B4.005 Prework 2 Adrenoreceptor Activating or Blocking Drugs Flashcards
what are adrenoceptors?
G protein coupled receptors
respond to endogenous catecholamines
where are a1 receptors and what do they control?
peripheral vasculature
contraction of smooth muscle and increased BP
where are a2 receptors and what do they control?
presynaptic neuron
autoregulation of neurotransmitter release
inhibit release of NA from neuroterminals
how are beta adrenoceptors defined?
by affinity for Epi and NE
b1 receptor affinity
equal for Epi and NE
b2 receptor affinity
higher for Epi than NE (negligible)
describe how receptor responsiveness is regulated by activity & how this affects drug interactions
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)
what are 4 major sympathomimetic drugs
catecholamines: epinephrine norepinephrine isoproterenol dobutamine
describe epinephrine’s action
very potent vasoconstrictor (a1)
cardiac stimulant (b1)
positive inotropic and chronotropic actions on the heart (b1)
activates b2 receptors (smooth muscle relaxation)
describe NE’s action
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
describe isoproterenol’s action
nonselective b receptor agonist
positive chronotropic and inotropic effects
decreases diastolic and MAP due to activation of b2 in peripheral vasculature
describe dobutamine’s action
relatively b1 specific synthetic catecholamine
also activates a1 receptors
increases cardiac output with less reflex tachy
what are some a1 specific sympathomimetic drugs that do not have catecholamine structures?
phenylephrine ephedrine pseudoephedrine oxymetazoline xylometazoline
describe phenylephrine and its action
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
ephedrine
first orally active sympathomimetic drug
pseudoephedrine
OTC decongestant
indirect effects of releasing endogenous NE which bolsters therapeutic effects
oxymetazoline and xylometazoline
direct a1 agonists
topical decongestants
long action
what are a2 selective agonists and how do they work?
clonidine and methyldopa
inhibit NE release
used (poorly) as antihypertensives
diminish SNS outflow
what are b2 selective agonists and how do they work?
albuterol and salmeterol
relax bronchial smooth muscle
treatment of asthma and premature labor
what are some examples of indirect sympathomimetics
amphetamine
methamphetamine
cocaine
tyramine
mechanism of amphetamine and methamphetamine
increase NE release by a1 stimulation
marked stimulant effects on mood and alertness
depressant effect on appetite
common drug of abuse
mechanism of cocaine
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
mechanism of tyramine
releases stored catecholamines
MAO inhibitors potentiate effects and can produce hypertension
found in fermented foods like cheeses
what are some alpha receptor antagonists?
phentolamine phenoxybenzamine prazosin terazosin doxazosin yohimbine
phentolamine
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)
phenoxybenzamine
irreversible, covalent binding to alpha receptors
postural hypotension and tachycardia limit use
prazosin/terazosin/doxazosin
selective for a1 receptors
yohinbine
a2 selective antagonist
no established clinical role
what is the action of beta receptor antagonist? (beta blockers)
block effects of catecholamines at beta adrenoceptors
varied affinity for b1 and b2 receptors (none absolutely specific for b1 receptors)
effects of beta blockers
lower BP in patients with hypertension
negative inotropic and chronotropic effects
-reduce oxygen demand of myocardium
what are beta blockers clinically useful for?
hypertension ischemic heart disease cardiac arrhythmias glaucoma hyperthyroidism
propanolol
protypical beta blocker
nonselective
metoprolol and atenolol
b1 selective (cardio selective)
nadolol and timolol
long duration of action
once daily dosing
glaucoma
labetalol
reversible a1 antagonist
nonselective beta antagonist
hypotension with less tachycardia than alpha blockers
butoxamine
selective b2 receptors
no clinical application
