Imipramine + Chlordiazepoxide Pharmacology

Imipramine + Chlordiazepoxide

About Imipramine + Chlordiazepoxide
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Mechanism of Action of Imipramine + Chlordiazepoxide
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Pharmacokinets of Imipramine + Chlordiazepoxide
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Onset of Action for Imipramine + Chlordiazepoxide
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Duration of Action for Imipramine + Chlordiazepoxide
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Half Life of Imipramine + Chlordiazepoxide
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Side Effects of Imipramine + Chlordiazepoxide
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Contra-indications of Imipramine + Chlordiazepoxide
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Special Precautions while taking Imipramine + Chlordiazepoxide
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Pregnancy Related Information
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Old Age Related Information
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Breast Feeding Related Information
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Children Related Information
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Indications for Imipramine + Chlordiazepoxide
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Interactions for Imipramine + Chlordiazepoxide
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Typical Dosage for Imipramine + Chlordiazepoxide
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Schedule of Imipramine + Chlordiazepoxide
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Storage Requirements for Imipramine + Chlordiazepoxide
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Effects of Missed Dosage of Imipramine + Chlordiazepoxide
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Effects of Overdose of Imipramine + Chlordiazepoxide
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Imipramine

About Imipramine
Tricyclic Antidepressant (Tertiary Amine) , dibenzazepine derivative, Antidepressant, migraine prophylatic.
Mechanism of Action of Imipramine
Imipramine acts by inhibiting the re-uptake of Noradrenaline and Serotonin (5 HT) in the CNS nerve terminals .This will result in an increased concentration of neurotransmitters in the synaptic cleft and produces antidepressant effect. Imipramine also has anticholinergic activity.
It is also useful in migraine prophylaxis. The monoamine uptake blocking property is related to migraine prophylactic activity. These are suited for patient with depression.

Pharmacokinets of Imipramine
Absorption: Imipramine is rapidly absorbed after oral administration.
Distribution: It is widely distributed in the body in protein bound form.
Metabolism: Imipramine is metabolised in the liver to the active metabolite Desipramine.
Excretion: Drug is excreted mainly through urine.
Onset of Action for Imipramine
3 weeks
Duration of Action for Imipramine
Up to 6 weeks
Half Life of Imipramine
12 - 16 hours
Side Effects of Imipramine
1. Dryness of mouth
2. Constipation
3. Difficulty in accommodation
4. Tachycardia
5. Difficulty in micturition
6. Impotence
7. Delayed ejaculation
8. Dizziness
9. Lethargy
10. Headache
11. Feeling of tiredness
12. Sedation
13. Tremor
14. Hyper-reflexia
15. Urticaria
16. Rash
17. Pruritis
18. Photosensitivity
19. Hypotension
20. Cardiomyopathy
21. Cholestatic jaundice
22. Edema
23. Agranulocytosis
24. Galactorrhoea
25. Gynaecomastia
26. Anorexia
Contra-indications of Imipramine
1. Hypersensitivity to Imipramine
2. Myocardial infarction
3. Patient on MAOI therapy
Special Precautions while taking Imipramine
1. Renal impairment
2. Hepatic impairment
3. Cardiac arrhythmia
4. Myocardial infarction
5. Tachycardia
6. Heart failure
7. Strokes
8. Angle closure glaucoma
9. History of urine retention
10. Increased intraocular pressure
11. Hyperthyroidism
12. Patient receiving thyroid medications
13. Patient at risk for suicide,
14. Slowly withdraw the drug with caution
15. Patient should be cautioned against driving vehicle, operating machine and activities requiring mental alertness or judgment

Pregnancy Related Information
Use with caution
Old Age Related Information
Use with caution
Breast Feeding Related Information
Use with caution
Children Related Information
Use with caution
Below 6 years: Contraindicated
Indications for Imipramine
1. Depressive illness
2. Nocturnal enuresis in children above 5 years
3. Migraine prophylaxis
Interactions for Imipramine
Anticholinergics: Enhanced effect of anticholinergics may occur.
Barbiturates: Serum level of imipramine decreased; additive respiratory depressant effect.
Clonidine: Hypertensive crisis.
Dicoumarol: Increase in anticoagulation effects.
Disulfiram: Acute organic brain syndrome.
Fluoxetine & Haloperidol: Potentiate action of imipramine.
Levodopa: Its bioavailability is reduced, hypertensive episodes.
MAOIs, Furazolidone: Seizures, sweating, coma, hyperexcitability, hyperthermia, tachycardia, mydriasis, confusion, DIC (Disseminated Intravascular Coagulation) and death.
Oral Contraceptives and Phenothiazines : Increase plasma levels of imipramine.
Smoking : Increases metabolic biotransformation.
Alcohol : Sedative effect of alcohol potentiated.
Typical Dosage for Imipramine
Adult: 25 mg 3 times a day dose can be gradually increased up to 200 mg / day.
Maximum daily dose: 300 mg
Children :
Nocturnal enuresis in children above 5 years: 25 mg/ day to be taken 1 hour before bed time. If satisfactory response does not occur then gradually increases the dose up to 75 mg / day.
Maximum dose: 5 mg / kg / day

Schedule of Imipramine
H
Storage Requirements for Imipramine
Store at 15 - 30 degree C. Keep out of the reach of children
Effects of Missed Dosage of Imipramine
Take the missed dose as soon as noticed and if it is the time to take the next dose then skip the missed dose.
If the missed dose is taken only at night then skip the missed dose.
Effects of Overdose of Imipramine
Give supportive measures and treatment. Remove the drug from the body by inducing emesis and gastric lavage. Activated charcoal can be given to reduce the absorption of the drug. Seizure can be treated with Diazepam or Phenytoin, arrhythmia with Lidocaine, and acidosis with Sodium bicarbonate

Chlordiazepoxide

About Chlordiazepoxide
Benzodiazepine derivative, Sedative /hypnotic, Antianxiety and skeletal muscle relaxant.
Mechanism of Action of Chlordiazepoxide
Chlordiazepoxide mainly acts on Limbic system and ascending reticular formation in the CNS. It binds to the BZD receptor. The binding will facilitates GABA mediated chloride channel opening and produce hyperpolarisation. This will increase the concentration of inhibitory neurotransmitter GABA and chloride ions in the CNS and decreases firing rate of neurons. This in turn alters normal excitatory functions of the body.
Pharmacokinets of Chlordiazepoxide
Absorption: It is absorbed after oral administration. Distribution: It is distributed widely in the body. Metabolism: It is metabolised to active metabolite in the liver. Excretion: Most metabolites are excreted through urine
Onset of Action for Chlordiazepoxide
1 - 2 hour
Duration of Action for Chlordiazepoxide
12 - 24 hour
Half Life of Chlordiazepoxide
5 - 30 hour
Side Effects of Chlordiazepoxide
1.Ataxia
2.Drowsiness
3.Lethargy
4.Hallucination
5.Nausea
6.Constipation
7.Amnesia
8.Dependence
9.Pain at the site of injection
10.Confusion
11.Depression
12.Mood changes
Contra-indications of Chlordiazepoxide
Hypersensitivity to Benzodiazepines
Special Precautions while taking Chlordiazepoxide
1.Renal impairment
2.Hepatic impairment
3.Myasthenia gravis
4.Respiratory disease
5.Jaundice
6.Use caution while driving vehicles, operating machines or other dangerous activities
Pregnancy Related Information
Contraindicated.
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated.
Children Related Information
Use with caution
children < 6 years: contraindicated
NEONATES- contraindicated
Indications for Chlordiazepoxide
1. Anxiety
2.Treatment of alcohol withdrawal symptom
3. Insomnia
4. Pre and post operative apprehension
Interactions for Chlordiazepoxide
Alcohol & Other CNS Depressants: Enhanced CNS effects.
Aminophylline: Antagonizes the sedative effect.
Cimetidine, Oral contraceptives, Disulfiram, Fluoxetine, Isoniazid, Ketoconazole, Metoprolol, Propoxyphene, Propranolol.
Valproic acid: Elimination of chlordiazepoxide decreased due to inhibition of hepatic metabolism leading to enhanced activity.
Digoxin: Increase in serum concentration of Digoxin.
Imipramine & Desipramine: Enhanced activity of these drugs.
Levodopa : Decrease in antiparkinsonism efficacy.
Morphine, Pethidine, Atropine and Magnesium trisilicate: Absorption of chlordiazepoxide is impaired.
Probenecid: May cause rapid onset or prolonged effect.
Rifampicin: Decreases efficacy.
Typical Dosage for Chlordiazepoxide
Adults: 5 - 10 mg 3 - 4 times daily
Severe anxiety: 20 - 25 mg 3 - 4 times daily
Treatment of alcohol withdrawal symptom: 25 - 100 mg daily; Depending on the patient`s condition dose can be reduced after 2 - 3 weeks
Pre and post operative apprehension: 5 - 10 mg 3 - 4 times daily; the drug should be given one day before surgery in pre operative apprehension
Children: 5mg 3 - 4 times daily.
Schedule of Chlordiazepoxide
H
Storage Requirements for Chlordiazepoxide
Store at temperature 15 - 30 degree C.Protect from light and moisture. Keep out of the reach of children.
Effects of Missed Dosage of Chlordiazepoxide
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose.
Effects of Overdose of Chlordiazepoxide
Give support and symptomatic treatment. Induce emesis or gastric lavage has to be done followed by charcoal administration. Flumazenil can be given as antagonist.

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