User:Colin/Antiepileptic drug

Pharmacokinetics
The speed, degree and duration of action of an antiepileptic drug (the pharmacokinetics) varies from drug to drug and with different routes of administration. Rapid drug delivery is important in an emergency situation but may not be important or even undesirable for chronic use.

The fastest route is intravenous as the drug does not need to be absorbed. Other choices in emergency situations include solutions for intranasal spray, drops against the inside of the cheek (buccal) or under the tongue, and rectal administration. Suitable formulations are readily absorbed by the mucosal membranes into the underlying veins. These routes may also initially bypass the liver, which means more of the drug is available for use and less is immediately metabolised. The absorption of intramuscular injections vary considerably with the chemical properties of the drug, the formulation and the location of injection. Injections are only suitable for administration by healthcare professionals, whereas the other methods may be used in the community with minimal training.

Drugs for chronic use are usually taken orally and these are mostly absorbed in the gut. Solutions and syrups are absorbed faster than pills, which must disintegrate first. Many countries' regulations ensure that the same drug from brands or generics are bioequivalent, which is important to avoid a change in seizure control, or side effects, if the drug manufacturer is switched. Some drugs may irritate the stomach and are available as enteric-coated pills to delay disintegration until it reaches the gut. If a drug is quickly absorbed and eliminated, this can cause fluctuations of the levels in the body and require frequent doses. A sustained-release formulation can reduce this effect and allow for fewer doses. The speed and degree of absorption of a drug is also affected by whether it is taken before, whilst or after eating.

Once it reaches the circulation, the drug is distributed around the body's tissues. The speed and degree of distribution are affected by many factors. For example, lipophilic drugs will better penetrate fatty tissues like the brain than water-soluble drugs. Tissues that are highly perfused (good blood supply) will take up the drug quickly. Some of the drug may bind to proteins in the blood, which means less of the drug is available to other tissues and can act as a reservoir. The degree of protein binding can vary from 0 to 98%. For a drug to be effective with epilepsy, it must be able to cross the blood-brain barrier. Generally, antiepileptic drugs easily cross the placenta, exposing the foetus to the same concentration as the mother. Breast milk will also be contaminated to some degree by antiepileptic drugs, though for most drugs this does not rule-out breast-feeding.

A portion of the drug may be eliminated by the intestine or kidneys before it reaches the circulation (first pass effect). Drugs are eliminated from the body either unchanged via kidneys into the urine or by being transformed into other chemicals (metabolised). These metabolites are often inactive or less active than the original drug. However, in some cases their activity in the body is therapeutic or toxic. Sometimes, as with primidone, fosphenytoin and oxcarbazepine, the metabolites contribute all or most of the therapeutic effect (pro-drugs).

A number of factors may increase or decrease the metabolism of anti-epileptic drugs. A significant portion of people have impaired metabolism of certain drugs due genetic factors surrounding metabolising enzymes, potentially leading to toxicity in those populations groups. In general, when compared with most adults, newborns and the elderly metabolise anti-epileptic drugs slower, and young children and pregnant women metabolise them faster. Other drugs (either anti-epileptic or for other illnesses) and even diet (such as grapefruit juice) can significantly affect the metabolism of drugs. Liver disease significantly impairs drug metabolism. These factors mean that estimating the dose based simply on the patient's weight (milligrams-per-kilogram) is often inadequate.

Initiation
The choice of therapy is based on the seizure type(s), and (if known) the cause and the epilepsy syndrome. The Health-related Quality of Life (HRQoL) involves more than just reducing seizure frequency or aiming for seizure freedom. Many factors determine whether to treat the epilepsy at all. These may include the person's age, occupation, abilities, and (if female) desire to start a family; how hazardous the seizure type is; the seizure frequency; the predictability of the seizures. . Some epilepsy syndromes are so benign that treatment is unnecessary. Higher frequency and severity of seizures is associated with poorer quality of life. People with depression (which is frequently co-morbid with epilepsy) perceive their epilepsy as more severe and disabling. The ability to drive is related to independence for many people, and a driving licence is generally only permitted after a period of seizure freedom. For many people being completely seizure free is very important; for others (such as those with certain epilepsy syndromes) it may be an unrealistic expectation.

Although some drugs are used prophylactically for short periods (such as after a head injury) antiepileptic drugs are not able to prevent epilepsy developing (epileptogenesis).

Side effects from one drug can be bad enough in nearly a third of cases that another drug is required. In children, these drugs may affect the developing brain, their behaviour or ability to learn.

Positive response to an antiepileptic drug does not confirm the seizures were actually epileptic. This is due to the placebo effect and also to many antiepileptic drugs having therapeutic value in treating psychiatric disorders.

History

 * How drugs are discovered