2 - Antiadrenergics

Question 1

Which alpha-adrenergic receptor antagonists can be used for pheochromocytoma?

Answer 1

phenoxybenzamine

phentolamine

Question 2

Which alpha-adrenergic receptor antagonists have selectivity for both 1 and 2 receptors ?

Answer 2

phenoxybenzamine

phentolamine

Question 3

Which alpha-adrenergic receptor antagonists can be used for hypertensive crisis?

Answer 3

phenoxybenzamine

phentolamine

Question 4

Which alpha-adrenergic receptor antagonists can be used for male impotence?

Answer 4

phentolamine

Question 5

Which alpha-adrenergic receptor antagonists are selective for alpha1 ?

Answer 5

prazosin
terazosin
doxazosin

Question 6

Which alpha-adrenergic receptor antagonists can be used for HTN?

Answer 6

prazosin
terazosin
doxazosin

Question 7

Which alpha-adrenergic receptor antagonists can be used for BPH?

Answer 7

prazosin
terazosin
doxazosin

Question 8

What are the side effects of alpha1 receptor antagonists

Answer 8

orthostatis hypoTN
inhibition of ejaculation
nasal sruffiness
tachycardia

Question 9

Describe phenoxybenzamine (Dibenzyline) and its moa.

Answer 9

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.

Question 10

Describe phenotolaamine (REgitine) and its moa.

Answer 10

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

Question 11

How can reversible and irreversible receptor blockade be distinguished using D-R curves?

Answer 11

reversible (competitive) shifts cuve to the right. still reaches max activity

irreversible can never reach max activity no matter how much ag added

Question 12

Describe the quinazolines alpha-1 receptor antagonists and their moa and clinical considerations.

Answer 12

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

Question 13

Which natural products is an alpha-2 adrenergic receptor antagonist?
Describe its moa.
What is it used to treat?

Answer 13

Yohimbine
blocks alpha2 r and incr sympathetic discharge

male impotence

Question 14

What type of compounds are beta-adrenergic receptor antagonists?

What common suffix do their names share?

Answer 14

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

Question 15

What are therapeutic uses for beta-adrenergic receptor antagonists?

Answer 15

HTN
angina
cardiac arrhythmias
migraine
stage fright
thyrotoxicosis
glaucoma
CHF (II and III)

Question 16

What are the non-selective beta-adrenergic antagonists?

Answer 16

propranolol
nadolol
timolol
pindolol
carteolol

Question 17

What are the selective beta-adrenergic receptor antagonists?

Answer 17

metoprolol
bisoprolol
atenolol
esmolol

Nebivolol–also produces NO

Question 18

Describe propranolol and its effects.

Answer 18

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

Question 19

Describe nadolol and its effects.

Answer 19

less lipophil than propranolol
long half life ~20 hr
omstly ex unchange din urine
po admin

Tx of HTN, angina, migraine

Question 20

Describe timolol and its effects.

Answer 20

thiadiazole nucleus w morpholine ring

po or opthalmic admin

uses: HTN, angina, migraine, **glaucoma

Question 21

How will beta blockers affect pupil size?

Answer 21

no beta receptors in pupil, so it won’t.

will however decr aq humor production (beta2)

Question 22

Describe pindolol and its effects.

Answer 22

possess intrinsic sympathomimetic activity
–> partial agonist

less likely to cause bradycardia and lipid abnormalities

po

HTN, angina, migraine

Question 23

What does a partial agonist dose-response curve look like?

Answer 23

activity can never reach max levels

also partial antag–will compete ag away but still have some activity

Question 24

Describe carteolol and its effects.

Answer 24

possess ISA
partial ag
less likely to cause bradycardia and lipid abnormalities

po, opththalmic

uses: HTN, glaucoma

Question 25

Describe metoprolol and bisoprolol and their effects.

Answer 25

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*****

Question 26

Describe atenolol and its effects.

Answer 26

B1 sel antag
"cardioselective" 
less bronchoconstriction
low lipophilicity
t1/2 6-9 hr

po or PE

Tx of HTN, angina

Question 27

Describe esmolol and its effects.***

Answer 27

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

Question 28

Describe nebivolol and its effects.

Answer 28

3rd gen beta1 antag
**beta1 sel
low lipid sol
***vasodilation d/t NO production

use for HTN

Question 29

Which are the mixed adrenergic receptor antagonists?

Answer 29

labetalol

carvedilol

Question 30

Describe labetalol and its effects.

Answer 30

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

Question 31

Describe carvedilol and its effects.

Answer 31

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)

Question 32

What are side effects of beta-blockers?

Answer 32

bradycardia
AV block
sedation (cross BBB)
mask sx of hypoglycemia
withdrawl syndrome

Question 33

Describe withdrawl syndrome for beta-blockers.

Answer 33

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.

Question 34

What are contraindications to beta-blockers.

Answer 34

asthma
COPD
CHF (type IV)

Question 35

What are the two mechanisms of action of indirect antiadrenergic activity?

Answer 35

inhib NE synthesis

decr NE storage and release

Question 36

Describe metyrosine and its effects and moa.

Answer 36

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

Question 37

Describe reserpine and its moa and effects.

Answer 37

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

Question 38

Describe betrylium tosylate and its effects.

Answer 38

aromtic quaternay ammonium
precise moa unknown
displaceand release NE and prevent further release (depletion)
local anesthetic
admin PE

uses: antiarrhythmic (vfib)

Question 39

Why doesn’t the antihypertensive effects of reserpine evoke the baroreceptor response?

Answer 39

baroreceptor response is min to min

reserpine has a slow moa