Classification: Group of compounds which selectively interfere with inward calcium ion movement across myocardial and vascular smooth muscle.

Four classes-

Class I: Phenyl alkyl amines:

1. Verapamil

Class II: 1 ,4 dihydroxy pyrimidines:

1. Nifedipine
2. Nicardipine
3. Nimodipine
4. Israpidine
5. Felodipine
6. Amlodipine

Class III: Benzothiazines

• Diltiazem

Class IV: Di aryl amino propyl amine

• Ether (Ltype) eg: bepridil

 

Mechanism

Voltage gated calcium ion channels are present in cell membrane of skeletal muscles , vascular, smooth muscles, cardiac muscles, mesenteric muscle, glandular cells and neurons

Two types :

1. L type: slow sustained release
2. T type: notmuch affected by drugs

L type : 5 sub units

• Alpha 1
• Alpha 2
• Beta
• Gamma
• Delta

Excitation –  Contraction – Coupling

Calcium combines with calmodulin – calcium binds to protein to form the calcium calmodulin complex

This complex activates myosin and causes the formation of cross bridges with actin .These cross bridges begin muscle contraction

Phenyl alkyl amines:

Bind to L type channel alpha subunit when channel is an open state and actually occlude the channel

1-4- dihydropyridines:

Prevent calcium entry into vascular smooth cells by extracellular alllosteric modulation of Ltype voltage gated calcium channels

Benzothiazeoines:

L type channel alpha subunit

Mainly act on Na+ K+ , decreasing amount of intracellular sodium available for exchange with extracellular calcium and may inhibit calcium calmodulin binding

 

Comparitive Pharmacological Effects

SrNo	SPEC.	VERAPAMIL	NIFEDIPINE	NICARDIPINE	DILTIAZEM
1	SYSTEMIC BP	Decrease	Decrease	Decrease	Decrease
2	HEART RATE	Decrease	Increase/ No Change	Increase/ No Change	Decrease
3	MYOCARDIAL DEPRESSION	Moderate	Moderate	Slight	Moderate
4	SA NODE ACTIVITY	Moderate	None	None	Slight
5	CORONARY ARTERY DILATATION	Moderate	Marked	Gretest	Moderate
6	PERIPHERAL
7	ARTERTY DILATATION	Moderate	Marked	Marked	Moderate

 

 

 

VERAPAMIL

☛ Synthetic derivative of papaverine
☛ Dextro isomer acts as fast Na channel accounting for local anaesthetic effects

 

Side effects

☛ Major depression of AV node
☛ Negative ionotropic effects on coronary and systemic arteries – exaggerates in LV dysfunction

 

Clinical uses

1. Increase supra ventricular tachy dysarrythmias -à Drug Of Choice
2. Maternal and fetal tachdysrythmias amninister drug to patients verapa,ilprolonngs A V conduction of fetus despite limited placental transport of drug

pHk

oral verapamil – extensive hepatic first pass metabolism 80-160mg tds

 

NIFEDIPINE

Greater coronary and peripheral arterial vasodilator than verapamil

Peripheral vasodilatation and decrease systolic BP activates baroreceptors leading to increase peripheral venous sympatheic system activity

This increase sympathetic activity contains all negative ionotropic ,  chronotropic , dromotropic effects of nifedipine

Clinical uses:

1. 10 – 20 mg orally 3 times
2. Sublingual dose in HTN emergency shows increase CVA, myocardial ischaemia and severe hypotension

 

Side effects

☛ flushing , vertigo , headache , less common S/e: peripheral vasodilatation ,hypotension , parasthesias and skeletal muscle weakness
☛ Abrupt disease: coronary artery vasospasm

 

NICARDIPINE

Greatest coronary artery vasodilatation

 

NIMODIPINE

Higlhy lipid soluble so facilitates entrance into central nervous system
Uses: ability to cross bllod brain barrier is responsible for potential use in intracranial pathology attenuating cerebral vasospam
Dose: 0.7 mg/kg orally on initial dosage and then o.35 mg/kg 4 hours after 21 days

Cerebral protection after global ischaemia as associated with cardiac arrest

 

DILTIAZEM

☛ First line drug in supraventricular tachydysrthymias
☛ IV DOSAE:0.25 mg/kg over 2min repeated in 15minutes

Druginteraction: with inhalational anaesthetics myocardial depression is exaggerated

Anaesthetic drugs:

With fentanyl no additive depression of cardiac function

Neuro muscular bloackage skeletal muscle relaxation potientiate effect of depolarization and undepolarisation muscle relaxant

K= solutions: they slow the inward movement of K+ ion so hyperkalemia can be observed

 

Dantrolene:

Verapamil potentiates dantrolene action and can be  used with it  in malignant hyperthermia

Platelet function: CA channel blockers increase concentration of digoxin in plasma

Uses: Decrease mvo2 BY Decrease HR nad  contractility and decrease BP . dilatation of coronary and collateral vessels

☛ Symptomatic control of stableangina pectoris
☛ Situation for rate control when beta blocklers cant be used
☛ Treatment variant angina
☛ Different from betablocker in  preservation of coronary blood flow.

 

dr.ajita