2. NEW ANTIEPLEPTICS & CENTRALLY ACTING MUSCLE RELAXANTS

4. Vigabatrin:
Vigabatrin, the first 'designer drug' in the epilepsy field, is a vinyl-substituted analogue of GABA
acts by inhibitng GABA transaminase
effectve in patients unresponsive to conventional drugs
main side-effects: drowsiness, behavioral and mood changes.
Drug interaction: decreases phenytoin conc.

5. Lamotrigine acts by inhibiting sodium channels
broad therapeutic profile
main 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. FELBAMATE
Acute 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. Gabapentin
action 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.

12. Oxcarbazepine
Carbamazepine derivative
MOA
Blocking of sodium channels
Uses
Partial seizure
Tonic-clonic seizure
Side effects
Rashes
Hyponatremia
Headache & dizziness

13. Primidone MOA Converted into phenobarbital Na channels blocker Uses
Partial seizure
Tonic-clonic seizure
Side effects
Drowsiness
Sedation

14. Tiagabine
an 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 confusion
Tremors and difficulty to conc.
Weakness of knees
Agitation

16. TOPIRAMATE MOA Weak sodium channels blocker Enhances GABA action
blocks AMPA-receptor channel
Carbonic anhydrase inhibitor
Uses
Refractory cases of epilepsy

17. Side effects
Teratogenic
Dizziness
Ataxia
Nervousness
Memory problems
Drug interaction: increases valproate conc.

18. Zonisamide
MOA
Blocks voltage sensitive sodium channels
Blocks voltage dependent calcium channels
Suppresses neuronal hypersynchronization
Carbonic anhydrase inhibitor
Free radical scavenger
Uses
Partial seizure (adjunctive Tx)

19. Side effects
Confusion
Hyperthermia
Ataxia
Fatigue
Dizziness
Wt. gain
N.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
Somnolence
Ataxia
Anxiety
Agitation
Decrease in RBC
Advantages
No drug interaction
Can 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 , valproate
use of a single drug is preferred, when possible, to avoid pharmacokinetic interactions
newer 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 , gabapentin
To stabilise mood in mono- or bipolar affective disorder (as an alternative to lithium ): for example carbamazepine , valproate

23. Conclusion
Newer 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

24. CENTRALLY ACTING MUSCLE RELAXANTS

25. CENTRALLY ACTING MUSCLE RELAXANTS
Skeletal muscle relaxants may be used for relief of spasticity in neuromuscular diseases, such as multiple sclerosis, as well as for spinal cord injury and stroke

26. Mephenesin MOA Inhibition of polysynaptic excitation of motor neurons
Uses
Acute muscle spasm resulting from injury

27. Baclofen MOA Selective agonist at presynaptic GABA-B receptors Uses
Spasticity associated with multiple sclerosis or spinal injury

28. Side effects
Drowsiness
Motor incoordination
Nausea
Behavioral effects
Caution
Kidney diseases
CV & respiratory diseases
Peptic ulcer (CI)

29. Other central muscle relaxants
Benzodiazepine (diazepam, clonazepam)
Carisoprodol: acts on reticular formation
Cyclobenzaprine
Tizanidine: alpha-2 agonist
botulinum 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 increasing
dantrolene

30. Conclusion
Central 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