Diazepam + Propranolol Pharmacology

Diazepam + Propranolol

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

Propranolol

About Propranolol
A synthetic non-selective beta blocker , Antiarrhythmic,antihypertensive,antianxiety,migraine prophylatic.
Mechanism of Action of Propranolol
Propranolol is a non selective beta receptor antagonist. It have negative chronotropic and negative inotropic effects on heart. It decreases oxygen consumption; cardiac work and aortic pressure It decreases nor adrenaline and renin releases. It decreases central sympathetic out flow.
In sympathetic over activity, it prolongs systole by retarding conduction. It increases oxygen supply and exercise tolerance in angina patients. It decrease automaticity and abbreviates refractory period of myocardial fibers and decreases rate of depolarization in SA node, Purkinje fibers, and other ectoptic foci. Prolong effective refractory period of AV node and AV conduction is delayed. At higher doses direct depressant membrane stabilizing action is exerted. The drug decreases BP in hypertensive individuals. Initially total peripheral resistance increases due to blockade of beta mediated vasodilatation and decrease in cardiac output; so little change in BP. But when treatment is continued due to adaptation of resistance vessels to decreased cardiac output total peripheral resistance decreases and systolic and diastolic BP falls.
Antimigraine action: Propranolol is useful in migraine due to its beta blockade action. Through beta blockade action it inhibits vasodilation and relieves migraine.
Pharmacokinets of Propranolol
Absorption: well absorbed orally, bioavailabity is increased by administering along with food.
Distribution: Widely distributed in a plasma protein bound form.
Metabolism: Metabolized in liver.
Excretion: Excreted through urine.

Onset of Action for Propranolol
N/A
Duration of Action for Propranolol
Up to 12 hours
Half Life of Propranolol
4 hours
Side Effects of Propranolol
1.Congestive heart failure is precipitated or aggravated
2.Decreases coronary blood flow
3.Forgetfulness
4.Nightmares
5.Decreases exercise capacity
6.Decreases carbohydrate tolerance
7.Decrease insulin release
8.Increases free fatty acid levels and increase LDL to HDL ratio
9.Worsens chronic obstructive lung diseases
10.Gastrointestinal problems
11.Nausea
12.Sexual dysfunction
13.Cold extremities
14.Tiredness
15.Exacerbates prinzmetal`s angina
16.Bradycardia
17.Depression
18.Fever
19.Rash

Contra-indications of Propranolol
1.Hypersensitivity to the drug
2.Second or third degree heart block
3.Congestive heart failure
4.Cardiogenic shock
5.Bradycardia
6.Chronic obstructive pulmonary diseases
7.Hypoglycemia
8.Haemorrhage

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Special Precautions while taking Propranolol
1.Peripheral arterial diseases
2.Ischaemic heart disease
3.Congestive heart failure
4.Renal impairment
5.Hepatic impairment
6. Diabetes mellitus
7. The drug should be gradually withdraw with caution
8. Non allergic bronchospastic diseases
9. Thyrotoxicosis
10. Along with other antihypertensive drugs

Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Contraindicated
Children Related Information
Use with caution
Indications for Propranolol
1. Hypertension
2. Arrhythmias
3. Anxiety
4. Angina
5. Migraine
6. Prophylaxis of myocardial infarction
7. Tremors
8. Phaeochromocytoma
9. Hypertrophic sub aortic stenosis


Interactions for Propranolol
Quinidine: Orthostatic hypotension.
Rifampicin, Phenobarbital, NSAIDs, Thyroid hormones, Smoking: Decrease antihypertensive action of propranolol.
Corticosteroids: Antagonism of hypotensive effect.
Sympathomimetics: Marked hypertension and bradycardia.
Insulin: Hypoglycemic effects prolonged by propranalol and masking of symptoms of hypoglycemia in diabetes.
Lidocaine: Increased levels of lidocaine may occur resulting in toxicity.
Calcium channel blockers: Severe bradycardia especially in those with impaired LV function.
Phenothiazines: Chlorpromazine increases plasma levels of propranolol.
Reserpine: Additive effect resulting in vertigo, syncope or postural hypotension.
Clonidine: May increase the postural hypotension. Severity of rebound hypertension caused by abrupt withdrawal of clonidine enhanced.
Haloperidol: Severe hypotension.
Prazosin: May increase first dose response (acute postural hypotension) of prazosin.
Theophylline: Propranolol antagonises effect of theophylline.
Alcohol: Enhanced hypotensive effect.
ACE inhibitors: Enhanced hypotensive effect.
Lab tests: May interfere with Glaucoma screening test due to reduction in intraocular pressure.
Typical Dosage for Propranolol
40 to 240mg/day
Hypertension: Starts with 80mg once daily or in 2 divided doses and gradually increases up to 320mg/day based on patient`s response in divided doses 12th hourly or 8th hourly.
Maximum daily dose: 640mg.
Sustained release formulations: 120 to 160mg/day. Once daily.
Children: 1mg/kg/day gradually increases to 4mg/kg/day based on patient`s response in 4 divided doses
Maximum dose: 5mg/kg/day.
Arrhythmias & Anxiety: 30mg to 150mg/day in 3 to 5 divided doses.
Children: 0.5 to 4mg/kg/day in 3 to 4 divided doses.
Angina: 40 to 80mg two times daily to 4 times daily.
Migraine: 80 to 120mg/day in divided doses in 12th hourly to 8th hourly. And gradually increases at 1 week intervals to 160mg/day.
Children: 1mg/kg/day four times daily and gradually increases up to 5mg/kg/day based on patient`s response.
Prophylaxis of myocardial infarction: Initiate the therapy with 20mg dose 5days after myocardial infarction. Then give doses of 40mg thrice daily and gradually increases at weekly intervals up to 80mg based on patients response.



Schedule of Propranolol
H
Storage Requirements for Propranolol
Store at controlled room temperature between 20 to 25 degree celcious in a well closed container.
Effects of Missed Dosage of Propranolol
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Propranolol
Treatment is supportive and symptomatic. After ingestion empty the stomach by induced emesis or gastric lavage. Administer activated charcoal. Treat Bradycardia with atropine 0.5 to 1mg.If required administer isoproterinol with caution. Treat hypotension with glucagons and vasopressors like epinephrine. Treat cardiac failure with diuretics and cardiac glycosides. Treat bronchospasm with isoproterinol and aminophylline.

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