Imipramine + Diazepam Pharmacology

Imipramine + Diazepam

About Imipramine + Diazepam
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Mechanism of Action of Imipramine + Diazepam
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Pharmacokinets of Imipramine + Diazepam
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Onset of Action for Imipramine + Diazepam
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Duration of Action for Imipramine + Diazepam
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Half Life of Imipramine + Diazepam
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Side Effects of Imipramine + Diazepam
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Contra-indications of Imipramine + Diazepam
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Special Precautions while taking Imipramine + Diazepam
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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 + Diazepam
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Interactions for Imipramine + Diazepam
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Typical Dosage for Imipramine + Diazepam
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Schedule of Imipramine + Diazepam
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Storage Requirements for Imipramine + Diazepam
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Effects of Missed Dosage of Imipramine + Diazepam
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Effects of Overdose of Imipramine + Diazepam
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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

Diazepam

About Diazepam
A benzodiazepine derivative with CNS depressant, Anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant and amnestic.
Mechanism of Action of Diazepam
Diazepam mainly acts on Limbic system and ascending reticular formation in the CNS and binds to the BZD receptor. The binding will facilitates GABA mediated chloride channel opening and produce hyperpolarisation. This will produce an increase in the concentration of the inhibitory neurotransmitter GABA and chloride ions and decreases firing rate of neuron. These in turn alters normal functions of the body.
Antivertigo action: Although intravenous diazepam has been used to abort acute attacks of vertigo of peripheral origin, it can prolong compensation and recovery from vestibular lesions
Pharmacokinets of Diazepam
Absorption: It is well absorbed after oral administration. Distribution: It is distributed widely in the body in protein bound form. Metabolism: It is metabolised to active metabolite (((Desmethyl diazepam))) in the liver. Excretion: Most metabolites are excreted in urine
Onset of Action for Diazepam
0.5 - 2 hour
Duration of Action for Diazepam
1 day
Half Life of Diazepam
20 - 100 hour
Side Effects of Diazepam
1.Ataxia
2.Drowsiness
3.Lethargy
4.Hallucination
5.Nausea
6.Constipation
7.Amnesia
8.Dependence
9. Tremor
10.Confusion
11.Light headedness
12.Mood changes
13.Muscle cramp
14. Drug dependence
15.Respiratory depression
Contra-indications of Diazepam
1.Hypersensitivity to Benzodiazepines
2.Acute narrow angle glaucoma.
Special Precautions while taking Diazepam
1.Renal impairment
2.Hepatic impairment
3.Open angle glaucoma
4.Depression
5.Pulmonary insufficiency
6.Epileptic patients
7.Driving vehicles, operating machines and other hazardous activities
Pregnancy Related Information
Contraindicated.
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated.
Children Related Information
Use with caution
NEONATES contraindicated:
Indications for Diazepam
1.Anxiety
2.Preanaesthetic medication
3.Insomnia
4.Treatment of Febrile seizure and Status epilepticus
5.Acute alcohol withdrawal syndrome,
6.Relief of muscle spasm
7.Tetanus
8.Eclampsia
9.General anaesthesia
10. Vertigo.
Interactions for Diazepam
Alcohol and other CNS depressants: Enhanced CNS effects.
Aminophylline: Antagonizes the sedative effect.
Cimetidine, Oral contraceptives, Disulfiram, Fluoxetine, Isoniazid, Ketoconazole, Metoprolol, Propoxyphene, Propranalol, Valproic Acid: Elimination of diazepam decreased due to inhibition of hepatic metabolism leading to enhanced activity.
Digoxin, Imipiramine & Desipramine: Enhanced activity of these drugs.
Levodopa: Decrease in antiparkinsonism efficacy.
Ranitidine: Decreases GI absorption of Diazepam.
Rifampicin: Decreases efficacy.
Typical Dosage for Diazepam
Adult: 4 - 30 mg/day in 2 - 4 divided doses
Anxiety: 2 -10 mg 2 - 3 times a day; depending on the severity of the disease.

Muscle spasm: 2 -10 mg every 2 - 3 times a day; depending on the severity of the disease.

Acute alcohol withdrawal syndrome: Initial dose: 30 - 40 mg / day in 3 - 4 divided doses; if needed the dose can be reduced to 15 - 20 mg / day in divided doses.

Status epilepticus : 0.2 - 0.5 mg/ kg body weight as IV infusion followed by repeated doses.

PAM (((IM))): 5 - 10 mg before surgery

Children:
Anxiety: 3 - 10 mg / day in 3 - 4 divided dose. As needed dose can be increased gradually

Tetanus (((IM/IV infusion))): 1- 10 mg; repeated every 3 - 4 hour; dose is selected depending on the age and severity of the disease.

Status epilepticus :Above 7 years: 5 mg IV over 5 minutes; the dose may be repeated every 2 - 4 hour as needed; maximum dose: 10 mg

Status epilepticus 1 - 7 years: 2.5 mg IV over 5 minutes; the dose may be repeated every 2 - 4 hour as needed; maximum dose: 5mg
Schedule of Diazepam
H
Storage Requirements for Diazepam
The drug should be kept at 15 - 30 degree C in a tightly closed container.
Effects of Missed Dosage of Diazepam
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 Diazepam
Give support and symptomatic treatment. Flumazenil can be given as antagonist. Hypotension can be treated with vasopressors.If the patient is conscious induce emesis followed by charcoal administration

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