Chemistry of Antihypertensives

Question 1

How does calcium affect the vasculature

Answer 1

When there is a calcium influx the arteriole will start to contract

Question 2

What are the three drug structures for calcium channel blockers on the market, what are examples for each one

Answer 2

1.4-dihydro-pyridines (nifedipine), Phenylalkylamines (verapamil), Benzothiazepines (Diltiazem)

Question 3

T/F: Calcium channel blockers are selective for the long lasting type high-voltage activated calcium channel blockers

Answer 3

True

Question 4

What are the three calcium channel conformations

Answer 4

open, inactive, resting

Question 5

T/F: Calcium Channel Blockers are most effective when membrane depolarization is either short, moderate, and infrequent. They can also work when the channel is at any state.

Answer 5

False: Calcium Channel blockers are most effective when membrane depolarization is either longer, more intense, or more frequent. They only work when the channel is either open or inactive

Question 6

How does Verapamil enter the channel

Answer 6

Verapamil enters the back of the cell and enters the channel from the cytoplasmic side

Question 7

How does 1,4 DHPs and Diltiazem enter the channel

Answer 7

Enter the channel extracellularly

Question 8

What state of the calcium channel does 1,4 DHPs prefer

Answer 8

Inactive state

Question 9

T/F: Verapamil cannot be used at the same time as 1,4 DHP or dilitazem because they all compete for the same binding site

Answer 9

False: None of the Verapamil cannot be used at the same time as 1,4 DHP and Dilitazem because they have negative allosteric activity

Question 10

T/F: Diltiazem and 1.4 DHPs mutually enhance the binding of each other

Answer 10

True

Question 11

Which isomer of verapamil is most active

Answer 11

R isomer

Question 12

Verapamil is quickly absorbed after oral administration because of what, when does it reach peak plasma concentrations

Answer 12

High Lipid solubility, 1 and 2 hours after oral administration

Question 13

Verapamil can inhibit what efflux protein, leading to what

Answer 13

P-gp, drastic increase in the intestinal absorption of other P-gp substrate drugs such as digoxin

Question 14

T/F: Is well absorbed due to its lipid solubility but is extensively metabholized, It can stay active as long as the methoxy group is not de-methylated

Answer 14

True

Question 15

For 1,4 DHPs an ortho or met subsituted where at what carbon leads to optimal CCB activity

Answer 15

C4 on the phenyl ring

Question 16

T/F: 1,4 DHPs do like bulk because the substituents lock them at a 90 degree angle needed for activity

Answer 16

True

Question 17

What functional groups at C3 and C5 position provide the most optimal CCb activity

Answer 17

Ester groups

Question 18

How do 1,4 DHPs become inactive in the body, what enzyme causes this

Answer 18

Remove the hydrogen at the 1 position, CYP3A4

Question 19

T/F: No food or drink needs to be avoided when taking 1,4 DHPs

Answer 19

False: Co-administration with grapefruit jucie can lead to increased systemic concentration of the 1,4 DHPs

Question 20

What functional groups are usually in positions 2 and 6

Answer 20

methyl groups

Question 21

What is the name of 1,4 DHP that is intended for i.v use and has a half-life of 1-2 minutes after i.v administration

Answer 21

Clevidipine

Question 22

T/F: When replacing methyl esters with NO2 group the 4th carbon became optically active creating R and S sites that have activation and blocking activity

Answer 22

True

Question 23

What cause antagonism of Beta-adrenergic receptors

Answer 23

The removal of the hydroxy groups

Question 24

What makes B1-Adrenergic antagonists selective

Answer 24

Substitution at the para stie

Question 25

What are side effects of lipophillic non selective Beta-blockers

Answer 25

CNS side effects such as dizziness, confusion, or depression

Question 26

What are two Mixed alpha/beta adrenergic antagonists

Answer 26

Labetalol, Carvedilol

Question 27

Which drug is a pro-drug that crosses the BBB, turns into a alpha-1 agonist

Answer 27

Methyldopa

Question 28

Which drug is a centrally active alpha 2 agonist

Answer 28

Clonidine

Question 29

Which drug is a arterial vasodilators

Answer 29

Hydralazine