Home » Pharmacology » Calcium – Channel Blockers as Antihypertensive Drugs

Calcium – Channel Blockers as Antihypertensive Drugs

There are two types of calcium channels:

  1. Voltage gated
  2. Receptor operated
Type of Voltage gated Calcium Channels

Voltage gated channels open and close at a specific voltage. All types are found in neurons.

L Type -Muscle, Neurons ,Heart

T Type -Neurons , Heart, (thalamic neurons)           

N Type -Neurons

P Type -Cerebellar purkinje neurons

R Type -Neurons

Mechanism of Action
Blood Vessels

Arterioles are more sensitive to the effects of Ca++ channel blockers. They cause decrease in the entry of Ca++ leading to decreased Ca-calmodulin complex, decreased activation of myosin light chain kinases, resulting in dephosphorylation producing vasodilatation. This decreases blood pressure, preload and after load.

Cardiac Muscles

In cardiac muscles when given, cause decrease in entry of Ca++ into cardiac muscles. Cardiac muscles are dependent on Ca++ for normal activity. Impulse generation in SA node, conduction through AV node, excitation-contraction coupling and ultimately the contractility of heart, all decrease by the action of Ca++ channel blockers. This in turn leads to decreased cardiac output.

Dihydropyridines

Dihydropyridines have more affinity for smooth muscles of blood vessels. However, verapamil and diltiazem have more effects on cardiac muscles

Pharmacokinetics

They are well absorbed after oral administration. However, they have extensive first pass metabolism, this is why their bioavailability is decreased. They are also extensively bound to plasma proteins.

Drug Bioavailability Plasma protein binding
Nifedipine 55% 95%
Diltiazem 50% 80-85%
Verapamil 20% 90%

Half life varies between 4-5 hours; however, nifedipine has half life of 1.5 hours.

They are eliminated in urine, except diltiazem which is excreted in faeces.

Other Pharmacological Effects

1. Effect on other smooth muscles- bronchiolar, gastrointestinal , uterine & vascular muscles

Most smooth muscles are dependent on influx of Ca++ for tone and contractility, Ca++ blockers relax them.

2. Cardiac muscles

Effect AV conduction and contractility of heart, which are depressed by Ca++ channel blockers, thus are having cardio depressant effect.

3. Action on Skeletal muscles

Not depressed by Ca++ channel blockers as they use intracellular pools of Ca++ for their contractility, thus are not dependent on transmembrane Ca++ influx.

4. Cerebral vasospasm & infarct following subarachnoid hemorrhage

Among dihydropyridines, Nimodipine has affinity for cerebral blood vessels, so it is used to relieve cerebral vasospasm and infarcts.

5. Decreased release of insulin

Verapamil has been shown to inhibit the release of insulin, but the dose required is much higher.

6. Interfere with platelet aggregation

Due to interfere with platelet aggregation, preventing development of atheromatous lesions. However, this is not utilized in clinical practice.

7. Verapamil blocks transporter p-170 glycoprotein transporter

Can reverse resistance of cancer cells to chemotherapeutic agents.

Uses
  1. Treatment of hypertension
  2. Treatment of angina
  3. Anti-arrhythmic (supraventricular)
  4. Prophylactically in migraine
  5. Subarachnoid hemorrhage
  6. Raynaud’s phenomenon
Dose

10-20 mg depending upon condition of patient

Toxicity/Adverse effects

Most of the adverse cardiac effects are a direct extension of pharmacological actions, these include:

  1. Cardiac depression
  2.  Bradycardia
  3. Aggravation of heart blocks
  4. Immediate acting nifedipine as been shown to increase risk of MI in patients with HTN. Thus slow release preparations are given.
  5. Dihydropyridines increase the risk of cardiac events in patients with or without diabetes.
  6. Ca++ channel blockers should never be combined with beta blockers as both have cardiac depressing effects.
Minor Adverse Effects
  1. Vasodilatation causing flushing
  2. Headache
  3. Conjunctival congestion
  4. Nausea
  5. Constipation
  6. Dizziness
  7. Peripheral edema
Continue Reading

Anti hypertensive Drugs

Alpha and Beta Blockers

Vasodilators

Drugs Acting on Renin Angiotensin System

Browse all articles on Cardiovascular System

 

Check Also

oral drugs

Alkylating Agents

Alkylating agents are the broad spectrum agennts. Chemistry Different reactive moiety: Bis (chloroethyl) amine / …

Leave a Reply

Your email address will not be published. Required fields are marked *