Adrenergic Receptor

Question 0

Clonidine (Catapres)

Answer 0

Description: synthetic and selective a2 receptor agonist
Action: stimulate a2 receptor in brainstem, cause downregulation of sympathetic flow
Indication: treat hypertension and migrane
Other facts: may be given orally or patch, causes sedation and dry mouth, if given IV or OD, can cause increased BP

Question 1

Phenylephrine (Neosynephrine)

Answer 1

Description: synthetic alpha-receptor agonist, a1»a2
Action: vasoconstriction and venoconstriction of vessels in vascular smooth muscle
Indication: nasal decongestant, mydriatic (dilation of pupils), increase BP in vasodilated state
Other facts: less potent vasoconstrictor than NE, not inactivated by COMT, topical and intravenous

Question 2

Isoproterenol (Isuprel)

Answer 2

Description: synthetic b1 and b2 receptor agonist
Action: potent agonist at both receptors
Indication: increase cardiac contractility, increase HR, increase cardiac conduction
Other facts: given IV, no longer used as much in CCU, remember it causes vasodilation and tachyarrythmia

Question 3

Dobutamine (Dobutrex)

Answer 3

Description: synthetic b1 receptor agonist (with very little alpha stimulation on high doses)
Actions: potent agonist at b1 receptors at heart (increase contractility) and blood vessels (dilates renal and mesenteric vessels); increases contractility more than HR
Indication: increase contractility more than HR, useful in CCU for pts in cardiogenic shock, where you don’t want to produce tachycardia.
Other facts: given as IV, side effects include unwanted tachycardia, hypertension, actopy.

Question 4

Albuterol (Ventolin)

Answer 4

Description: Synthetic selective b2 receptor agonist, b2»>b1
Action: potent agonist at b2 receptors on smooth muscle cells in airways (e.g. Bronchioles)
Indication: promptly acting rescue inhaler for asthma, COPD, inhibit premature labor (relaxes smooth muscles in uterus)
Other facts: most often given as MDI (metered dose inhaler), can be given via nebulizer, rarely given any more as IV, side effects include anxiety, tachycardia, and tremor.

Question 5

Mirabegron (Myrbetriq)

Answer 5

Description: synthetic selective b3 receptor agonist (with much less activity at b1 and b2 receptors)
Action: reduces detrusor muscle tone
Indication: treatment of pts with overactive bladder with urinary incontinence, increases bladder capacity
Other facts: does not produce bothersome anticholinergic sx like tolteridine, approved by FDA in 2012, given orally as extended release tablets.

Question 6

Epinephrine (Adrenaline, EpiPen)

Answer 6

Drug class: Direct-acting adrenergic agonist, vasopressor, cardiac stimulant, bronchodilator, adjunct to local anesthetic, tx for anaphylaxis
Pharmacodynamics: major action is on a1, b1, b2 receptors; also helpful in anaphylaxis by stabilizing mast cells
Pharmacokinetics: can be given IV (immediate), IM (variable), SC (5-15min), and via inhalation (1-5min onset), opthalmic topical, metabolized by COMT, then renally secreted.
Toxicity: HTN, excessive vasoconstriction, hemmorahgic stroke, angina, arrhythmias
Interaction: risk of xs HTN, in pt taking propanolol
Special considerations: utility with local anesthetics, drug of choice in severe anaphylaxis
Monitor: BP, HR, Rhythm, infusion site, evidence of extravasation

Question 7

Norepinephrine (Noradrenaline, Levophed)

Answer 7

Drug class: direct-acting adrenergic agonist, vasopressor/constrictor
Action: majorly on a1 and b1 receptor. Increases CO, HR, TPR, but decreased flow to skin, muscle, and kidney.
Indication: adults with acute hypotension and shock
Kinetics: F ~100%, given IV only, metabolized by COMT and MAO, mostly in liver. Metabolites excreted in urine. Half-life is 1-2min, can cross placenta, but not BBB.
Toxicity: xs vasoconstriction in mesenteric vessels, peripheral arterioles causing ischemia, infarction, gangrene; reflex bradycardia.
Interaction: use cautiously in pts taking an MAO inhibitor like phenelzine (use lower doses), risk of xs HTN in pts taking propanolol
Special consideration: correct volume depletion with IV fluid before giving NE infusion, select infusion site carefully, as extravasation is a problem, monitor pts and BP continuously in ICU setting. Use cautiously in pediatric and geriatric pts.

Question 8

Dopamine (Intropin)

Answer 8

Description: endogenous and now synthetic agonist at DA, a1, and b1 receptors
Action: relative potency depends somewhat on dose being delivered, DA agonist at low dose, b1 agonist medium dose, a1 agonist at high dose
Indication: shock of various etiologies in ICU, can produce contractility, vasoconstriction, and “increased blood flow to mesenteric and renal arteries (via DA)”
Other facts: given IV, preferably for short duration

Question 9

Ephedrine

Answer 9

Description: alkaloid obtained from plant (Ephedra)
Action: indirectly to release NE from adrenergic nerve endings, also some direct agonism at receptors
Indication: mild to moderate hypotension during surgery, nasal congestion
Other facts: has somewhat prolonged duration of action, potent CNS stimulant, side effects include HTN, insomnia, OTC ephedra products now banned by the FDA dye to deaths

Question 10

Pseduoephedrine

Answer 10

Description: synthetic derivation of Ephedrine
Action: indirectly to release NE from adrenergic nerve endings, also some direct agonism at adrenergic receptors
Indication: nasal and sinus decongestion, less effective in bronchodilation than Ephedrine
Other facts: FDA approved in 1959, as of 2005 stored behind counter or locked cabinet, need photo ID, risk of diversion to produce methamphetamine, as of 2008 labeled as risk of injury/death, no cold products for kids <2yo

Question 11

Amphetamine

Answer 11

Description: synthetic analog to Ephedrine
Action: indirectly to release NE from adrenergic free nerve endings
Indication: obesity, narcolepsy, ADHD (none are FDA approved)
Other facts: FDA approved in 1939, high risk of dependence, insomina, restlessness, tremor

Question 12

Tyramine

Answer 12

Description: naturally occurring byproduct of tyrosine metabolism, present in many aged or fermented foods like red wine, smelly cheeses, and pickled herring.
Action: indirectly to release NE from adrenergic nerve endings
Indication: obesity, narcolepsy, ADHD (none are FDA approved)
Other facts: metabolized in the liver by MAO, watch out in pts with MAO inhibitor drugs (e.g. Phenelzine), chance of food/drug interaction

Question 13

Cocaine

Answer 13

Description: naturally occurring but purified alkaloid extracted from the coca plant
Action: indirectly to block reuptake of NE (also, Epi and DA) at the synapse, also acts as local anesthetic and CNS stimulant
Indication: nose bleeds (anesthesia plus vasoconstriction), anesthesia for cornea surgery
Other facts: CNS stimulation more intense, shorter lasting than amphetamine, can be smoked, snorted, or injected, side effects are HTN, MI, tachycardia, seizure, arrhythmia, controlled substance

Question 14

Prazosin (Minipress)

Answer 14

Drug class: selective a1 blocker, antihypertensive and treatment of BP
Dynamics: blocks receptors on arterioles and veins, thereby inhibiting NE-mediated vasoconstriction and venoconstriction
Kinetics: po or transdermal, variable oral bioavailability, onset 2hr, duration 12-24hr, extensively metabolized in liver
Toxicity: xs hypotension with passing out, esp orthostatic, esp in pts with diuretics
Special consideration: start gradually, and at bedtime, to avoid first time passing out, male pts with BPH
Monitor: BP, weight, edema

Question 15

Tamsulosin (Flomax)

Answer 15

Drug class: selective a1 blocker, treatment of obstructive symptoms of BPH
Dynamics: blocks receptors in the prostate, leading to relaxation of smooth muscles in the bladder neck and rostate, improving urine rate, and reducing obstructive sx of BPH venoconstriction
Kinetics: completely absorbed after oral ingestion, ~90% metabolized by CYP 450 ez, half-life 6hrs, duration of action is long at 15hr
Toxicity: xs hypotension with syncope, esp orthostatic, esp pts with diuretics, allergy rxn, decreased libido
Special consideration: rule out carcinoma of prostate before beginning tx, do not crush or chew tablets, as that will speed up absorption, can also be used to treat spasm of ureter in pts with kidney stones
Monitor: BP

Question 16

Phentolamine (Regitine)

Answer 16

Drug class: non-selective, competitive alpha blocker, antihypertensive drug for pts with pheochromocytoma
Dynamics: blocks a1 and a2 receptors at presynaptic and postsynaptic, decreasing preload and afterload
Kinetics: only comes in IV (F=100%), plasma half life about 20min
Toxicity: xs hypotension with syncope, esp orthostatic, allergic rxns, decreased libido
Indication and dose/route: aid in Dx of pheo, treatment of intra-op HTN during pheo removsl surgery, prevention of dermal sloughing after extravasation of NE infusion, hypertensive crisis from tyramine-MAO inhibitor interaction, dose 5mg IV, then titrate, repeat as needed
Monitor: BP

Question 17

Atenolol (Tenormin, Metoprolol, Toprol)

Answer 17

Drug class: specific b1 blocker, antihypertensive, antiarrythmic, primary and secondary prevention of MI, anti-anginal
Dynamic: bind preferentially to b1 over b2, leading to low BP, recent evidence suggests less effective in preventing strokes than other drugs
Kinetics: po or IV, variable oral F, onset 1-2hr, duration 12-24hr, can be given qd, renally excreted (longer half-life), metoprolol has hepatic mechanism (shorter half-life)
Toxicity: xs hypotension, bradycardia, heart block can worsen severe CHF (indicated for mild to moderate CHF), worsen bronchospasm in severe asthmatics
Interactions: additive effects with most other antihypertensives, additive AV block with CEBs
Special considerations: maybe esp useful for HTN pts with exertional angina, MI, atrial fibrillation, watch out for abrupt withdrawal, may no longer be first line drug for essential HTN unless other indications exist
Monitor: BP, HR, exercise tolerance
Atenolol-long acting, metoprolol-short acting

Question 18

Propranolol (Inderal)

Answer 18

Drug class: non-specific beta blocker, antihypertensive, antiarryhtmic, primary and secondary prevention of MI, anti-anginal
Kinetics: po or IV, variable oral F, onset 1-2hr, duration 12-24hr, can be given qd, renally excreted (longer half-life), metoprolol has hepatic mechanism (shorter half-life)
Toxicity: xs hypotension, bradycardia, heart block can worsen severe CHF (indicated for mild to moderate CHF), worsen bronchospasm in severe asthmatics
Interactions: additive effects with most other antihypertensives, additive AV block with CEBs
Special considerations: maybe esp useful for HTN pts with exertional angina, MI, atrial fibrillation, watch out for abrupt withdrawal, may no longer be first line drug for essential HTN unless other indications exist
Monitor: BP, HR, exercise tolerance
Nadolol-long acting, propanolol-short acting

Question 19

Labetalol (Trandate, Carvediolol, Coreg)

Answer 19

Drug class: mixed alpha and beta blocker, antihypertensive, tx of CHF
Dynamics: reduced BP by blocking access of NE to beta receptors and alpha-1 receptors, thereby lowering BP by several different mechanisms; pts differ in degree of beta-blockade vs alpha-blockade
Kinetics: excellent absorption but high first-pass effect, leading to F ~25%, onset 1-2hr after po, 2-5min when given IV, extensively metabolized in liver by IID6
Toxicity: avoid in pts with bradycardia, heartblock, CHF, asthma, shock; use with caution in pts with cardiomyopathy, pheochromocytoma, pregnancy class D
Interactions: additive with most other antihypertensives
Special considerations: used reduced doses in pts with impaired liver function; dizziness is most troubling early side effect; most often used for hypertensive crises (as with nitroprusside)
Monitor: BP and HR