Primidone is an anticonvulsant from the pharmacologically active group of anticonvulsant drugs. It is used for long-term therapy of various forms of epilepsy.
What is primidone?
Primidone records an anticonvulsant effect in patients with epilepsy. Primidone records an anticonvulsant effect in patients with epilepsy. It is classified in the antiepileptic drug group. It is chemically classified in the barbiturate group. It is a prodrug, a precursor of the medically active substance. The human organism converts primidone into the potent phenobarbital (deoxyphenobarbital), which resolves epilepsy convulsions. It is a degradation substance (metabolite). This drug is administered by physicians for specific forms of epilepsy.
Pharmacologic action
The medical mechanism has not yet been conclusively researched. However, physicians assume that primidone affects the membrane (cell wall) of nerve cells, thereby exerting a seizure-inhibiting effect. Primidone is known from the long-term therapy of various forms of epilepsy. These special forms include grand mal epilepsy, petit mal epilepsy, status epilepticus, and myoclonic seizures. In children with petit mal epilepsy, primidone has a preventive effect with regard to the development of grand mal epilepsy. These disorders appear as temporal lobe seizures, as well as by primary generalized seizures affecting the whole brain (grand mal epilepsy). Secondary generalized seizures that affect individual areas of the brain (petit mal epilepsy) form another group. Gran mal seizures are also called tonic-clonic seizures. The tonic phase lasts about 10 to 30 seconds and is characterized by muscle tension and spasms. During the clonic phase, muscle tremors and irregular spasms of great intensity occur. This phase can last from thirty seconds to three minutes. Symptoms include a brief intense cry immediately before the onset of convulsions, salivation, twitching, wetting, eye-twisting, sudden cessation of convulsions, unconsciousness, and subsequently increased fatigue. Since it is not possible to accurately predict the onset of seizures, the only option is preventive or palliative treatment with appropriate medications such as primidone. This drug is the second choice for anesthetic preparation as well as for the treatment of essential tremor when first-line drugs have proved ineffective.
Medical application and use
After the absorption of the substance by the organism, the immediate metabolism or conversion of the basic substance into phenobarbital occurs. Another active substance that develops through this process is phenylethylmalonamide, but it is of little importance. Primidone, together with its degradation product phenobarbital, acts at the central switch point of the neurotransmitter gamma-aminobutyric acid (GABA). Along with glutamate, it is the most important inhibitory neurotransmitter of the central nervous system. It plays a prominent role in many neuronal processes of the CNS. It has a modulatory effect and acts as an antagonist to the excitatory glutamate. Phenobarbital has a reinforcing effect on the concentration of the neurotransmitter gamma-aminobutyric acid and decreases the propensity for seizures.
Risks and side effects
Primidone also records side effects as well as interactions with other medications. The drug should not be administered in cases of known hypersensitivity to the drug substance as well as other barbiturates. Centrally depressant medications such as antidepressants, sleeping pills, opioid analgesics, and neuroleptics are contraindications because their effects are enhanced by primidone. Concurrent use of the calcium blocker nimodepine for the treatment of angina pectoris (chest tightness), hypertension (high blood pressure), and tachycardia (rapid heartbeat) may endanger life. This drug is not administered to patients with signs of acute alcohol intoxication. A careful risk-benefit assessment must be made in patients with cardiac arrhythmias, diseases of the respiratory system, severe sepsis, and liver and kidney dysfunction. The reason for a possible contraindication lies in the considerable delay in the degradation of the substance if the organism is already damaged.In most cases, physicians use a reduced dose of primidone with careful monitoring of the patient. The barbiturate should be administered only in very low doses during pregnancy and lactation, should treatment be absolutely necessary. Common side effects include nausea, vomiting, headache, dizziness, increased excitability, impaired memory and speech, impaired coordination, impaired perception, indigestion, convulsions, tremor, drowsiness, and delayed reaction time. Rarely, cardiac arrhythmias, pigmentation disorders, hematopoietic disorders, anemia, skin changes, allergies, muscle fatigue, and liver dysfunction occur. Long-term therapy increases the risk of osteoporosis disorders. Increased excitability, aggressiveness, and moodiness have often been observed in the elderly and children. The degradation of beta-blockers used to treat cardiac disorders and hypertension is accelerated, while the effect is reduced. Primidone decreases the effect of cardiac glycosides such as digitoxin and cytostatic drugs for the treatment of tumor diseases. The effect of antiepileptic drugs such as diazepam, clonazepam, phenytoin, carbamazepine is reduced. Side effects and toxicity of methotrexate used to treat cancer are increased. Regular monitoring of liver enzyme levels and blood counts is indicated, especially in the initial phase. There is an increased risk of osteoporosis in patients with prior disease and concomitant use of [cortisone]]. Primidone may interfere with the effects of contraceptives, so further contraceptive measures should be taken. Experts assume that there is an increased risk of suicide when taking the drug, so regular monitoring of the patient is essential. As with most medications, there is a possibility of a habituation effect with primidone. To avoid withdrawal symptoms, the drug should not be discontinued abruptly, but should be gradually reduced. During cold turkey withdrawal, seizures of the brain are possible. Due to its unfavorable side effect profile, primidone is a second-line drug. It is used only when no alternative drugs with a more favorable appearance are available or when first-line drugs have proven ineffective.
