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Healthcare Communications

Amlodipine

 

Calcium Channel Blockers

Selective for Slow Calcium Channels
1. Phenylalkylamines - verapamil
2. Dihydropyridines - nifedipine, felodipine, nitrendipine, nicardipine, nimodipine, isradipine, nisoldipine, amlodipine
3. Benzothiazepines - diltiazem

Non-selective for Slow Calcium Channels
4. Flunarizine-like - flunarizine, cinnarizine
5. Prenylamine-like - prenylamine, fendiline, teridiline
6. Other drugs - perhexilene, bepridil and caroverine

 

 

Mode of Action

- Contractile process in muscle is dependent on calcium
- Calcium channel blockers inhibit calcium inflow through the sarcolemma during membrane activation
- Inhibits muscular activity in cardiac and smooth muscle
- Does not affect skeletal muscle, because excitation
-contraction coupling does not depend on calcium transport, but on internal release of calcium

 

Amlodipine

- Dihydropyridine derivative
- Acts largely on the vasculature
- Useful in hypertension

 

Amlodipine - Actions

* Calcium channel blockade can result in relaxation of vascular smooth muscle and reduced myocardial contractility
* Amlodipine’s action is on the peripheral vasculature rather than on the heart
* Thus, amlodipine produces peripheral arteriolar vasodilation resulting in reduced peripheral resistance and fall in blood pressure. This is its main action.

 

Pharmacokinetics

* Slowly absorbed from G.I. Tract
* Peak level 6-12 hours after dosing
* Bioavailability 64%
* Metabolised by liver; 90% converted to inactive metabolites
* Excreted in urine and faeces
* Half life 35-50 hours

 

Indications

* Hypertension (through vasodilation and reduction in peripheral resistance)
* Myocardial Ischaemia (by vasodilation of coronary and peripheral arterioles, with secondary reduction in afterload, increased myocardial oxygen supply and a reduction in myocardial oxygen demand)

 

Amlodipine in Hypertension

* Smooth in B.P., avoids reflex tachycardia
* Sustained effect over 24 hours; convenient once daily dosing
* May be employed alone or in combination with other drugs, e.g., beta-blockers, ACE inhibitors

 

Amlodipine in Myocardial Ischaemia

* Effective as single agent or in combination with other drugs
* May be used in combination with beta blockers and/or nitrates
* Effective in exertional or vasospastic angina

 

Dosage

5 or 10 mg once daily

 

Tolerability

* Well tolerated
* Oedema, flushing, headache
* Safe in patients with diabetes mellitus, peripheral vascular disease, chronic obstructive lung disease and abnormal lipid profiles

 

Advantages over Nifedipine

* Gradual onset of action with amlodipine avoids reflex tachycardia associated with nifedipine. Hence better tolerability with amlodipine
* Nifedipine has a short duration of action - requires frequent administration, unlike convenient once-daily administration with amlodipine

 

Advantages over Beta-blockers

Beta-blockers produce adverse effects such as bronchospasm, peripheral arterial insufficiency, and sexual dysfunction, and may aggravate congestive heart failure and mask the symptoms of hypoglycaemia.

 

Advantages over ACE-inhibitors

* ACE inhibitors commonly cause adverse effects such as cough
* Other adverse effects include rash, angioneurotic oedema, hyperkalaemia and taste disturbance