Paracetamol + Metoclopramide Pharmacology

Paracetamol + Metoclopramide

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

About Paracetamol
Acetanilide derivative, Non narcotic Analgesic,Antipyretic.
Mechanism of Action of Paracetamol
Paracetamol has analgesic and antipyretic action.
It is more active on cyclo-oxygenase enzyme in brain. Peripherally it is a poor inhibitor of prostaglandin synthesis.
Analgesic action: Paracetamol raises the pain threshold and produces analgesic effect.
Antipyretic action: Paracetamol lowers fever by direct action on the thermoregulatory centre in the Hypothalamus and block the effects of endogenous pyrogen.
Pharmacokinets of Paracetamol
Absorption: Paracetamol is rapidly and completely absorbed after oral administration.
Distribution: It is distributed mostly in the body in unbound form.
Metabolism: It is extensively metabolised in the liver.
Excretion: Excreted in the urine.
Onset of Action for Paracetamol
30 - 60 minutes
Duration of Action for Paracetamol
6 hours
Half Life of Paracetamol
1-4 hours
Side Effects of Paracetamol
1. Nausea
2. Abdominal distress
3. Allergic reactions
4. Rash
Contra-indications of Paracetamol
1. Hypersensitivity to Paracetamol
Special Precautions while taking Paracetamol
1. Hepatic impairment
2. Renal impairment
3. Hypertension
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
NEONATES : Contraindicated
Indications for Paracetamol
1. To relieve pain and fever
2. Acute gout
3. Migraine
Interactions for Paracetamol
Cholestyramine: Reduces absorption of paracetamol.
Charcoal: Activated, administered immediately reduces absorption of paracetamol.
Domperidone and metochlopramide: Enhance absorption of paracetamol.
Alcohol: Chronic excessive ingestion of alcohol potentiates hepatotoxicity of paracetamol.
Zidovudine: Effects zidovudine may be decreased.
Typical Dosage for Paracetamol
Adult:
500 - 1000 mg in 3 times daily
Maximum dose: 4 g / day
For migraine: 500 mg to be taken at the first sign of migraine attack and repeated 4 - 6 hourly until suppress mild attacks.
Children:
60 mg / kg body weight /day in 4 divided doses.
Schedule of Paracetamol
H
Storage Requirements for Paracetamol
Store at 15-30 degree C in a tightly closed container. Protect from heat and moisture. Keep out of the reach of children.
Effects of Missed Dosage of Paracetamol
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 Paracetamol
Give supportive measures and symptomatic treatment. Drug can be removed from the body by gastric lavage or by inducing emesis. Absorption of the drug can be reduced by administration of activated charcoal. N-acetylcysteine is the specific antidote for Paracetamol poisoning. Dose: 150 mg /kg body weight as IV infusion over 15 minutes followed by same dose over 20 hours.
Maintenance dose: 75 mg / kg orally every 4 - 6 hours for 2 - 3 days. Haemodialysis can be done in emergency conditions.

Metoclopramide

About Metoclopramide
It is a dopamine antagonist - antiemetic gastroprokinetic agent.
Mechanism of Action of Metoclopramide
Metoclopramide acts through both serotonergic and dopaminergic receptors. Metoclopramide binds to Serotonin (5 HT3 &5HT4) and Dopamine (D2) receptor.
Antiemetic action: Metoclopramide inhibits Dopamine receptor in the chemoreceptor trigger zone and produces antiemetic action.
Intestinal motility modifying action: The binding of Metoclopramide on 5HT4 receptor will activate interneuron and enhance the release of acetylcholine innervating the smooth muscles. This produces gastric emptying and enhances lower esophageal sphincter tone.
Migraine: Metoclopramide is used in migraine to relieve nausea and vomiting
Anaesthetic adjuncts: It is used preoperatively in order to reduce the post operative vomiting.
Pharmacokinets of Metoclopramide
Absorption: Metoclopramide is rapidly and well absorbed after oral administration. Distribution: It is extensively distributed to tissues and fluids, brain.
Metabolism: Only a small amount undergoes hepatic metabolism. Excretion: It is excreted mainly in urine and faeces.
Onset of Action for Metoclopramide
Oral: ? - 1 hour.
IM: 10 - 15 minutes
IV: 1 - 3 minutes
Duration of Action for Metoclopramide
1-2 hours.
Half Life of Metoclopramide
3 - 6 hour.
Side Effects of Metoclopramide
1.Drowsiness
2.Confusion
3.Constipation
4.Muscle spasm
5.Tremor
6.Bronchospasm
7.Bradycardia
8.Fatigue
9.Headache
10.Dizziness
11.Nervousness
12.Sedation
13.Nausea
14.Rash
Contra-indications of Metoclopramide
1.Hypersensitivity to Metoclopramide
2.Gastrointestinal haemorrhage
3.Mechanical obstruction
4.Pheochromocytoma
5.Epilepsy
6.Parkinsonism
7.Pyloric stenosis
8.Previous history of dystonia
Special Precautions while taking Metoclopramide
1. Hypertension
2. Depression
3. Renal impairment
4. Hepatic impairment
5. Use with caution while driving vehicles, operating machines and people involving any 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
NEONATES: contraindicated
Indications for Metoclopramide
1. Nausea and vomiting (except motion sickness)
a)associated with various gastrointestinal disorders and migraine
b) Nausea and vomiting associated with cytotoxic chemotherapy or radiotherapy.
c) Post operative nausea and vomiting
2. Treatment of delayed gastric motility
3. Gastroesophageal reflux
4. Diagnostic procedure in gastroenterology

Interactions for Metoclopramide
Anticholinergic drugs and narcotic analgesics: Effects on GI motility are antagonised by these drugs.
Alcohol, sedatives, hypnotics, narcotics or tranquilizers: Additive sedative effect may occur.
Digoxin, Cimetidine: Absorption of these drugs decreased.
Acetaminophen, Aspirin: The absorption of these agents increased.
Phenothiazines, Butyrophenone, Lithium and Thioxanthine drugs: May potentiate extrapyramidal effects.
Bromocriptine: Antagonism of hypoprolactinaemic effect of bromocryptine.
Cyclosporine: May lead to increased cyclosporine absorption, possibly increasing immunosupressive and toxic effect.
Succinylcholine: Metoclopramide may increase the neuromuscular blocking effects of succinylcholine.
Typical Dosage for Metoclopramide
Adult:
ORAL: 15 - 30 mg / day in 3 divided doses.
Treatment of delayed gastric motility: 10 mg to be taken 30 minutes before each meal and at bed time for3 months. Drug is given depending upon the symptom being treated and clinical response.
Gastroesophageal reflux: 10 - 15 mg 4 times a day, drug to be taken half an hour before each meal and at bed time.
INJECTION:
Post operative nausea and vomiting: 10 - 20 mg IM at the end of surgical procedure and repeat the dose every 4 - 6 hours if needed
Nausea and vomiting associated with cytotoxic chemotherapy or radiotherapy: 2 - 4 mg / kg as IV infusion over 15 - 30 minutes.
Maintenance dose: 3 - 5 mg / kg given over 8 hours
Maximum dose: 10 mg / kg / day.
Children:
ORAL: 0.4 mg / kg / day in 4 divided doses.
Schedule of Metoclopramide
H
Storage Requirements for Metoclopramide
Store at 15 - 30 degree C in a tightly closed container. Protect from heat and light.
Effects of Missed Dosage of Metoclopramide
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 Metoclopramide
Give supportive measures and symptomatic treatment. Extrapyramidal effects may be controlled by administration of antimuscarinic or antiparkinsonian agents or antihistamine with antimuscarinic activity

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