Adrenergic Pharmacology

Question 1

What are the examples of adrenergic receptors?

Answer 1

Alpha1, Alpha2, Beta1, Beta2, Beta3

Question 2

What type of adrenoreceptor causes increase in heart rate?

Answer 2

B1 Adrenoreceptor,
It is distributed at the heart, and juxtaglomerular cells,
It causes the increase in farces and rate of contraction; increase renin release

Question 3

Phenylephrine is a1 agonist, what is the clinical usage?

Answer 3

clinically useful for treatment of hypotension and shock, although it is not commonly used for this purpose.
causes hypertension, reflex bradycardia, restlessness

Question 4

Clonidine (agonist) clinical use

Answer 4

decrease BP thriugh central effects (presynaptic a2 receptors in lower brainstem)

Question 5

Dobutamine (mainly B1 agonist with some a1 agonist)

Answer 5

indicated for cardiogenic shock
Increases cardiac output without vasoconstriction. It increases the force of contraction with much less effort on heart rate and conduction.
given IV under close supervision

Question 6

Salbutamol

Answer 6

B2 adrenoreceptors
direct action
dilate the bronchi (smooth muscle)
-given via inhalation
ADRs -tremors, -tachycardia

Question 7

Tyramine

Answer 7

Inc Norepinephrine

Question 8

Amphetamine

Answer 8

Stimulate central NA release (also MAO inhibitor, NET inhibitor)
CNS stimulant (elevation of mood, self-confidence, alertness and ability to concentrate)-drug abuse
ADRs-

Question 9

What is the pathway for the synthesis of catecholamines?

Answer 9

1. Tyrosine (tyrosine hydroxylase)
2. DOPA (DOPA decarboxylase)
3. Dopamine (Dopamine beta-hydroxylase)
4. Norepinephrine (phenylethanolamine N-methyltransferase)
5. Epinephrine (this last step doesn’t occur at the nerve endings)

Question 10

Phenoxybenzamine

Answer 10

Non-competitive, non selective alpha adrenergic receptor antagonist.
Decrease peripheral resistance, with reflex sympathetic activation.
-used to treat adrenal medulla and sympathetic neurons that secrete enormous quantities of catecholamines.

Question 11

What are some of the examples of Alpha-adrenoceptor antagonist?

Answer 11

-Phenoxybenzamine
-Prazosin
-Phentolamine
-Yohimbine
Terazosin

Question 12

Prazosin

Answer 12

Selective Alpha1 receptor antagonist (1000-fold less potent at Alpha2 receptors)
produce less reflex tachycardia compared with other alpha-adrenoceptor antagonists.
Syncopal reactions may follow the first dose of prazosin
- Treatment of primary hypertension

Question 13

What are some of the examples of Beta-adrenoceptor antagonist?

Answer 13

• Propanolol
• Nebivolol
• Carvedilol
• Atenolol

Question 14

MOA

Answer 14

in hypertension - negative chronotropic/inotropic effects. - Reductin of beta1-stimulated renin release from juxtaglomerular cells

Question 15

Propanolol

Answer 15

Non-selective Beta-adrenoceptor antagonist (both beta 1 and beta 2)

• Treat various arrhythmias, myocardial infarction, congestive heart failure, pheochromocytoma
• antiarrhythmic effect

metabolized by liver and elimination is through hepatic metabolism

Question 16

Propanolol (additional function)

Answer 16

blunt glycogenolysis and may delay recovery from hyperglycemia in type1 diabetes mellitus.
– can also blunt the perception of hyperglycemia symptons– tremor, tachycardia, nervousness

Question 17

Atenolol

Answer 17

Beta-adrenoceptor antagonist (selective for beta 1) —->Selectivity is dose related; it tends to diminish at higher drug concentration.

Question 18

Nebivolol

Answer 18

Most highly selective Beta1 adrenergic receptor blocker

*Has additional quality of eliciting vasodilation –> due to the action of the drug on endothelial nitric oxide production.

Question 19

Carvedilol

Answer 19

Nonselective B-receptor antagonist, some capacity to block alpha1 adrenergic receptors
Antagonizes the actions of cathecholamines more potently at B-receptors than a1-receptors.

free radical scavenger that may protect heart cells from damage. Treats patients with congestive heart failure.

Question 20

What effects will you have on vasodilation/vasoconstriction if you add epinephrine?

Answer 20

low dose = decrease in blood pressure due to vasodilation. This is because beta2 adrenoceptors are fewer in number but more sensitive than alpha adrenoceptors.

high dose = increase in blood pressure due to vasoconstriction and vasoresponse. This is because alpha adrenoceptors are more numerous but not as sensitive as beta 2 receptors.

Question 21

How is the synthesis of NE and EPI “controlled”?

Answer 21

Through a negative feedback system. NE and EPI act on tyrosine hydroxylase to inhibit further hydroxylation of tyrosine. This is the rate limiting step in sympathetic nerve terminals and for epinephrine in the adrenal gland.

(can refer pictures in lecture notes)

Question 22

What are the effects of epinephrine on the body?

Answer 22

Epinephrine acts via beta-adrenoceptor mechanisms to increase adenylate cyclase activity to form the second messenger cAMP that has the following metabolic effects:

1. increases plasma glucose by breakdown of liver glycogen
2. inhibits synthesis of glycogen
3. stimulates gluconeogenesis
4. breaks down fat (triglycerides) to fatty acids

Question 23

What are the catecholamine reuptake inhibitors?

Answer 23

Cocaine and Tricyclic Antidepressants

Question 24

What are the implications of catecholamine reuptake inhibitors?

Answer 24

Those inhibitors can be a problem if you administer them with other drugs that need to get into the nerve terminal to act. If you block the channel, you can’t get NE or any of the other drugs in. Some of those drugs are:

1. tyramine
2. guanethidine
3. 6-OH dopamine

Question 25

Trimethaphan

Answer 25

Occasionally used in treatment of hypertensive emergencies and dissecting aortic aneurysm
(can reduce bleeding in surgery)