Adrenergic Agonist and Antagonist

Question 1

Adrenoreceptor physiology

Answer 1

NE is released from postganglionic sympathetic fibers at the end organs
*Exocytosis => NE is terminated by reuptake into postganglionic nerve endings

Question 2

Prolonged activation of adrenoreceptors

Answer 2

can lead to desensitization and hyporesponsiveness

Question 3

Eye Innervation

Answer 3

Superior cervical plexus

• Alpha: mydriasis
• Beta - ciliary relaxation

Question 4

Salivary Innervation

Answer 4

Superior cervical plexus

- Alpha 1 and Beta 2 : increased secretions

Question 5

Heart Innervation

Answer 5

Superior Cervical Plexus

- beta 1: increased HR, conduction and contractility

Question 6

Lung Innervation

Answer 6

Middle and Lower Cervical Plexus

• Alpha 1 : bronchoconstriction
• beta 2: bronchodilation

Question 7

Pancreas Innervation

Answer 7

Celiac Ganglion

• Alpha 1: decreased insulin
• Beta 2: increased insulin

Question 8

Upper GI Tract Innervation

Answer 8

Celiac Ganglion

• alpha 1: sphincter relaxation
• beta 2: decreased motility

Question 9

Liver Innervation

Answer 9

Celiac Ganglion

• alpha 1: glycogenolysis
• beta 2 & 3: gluconeogenesis

Question 10

Abdominal Vessels Innervation

Answer 10

Celiac Ganglion

• alpha 1 : vasoconstriction
• beta 2 : vasodilation

Question 11

Bladder Innervation

Answer 11

Inferior Mesenteric Ganglion

• alpha 1 : sphincter contraction
• beta 2: detrusor relaxation

Question 12

Alpha 1 Receptors

Answer 12

1) post-synaptic adrenoreceptors in smooth muscle
- activation –> increased Calcium –> contract smooth muscle –> vasoconstriction
2) inhibits insulin secretion
3) (+) inotropic effect on heart

Question 13

Alpha 2 Receptors

Answer 13

1) Presynaptic nerve terminals –> inhibits adenylyl cyclase –> decreased Calcium –> limits amount of NE released
* stimulation of alpha 2 in CNS –> sedation and decreased sympathetic outflow

Question 14

Beta 1 Receptors

Answer 14

1) Postsynaptic membranes of heart –> (+) adenylyl cyclase –> kinase phosphorylation –> (+) chronotropy and inotropy
* Equal potency for NE and Epi

Question 15

Beta 2 Receptors

Answer 15

1) Postsynaptic receptors in smooth muscle –> (+) adenylyl cyclase –> smooth muscle relaxation
* bronchodilation, vasodilation*
* Epi > NE in potency

Question 16

Beta 3 Receptors

Answer 16

found in gallbladder and brain adipose tissue

Question 17

Dopaminergic Receptors

Answer 17

activated by dopamine
D1 = vasodilation of heart, kidney, gut
D2 = antiemetic (droperidol)

Question 18

Phenylephrine

Answer 18

DIRECT non-catecholamine
- pure alpha 1 agonist -> vasoconstriction
- SHORT acting (10-15 minutes)
- reflex bradycardia
Dose: 50-100 mcg bolus

Question 19

Clonidine

Answer 19

Alpha 2 agonist

• anti-hypertensive and (-) chronotropy
• sedative and anxiolytic
• circulatory stability by decreasing catecholamine levels

Question 20

Dexmedetomidine

Answer 20

PURE alpha 2 agonist –> acts centrally on locus cereleus –> sedative, analgesic, sympatholytic effect
*can reduce other anesthetic needs intraop
*good in the ICU for sedation/extubation
**short t1/2 = 2-3 hrs
**prolonged duration = upregulation of receptors
Hypotension and Bradycardia

Question 21

Milrinone

Answer 21

PDE-3 inhibitor (vasodilator) –> needs loading dose
(+) inotropy, chronotropy, lusitropy => vasodilation
*GREAT for R heart failure and pulm HTN

Question 22

Epinephrine

Answer 22

endogenous catecholamine from the adrenal medulla
- direct beta1 stimulation -> increased BP, CO, HR, contractility
- alpha 1 stimulation -> vasoconstriction
*decreased splanchnic and renal blood flow
*increased coronary perfusion pressure (ADP - LVEDP)
Dose: 0.05-0.1 mg boluses
100-500 mcg for anaphylaxis

Question 23

Effects of Epi with differing doses

Answer 23

Lower dose = beta > alpha

Higher dose = alpha > beta

Question 24

Ephedrine

Answer 24

indirect noncatecholamine sympathomimetic - plant derived
- alpha 1 stimulation : vasoconstriction
- beta 1 stimulation : increased HR
Dose: 2.5-10 mg boluses
*have to increase subsequent doses to avoid tachyphylaxis

Question 25

Norepinephrine

Answer 25

``` DIRECT alpha 1 stimulation -> intense vasoconstriction or arterial and venous systems - beta 2 activity * mild reflexive bradycardia Dose: 0.1 mcg/kg bolus 2-20 mcg/min for infusions ```

Question 26

Dopamine

Answer 26

endogenous nonselective direct and indirect adrenergic and dopaminergic agonist - promotes the release of NE from presynaptic membranes Dose: 1-20 mcg/kg/min for infusion

Question 27

Doses of Dopamine

Answer 27

Low dose: dopaminergic (vasodilation and diuresis) Moderate: beta 1 stim (increased HR, CO) High : alpha 1 effects (increased SVR)

Question 28

Isoproterenol

Answer 28

PURE beta agonist - beta 1 = increased HR, contractility and CO - beta 2 = decreased PVR * drops myocardial oxygen supply while increasing demand

Question 29

Dobutamine

Answer 29

racemic mixture of 2 isomers w/ affinity for beta 1 and 2 receptors - increased CO and contractility - drops LV filling pressure = increases coronary blood flow DOSE: 2-20 mcg/kg/min

Question 30

Phentolamine

Answer 30

competitive blocker of alpha 1 and 2 receptors - alpha 1: peripheral vasodilation -> decreased MAP - reflexive tachycardia - alpha 2: augments tachycardia by promoting NE release

Question 31

Labetalol

Answer 31

``` blocks alpha 1, beta 1, beta 2 receptors - decreased PVR and BP - HR and CO are unchanged/decreased - peaks in 5 minutes, lasts 5 hours DOSE: 2.5-10 mg ```

Question 32

Esmolol

Answer 32

ULTRA short acting selective beta 1 blocker - drops HR w/ some BP effect - shortest duration due to rapid redistribution and hydrolysis by RBCesterase (10 minutes) Dose: anywhere from 10-60 mg

Question 33

Metoprolol

Answer 33

selective beta 1 antagonist w/ no intrinsic sympathomimetic activity - every 2-5 minutes as needed DOSE: 2.5-5 mg boluses

Question 34

Propranolol

Answer 34

nonselective beta 1+2 blocker - lowers BP by: - decreasing contractility, HR, renin release - slows AV nodal conduction *Great for thyrotoxicosis, pheochromocytoma SE: bronchospasm, CHF, bradycardia, heart block

Question 35

Nebivolol

Answer 35

newer beta-blocker w/ beta 1 selectivity | - direct vasodilation by stimulating endothelial NO synthetase

Question 36

Carvedilol

Answer 36

Mixed alpha and beta blocker | - GREAT for CHF