound HTN if d/c abruptly so taper dose
what is metoprolol?
para-substituted phenyl derivative and selective beta-1 antagonist that is cardioselective and has moderate lipophilicity
what is the half life of metoprolol?
3 to 4 hours
what is the indication of bisoprolol?
reduces mortality in systolic HF
what is atenolol?
cardioselective beta-1 antagonist that has low lipophilicity (water-soluble metoprolol)
what is the half life of atenolol?
6 to 9 horus
what is the indication of atenolol?
HTN
angina
what is esmolol?
very short acting (9 minute half life) selective beta-1 antagonist that is administered parenterally and exhibits rapid hydrolysis via esterases
what is the indication of esmolol?
supra ventricular tachycardia
atrial flutter/fibrillation
perioperative HTN
what is the CI of esmolol?
sodium bicarbonate
what is nebivolol?
3rd generation beta-1 antagonist that possesses vasodilation due to nitric oxide production
what is the indication for nebivolol?
HTN
what is the effect of beta blockers?
decrease HR, contractility, renin release
no effect on BP in normotensive patients
what is the indication of beta blockers?
HTN
angina
cardiac arrhythmias
MI
HF
migraine prophylaxis (propranolol)
glaucoma (timolol)
intraoperative HTN (esmolol)
what is beta blocker withdrawal syndrome?
abrupt d/c can result in exacerbations of HTN or angina and MI
what drugs are mixed beta antagonists?
carvediolol
labetolol
what are the problems of beta blockers?
bradycardia
AV block
negative inotrophy
decrease CO
extremity vasoconstriction particualry cold extremities
CNS symptoms
ED
mask of hypoglycemia
beta blocker withdrawal syndrome
bronchoconstriction
what are the CI of beta blockers?
asthma
COPD
congestive HF (type 4)
what is the action of labetolol?
alpha-1 antagonism and non selective beta-1 and beta-2 antagonism with beta-2 partial agonism (3:1 beta-alpha)
what is action of carvediolol?
alpha-1 antagonism and non selective beta-1 and beta 2 antagonism (10:1 beta alpha)
what are the effects of mixed beta antagonists?
decrease TPR via reduced alpha-medicated vasoconstriction resulting in lowering BP
prevents reflex tachycardia (due to beta blocking activity)
vasodilation via alpha-1 blockade helps prevent bradycardia associated with beta blockade
what is the indication of labetolol?
HTN emergencies
pheochromoctyoma
what is the indication of carvediolol?
HF
HTN
what are the problems of mixed beta antagonists?
similar to beta blockers
taper dose when d/c
what is fenoldopam?
dopamine-1 receptor agonist that does not activate alpha 1 or beta receptors for severe HTN
what are the effects of fenoldopam?
maintains or increases renal perfusion while lowering BP
useful for patients with renal impairment
what is the CI of fenoldopam?
glaucoma increases IOP