Download NEWER ANTIEPLEPTICS CENTRALLY ACTING MUSCLE

NEW ANTIEPLEPTICS
&
CENTRALLY ACTING MUSCLE
RELAXANTS
Vigabatrin:
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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.
Lamotrigine
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acts by inhibiting sodium channels
broad therapeutic profile
main side-effects are hypersensitivity
reactions (especially skin rashes
FELBAMATE
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2.
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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 .
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 (LennoxGastaut 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.
Gabapentin
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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.
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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.
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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.
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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.
Oxcarbazepine
Carbamazepine derivative
MOA
Blocking of sodium channels
Uses
• Partial seizure
• Tonic-clonic seizure
Side effects
• Rashes
• Hyponatremia
• Headache & dizziness
Primidone
MOA
 Converted into phenobarbital
 Na channels blocker
Uses
•
Partial seizure
• Tonic-clonic seizure
Side effects
 Drowsiness
 Sedation
Tiagabine
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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.
TIAGABINE
MOA
Blocks GABA reuptake
Uses
Partial seizure
Side effects
• Drowsiness and confusion
• Tremors and difficulty to conc.
• Weakness of knees
• Agitation
TOPIRAMATE
MOA
 Weak sodium channels blocker
 Enhances GABA action
 blocks AMPA-receptor channel
 Carbonic anhydrase inhibitor
Uses
Refractory cases of epilepsy
Side effects
 Teratogenic
 Dizziness
 Ataxia
 Nervousness
 Memory problems
Drug interaction: increases valproate conc.
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)
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
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
Clinical uses of antiepileptic drugs
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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 .
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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
Conclusion
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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
CENTRALLY ACTING MUSCLE
RELAXANTS
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
Mephenesin
MOA
Inhibition of polysynaptic excitation
of motor neurons
Uses
• Acute muscle spasm resulting from
injury
Baclofen
MOA
Selective agonist at presynaptic GABA-B
receptors
Uses
Spasticity associated with multiple sclerosis or
spinal injury
Side effects
• Drowsiness
• Motor incoordination
• Nausea
• Behavioral effects
Caution
• Kidney diseases
• CV & respiratory diseases
• Peptic ulcer (CI)
Other central muscle relaxants
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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
Conclusion
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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