Amlodipine
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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
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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
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Amlodipine
- Dihydropyridine
derivative
- Acts largely on the vasculature
- Useful in hypertension
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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.
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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
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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)
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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
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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
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Dosage
5 or 10 mg once
daily
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Tolerability
* Well tolerated
* Oedema, flushing, headache
* Safe in patients with diabetes mellitus, peripheral vascular disease,
chronic obstructive lung disease and abnormal lipid profiles
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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
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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.
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Advantages
over ACE-inhibitors
* ACE inhibitors
commonly cause adverse effects such as cough
* Other adverse effects include rash, angioneurotic oedema, hyperkalaemia
and taste disturbance
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