CHLORPROMAZINE HCL

Chemistry - A propylamino phenothiazine derivative, chlorpromazine is the prototypic phenothiazine agent. It occurs as a white to slightly creamy white, odorless, bitter tasting, crystalline powder.
One gram is soluble in 1 ml of water and 1.5 ml of alcohol. The commercially available injection isa solution of chlorpromazine HCl in sterile water at a pH of 3-5.

Storage, Stability, Compatibility

Protect from light and store at room temperature; avoidfreezing the oral solution and injection. Dispense oral solution in amber bottles. Store oral tablets intight containers. Do not store in plastic syringes or IV bags for prolonged periods of time as thedrug may adsorb to plastic.
Chlorpromazine will darken upon prolonged exposure to light; do not use solutions that are darklycolored or if precipitates have formed. A slight yellowish color will not affect potency or efficacy.
Alkaline solutions will cause the drug to oxidize.
The following products have been reported to be compatible when mixed with chlorpromazine
HCl injection: all usual intravenous fluids, ascorbic acid, atropine sulfate, butorphanol tartrate, diphenhydramine, droperidol, fentanyl citrate, glycopyrrolate, heparin sodium, hydromorphone HCl, hydroxyzine HCl, lidocaine HCl, meperidine, metoclopramide, metaraminol bitartrate, morphinesulfate, pentazocine lactate, promazine HCl, promethazine, scopolamine HBr, & tetracycline HCl.
The following products have been reported as being incompatible when mixed with chlorpromazine: aminophylline, amphotericin B, chloramphenicol sodium succinate, chlorothiazide sodium, dimenhydrinate, methicillin sodium, methohexital sodium, nafcillin sodium, penicillin g potassium, pentobarbital sodium, phenobarbital sodium, and thiopental sodium. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for more specific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).

Pharmacology - CHLORPROMAZINE HCL

Once the principle phenothiazine used in veterinary medicine, chlorpromazine hasbeen largely supplanted by acepromazine. It has similar pharmacologic activities as acepromazine, but is less potent and has a longer duration of action. For further information refer to theacepromazine monograph.

Uses, Indications

The clinical use of chlorpromazine as a neuroleptic agent has diminished, butthe drug is still used for its antiemetic effects in small animals and occasionally as a preoperativemedication and tranquilizer. As an antiemetic, chlorpromazine will inhibit apomorphine-inducedemesis in the dog but not the cat. It will also inhibit the emetic effects of morphine in the dog. Itdoes not inhibit emesis caused by copper sulfate, or digitalis glycosides.

Pharmacokinetics - CHLORPROMAZINE HCL

Chlorpromazine is absorbed rapidly after oral administration, but undergoesextensive first pass metabolism in the liver. The drug is also well absorbed after IM injection, butonsets of action are slower than after IV administration.
Chlorpromazine is distributed throughout the body and brain concentrations are higher than thosein the plasma. Approximately 95% of chlorpromazine in plasma is bound to plasma proteins(primarily albumin).
The drug is extensively metabolized principally in the liver and kidneys, but little specific information is available regarding its excretion in dogs and cats.
Contraindications/Precautions - Chlorpromazine causes severe muscle discomfort and swellingwhen injected IM into rabbits; use IV only in this species. See other contraindications/precautionsin the acepromazine monograph found earlier in this section.

Adverse Effects, Warnings

In addition to the possible effects listed in the acepromazinemonograph, chlorpromazine may cause extrapyrimidal symptoms in the cat when used at highdosages. These symptoms can include tremors, shivering, rigidity & loss of the righting reflexes.
Lethargy, diarrhea, and loss of anal sphincter tone may also be seen.
Horses may develop an ataxic reaction with resultant excitation and violent consequences. Theseataxic periods may cycle with periods of sedation. Because of this effect, chlorpromazine is rarelyused in equine medicine today.
Overdosage - Refer to the information listed in the acepromazine monograph.

Drug Interactions

Phenothiazines should not be given within one month of worming with anorganophosphate agent as their effects may be potentiated. Physostigmine toxicity may be enhanced by chlorpromazine. Toxicity of the herbicide paraquat is increased by chlorpromazine.
Other CNS depressant agents (barbiturates, narcotics, anesthetics, etc.) may cause additive
CNS depression if used with phenothiazines.
Quinidine given with phenothiazines can cause additive cardiac depression.
Antidiarrheal mixtures (e.g., Kaolin/pectin, bismuth subsalicylate mixtures) and antacids maycause reduced GI absorption of oral phenothiazines.
Increased blood levels of both drugs may result if propranolol is administered with phenothiazines. Phenothiazines block alpha-adrenergic receptors, if epinephrine is then given, unopposedbeta-activity causing vasodilation and increased cardiac rate can occur.
Phenytoin metabolism may be decreased if given concurrently with phenothiazines.
Procaine activity may be enhanced by phenothiazines.
Dipyrone used with chlorpromazine has been reported to cause serious hypothermia.