Primidone
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Uses
Action
- Raises electrically induced seizure thresholds and alters seizure patterns.
- The exact mechanism of seizure prevention is unknown.
- Rapidly metabolized to the active metabolites phenobarbitone
and phenylethamalonamide (PEMA).
- In dogs the major anti-seizure activity is thought to be due to the phenobarbitone, with some potentiation by PEMA.
Indications
- Management of seizures
.
Adverse reactions
Other reported reactions
- Acute toxicity includes:
- Sedation.
- Ataxia.
- PU/PD.
- Nystagmus.
- Profound tachycardia.
- Episodic hyperventilation.
- Anorexia.
- Hepatotoxicity: associated with the duration rather than daily dose.
- Histopathological changes after 6 months of therapy include hepatocellular hypertrophy and necrosis, lipidosis, and extramedullary hematopoiesis.
- If medication is discontinued after this time, these changes will result in hepatic fibrosis with some permanent loss of function.
- Primidone intoxication associated with concurrent use of chloramphenicol.
- Dermatitis associated with the use of primidone in a dog:
- Excessive licking of paws.
- Alopecia.
- Pruritus.
- Scaling.
- Pigmentation.
- Ulceration over back, elbows, hocks, face and ears.
- Biopsy - severe diffuse parakeratotic hyperkeratosis of epidermis and hair follicles, frequently associated with epidermal hyperplasia, dyskeratosis, and intra-cellular vacuolation. Hint of anti-IgG staining.
- Polyphagia.
- Personality changes.
- Sedation and ataxia (often seen early in therapy and may subside with time) may indicate development of toxic serum levels.
- Chronic therapy may cause hepatic abnormalities:
- Increase in liver enzymes (ALT, ALP, glutamate dehydrogenase).
- Decreased serum albumin.
- Neutropenia, thrombocytopenia, anemia and splenomegaly reported in dogs receiving phenobarbitone therefore potential for these to develop on primidone.
Investigation of adverse reaction
- Dose reduction or monitoring of serum levels is indicated if any adverse effects are present.
- Therapeutic serum levels vary with different laboratories but are in the region of 20-40 ug/ml.
- Chronic therapy; liver enzymes should be monitored at least yearly.
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