Pharm - Lecture 8 - Adrenergic antagonists

Question 1

What is the mechanism of adrenergic neuron blockers?

Answer 1

drugs that disrupt the synthesis, storage or release of norepinephrine

Question 2

Which drugs are Adrenergic neuron blockers? (3)

Answer 2

1) Guanethidine
2) Guanadrel
3) Reserpine

Question 3

What is the mechanism of Guanethidine and Guanadrel? (2)

Answer 3

Inhibits norepinephrine release and depletes neuronal amine stores

Question 4

What is the therapeutic use of Guanethidine and Guanadrel?

Answer 4

Severe hypertension

Question 5

What is the difference between Guanethidine and Guanadrel?

Answer 5

Guanethidine is a polar compound that does not enter the CNS

Question 6

How are Guanethidine and Guanadrel taken up into the cell?

Answer 6

NET - therfore they are inhibited by tricyclic antidepressants that inhibit NET

Question 7

What are the side effects of Guanethidine and Guanadrel?

Answer 7

Many side effects: orthostatic hypotension, interferes with sexual function, diarrhae, muscle weakness, edema

Question 8

What is the mechanism of Reserpine?

Answer 8

It inhibits he vesicular monamine oxidase transporter 2 (VMAT2) therby inhibiting the synthesis of norepinephrine

Question 9

How does Reserpine get into the cell?

Answer 9

diffusion (does not need VMAT2)

Question 10

What is the therapeutic use of Reserpine?

Answer 10

treats essential hypertension - rarely used

Question 11

What are the side effects of Reserpine?

Answer 11

Many CNS side effects, depression, suicide, sedation

Other side effects: diarrhae, orthostaic hypo-tension, increased gastric acid secretion

Question 12

What is Reserpine’s length of onset and how long does it last?

Answer 12

Slow onset and Long acting

Question 13

What is the mechanism of adrenergic receptor blockers?

Answer 13

Agents produce their major actions by inhibiting alpha and beta receptors. Both exogenously administered as well as endogenously released catecholamines are blocked

Question 14

What drugs are alpha adrenergic receptor antoganists? (4)

Answer 14

1) Phenoxybenzamine
2) Phentolamine
3) Prazosin
4) Tamsulosin

Question 15

Which receptors does Phenoxybenzamine and Phentolamine block?

Answer 15

a₁ and a₂

Question 16

What is the mechanism of Phenoxybenzamine?

Answer 16

Irreversible antagonist via covalent bonding with receptor. New receptors need to be synthesized, so it is very long lasting

Question 17

What is the effect of Phenoxybenzamine?

Answer 17

produces vasodilation proportional to the degree of sympathetic tone

Question 18

What is the mechanism of phentolamine?

Answer 18

Competitive reversible antagonist

Block can be overcome by increasing the agonist

Question 19

What is the therapeutic use of Phenoxybenzamine? (2)

Answer 19

1) pheochromocytoma
2) To reverse or shorten the duration of soft-tissue anesthesia produced by combined local anesthetic and sympathomimetic

Question 20

What is the therapeutic use of Phentolamine? (3)

Answer 20

1) hypertension
2) pheochromocytoma
3) to reverse or shorten the duration of soft tissue anesthesia produced by combined local anesthetic and sympathomimetic

Question 21

What are the side effects of phenoxybenzamine and phentolamine? (2)

Answer 21

1) tachycardia and salt/water retention (edema)
2) Orthostatic hypotension

Question 22

What is the mechanism of Prazosin? How is it administered?

Answer 22

orally active - competitive blocker of a₁ receptors

Question 23

What is the effect of Prazoisn?

Answer 23

1) minimal tachycardia
2) decreases vascular tone in resistance (arterioles) and capacitance (veins)
3) produce favorable lipid profile: low LDL, high HDL

Question 24

Why is reflex tachcardia less problamatic with Prazosin?

Answer 24

Prazosin doesn’t block the pre-synpatic a₂ receptors very much

Question 25

What are the major therapeutic uses of Prazosin?

Answer 25

1) hypertension 2) short-term treatment of congestive heart failure (because of preload and afterload reducing agent) 3) Benign prostatic hyperplasia (BPH) - relaxes a₁ mediated contraction of prostate and bladder neck that contributes to resistance to urine flow

Question 26

What are the side effects of prazosin?

Answer 26

1) "first dose" phenomenon - hypotension and syncope 30-90 minutes after first dose 2) presistent orthostatic hypotension 3) salt and water retention (edema)

Question 27

What is the mechanism and receptor selectivty for Tamsulosin?

Answer 27

a₁ receptor antagonist with ome selectivity for a_1A versus a_1B (favors a_1A receptor blockage in prostate)

Question 28

What is the therapeutic use of Tamsulosin?

Answer 28

Effective for treatement of BPH with little effect on blood pressure Not approved for treatmenet of hypertension

Question 29

What are the non-selective beta adrenergic receptor antagonists?

Answer 29

1) Propranolol 2) Timolol 3) Metoprolol 4) Atenolol

Question 30

What is the mechanism and receptor specificty of Propranolol?

Answer 30

Competitive reversible blockade of both B₁ and B₂ receptors

Question 31

What are the therapeutic uses of Propanolol? (5)

Answer 31

Hypertension Angina cardiac arrhythmias due to excess catecholamines or that respond to a reduction in heart rate/AV conduction velocity Acute myocardial infarction migraine prophylaxis

Question 32

What are the side effects of Propranolol? (4)

Answer 32

Cardiac depression, bradycardia/heart block May increase airway resistance Mask sympoms of hypoglycemia sedation, impotence, nightmares

Question 33

What types of patients should you be warry about giving Propranolol to? (6)

Answer 33

Patients with: Asthma CHF bradyarrhythmias, AV block insulint-dependentdiabetes prone to hypoglycemic episodes hypotension vasopastic angina

Question 34

What is the mechanism for Timolol?

Answer 34

Non-selective beta receptor antagonist?

Question 35

What is the therapeutic use of Timolol?

Answer 35

Similar to propranolol along with treatment of wide angle glaucoma

Question 36

What is the mechanism of Metoprolol?

Answer 36

Competitive, reversible B₁ receptor blocker (low doses it is more selective at blocking the B₁ receptor)

Question 37

What is the therapeutic use of metoprolol?

Answer 37

Similar to propranolol - also used to treate heart failure

Question 38

What is the mechanism of Atenolol?

Answer 38

B₁ receptor antagonist

Question 39

What is the therapeutic use of Atenolol?

Answer 39

Similar to propranolol (except for migraine prophylaxis)

Question 40

What is the mechanism of Labetalol?

Answer 40

Competitive antagonist of a₁ receptor and both B receptors (non-selective)

Question 41

What is the therapeutic use of Labetalol?

Answer 41

Essential hypertension and hypertensive emergencies

Question 42

What is the mechansim of Carvedilol?

Answer 42

Competitive antagonist of a₁ receptor and both B receptors (non-selective)

Question 43

What is the effect of Carvedilol? (2)

Answer 43

1) anti-oxidant properties and anti-inflammatory effects 2) blocks L-type calcium channels at higher doses

Question 44

What is the therapuetic use of Carvedilol? (3)

Answer 44

1) CHF 2) Hypertension 3) Acute MI