4 Vigabatrin:Vigabatrin, the first 'designer drug' in the epilepsy field, is a vinyl-substituted analogue of GABAacts by inhibitng GABA transaminaseeffectve in patients unresponsive to conventional drugsmain side-effects: drowsiness, behavioral and mood changes.Drug interaction: decreases phenytoin conc.
5 Lamotrigine acts by inhibiting sodium channels broad therapeutic profilemain side-effects are hypersensitivity reactions (especially skin rashes
6 FELBAMATE is an analogue of an obsolete anxiolytic drug, meprobamate M.O.A. It has only a weak effect on sodium channels .little effect on GABA.block of the NMDA receptor channel .
7 FELBAMATEAcute side effects are mild, mainly nausea, irritability and insomnia, but it occasionally causes severe reactions resulting in aplastic anaemia or hepatitis. For this reason, its recommended use is limited to a form of intractable epilepsy in children (Lennox- Gastaut syndrome) that is unresponsive to other drugs. Its plasma half-life is about 24 hours, and it can enhance the plasma concentration of other AEDs given concomitantly.
8 Gabapentinaction appears to be on T-type calcium channel function, by binding to a particular channel subunit (α2δ), and it inhibits the release of various neurotransmitters and modulators.The side effects of gabapentin (mainly sedation and ataxia) are less severe than with many antiepileptic drugs.
9 The absorption of gabapentin from the intestine depends on the amino acid carrier system and shows the property of saturability, which means that increasing the dose does not proportionately increase the amount absorbed. This makes gabapentin relatively safe and free of side effects associated with overdosing.
10 Its plasma half-life is about 6 hours, requiring dosing two to three times daily. It is excreted unchanged in the urine and is free of interactions with other drugs. It has limited efficacy when used on its own, so is used mainly as add-on therapy.
11 It is also used as an analgesic to treat neuropathic pain. A recently introduced follow-up drug, pregabalin , is more potent than gabapentin but otherwise very similar. These drugs are excreted unchanged in the urine, and so must be used with care in patients whose renal function is impaired.
13 Primidone MOA Converted into phenobarbital Na channels blocker Uses Partial seizureTonic-clonic seizureSide effectsDrowsinessSedation
14 Tiagabinean analogue of GABA that is able to penetrate the blood-brain barrier, acts by inhibiting the reuptake of GABA by neurons and glia.It enhances the extracellular GABA concentration, as measured in microdialysis experiments, and also potentiates and prolongs GABA-mediated synaptic responses in the brain.It has a short plasma half-life, and its main side effects are drowsiness and confusion.
15 TIAGABINE MOA Blocks GABA reuptake Uses Partial seizure Side effects Drowsiness and confusionTremors and difficulty to conc.Weakness of kneesAgitation
17 Side effectsTeratogenicDizzinessAtaxiaNervousnessMemory problemsDrug interaction: increases valproate conc.
18 ZonisamideMOABlocks voltage sensitive sodium channelsBlocks voltage dependent calcium channelsSuppresses neuronal hypersynchronizationCarbonic anhydrase inhibitorFree radical scavengerUsesPartial seizure (adjunctive Tx)
19 Side effectsConfusionHyperthermiaAtaxiaFatigueDizzinessWt. gainN.B. long t1/2 (60 hrs.)Drug interactions: increases conc. of carbamazepine , its level is increased by enz. inducer
20 Levetiracetam MOA UNKNOWN Uses Generalized seizure Side effects SomnolenceAtaxiaAnxietyAgitationDecrease in RBCAdvantagesNo drug interactionCan be used in hepatic and renal impairment
21 Clinical uses of antiepileptic drugs Tonic-clonic (grand mal) seizures:carbamazepine (preferred because of a relatively favourable effectiveness:risk ratio), phenytoin , valproateuse of a single drug is preferred, when possible, to avoid pharmacokinetic interactionsnewer agents include vigabatrin, lamotrigine , felbamate , gabapentin .Partial (focal) seizures: carbamazepine , valproate; alternatives are clonazepam or phenytoin .
22 Absence seizures (petit mal): ethosuximide or valproate valproate is used when absence seizures coexist with tonic-clonic seizures, because most other drugs used for tonic-clonic seizures can worsen absence seizures.Myoclonic seizures: diazepam intravenously or (in absence of accessible veins) rectally.Neuropathic pain: for example carbamazepine , gabapentinTo stabilise mood in mono- or bipolar affective disorder (as an alternative to lithium ): for example carbamazepine , valproate
23 ConclusionNewer AEDs have higher effectiveness, better PK profile, less drug interactions and lower side effects which made them quite popular. However, more clinical studies are needed to clarify the teratogenicity and drug interactions
29 Other central muscle relaxants Benzodiazepine (diazepam, clonazepam)Carisoprodol: acts on reticular formationCyclobenzaprineTizanidine: alpha-2 agonistbotulinum toxin injected into a muscle, this neurotoxin causes long-lasting paralysis confined to the site of injection, and its use to treat local muscle spasm is increasingdantrolene
30 ConclusionCentral skeletal muscle relaxants are used to reduce the rigidity of skeletal muscles in treatment of muscles spasticity. Different agents with different MOAs can be used in the treatment of diseases like multiple sclerosis