Lecture 6: Adrenergic Drugs Flashcards Preview

Neuro II Exam 1 - Pharm Week > Lecture 6: Adrenergic Drugs > Flashcards

Flashcards in Lecture 6: Adrenergic Drugs Deck (69):

The α1 AR is what type of GPCR?

What are the downstream effects?

- Gq

- Activates PLC; increased IP3, DAG; Ca2; activates PKC


The α2 AR is what type of GPCR?

What are the downstream effects?

- Gi

- Decreased cAMP


The β AR's is what type of GPCR?

What are the downstream effects?

- Gs

- Increased cAMP


There are 5 dopamine receptors, what type of GPCR is each and what are the downstream effects of each?

D1 = Gs = Increased cAMP

D2 = Gi = Decreased cAMP

D3 = Gi = Decreased cAMP

D4 = Gi = Decreased cAMP

D5 = Gs = Increased cAMP


What are 4 major effects produced by stimulation of α1 AR's?

1) Contraction of most vascular smooth muscle

2) Contraction pupillary dilatory muscle (dilates pupil)

3) Contraction of the prostate

4) Increases force and contraction of the heart


What are 4 major effects produced by stimualtion of α2 AR's?

1) Aggregation of platelets

2) Inhibition of NT release at adrenergic and cholinergic nerve terminals

3) Contraction of some vascular smooth muscle

4) Inhibition of lipolysis in adipocytes


What is the major effect of stimulation of β1 AR's on the heart and juxtaglomerular cells?

- Increases force and rate of contraction

- Increases renin release


What are the major effects of stimulation of β2 AR's on the liver, skeletal muscle, and respiratory, uterine, and vascular smooth muscle?

- Relaxation of respiratory, uterine and vascular smooth muscle

- Promotes skeletal muscle potassium uptake 

- Activates glycogenolysis and gluconeogenesis in the liver


What is the major effect of stimulation of β3 AR's on the bladder and fat cells?

- Relaxes detrusor muscle in bladder

- Activates lipolysis in adipocytes


What is the major effect of stimulation of D1 and D2 receptors?

D1 = dilation of renal blood vessels

D2 = modulation of transmitter release at nerve endings


What 2 drugs are direct adrenomimetic alpha agonists?

1) Phenylephrine - α1 > α2 >>>> β

2) Clonidine - α2 > α1 >>>>> β


What 2 drugs are direct adrenomimetic mixed alpha and beta agonists?

1) Norepinephrine - α1 = α2; β1 >> β2

2) Epinephrine - α1 = α2; β1 = β2


What 4 drugs are direct adrenomimetic beta agonists?

1) Dobutamine  β1 > β2 >>> α

2) Isoproterenol β1 = β2 >>> α

3) Terbutaline β2 >> β1 >>> α

4) Albuterol β2 >> β1 >>>> α


What 2 drugs are direct adrenomimetic Dopamine agonists?

1) Dopamine D1 = D2 >> β >> α

2) Fenoldopam D1 >> D2


Which receptors does Norepinephrine act on?

α1 = α2; β1 >> β2


What are the major effects of Norepinephrine?

- Potent cardiac stimulant, but reduces HR

- Potent vasoconstrictor = increases peripheral vascular resistant and BP ---> baroreflex will decrease the HR


Which receptors does Phenylephrine activate?

- α agonist

α1 > α2 >>>> β


What is Phenylephrine used for and what are its effects?

- Effective mydriatic (pupil dilator) and decongestant

- Causes severe vasoconstrictionBP elevation and severe bradycardia

- Role of baroreflex in the severe bradycardia


Which receptors does Clonidine activate most specifically?

- Selective α2 agonist

α2 > α1 >>>> β


What are the central effects of Clonidine?

- Act on α2 receptors in lower brainstem area

- Decrease sympathetic outflow; reduction in BP; bradycardia

- Local application produces vasoconstriction


Which receptors does Isoproterenol activate most specifically?

- Non-selective beta agonist

- β1 = β2 >>> α


What are the effects of Isoproterenol?

- Non-selective beta agonist

- Positive inotropic and chronotropic action, increases CO (β1)

- Vasodilator, decreases arterial pressure (β2)

- Bronchodilation (β2) 


Which receptors does Dobutamine activate most specifically?

- Selective β1 agonist

β1 > β2, α1


What is the effect of the (-) isomer vs. (+) isomer of Dobutamine on α1 receptors?

(-) isomer is an agonist

(+) isomer is an antagonist


What are the effects of Dobutamine?

Potent inotropic action

- Less prominent chronotropic action as compared to isoproterenol


Which receptors do Terbutaline and Albuterol activate most specifically? 

- Selective β2 agonists

- β2 > β1 >>>> α


What are the effects of Terbutaline and Albuterol?

- Selective β2 agonists

- Bronchodilation and relaxation of uterus


Where are there a high density of D1 receptors?

Activation by Dopamine causes?

- Renal, cerebral, mesenteric and coronary vessels

- Causes vasodilation


Activation of presynaptic D2 receptors by dopamine causes what?

β1 receptors in heart?

α1 receptors of vasculature?

- Suppresses NE release when D2 receptors activated presynaptically

- At higher doses activates β1 receptors in heart

- At even higher doses stimulates vascular α1 AR to cause vasoconstriction


Which receptors does Dopamine effect most specifically?

D1 = D2 >> β1 >> α1


What is the MOA of Ephedrine?

How is it classified?

- Indirect adrenergic agonist

- Released stored catecholamines w/ some direct action (similar to epinephrine in action)


What is the clinical use of Ephedrine?

- Nasal decongestant

- Increases BP

- Stress incontinence in women


What is the MAO of Phenelzine and Selegiline?

How are they classified?

- Indirect adrenergic agonist

- Inhibitors of Monoamine oxidases (MAO)

- Increase NE stores in CNS

- Antidepressant action


What is the MOA of Tyramine?

How is it classifed

- Indirect adrenergic agonist

- When administered parenterally releases stored NE from presynaptic adrenergic terminals (aka postganglionic sympathetic terminal)


Administration of Tyramine may lead to marked increases in BP if given to patients taking what?

MAO inhibitors; since is metabolized by MAO in liver (first-pass effect)


Tyramine is found in high concentrations in what types of food?

- Smoked and pickled fish

- Cheese

- Cured meats



Which 2 drugs would we use clinically to increase BP during hypotensive emergencies i.e., hemorrhagic shock, OD of antihypertensives, CNS depressants?

- Norepinephrine (mixed alpha and beta agonist)

- Phenylephrine (alpha agonist α1 > α2)


Which drug would we use clinically to increase BP for chronic hypotension?

Ephedrine (indirect adrenergic agonist)


Which 2 drugs would we use clinically to increase BP for cardiogenic shock (due to massive acute MI)?

1. Dopamine

2. Dobutamine


What class of drugs would be used for long-term treatment of HTN?

Alpha-2 agonists (i.e., Clonidine)


Which 3 adrenergic drugs would be used for Obesity?

1) Phentermine

2) Ephedrine

3) Amphetamines


What are 2 adrenergic drugs that are beta-2 selective agonists used clinically for bronchial asthma?

1) Albuterol

2) Terbutaline


Which 3 adrenergic drugs are used clinically for decongestion of mucous membranes?

1) Phenylephrine

2) Ephedrine

3) Pseudoephedrine


Which drug is used clinically for examination of the retina due to its ability to induce mydriasis?

Phenylephrine (an α agonist - α1 > α2)


Which class and 2 adrenergic drugs are used in the treatment of Glaucoma?

- Alpha-2 selective agonists

- Apraclonidine and Brimonidine


Which class and what drug is used clinically for the suppression of pre-mature labor?

Beta-2 agonists (Terbutaline)


What is the MOA of Metyrosine?

- Indirect antiadrenergic drug

- Inhibits tyrosine hydroxylase, which is a necessary enzyme in the synthesis of catecholamines


What is the MOA of Guanethidine and what class does it belong to?

- Prevents storage, depletes NE

- Indirect antiandrenergic drug


What are the 2 non-selective (α1 and α2) receptor antagonists?

- Phentolamine

- Phenoxybenzamine


What are the 6 α1 receptor selective antagonists? (hint: the suffix is the same for all)

1) Prazosin

2) Terazosin

3) Tamsulosin

4) Doxazosin

5) Alfuzosin

6) Silodosin


Phentolamine and Phenoxybenzamine are both non-selective (α1 and α2) receptor antagonists, but how do they differ in binding/enzyme kinetics?

Phentolamine is a reversible competitive α antagonist = non-covalent binding to receptor = shorter acting 

Phenoxybenzamine is a irreversible non-competitive α antagonist = covalent binding to receptor = longer acting


What are the adverse effects produced by alpha antagonists?

- Decreased peripheral vascular resistance and BP

- Postural hypotension

- Reflex tachycardia

- Retention of fluid and salt

- Impaired ejaculation

- Nasal stuffiness


Which 2 drugs are used in the treatment of Pheochromocytomas?

1) Phentolamine

2) Phenoxybutamine


Which 3 drugs are used clinically for chronic (essential) HTN?

- Prazosin, Terazosin, and Doxazosin = α1 selective

*Non-selective α-blockers NOT used


Which α receptor subtype is the most important in mediating prostate smooth muscle contraction?

Due to this what 2 drugs are used clinically for BPH?

- α1A is the most important

- Use Tamsulosin and Silodosin = greater selectivity for α1A


Which beta-blockers are Antagonists?

Partial agonists?

Inverse agonists?

Antagonist: atenolol, nadolol, propranolol, and betaxolol

Partial: acebutolol, labetalol, penbutolol, pindolol

Inverse: carvedilol and metoprolol


Which 4 beta-blockers are β1 selective?

- Metoprolol

- Acebutolol

- Betaxolol

- Atenolol

MABA - Make America Bitches Again


Which 4 beta-blockers are β1 and β2 (non-selective) blockers?

- Propranolol

- Pindolol

- Penbutolol

- Nadolol


What are beta blockers w/ ISA (intrinsic sympathomimetic activity) and what do they do?

Why are they useful clinically?

- Partial agonists at beta adrenergic receptors (i.e., Acebutolol, Labetalol, Penbutolol, Pindolol)

- Block sympathetic effects BUT have submaximal effects of their own = a blunted sympathetic response

- Less risk for bradycardia, increase in VLDL/HDL, amongst others


What are the effects of beta-blockers on the heart?

- Negative inotropic and chronotropic effect

- Block AV node: slowed AV conduction and increased PR interval


What is the effects of beta-blockers on the blood vessesl, both initially and after chronic use?

Initially --> rise in peripheral vascular resistance

Chronic use --> decrease in PVR (lowers BP in hypertensive individuals)


What are the effects of beta-blockers on the RAAS, respiratory system, and eye?

RAAS --> inhibits renin release

Respiratory --> increase airway resistance

Eye --> reduce production of aqueous humor - reduce intraocular pressue


What are the metabolic effects of beta blockers?

- Inhibit lipolysis

- Increase VLDL and decrease HDL, reduce HDL cholesterol/LDL cholesterol ratio

- Inhibit glycogenolysis and gluconeogenesis in liver


What are the 2 mixed (α and β) blockers?

- Labetalol (β- and α1 antagonist)

- Carvedilol (β- and α1 antagonist)


How are beta-blockers used clinically for HTN?

- Antihypertensive effect is delayed

- Both beta-blockers and mixed α and beta-blockers (Labetalol) are used


Which 4 heart conditions are beta-blockers used for?

1) Angina pectoris

2) MI --> long-term use in post-infarction period - prolong survival

3) Cardiac arrhythmias --> both ventricular and supraventricular arrhythmias

4) Heart failure --> only in chronic, not acute


Which 3 beta-blockers can be used long-term post-MI and have been shown to prolong survival?

- Timolol

- Propranolol

- Metoprolol


Which 2 beta-blockers may be used for Glaucoma?


- Timolol

- Betaxolol

*Blockers w/o local anesthetic acitivity


Which beta-blocker is used for Hyperthyroidism?