Adrenoceptor Agonists/Antagonists Flashcards
what amino acid are catecholamines derived from
tyrosine
what is the order of epinephrine formation from tyrosine
tyrosine –> dopa –> dopamine –> norepinephrine –> epinephrine
what catecholamine is secreted by the adrenal medulla
epinephrine
What is the role of MAO and COMT
metabolism of catecholamines
where is COMT absent
intraneuronal
what is the MOA of cocaine
neuronal reuptake inhibitor (of NE and E)
what is the MOA of reserpine (no longer used clinically)
vesicular reuptake inhibitor
where is MAO-A located
adrenergic neurons, intestine, liver, kidney, and placenta
where is MAO-B located
dopaminergic neurons, brain, platelets, and liver
what is the MOA of clorgyline and moclobemide
MAO-A inhibitors
What is the most widely used MAO-B inhibitor and what is it used to treat
selegiline; Parkinson’s Disease
what is the role of alpha2 adrenergic receptor
inhibits further release of NE from presynaptic adrenergic neurons
what receptor does clonidine target
alpha 2
what receptor does terbutaline target
beta 2
what receptor does phenylephrine target
alpha 1
what receptor does dobutamine target
beta 1
what receptor does oxymetazoline target
alpha 1 and 2 (non-specific)
what receptor does isoproterenol target
nonspecific beta 1 and 2
what receptor does epinephrine target
all! alpha 1, 2 and beta 1, 2
what receptor does norepinephrine target
all except beta 2 (alpha 1, 2, and beta 1)
what is the MOA of amphetamines and tyramine
release/displace NE from vesicles of sympathetic nerve varicosities
what are some of the effects of phenylephrine
mydriasis, increased TPR, increased DBP, increased afterload, increased venous return and increased preload, increased glycogenolysis, and decreased renin release
what drug results in reflex bradycardia and why
phenylephrine; HR is decreased to compensate for the increase in peripheral vascular resistance and BP
What is the MOA of clonidine
alpha 2 selective agonist: decrease sympathetic outflow and suppress NE release
adverse effects of clonidine
dry mouth, sedation, nasal stuffiness, constipation, impotence (ed)
list common uses of clonidine
moderate HTN, prophylaxis of migraine, manage opiate, alcohol and nicotine withdrawal, menopause hot flashes, control diarrhea in diabetics w autonomic neuropathy
what is the MOA of tizanidine
centrally acting alpha-2 adrenoceptor agonist: presynaptic inhibition of motor neurons to decrease spasticity (used in MS)
what are the uses of albuterol, salmeterol, and terbutaline
- asthma relief (immediate)
- arrest uncomplicated premature labor
what are the adverse effects of beta2 selective agonists (albuterol, salmeterol, terbutaline)
tremors, palpitations, hypokalemia
what are the effects of beta-2 selective agonists
vasodilation, decreased TPR, decreased DBP, increased glycogenolysis, increased insulin secretion
what is mirabegron used to treat
overactive bladder (beta 3 selective agonist)
what are the clinical effects of dobutamine
as a selective beta 1 agonist, it will increase HR, conduction velocity, force of contraction, and renin release
why is dobutamine useful in heart failure
it increases CO and stroke volume without significantly increasing heart rate
what receptor is the primary target for epinephrine at low doses
beta 2 receptors
what receptor is the primary target for epinephrine at a moderate dose
beta 1
what receptor is the primary target for epinephrine at a high dose
alpha 1
what is the effect of epinephrine on SBP an DBP
overall increase in SBP and decrease in DBP
uses of EPI
anaphylactic shock, prolong duration of local anesthetic agents, control epistaxis and cardiac resuscitation
what are the adverse effects of epinephrine
angina, palpitation and arrhythmias, anxiety, tremors, headache, and cerebral hemorrhage
list the contraindications of epinephrine
HTN, angina, hyperthyroidism, and concomitant use of MAO
Epi/NE has poor beta2 action
NE
how does NE differ from EPI with regard to SBP and DBP
NE: raises both SBP and DBP (via beta 1 and alpha 1)
E: raises SBP but lowers DBP
list the uses of NE
cardiac arrest, hypotensive states in surgical shock and MI, alongside local anesthetics
NE contraindications
may cause renal shutdown so dopamine is preferred in cardiogenic shock
what receptors does dopamine work on
D1, D2, and B1 based on dosage (similar to that of epi)
what is the dosage effect of dopamine
D1/D2 0.5-2mcg/kg/min
beta 1 2-10mcg/kg/min
alpha effect >10mcg/kg/min
what is the effect of low dose dopamine (iv infusion)
increased urine output and renal blood flow
what is the effect of moderate dose of dopamine
increased renal blood flow, CO, HR, and cardiac contractility
what is the effect of high dose dopamine
increased BP and vasoconstriction
list the uses of DA
cardiogenic shock, CCF, liver and renal failure, hypotensive states
list the adverse effects of DA
nausea, tachycardia (high doses), hypertension, ectopic beats, arrhythmias
what receptors does isoproterenol target?
beta 1, 2, 3 but no alpha action
label the three graphs based on the drug its depicting
NE, E, ISO (L to R)
explain Dale’s vasomotor reversal
its the effect of Epi when given after pretreatment of an alpha blocker: hypotension due to predominant beta2 effect
what happens when epi is given after pretreatment of a beta blocker
accentuated hypertensive effect
fill in the blank
how can tyramine cause a “cheese rxn”
bc its metabolized by MAO so if a pt is on an MAO inhibitor, it can trigger a hypertensive crisis
what is the common suffix of alhpa-1 selective antagonists
“zosin”
prazosin, terazosin, doxazosin, alfuzosin, tamsulosin
phenoxybenzamine is an (alpha/beta) receptor antagonist
alpha; along with phentolamine
what type of receptor antagonist is the drug phentolamine
non-selective alpha antagonist
beta blockers typically have the suffix:
“olol”
what are the effects of phenoxybenzamine
vasodilation, hypotension, tachycardia (reflex)
due to being a nonselective alpha antagonist
what is phenoxybenzamine used to treat
pheochromocytoma, raynaud’s syndrome frostbite
what are the adverse effects of phenoxybenzamine
postural hypotension, inhibition of ejaculation, sedation
what is the MOA of phentolamine
competitive, reversible antagonist of alpha 1 and alpha 2
what are the effects of phentolamine
vasodilation, decreased peripheral vascular resistance, hypotension, and reflex tachycardia
what are the clinical uses of phentolamine
pheochromocytoma, peripheral vascular disease, and hypertensive crisis
what is the MOA of prazosin
alpha-1 selective blocker
what are the uses of prazosin
PTSD, nightmares, BPH, HTN, Raynaud’s syndrome
what are the adverse effects of prazosin
postural hypotension, and the first dose phenomenon
why are tamsulosin and silodosin more effective in BPH with little effect on BP?
because they are alpha 1 A antagonists which are specific to the bladder neck and urethra
what are the adverse effects of tamsulosin and silodosin
abnormal ejaculation and floppy iris syndrome
what’s the MOA of tamsulosin and silodosin
alpha 1A antagonists
what is the MOA of yohimbine
alpha-2 antagonist
what is the MOA of propranolol
nonselective beta blocker
what are the effects of propranolol
bronchoconstriction (beta 2 block), decreased renin, decrease HR, B, contractility, CO, and velocity
what are the cardiovascular uses of propranolol
CCF, angina pectoris (bc it decreases cardiac workload), Arrhythmias, and MI
list the adverse effects of propranolol
bronchoconstriction, bradycardia, cold extremities, hypoglycemia, fatigue, sleep disturbances, rebound hypertension, adverse lipid profile, sexual dysfunction
what is the treatment for a pt with beta blocker toxicity
maintain ABC
IV fluid, ATROPINE
glucagon
what is the MOA and clinical use of timolol
non-selective beta blocker; treats open angle glaucoma
what is the MOA and clinical use of sotalol
non-selective beta blocker; class III anti-arrhythmic
what beta blockers are safer in asthmatics
beta-1 selective blockers; esmolol and metoprolol
what are the advantages of the beta-1 selective blockers, esmolol and metoprolol
what is the MOA of labetolol
mixed alpha-1 and beta-1 antagonist
what are the effects of labetolol
decrease BP, vaso and bronchodilation
what are the clinical uses of labetolol
HTN, pheochromocytoma, and rebound HTN in clonidine withdrawal
what are the adverse effects of labetolol
postural hypotension and heptotoxicity
what is the MOA of Carvedilol
mixed beta-1, beta-2, and alpha-1 blocker (lesser alpha)
what are the effects of carvedilol
inhibits free radical induced lipid peroxidation, inhibits smooth muscle mitogenesis, blocks L-type VGCa++ channels
what are the clinical uses of carvedilol
CCF, HTN, angina
what are the effector tissues for alpha-1 receptors and what do they cause
smooth muscles, eye, arterioles veins, vas deferens, liver, kidneys, pancreas
Gq (IP3/DAG)
increase Ca++, cause contraction
mydriasis, increased TPR, DBP, and Venous return; ejaculation, increased glycogenolysis and decreased insulin secretion
what are the effector tissues for alpha-2 receptors and what do they cause
mostly nerve endings
Gi (decrease cAMP)
decrease transmitter release (nerves) by inhibiting further release of NE from presynaptic adrenergic neuron, inhibit digestive activity, and decrease insulin secretion and increase platelet aggregation
what are the effector tissues for beta-1 receptors and what do they cause
cardiac muscle (SA and AV node), JG apparatus
Gs (increase cAMP)
increase HR, increase force/contractility, conduction velocity and increase renin release
what are the effector tissues for beta-2 receptors and what do they cause
smooth muscle (blood vessels, uterus, bronchioles), pancreas, liver
Gs (increase cAMP)
relax smooth muscle, decrease TPR and DBP, uterine relaxation, bronchodilation, increase glycogenolysis and increased insulin secretion
what are the effector tissues of beta-3 receptors and what do they cause
adipose cells
Gs
increase lipolysis
what are the effector tissues of D1 receptors and what do they cause
smooth muscle
Gs (increase cAMP)
relax renal vascular smooth muscle, increases RBF and GFR
