2 - Antiadrenergics Flashcards
Which alpha-adrenergic receptor antagonists can be used for pheochromocytoma?
phenoxybenzamine
phentolamine
Which alpha-adrenergic receptor antagonists have selectivity for both 1 and 2 receptors ?
phenoxybenzamine
phentolamine
Which alpha-adrenergic receptor antagonists can be used for hypertensive crisis?
phenoxybenzamine
phentolamine
Which alpha-adrenergic receptor antagonists can be used for male impotence?
phentolamine
Which alpha-adrenergic receptor antagonists are selective for alpha1 ?
prazosin
terazosin
doxazosin
Which alpha-adrenergic receptor antagonists can be used for HTN?
prazosin
terazosin
doxazosin
Which alpha-adrenergic receptor antagonists can be used for BPH?
prazosin
terazosin
doxazosin
What are the side effects of alpha1 receptor antagonists
orthostatis hypoTN
inhibition of ejaculation
nasal sruffiness
tachycardia
Describe phenoxybenzamine (Dibenzyline) and its moa.
beta-haloakylamine.
non-selective alpha R antag
blcoks ACh, histamines, 5-HT Rs
**irrev antag d/t cov mod of R
amine attacks electrophilic halo-carbon. aziridium ion is attacked by nucleophlic atom on receptor, which is then alkylated.
Describe phenotolaamine (REgitine) and its moa.
non-sel alpha R antag
competitive (rev)
potent vasodilator but induces pronounced reflex tachycardia
block of presynapic alpha2 recpeotrs may promote release of NE
also may block 5-HT receptors and is a muscarinic and histamine receptor ag
How can reversible and irreversible receptor blockade be distinguished using D-R curves?
reversible (competitive) shifts cuve to the right. still reaches max activity
irreversible can never reach max activity no matter how much ag added
Describe the quinazolines alpha-1 receptor antagonists and their moa and clinical considerations.
quinazolines
vary in half life
prazosin 3 hr
terazosin 12 hr
doxazosin 20 hr
undergo extensive metabolsim, exreted minaly in bile
Tx of HTN: vasodilators
Tx of BPH: relax SM in enlarged prostate and in bladded base
Caution for “first-dose” effect –orthostatic hypotention
Which natural products is an alpha-2 adrenergic receptor antagonist?
Describe its moa.
What is it used to treat?
Yohimbine
blocks alpha2 r and incr sympathetic discharge
male impotence
What type of compounds are beta-adrenergic receptor antagonists?
What common suffix do their names share?
aryloxypropanolamines
bulky head group in amine to target beta receptor
putting a non-carbon atom in the side chain causes them to lose agonist activity
-olol
What are therapeutic uses for beta-adrenergic receptor antagonists?
HTN angina cardiac arrhythmias migraine stage fright thyrotoxicosis glaucoma CHF (II and III)
What are the non-selective beta-adrenergic antagonists?
propranolol nadolol timolol pindolol carteolol
What are the selective beta-adrenergic receptor antagonists?
metoprolol
bisoprolol
atenolol
esmolol
Nebivolol–also produces NO
Describe propranolol and its effects.
non-sel
lipophil (BBB)
local anesthetic
need endogenous act for blockage
decr CO and HR **decr renin release incr VLDL, decr HDL inhib lipolysis inhib compensatory glycogenolysis and glucose release in response to hypoglycemia (caution in DM pts) incr bronchial airway resistance
Describe nadolol and its effects.
less lipophil than propranolol
long half life ~20 hr
omstly ex unchange din urine
po admin
Tx of HTN, angina, migraine
Describe timolol and its effects.
thiadiazole nucleus w morpholine ring
po or opthalmic admin
uses: HTN, angina, migraine, **glaucoma
How will beta blockers affect pupil size?
no beta receptors in pupil, so it won’t.
will however decr aq humor production (beta2)
Describe pindolol and its effects.
possess intrinsic sympathomimetic activity
–> partial agonist
less likely to cause bradycardia and lipid abnormalities
po
HTN, angina, migraine
What does a partial agonist dose-response curve look like?
activity can never reach max levels
also partial antag–will compete ag away but still have some activity
Describe carteolol and its effects.
possess ISA
partial ag
less likely to cause bradycardia and lipid abnormalities
po, opththalmic
uses: HTN, glaucoma
Describe metoprolol and bisoprolol and their effects.
B1 sel antag
“cardioselective” (but also kidneys)
less bronchoconstriction
mod lipphilicity
t1/2 = 3-4 h
sig first pass metab
po, PE admin
Uses: HTN, angina, aniarrhythmic, CHF*****
Describe atenolol and its effects.
B1 sel antag "cardioselective" less bronchoconstriction low lipophilicity t1/2 6-9 hr
po or PE
Tx of HTN, angina
Describe esmolol and its effects.***
sel B1 antag
very short-acting
t1/2: 9 min
rapid hydrolysis by esterases found in RBCs
PE admin
incompatible w NaHCO3
Uses: supraventricular tachycardia, Afib, perioperative HTN
Describe nebivolol and its effects.
3rd gen beta1 antag
**beta1 sel
low lipid sol
***vasodilation d/t NO production
use for HTN
Which are the mixed adrenergic receptor antagonists?
labetalol
carvedilol
Describe labetalol and its effects.
racemic mix
(R,R) isomer possesses beta-blcokng activity
(S,R) isomer possess greatest alpha1 receptor blocking activity
beta-blocking activity rpevents reflex tacycardia normally associated with alpha1 receptor antag
po or PE admin
Uses: HTN, hypertensive crisis
Describe carvedilol and its effects.
both enantiomers are alpha1 antag
(s) enantiomer blocks beta non-sel
beta-blocking activity prevents reflex tachycardia normally assoc’d w alpha 1 antag
po admin
HTN, CHF (II and III)
What are side effects of beta-blockers?
bradycardia AV block sedation (cross BBB) mask sx of hypoglycemia withdrawl syndrome
Describe withdrawl syndrome for beta-blockers.
chronic blockages causes upreg of receptors. if suddenly stop the drug, can get reflex HTN, tachycardia d/t excesss beta R.
taper off over several wks.
What are contraindications to beta-blockers.
asthma
COPD
CHF (type IV)
What are the two mechanisms of action of indirect antiadrenergic activity?
inhib NE synthesis
decr NE storage and release
Describe metyrosine and its effects and moa.
inhibits tyrosine hydroylase, which converts tyrosine into dopa alpha blocks synth of dopamine "dirty" SE: hypotension parkinson-like syndrome tremors movements disorders
used in rare cases of adrenal tumors
Describe reserpine and its moa and effects.
indole alkaloid obtained from root of Rauwolfia serpenina.
Blocks VMAT: vesicular monoamine transporters
deplete vesicular pool of NE
slow ooa
sustained effect
used in tx of HTN
may precipitate depression
Describe betrylium tosylate and its effects.
aromtic quaternay ammonium precise moa unknown displaceand release NE and prevent further release (depletion) local anesthetic admin PE
uses: antiarrhythmic (vfib)
Why doesn’t the antihypertensive effects of reserpine evoke the baroreceptor response?
baroreceptor response is min to min
reserpine has a slow moa
