Chemistry of Antihypertensives Flashcards
How does calcium affect the vasculature
When there is a calcium influx the arteriole will start to contract
What are the three drug structures for calcium channel blockers on the market, what are examples for each one
1.4-dihydro-pyridines (nifedipine), Phenylalkylamines (verapamil), Benzothiazepines (Diltiazem)
T/F: Calcium channel blockers are selective for the long lasting type high-voltage activated calcium channel blockers
True
What are the three calcium channel conformations
open, inactive, resting
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.
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
How does Verapamil enter the channel
Verapamil enters the back of the cell and enters the channel from the cytoplasmic side
How does 1,4 DHPs and Diltiazem enter the channel
Enter the channel extracellularly
What state of the calcium channel does 1,4 DHPs prefer
Inactive state
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
False: None of the Verapamil cannot be used at the same time as 1,4 DHP and Dilitazem because they have negative allosteric activity
T/F: Diltiazem and 1.4 DHPs mutually enhance the binding of each other
True
Which isomer of verapamil is most active
R isomer
Verapamil is quickly absorbed after oral administration because of what, when does it reach peak plasma concentrations
High Lipid solubility, 1 and 2 hours after oral administration
Verapamil can inhibit what efflux protein, leading to what
P-gp, drastic increase in the intestinal absorption of other P-gp substrate drugs such as digoxin
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
True
For 1,4 DHPs an ortho or met subsituted where at what carbon leads to optimal CCB activity
C4 on the phenyl ring
T/F: 1,4 DHPs do like bulk because the substituents lock them at a 90 degree angle needed for activity
True
What functional groups at C3 and C5 position provide the most optimal CCb activity
Ester groups
How do 1,4 DHPs become inactive in the body, what enzyme causes this
Remove the hydrogen at the 1 position, CYP3A4
T/F: No food or drink needs to be avoided when taking 1,4 DHPs
False: Co-administration with grapefruit jucie can lead to increased systemic concentration of the 1,4 DHPs
What functional groups are usually in positions 2 and 6
methyl groups
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
Clevidipine
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
True
What cause antagonism of Beta-adrenergic receptors
The removal of the hydroxy groups
What makes B1-Adrenergic antagonists selective
Substitution at the para stie
What are side effects of lipophillic non selective Beta-blockers
CNS side effects such as dizziness, confusion, or depression
What are two Mixed alpha/beta adrenergic antagonists
Labetalol, Carvedilol
Which drug is a pro-drug that crosses the BBB, turns into a alpha-1 agonist
Methyldopa
Which drug is a centrally active alpha 2 agonist
Clonidine
Which drug is a arterial vasodilators
Hydralazine
