EAR PROBLEMS
sansveria roxburghina-Agaveceae
Agave americana--agavaceae
Anti- Epileptic drugs
Thursday, December 16, 2010
It is a collective term applied for a group of convulsive disorders
The common features of epilepsy are
Loss or disturbance of consciousnesses
Characteristic body movements (usually, but not always)
CLASSIFICATION
1. Hydantoins
Phenytoin
2. Barbiturates
Phenobarbitone
Primidone
3. Iminostilbbenes
Carbamazepine
4. Succinimides
Ethosuximided
5. Aliphatic carboxylic acid
Sodium valproate
6. Benzodiazepines
Clonazepam
Clobazam
Diazepam
7. Newer antiepileptic
Lamotrigine
Gbapentine
8. Miscellaneous
Trimethadione
Acetazolamide
Phenytoin
Phenytoin was synthesized in 1908, but its anticonvulsant property was discovered only in 1938
It is effective in suppressing tonic-clinic and partial seizures and is a drug of choice for initial therapy, particularly in treating adults
Mechanism of action
Phenytoin blocks voltage-gated sodium channels by selectively binding to the channel in the inactive state and stabilizes the neuronal membrane
It inhibits the generation of repetitive action potentials
At much higher concentrations , phenytoin can block voltage-dependent calcium channels and interfere with the release of monoaminergic neurotransmitters
Pharmacological action
Phenytoin exerts antiseizure activity without causing general depression of the CNS
It is one of the most effective drugs against generalized tonic-clonic seizures and partial seizures
Phenytoin reduces the propagation of abnormal impulses in the brain
Pharmacokinetics
Phenytoin is poorly water soluble hence absorption is slow
It is 90% bound to plasma proteins
It is metabolized in liver
Phenytoin is enzyme inducer
Therapeutic uses
Phenytoin is highly effective for all partial seizures ( simple and complex), for tonic-chronic seizures and in the treatment of status epileptics
Phenytoin is not effective for absence seizures, which often may worsen if treated with this drug
Adverse effects
It depend dose , duration and route
Nausea, vomiting, epigasric pain, anorexia
Nystagmus, diplopia, ataxia are common
Gingival hyperplasia is more common in children on prolonged use
Peripheral neuropathy
Phenytoin inhibits insulin release and produces hyperglycemia
Decreases the release of ADH
Osteomalacia , hypocalcaemia due to altered metabolism of vitamin D and inhibition of intestinal absorption of Ca
Hypersensitivity - Rashes , SLE, hepatic necrosis , and neutropenia
Megaloblastic anemia – Phenytoin decreases absorption and increases excretion of folates
Teratogenicity
When taken by the pregnant lady, phenytion produces foetal hydantion syndrome characterized by hypo plastic phalanges, cleft palate, and harelip
Drug interactions
Phenytoin is an enzyme inducer
Phenytoin given with phenobarbitone , both increases each other metabolism
Phenytoin and carbamazepine enhance each others metabolism
Valproate displaces protein bound phenytoin
Cimetidine and chloramphenicol inhibit the metabolism of phenytioin resulting in toxicity
Antacids decreases the absorption of phenytoin
Phenobarbitone
Phenobartitone was the first effective antiepileptic drug to be introduced in 1912. It still remains one of the widely used drugs
It has antiepileptic activity and raises the seizure threshold
Mechanism of action
Barbiturates enhances the inhibitory neurotransmission in the CNS by enhancing the activation of GABA receptors and facilitating the GABA mediated opening of chloride ion channels
Pharmacokinetics
It is well absorbed orally
The drug freely penetrates the brain
Approximately 75 % of the drug is inactivated by the hepatic mocrosomal system, whereas the examining drug is excreted unchanged by the kidney
It is a potent inducer of the cytochrome P450 system and when given chronically, it enhances the metabolism of their agents
Therapeutic uses
It provides favorable response for simple partial seizures, but it is not very effective for complex partial seizures
The drug had been regarded as the first choice in treating recurrent seizures in children, including febrile seizures
It also used to treat recurrent tonic-clonic seizures, especially in patients who donot respond to diazepam plus phenytoin
It also used as a mild sedative to relieve anxiety, nervous tension and insomnia
Adverse effects
Sedation, ataxia, vertigo , nausea and vomiting
Agitation and confusion occur at high doses
Rebound seizures can occur on discontinuance of Phenobarbital
Primdone
It structurally related to Phenobarbital and it resembles Phenobarbital in its anticonvulsant activity
It is an alternative choice in partial seizures and tonic – clonic seizures
It has more efficacy due to the its metabolites Phenobarbital and phenyl-ethyl-malonamide which have longer half- lives than the parent drug
It is effective against tonic-clinic and simple partial seizures and phenyl-ethy-lmalonamide is effective against complex partial seizures
Primidone is often used with carbamazepine and phenytoin
It is well absorbed orally
It exhibits poor protein binding
These drug has the same adverse effects as those seen with Phenobarbital
Benzodiazepines
Several of the benzodiazepines show antiepileptic activity
Diazepam and lorazepam are the drugs of choice in the acute treatment whereas Clonazepam and clorazepate and clorazepate are used for chronic treatment of status epilepticus
Clonazepam
It suppresses seizure spread from the epileptogenic focus and is effective in absence and myoclonic seizures , but tolerance develops
Clonazepate
Clorazepate is effective in partitial seizures when used in conjunction with other drugs
Diazepam
It is effective against
Petitmal epilepsy
Mylclonic seizures
Status epilepsy
It is drug of choice for status epilepticus
Lorazepam
Lorazepam and diazepam are both effective in interrupting the repetitive seizures of status epilepticus.
Lorazepam has a longer duration of action and is preferred by some clinicians
All of the antiepileptics, the benzodiazepines are the safest and most free from severe side effects
All benzodiazepines have sedative properties
Side effects
Drowsiness,
Somnolence,
Fatigue,
Ataxia,
Dizziness and behavioral changes
Respiratory depression and cardiac depression may occur when given intravenously in acute situations
Ethosuximide
It reduces propagation of abnormal electrical activity in the brain, most likely by inhibiting t- type calcium channels in a manner similar to the action of phenytoin on sodium channels
It is the first choice in absence seizures
It is well absorbed orally and is not bound to plasma proteins
About 25% of the drug is excreted unchanged in the urine and 75% is converted to inactive metabolites in the liver by the microsomal cytochrome P450 system
It does not induce P450 enzyme synthesis
The drug is irritating to the stomach and nausea and vomiting may occur on chronic administration
Drowsiness, lethargy, dizziness , restlessness , agitation , anxiety and the inability to concentrate are often observed
Valproic Acid
It is a broad spectrum anticonvulsant
It has multiple actions , including sodium channel blockade and enhancement of GABAergic transmission
It is the most effective agent available for treatment of myoclinec seizures
It also diminishes absence seizures, but because of its hepatotixic potential, it is a second choice
It also reduces the incidence and severity of tonic-clonic seizures
The drug is effective orally and is rapidly absorbed
About 90% is bound to the plasma proteins ,only 3% of the drug is excreted unchanged, the rest is converted into active metabolites by the liver
It is metabolized by cytochrome P450 enzymes
Metabolites are excreted by kidney
It can cause nausea, vomiting ,sedation, ataxia and tremor are common
It inhibits the metabolism of a number of antiepileptic drugs , including Phenobarbital, carbamazepine and ethosuximide
Carbamaepines
Actions
It reduces the propagation of abnormal impulses in the brain by blocking sodium channels, thereby inhibiting the generation of repetitive action potential in the epileptic focus and preventing their spread
ADME
It is absorbed slowly following oral administration
It enters the brain rapidly because of its high lipid solubility
It induces the drug metabolizing enzymes in the liver
The enhanced hepatic cytochrome p450 system activity also increases the metabolism of many drugs including other antiepileptic drugs
It is an inducer of the cytochromep450 isozyme cyp3a4, which decrease the effects of drugs that are metabolized by his enzyme
Therapeutic uses
It is effective in Temporal lobe epilepsy
Trigeminal neuralgia
Used in post hepatic pain
Adverse effects
Chronic administration of carbamazepine can cause stupor, coma and respiratory depression
It also produces drowsiness, vertigo, ataxia, and blurred vision
The drug is irritating to the stomach and nausea and vomiting may occur
Drug interaction
The hepatic metabolism of carbamazepine is inhibited by several drugs
Toxic symptoms may arise if the dose is not adjusted
Subscribe to:
Posts (Atom)
