CVD WK8 CCB

What are the four classes of calcium channel blockers?

1,4-dihydropyridines, phenylalkylamines, benzothiazepines, diaminopropanol ethers

What is the example of a 1,4-dihydropyridine?

Nifedipine, Amlodipine

What is the example of a phenylalkylamine?

Verapamil

What is the example of a benzothiazepine?

Diltiazem

What is the selectivity of 1,4-dihydropyridines?

Vascular smooth muscle (vasodilation)

What is the selectivity of phenylalkylamines?

Cardiac (heart)

What is the selectivity of benzothiazepines?

Intermediate (heart and vessels)

What is the clinical use of dihydropyridines?

Hypertension, angina

What is the clinical use of verapamil?

Cardiac arrhythmias, angina

What is the clinical use of diltiazem?

Angina, hypertension

What is the core structure of dihydropyridines?

1,4-dihydropyridine ring

What is the Hantzsch synthesis?

Classic synthesis of 1,4-dihydropyridines (aldehyde + β-ketoester + ammonia)

What is allosteric binding?

Binding at a site different from the active site, affecting binding at other sites

What are the three binding sites on the L-type channel?

Dihydropyridine site (DHP), Phenylalkylamine site (PA), Benzothiazepine site (BTZ)

Which CCB binds to the DHP site?

1,4-dihydropyridines (nifedipine)

Which CCB binds to the PA site?

Phenylalkylamines (verapamil)

Which CCB binds to the BTZ site?

Benzothiazepines (diltiazem)

What is the L in L-type calcium channel?

Long-lasting (sustained calcium influx)

Which subunit of the L-type channel forms the pore?

α1 subunit

What type of channels are L-type calcium channels?

Voltage-gated, high voltage activated

What is the difference between dihydropyridines and verapamil?

Dihydropyridines are vascular selective; verapamil is cardiac selective

What is the difference between dihydropyridines and diltiazem?

Dihydropyridines are vascular selective; diltiazem is intermediate

What is the nifedipine structure?

1,4-dihydropyridine ring with nitrophenyl, dimethyl esters, and methyl groups

What is the effect of CCBs on blood vessels?

Vasodilation

What is the effect of verapamil on the heart?

↓ Heart rate, ↓ contractility

What is the effect of diltiazem on the heart?

↓ Heart rate, ↓ contractility (less than verapamil)

What is the clinical use of CCBs?

Hypertension, angina, arrhythmias (verapamil)

Why do CCBs have different clinical effects?

They bind to different sites on the L-type channel with different tissue selectivities

What does allosteric mean?

Affecting binding at a different site - CCBs bind to different sites that affect each other