Adrenergic Receptor- Agonists and Antagonists Flashcards
Alpha-1 Receptor Organs
Vascular Smooth Muscle
Pupillary Dilator Muscle
Alpha-2 Receptor Organs
Adrenergic and cholinergic nerve terminals
Beta-1 Receptor Organs
Heart
Juxtaglomerular Cells
Beta-2 Receptor Organs
Respiratory Smooth Muscle
Uterine smooth muscle
Vascular smooth muscle
Somatic Motor nerve terminals
Dopamine 1 Receptors
Renal vessels
Sphlancinc Vessels
Alpha-1 signaling
Positively coupled to Phospholipase C by G-alpha-q to increase IP3 and DAG.
IP3 causes calcium channels to open and increase- activating calmodulin and MLCK for muscle contraction
Alpha-2 Signaling
Negatively coupled to adenylyl cyclase by G-alpha-i to inhibit PKA activation, cAMP and therefore calcium influx in order to reduce propagation and release of neurotransmitter in pre-synaptic neurons. Also in vascular smooth muscle- inactivated PKA= activated MLCK and therefore constriction.
Beta-1 Signaling
Positively coupled to adenylyl cyclase by G-alpha-s. Increasing cAMP and having positive chonotropic and ionotropic effects due to PKA activation and therefore high calcium.
SA Node
Beta-1 activated G-alpha-s. AC-cAMP-PKA causes increased calcium channel and IF to reduce threshold of activation and more rapid depolarization
Myocytes
Beta-1 activated G-alpha-s. AC-cAMP-PKA that increases L-type calcium channels, ryanodine receptor on SR and SERCA
Sympathetic nerve terminals
Negative feedback to alpha-2 G-alpha-i that inhibits AC, cAMP and PKA to decrease calcium propagation and therefore no NT release
Vascular smooth muscle
Alpha-1 coupled to G-alpha-q stimulates phospholipase C to increase PIP2 to IP3 and increase calcium for muscle contraction by MLCK
Direct Acting Adrenergic Agonists
A1- phenylephrine A2- Clonidine BNS- Isoproterenol B1- Dobutamine B2- Terbutaline, Albuterol
Indirect Acting Adrenergic Agonists
Releasing- amphetamine, methamphetamine, methylphenidate, ephedrine, pseudoephedrine, tyramine
alpha-1 affinities
Epinephrine >= Norepinephrine»_space;» isoproterenol
alpha-2 affinities
Epinephrine >= Norepinephrine»_space;» isoproterenol
beta-1 affinities
isoproterenol > epinephrine»_space;» norepinephrine
beta-2 affinities
isoproterenol > epinephrine = norepinephrine
Epinephrine
Stimulates a1,a2,b1,b2, short half life
Low dose- decrease diastolic (b2), increase CO (b1)
High dose- increase diastolic (a1,a2>b2), increase CO
Bronchodilation (b2), decrease secretions (1a)
Toxicity - arrythmia
Use in anaphylaxis, cardiac arrest, bronchospasm
Contra- late term preggos
Norepinephrine
Stimulates a1, a2, b1, short half life
Increase cardiac output and systolic (b1)
Increase resistance and diastolic (a1, a2) (increase MAP)
DECREASE HR (baroreceptor to constricted vessels)
Toxicity- ischemia
Indication- vasodilatory shock
Contra- pre-existing vasoconstriction/ischemia
Dopamine
Stimulates D1, D1, a1, a2, b1, short half life
Low doses- increase CO (b1), decrease TPR (d1)
High dose- increase CO, increase TPR (reaches a1,a2)
-Will still relax sphlancninc/renal wit D1
Indications- cardiogenic shock
Toxicity- low blood pressure at low dose, ischemia at high dose
Contra- tachycardic arrythmia, V fib
Isoproterenol
non- selective beta agonist- higher half life
Decrease TPR with b2
Initial increase CO with b1 but low low diastolic will bring down systolic and therefore decrease MAP
Increase HR- baroreceptor reflex to vasodilation
Bronchodilation (b2)
Toxicity- tachyarrythmias
Indication- bradycardia, heart block with high TPR
Contra- angina + arrythmias
Dobutamine
selective b1 (some b2 stimulation at higher doses) increase CO (b1) for cardiogenic shock Toxicity- hypotension at HIGH doses due to b2 stim Indications- short term for CHF, cardiogenic shock
Beta-2 Signaling
Positively coupled to G-alpha-s proteins that will activate adenylyl cyclase and increase cAMP and activate PKA that INACTIVATES MLCK–>relaxation of muscle
Indirect Adrenergic Agonists (Releasing)
Amphetamine: COMT resistant with long half-life, cross BBB
Taken up by re-uptake proteins, cause reversal of the re-uptake mechanism and release NT in a CALCIUM-INDEPENDENT manner.
Cardio- NE release, peripheral vasoconstriction (increase diastoic) and positive ionotropy/conotropy (increase systolic)
CNS- stimulant, anorexic agent
Toxicity- Tachycardia
Use- ADD, narcolepsy, nasal congestion
Contra- Rx with MAO inhibitors withing previous 2 weeks, hypertension
Terbutaline
Selective b2 agonist
Prevent/reverse bronchospasm in asthma, bronchitis and emphysema
Eliminates via urine
Phenylephrine
Selective a1 agonist
Pressor for anesthesia, nasal congestion, pupil dilator, supraventricular tachycardia, HTN
Less than 1 hr half life, eliminated by MAO
Clonidine
Selective a2 agonist
Treat HTN, eliminated via urine with a long half life
Beta- adrenergic antagonists
Non-selective- propranalol,. timolol, nadolol
B1 cardio selective- atenolol, metoprolol, esmolol
Partial Agonist- pindolol
Propranolol
Non-selective b-blockers
Treat HTN, angina due to atherosclerosis, MI
4 hour half life, eliminated by liver
Metoprolol
Cardioselective B1-blockers
Treat HTN, long term angina
Pindolol
Partial Agonist b-blocker
Treat HTN
Alpha-adrenergic antagonists
Non-selective- phenoxybenazmine, phentolamine
Selective A1- prazosin, doxazosin, terazosin
Penoxybenazmine
Non-selective alpha-antagonists
Irreversible alpha-blocker to treat pheochrome-cytoma
Prazosin
A1 antagonist
treat HTN
Albuterol
B2- agonist
Use for bronchial relaxation durin asthma attack
Nadolol
Beta- blocker for long term angina and hypertension with a long half life (a day)
Timolol
Beta blocker for glaucoma
Atenolol
Cardioselective B1 blocker for hypertension, angina and MI
Esmolol
Emergency used b1 blocker with a short half life to treat supraventricular tachycardia
Phentolamine
Reversible alpha-blocker to test for pheochrome-cytoma
Treat rx for pheo. before surgery
Doxazosin
alpha 1 antagonist
Terazosin
a1 blocker for prostatic hyperplasia and HTN
Methylphenidate
Indirect sympathomimetic
Treat ADHD
Ephedrine
Indirect sympathomimetic
Pressor durin anesthesia
Psuedo-ephedrine
Indirect sympathomimetic
Treat nasal congestion
Tyramine
Super short half life that displaces NE and increases ints activity in the synaptic cleft, MAO degrades it
