PREPARATION OF DRUG PROFILE OF ATROPINE

Drug name: Atropine Active ingredient: Atropine sulphate Drug category (prescription/OTC): Prescription WHO essential drug list: Present National essential drug list: Present 1. PRODUCT DESCRIPTION Sr. Brand Name No. 1 2
Atropine ATROPISOLE

Manufacturer
Novartis pharma (pak) ltd Lahore chemical & pharmaceutical works (pvt) ltd Hospira Shifa laboratories.(pvt) ltd. Ophth-pharma (pvt) ltd Remington pharmaceutical industries (pvt) lt

Dosage Form
Eye drops

Strength
10ml 15ml

price/unit
59.89 Rs. 37.22 Rs.

Injection

3 4

Atropine Sulfate Injection Atropine Sulfate

Injection Injection

0.05 mg/mL 1mg/ml]

25 Rs. 150 Rs.

5
6

Ophth-atropine Opta atropine

Eye drops Eye drops

10ml 10ml

22 Rs. 15.71 Rs.

How to store this Drug:

Store at less than 25oC. Tablets are stored below 86oF and injections are stored at controlled room temperature. Protect the drug from light and freezing.

2. CHEMISTRY OF DRUG
Chemical class: Tertiary amine belladonna alkaloids

Chemical Structure:

Physical properties Physical state: solid Melting point: 118.5oC Water solubility: 2200mg/L Mol. Weight: 289.369g/mol 3. PHARMACOKINETICS

I) Absorption: Atropine is well absorbed from small bowel and not at all from the
stomach thus the effect of oral dosing is much slower in onset than after parenteral dosing. It is also absorbed by mucous membrane but less readily from eye and skin.

II) Distribution
BioProtein availability Binding 90% well Absorbed Principally From upper small intestine Poor binding. 44% mainly to 1acid gycoprotien Placental Barrier Atropine can cross the placental barrier Blood Brain barrier Atropine can cross the BBB Secreted in milk Yes but in small quantity Volume of Time for onset of distribution action 2-4 L/kg Inhibition of salivation occurs within 30 min. Increase in heart rate 2-3 min. with IV Bronchodilation occurs within 15 min.

III) Elimination

Half Life 4 hours

Site of Metabolism Liver

Active Metabolite No

Route of Excretion 94% excreted through urine

4. CLINICAL PHARMACOLOGY

Pharmacological class Mechanism of Action

Antimuscarinic agents It competatively antagonizes acetylcholine at post ganglionic nerve endings. Thus by blocking the actions of Ach, mucarinic receptor antagonists very effectively block the effects of vagal nerve activity on the heart and also affecting the exocrine glands, smooth muscles, cardiac muscles and CNS. Atropine is not an antibiotic.

Spectrum Sr. Indication (in case of no antiboitics0

1. Symptometic Contraindications Bradycardia 2. Surgery 3. Organophosphate

Route of Recommended Recommended Duration of Administration Dosage Dosage Therapy Child Adult
1. Hypersensitivity0.1-0.5mg to atropine. 2. Glucoma. 3. Tachycardia IV 0.5mg every 5 As 4. Obstructive GI diseases. 5. Hepatic diseases. 6. Renal diseases min. recommened 7. Asthma 8. Thyrotoxicosis. 9. 3rd degree heart block. 10. Mobitz type II block SC/IV/IM 0.01mg/kg to 0.4-0.6mg every max. of 0.4mg 4 to 6 hours. IV 0.03-0.05g/kg 1-5mg 1. Donot administered if soln. is discolored, cloudy or if particulate matters < 6.8kg child are present IM 0.5-1mg/hr _ 0.05mg/kg 2. Advise Pt. that dose or frequency of use may be changed 6.8-18kg child 2mg periodically to achieve maximum benefits. 0.5g/dose Topical instilling1-2 drops (0.5% or ointment wash hands and 3. Before(eye) ophthalmic soln. 1-2 drops (0.5soln.) 0.1% touch donot allow tip of dropper bottle or tube to soln.) eye. Atropine(eye) be systemically absorbed after ocular Topical may 1-2 drops (0.5% 1-2 drops (1% _ administration, however significant effect on the foetus have not soln.) soln.) been reported.

Precautions

4. Ophthalmic uveitis 5. Ophthalmic FDA pregnancy refraction class

5. Dosage Schedule

Clinical Monitoring parameters

Continuously moniter serum ChE level (U/L) in patients of OP poisoning. rate should be monitored. Pulse

6.

SIDE EFFECTS

Most Severe (with mechanism)

An allergic reaction (swelling of your lips, tongue, or face, difficulty breathing, closing of your throat, or hives) an irregular or fast heart rate, rash or flushing, or eye pain.These effects are due to its anticholinergic effect. Other major side effects are tachyarrhythmias, ventricular irritability, agitation to delirium.

Common Effects (with mechanism):

Blurred vision and mydriasis because atropine blocks all cholinergic activity on the eye so there would be dilation of pupils. Constipation because atropine blocks cholinergic receptors and decrease the gastric motility. Urinary urgency occurs because atropine reduces the hypermotility of the urinary bladder by blocking cholinergic receptors. Other common side effects are nausea, bloating, heartburn, changes in taste, decreased sweating, nasal congestion, stuffiness, or a dry mouth.

7. ADMINISTRATION GUIDLINENES FOR ORAL USE Atropine does not use orally FOR I/V ROUTES

I.V bolus, rate of Administration

Preferably give IV rapidly because slow injection may cause a paradoxical slowing of the heart rate.For children it is infused IV at a rate of 0.025 mg/kg per hour and in adults it is infused IV at an initial rate of 0.51 mg/hour. 0.9% sodium chloride 510 mL and 0.9% soln.

Solvent For Reconstitution Volume to be added/concentration Temperature and storage time after reconstitution Compatible I.V fluids

Store at room temperature below 25C

Dilution in IV fluids is not recommended Atropine sulphate is stated to be compatible, when mixed in a syringe immediately before use, with the following: Chlorpromazine Droperidol Metoclopramide Midazolam Prochlorperazine Promethazine

8. DRUG DRUG INTERACTIONS Interacting drug Severity Outcomes

Acetylcholinesterase inhibitors There would be more Increase level of side effects, it may also Atropine lead to OP poisoning

Pralidoxime

Signs of atropinization May potentiate the effect (flushing, mydriasis, of atropine tachycardia, dryness of mouth and nose) may occur earlier. Result in additive anticholinergic side effects Increase level of Atropine

Psychotropics

Potassium suupliments or potassium citrate Amantadine, some antihistamines, butyrophenones

Increase chance of toxicity Potentiated anticholinergic effect

9. DRUG FOOD INTERACTIONS. Food Ethanol Nature of Interactions It can cause additive CNS effect which leads to impaired coordinated sedation and death because of inhibition of microsomal enzymes acutely.

10. DRUG- LAB INTERACTIONS Lab Test Non well documented Nature of interactions

11. TOXICOLOGY Toxic Dose The fetal dose of atropine in children may be as low as 10mg. Signs and Symptoms of Toxicity Management/ treatment (including Antidote) Dry mouth, thurst, nausea, vomiting, abdominal distention, CNS stimulation, delirium, drowsiness, fever, seizures, -For atropine poisoning, respiratory assistance and symptometic support is indicated.

In an adult recovery after 1000mg of atropine sulphate has been reported

hellucination, convulsion, coma, circulatory failure, tachycardia, weak pulse, dilated pupil photobia, rash, dry and hot skin.

-An adequate airway should be maintained. -Diazepam may be administered to control excitement and convulsion but the risk of CNS depression should be considered. -hypoxia and acidosis should be corrected.