CCBs Flashcards
How many types of Ca channels are there?
4
What are L-channels responsible for?
inward movement of Ca into skeletal, cardiac and smooth muscle
What do CCBs treat?
angina
hypertension
AF
What do CCBs block?
block the flow of Ca ions into heart muscle cells and arteries
Classes of CCBs
- 1,4-Dihydropyridine
- Benzothiazepines
- Phenylalkylamines
How do they block Ca ion flow?
they bind at specific sites in the open form of the channel
Is there structural similarity between classes?
no
Example of a benzothiazepine drug
diltiazem
Phenylalkylamine drug
verapamil
1,4-Dihydropyridine drug
amlodipine
nifedipine
What does each contain?
an amine
What does the amine allow for?
oral administration
because it can form water soluble hydrochloride salt
Does first pass metabolism take place?
yes
What first pass metabolism happens to amlodipine?
aromatic hydroxylation
dihydropyridine oxidation
What first pass metabolism happens to verapamil?
N and O demethylation
What first pass metabolism happens to diltiazem?
hydrolysis
Where are 1,4-dihydropyridine Ca channels located?
vascular smooth muscle
Where are benzothiazepine Ca channels located?
cardiac muscle
Where are phenylalkylamine Ca channels located?
cardiac muscle
What 2 CCBs have an synergistic effect?
dihydropyridines and benzothiazepines
Plasma half life of nifedipine
1.5 - 2 hrs
What metabolic transformation occurs in nifedipine?
oxidation
gives a pyridine, loses 2 Hs
What is amlodipine administered as?
as a racemate
maleate salt
Which isomer of amlodipine is x1000 more active?
S isomer
What reduces activity at N1 on 1,4-dihydropyridine?
substitution
What can be added to C 2/6 on dihydropyridine to add to activity?
small groups
CH3
CHO
CN
What decreases activity on C 2/6 on dihydropyridines?
H or Ph
What is essential at C4 in dihydropyridine?
phenyl ring
What needs to be at C3 on dihydropyridines?
ester group
What adds lipophilicity at C5 on duhyfropyridines?
ester
How many chiral centers in diltiazem?
2
Which from is x10 more active in diltiazem?
cis form
What can diltiazem also be prescribes as?
inhibitor of CTP3A4
What is verapamil administered as?
a racemate
hydrochloric salt
What is the active metabolite of verapamil?
norverapamil
