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Atropine

Atropine is a tropane alkaloid extracted from the deadly nightshade (Atropa belladonna) and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects. Being potentially deadly, it derives its name from Atropos, one of the three Fates who, according to Greek mythology, chose how a person was to die. more...

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Physiological effects and uses

Generally, atropine lowers the "rest and digest" activity of all muscles and glands regulated by the parasympathetic nervous system. This occurs because atropine is a competitive inhibitor of the muscarinic acetylcholine receptors. (Acetylcholine is the neurotransmitter used by the parasympathetic nervous system.) Therefore, it may cause swallowing difficulties and reduced secretions.

Ophthalmic use

Topical atropine is used as a cycloplegic, to temporarily paralyze accommodation, and as a mydriatic, to dilate the pupils. Atropine degrades slowly, typically wearing off in 2 to 3 days, so tropicamide is generally preferred as a mydriatic. In atropine-induced mydriasis, the mechanism of action involves blocking the contraction of the circular pupillary sphincter muscle (which is normally stimulated by acetylcholine release), thereby allowing the radial pupillary dilator muscle to contract and dilate the pupil. Atropine is contraindicated in patients predisposed to narrow angle glaucoma.

Resuscitation

Injections of atropine are used in the treatment of bradycardia (an extremely low heart rate) and asystole, which is a condition of pulseless electrical activity (PEA) in cardiac arrest. This works because the main action of the vagus nerve of the parasympathetic system on the heart is to slow it down. Atropine blocks that action and therefore may speed up the heart rate.

The main action of the parasympathetic nervous system is to stimulate the M2 muscarinic receptor in the heart, but atropine inhibits this action.

Secretions and brochoconstriction

Atropine's actions on the parasympathetic nervous system inhibits salivary, sweat, and mucus glands. This can be useful in treating Hyperhidrosis and can prevent the death rattle of dying patients, even though it has not been officially indicated for either of these purposes.

Antidote for organophosphate poisoning

By blocking the action of acetylcholine at muscarinic receptors, atropine also serves as an antidote for poisoning by organophosphate insecticides and nerve gases. Troops who are likely to be attacked with chemical weapons often carry autoinjectors with atropine and obidoxime which can be quickly injected into the thigh. It is often used in conjuntion with Pralidoxime chloride.

Some of the nerve gases attack and destroy acetylcholinesterase, so the action of acetylcholine becomes prolonged. Therefore, atropine can be used to reduce the effect of ACh.

Side effects and overdoses

Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, giddiness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, and possibly, notably in the elderly, confusion, hallucinations and excitation. These latter effects are due to the fact that atropine is able to cross the blood-brain barrier. Because of the hallucinogenic properties, some have used the drug recreationally, though this is very dangerous.

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Meperidine Hydrochloride 50-mg and Atropine Sulfate 0.4-mg/mL Injection
From International Journal of Pharmaceutical Compounding, 9/1/05

METHOD OF PREPARATION

Note: This formulation should be prepared in a laminar airflow hood in a cleanroom or via isolation barrier technology by a validated aseptic compounding pharmacist using strict aseptic technique. This is a high-risk preparation.1

1. Calculate the required quantity of each ingredient for the total amount to be prepared.

2. Accurately weigh and/or measure each ingredient.

3. Dissolve the meperidine hydrochloride and atropine sulfate in about 95 mL of sterile water for injection.

4. Add sufficient sterile water for injection to volume and mix well.

5. Filter through an appropriate sterile 0.22-pm filter into a suitable sterile, single-use container (vial, syringe).

6. Package and label.

PACKAGING

Package in sterile containers.1

LABELING

Keep out of reach of children. Use only as directed. For professional use only.

STABILITY

If not sterility tested: A beyond-use date of up to 24 hours at room temperature, up to 3 days at refrigerated temperature (2° to 8°C), or up to 45 days if frozen can be used for this preparation.

If sterility tested: A beyond-use date of up to 14 days stored in a refrigerator can be used for this preparation.1

USE

Meperidine hydrochloride/atropine sulfate injection is used in the treatment of severe pain.

QUALITY CONTROL

Quality-control assessment can include weight/volume, physical observation, pH, specific gravity, osmolality, assay, color, clarity, paniculate matter, sterility, and pyrogenicity.2,3

The endotoxin unit (EU) maximum would be 12,000 for 5,000 mg of meperidine hydrochloride. The EU maximum would be 2,224 for 40 mg of atropine sulfate. The total maximum endotoxin level would be 12,000 + 2,224 = 14,224 EU for the 100 mL, or 142.24 EU per milliliter.

DISCUSSION

Meperidine hydrochloride (C^sub 15^H^sub 21^NO^sub 2^.HCl, MW 283.79, isonipecaine hydrochloride, pethidine hydrochloride) occurs as a fine, white crystalline, odorless powder. Meperidine hydrochloride is very soluble in water and soluble in alcohol. It melts between 186° and 189°C and should be preserved in well-closed, lightresistant containers. A solution of 5 g in 100 mL of water has a pH of about 5. Meperidine hydrochloride injection has a pH of 3.5 to 6.0 and a maximum endotoxin limit of not more than 2.4 EU per milligram of meperidine hydrochloride. Meperidine hydrochloride is used in the management of moderate to severe pain and as an adjunct to anesthesia and preoperative sedation.4

Atropine sulfate [(C^sub 17^H^sub 23^NO^sub 3^)^sub 2^.H^sub 2^SO^sub 4^.H^sub 2^O, MW 694.33] occurs as colorless crystals, or as a white, crystalline powder. It is odorless and effloresces in dry air. It is slowly affected by light. It is very soluble in water and freely soluble in alcohol and glycerin. It should be preserved in tight containers. Atropine sulfate injection contains not more than 55.6 EU per milligram of atropine sulfate.1

Sterile water for injection is water for injection that has been sterilized and suitably packaged; it contains no added substance. Water for injection is water purified by distillation or a purification process that is equivalent or superior to distillation in the removal of chemicals and microorganisms. It is prepared from water that complies with the U.S. Environmental Protection Agency National Primary Drinking Water Regulations or comparable regulations of the European Union or Japan. It contains no added substance.4

References

1. United States Pharmacopeial Convention, Inc. United States Pharmacopeia 28-National Formulary 23. Rockville, MD: US Pharmacopeial Convention, Inc.; 2004: 200-201, 1208, 2345-2349, 2457-2477, 2878, 2901.

2. Allen LV Jr. Standard operating procedure for participate testing for sterile products. IJPC 1998; 2(1): 78.

3. Allen LV Jr. Standard operating procedure: Quality assessment for injectable solutions. IJPC 1998; 3(5): 406-407.

4. Ellison A, Nash RA, Wilkin MJ. Water. In: Rowe RC, Sheskey PJ, Weller PJ, eds. Handbook of Pharmaceutical Excipients. 4th ed. Washington, DC: American Pharmaceutical Association; 2003: 672-676.

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