Exam 4 - Lecture 44, Medical Chemistry Adrenergic Antagonists

Question 1

Reserpine

Answer 1

binds tightly for prolonged period of time to adrenergic storage vesicles in CNS and PNS

decreases storage of NE and DA which leak into cytoplasm, Ne and DA gets metabolized by MAO

Question 2

Guanethidine

Answer 2

acts by inhibiting the release of NE

PNS only cause doesn’t cross BBB, drug always charged

antihypertensive drug

Question 3

Phenoxybenzamine

Answer 3

forms covalent bond with receptor (N-2C-Cl), forms aziridinium intermediate. happens in basic forms

New receptors have to be made before effect can be overcome

non-selective a antagonist

Question 4

prazosin

Answer 4

contains piperazinly quinazoline nucleus

up to 1000 times selective for a1 over a2

Terazosin - 18hr, 90% Bio av
Doxazosin - 36hr, 50-70% bio avi

Prazosin - 7-10hr, 50-70% Bio avi

Question 5

Indoramin

Answer 5

poor oral bio avail <30% and undergoes extensive first pass

Question 6

Aryloxypropanolamines

Answer 6

added oxymethylene bridge to molecule and it started working well.

angina, antihypertensive, and cardia arrhythmia

OH essential for H-bond
O involved in H binding too
Branching important to fit hydrophobic pocket

Question 7

Nadolol

Answer 7

Difference between propranolol, has 2 OH on ring making it hydrophilic.

high water soluble drugs cleared by kidney
more lipophilic drugs cleared by liver

Question 8

Sotalol

Answer 8

Has 1 ring not 2 like propranolol, and no oxymethyline bridge

Question 9

timolol

Answer 9

hydrophilic, cleared by kidney primarily

Question 10

Metipranolol

Answer 10

exception for para substitution rule which would make it selective for B1

drug is nonselective to b1/b2

Question 11

Esmolol

Answer 11

COO linkage is where esters chop and make it useless, which is why it has very short duration of action

Question 12

Labetalol

Answer 12

b blocking is about 1.5 time that of a blocking

Question 13

carvedilol

Answer 13

b blocking is about 10-100 times that of a blocking