Transcript Diltiazem

Diltiazem
ONE OF The CALCIUM CHANNEL
BLOCKER DRUGS
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Generic Name:
diltiazem (dil TYE a zem).
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Brand Names:
Cardizem, Cardizem CD, Cardizem LA,
Cardizem SR, Cartia XT, Dilacor XR, Diltia
XT, Tiazac.
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Description :
Diltiazem hydrochloride, is a Calcium channel
antagonist and widely used in the treatment of
certain types of cardiovascular.
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Chemically :
Chemically, diltiazem hydrochloride is 1,5Benzothiazepin-4(5H)-one,3-(acetyloxy)-5[2(dimethylamino)ethyl]-2,-3-dihydro-2( 4methoxyphenyl)-, mono-hydrochloride, (+ )-cis.
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The chemical structure :
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Physical properties :
Diltiazem hydrochloride It is soluble in
water, methanol and chloroform and has a
molecular weight of 450.98 .
the drug was stable at storage
temperatures, 5-55°C, for 12 weeks.
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Clinical Pharmacology :
Diltiazem (DTZ) is a calcium antagonist widely used
in the treatment of angina and-related heart diseases.
The therapeutic effects of diltiazem hydrochloride its
ability to inhibit the cellular influx of calcium ions
during membrane depolarization of cardiac and
vascular smooth muscle.
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Pharmacodynamic :
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1- Mechanisms of Action:
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Diltiazem blocks the transport of calcium into
the smooth muscle cell.
Since calcium is important in muscle
contraction.
blocking calcium transport relaxes artery
muscle and dilates coronary arteries and other
arteries of the body
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Hypertension:
Diltiazem produces its antihypertensive effect by
relaxation of vascular smooth muscle.
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Angina :
This is With calcium antagonists has several
advantages. Unlike other antianginal agents it does
not alter heart rate, blood pressure, or conduction.
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2- Pharmacological Effect :
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Like other calcium channel antagonists,
diltiazem decreases SA and AV conduction and
has a negative inotropic effect.
Diltiazem hydrochloride decreases vascular
resistance (VR), increases cardiac output
(COP) (by increasing stroke volume), and
produces a slight decrease in heart rate.
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Pharmacokinetic :
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1. Absorption :
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Diltiazem is well absorbed from the
gastrointestina1tract .
Route of drug administeration: Intranasal,
Intraperitoneal,Oral,
Intracerebroventricular,Intravenous.
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2. Distribution :
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The plasma half-life of diltiazem is approximately
3.0-4.5 h.
Therapeutic blood levels of diltiazem appear to be
in the range of 40-200 ng/mL.
The diltiazem hcl is 70% to80% bound to plasma
protein.
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3. Metabolism :
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Diltiazem hydrochloride is metabolized by the liver
it is hepatic first-pass effect .
The two primary metabolites of diltiazem are
desacetyldiltiazem and desmethyldiltiazem.
Drugs which induce or inhibit hepatic microsomal
enzymes may alter diltiazem disposition.
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4. Excreation :
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The diltiazem excreated by kidney and in bile.
Diltiazem metabolites have been identified in the
urine of humans. Only 2% to 4% of unchanged
diltiazem appears in the urine.
These metabolites are more slowly excreted.
The elimination half-life after single or multiple
dosing is 4 to 9.5 hours (mean 6.5 hours).
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CONTRAINDICATION
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1. Cardiac Conduction :
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Diltiazem hydrochloride prolongs AV node
refractory periods.
2. Congestive Heart Failure :
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Diltiazem has a negative inotropic effect.
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3. Hypotension :
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Decreases in blood pressure.
4. Acute Hepatic Injury :
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Mild elevations of transaminases with and
without elevation in alkaline phosphatase
and bilirubin.
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5. Nursing Mothers :
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Diltiazem is excreted in human milk.
6. Pregnancy :
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Have embryo and fetal lethality, a propensity
to cause abnormalities of the skeleton, heart,
retina, and tongue of embryo.
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Drug Interactions
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1. Beta Blockers :
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Diltiazem hydrochloride with propranolol
resulted in increased propranolol 50%.
2. Cimetidine :
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Increase in diltiazem plasma levels (58%)
after a 1-week course of treatment.
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3. Digitalis :
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Diltiazem hydrochloride with digoxin increased
plasma digoxin concentrations approximately 20%.
4. Cyclosporine :
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A reduction of cyclosporine dos ranging from 15%
to 48% .
The effect of cyclosporine on diltiazem plasma
concentrations has not been evaluated.
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5. Carbamazepine :
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Diltiazem with carbamazepine result in
elevated serum levels of carbamazepine
(40% to 72% increase).
6. Benzodiazepines :
Diltiazem increased of benzodiazepines
(midazolam and triazolam).
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7. Lovastatin :
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Diltiazem (120 mg)with lovastatin resulted
in a 3-4 times increase in lovastatin.
8. Rifampin :
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Rifampin with diltiazem lowered the
diltiazem plasma concentrations to
undetectable levels.
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9. Anesthetics :
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with anesthetics may be potentiated by
calcium channel blockers.
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ADVERSE
REACTIONS
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1. Cardiovascular :
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Angina, arrhythmia, AV block (second- or
third-degree), congestive heart failure,
hypotension, palpitations, tachycardia.
2. Nervous System :
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Abnormal dreams, gait abnormality,
hallucinations, insomnia, nervousness,
personality change, tremor.
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3. Gastrointestinal :
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Anorexia, constipation, diarrhea, dry mouth,
nausea,vomiting, weight increase.
4. Dermatological :
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Petechiae, photosensitivity, pruritus.
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OVERDOSAGE
The toxic dose in man is not known.
The resultant are bradycardia, hypotension,
heart block, and cardiac failure.
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1. Bradycardia :
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Administer atropine (0.60 to 1.0 mg).
2. High-Degree AV Block :
 Administer atropine (0.60 to 1.0 mg).
 should be treated with cardiac pacing.
3. Cardiac Failure :
 Administer inotropic agents (isoproterenol,
dopamine, or dobutamine) and diuretics.
4. Hypotension :
 Vasopressors (e.g., dopamine or levarterenol
bitartrate).
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DOSAGE AND
ADMINISTRATION
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1. Hypertension :
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Usual starting doses are 120 to 240 mg once
daily. usually observed by 14 days of chronic
therapy.
2. Angina :
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Starting with a dose of 120 mg to 180 mg
once daily. over 7 to 14 days.
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 Route
of drug administeration:
Intranasal,Intraperitoneal,Oral,
Intracerebroventricular,Intravenous.
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Doasage :
Usual capsules contain diltiazem
hydrochloride beads at doses of
120,180,240,300,360and 420 mg.
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Side Effects
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Less serious side effects :
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Flushing(redness).
headache.
Constipation,diarrhea,or nausea.
Fatigue or triedness .
Decrease blood pressure and worsening.
rash.
Difficulty urinating.
Slow heart rate
Tingaling sensation in the arm.
but more common slow heart rate and constipation.
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More serious side effects :
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Allergic reaction.
Abnormal behavior or psychosis.
Jaundice.
Sever dizziness.
Slurred speech.
Confusion..
Pruritis
Leg swelling.
Heart failure.
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Conclusion:
Amldipine:
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it is widely used ca channel blocker in controlling
morning blood pressure because of its long half
life 30-50h .
Nifedipine:
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Is used in treatment of hypertension,angina and
to control preterm labour.It is not used if there is
ischemic heart disease,hepatic dysfunction or
chronic malabsorption syndrome.
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Feldopine(piendil):
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Is indicated mainly for treatment
hypertension and arrhythmia and the most
common side effect reported with
feldopine administerated as monotherepy
were peripheral edema and headache.
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Verpamil:
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It is used to tretment stable angina,un
stable angina .Most common adverse
reaction : constipation ,dizziness and
nausea.
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Diltiazem :
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its used to treatment the high blood
pressure ,control chest pain and to slow
unusually fast heartbeats.
contraindication:is pregnancy ,nursing
mother,allergic reaction ,kidney,liver,BV,or
heart disease.
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Thank you
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Provised by:
Dr. Hanan
Produced by:
Ahlam Fahd
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