B4.005 Prework 2 Adrenoreceptor Activating or Blocking Drugs

Question 1

what are adrenoceptors?

Answer 1

G protein coupled receptors

respond to endogenous catecholamines

Question 2

where are a1 receptors and what do they control?

Answer 2

peripheral vasculature

contraction of smooth muscle and increased BP

Question 3

where are a2 receptors and what do they control?

Answer 3

presynaptic neuron
autoregulation of neurotransmitter release
inhibit release of NA from neuroterminals

Question 4

how are beta adrenoceptors defined?

Answer 4

by affinity for Epi and NE

Question 5

b1 receptor affinity

Answer 5

equal for Epi and NE

Question 6

b2 receptor affinity

Answer 6

higher for Epi than NE (negligible)

Question 7

describe how receptor responsiveness is regulated by activity & how this affects drug interactions

Answer 7

desensitization may limit therapeutic response
denervation super sensitivity (removal of source of agonist or presence of antagonist) may exacerbate side effects (heightened coupling to signaling pathways)

Question 8

what are 4 major sympathomimetic drugs

Answer 8

catecholamines:
epinephrine
norepinephrine
isoproterenol
dobutamine

Question 9

describe epinephrine’s action

Answer 9

very potent vasoconstrictor (a1)
cardiac stimulant (b1)
positive inotropic and chronotropic actions on the heart (b1)
activates b2 receptors (smooth muscle relaxation)

Question 10

describe NE’s action

Answer 10

similar effects on a1 and b1 as epi, but little effect on b2
compensatory vagal reflexes overcome direct positive chronotrophy
-at high doses may directly increase HR

Question 11

describe isoproterenol’s action

Answer 11

nonselective b receptor agonist
positive chronotropic and inotropic effects
decreases diastolic and MAP due to activation of b2 in peripheral vasculature

Question 12

describe dobutamine’s action

Answer 12

relatively b1 specific synthetic catecholamine
also activates a1 receptors
increases cardiac output with less reflex tachy

Question 13

what are some a1 specific sympathomimetic drugs that do not have catecholamine structures?

Answer 13

phenylephrine
ephedrine
pseudoephedrine
oxymetazoline
xylometazoline

Question 14

describe phenylephrine and its action

Answer 14

prototypic a1 agonist
not inactivated by COMT (catecholamine degrading enzyme)
longer duration of action
used as a mydriatic and decongestant
can raise BP at sufficient doses

Question 15

ephedrine

Answer 15

first orally active sympathomimetic drug

Question 16

pseudoephedrine

Answer 16

OTC decongestant

indirect effects of releasing endogenous NE which bolsters therapeutic effects

Question 17

oxymetazoline and xylometazoline

Answer 17

direct a1 agonists
topical decongestants
long action

Question 18

what are a2 selective agonists and how do they work?

Answer 18

clonidine and methyldopa
inhibit NE release
used (poorly) as antihypertensives
diminish SNS outflow

Question 19

what are b2 selective agonists and how do they work?

Answer 19

albuterol and salmeterol
relax bronchial smooth muscle
treatment of asthma and premature labor

Question 20

what are some examples of indirect sympathomimetics

Answer 20

amphetamine
methamphetamine
cocaine
tyramine

Question 21

mechanism of amphetamine and methamphetamine

Answer 21

increase NE release by a1 stimulation
marked stimulant effects on mood and alertness
depressant effect on appetite
common drug of abuse

Question 22

mechanism of cocaine

Answer 22

local anesthetic
sympathomimetic due to blockade of Uptake 1 (a catecholamine transmitter that stops action of catecholamines)
blockade increases synaptic concentration and duration of NE and Epi

Question 23

mechanism of tyramine

Answer 23

releases stored catecholamines
MAO inhibitors potentiate effects and can produce hypertension
found in fermented foods like cheeses

Question 24

what are some alpha receptor antagonists?

Answer 24

phentolamine
phenoxybenzamine
prazosin
terazosin
doxazosin
yohimbine

Question 25

phentolamine

Answer 25

prototypic alpha antagonist nonselective between a1 and a2 competitive blockage of receptors (reversible) reduces TPR, MAP produces reflex tachycardia (SNS reflex due to initial drop in BP)

Question 26

phenoxybenzamine

Answer 26

irreversible, covalent binding to alpha receptors | postural hypotension and tachycardia limit use

Question 27

prazosin/terazosin/doxazosin

Answer 27

selective for a1 receptors

Question 28

yohinbine

Answer 28

a2 selective antagonist | no established clinical role

Question 29

what is the action of beta receptor antagonist? (beta blockers)

Answer 29

block effects of catecholamines at beta adrenoceptors | varied affinity for b1 and b2 receptors (none absolutely specific for b1 receptors)

Question 30

effects of beta blockers

Answer 30

lower BP in patients with hypertension negative inotropic and chronotropic effects -reduce oxygen demand of myocardium

Question 31

what are beta blockers clinically useful for?

Answer 31

``` hypertension ischemic heart disease cardiac arrhythmias glaucoma hyperthyroidism ```

Question 32

propanolol

Answer 32

protypical beta blocker | nonselective

Question 33

metoprolol and atenolol

Answer 33

b1 selective (cardio selective)

Question 34

nadolol and timolol

Answer 34

long duration of action once daily dosing glaucoma

Question 35

labetalol

Answer 35

reversible a1 antagonist nonselective beta antagonist hypotension with less tachycardia than alpha blockers

Question 36

butoxamine

Answer 36

selective b2 receptors | no clinical application