drugs for epilepsy and muscle spasms/spasticity

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Chapter 24:

Chapter 24 Drugs for Epilepsy

Definition of Epilepsy:

Definition of Epilepsy Group of disorders characterized by excessive excitability of neurons in the CNS Can produce a variety of symptoms ranging from brief periods of unconsciousness to violent convulsions

Seizure: Generation:

Seizure: Generation Initiated by synchronous, high-frequency discharge from a group of hyperexcitable neurons called a focus Focus may result from Congenital defects Hypoxia at birth Head trauma Cancer

Seizures: Types:

Seizures: Types Partial (focal) seizures Simple partial Complex partial Secondarily generalized Generalized seizures Tonic-clonic (grand mal) Absence (petit mal) Atonic Myoclonic Status epilepticus (SE) Febrile

Mixed Seizures: Lennox-Gastaut Syndrome:

Mixed Seizures: Lennox-Gastaut Syndrome Severe form of epilepsy that usually develops during the preschool years Developmental delay and a mixture of partial and generalized seizures

Antiepileptic Drugs:

Antiepileptic Drugs Effects Suppress discharge of neurons within a seizure focus Suppress propagation of seizure activity from the focus to other areas of the brain Mechanisms of action Suppression of sodium influx Suppression of calcium influx Antagonism of glutamate Potentiation of GABA

Epilepsy: Therapeutic Considerations:

Epilepsy: Therapeutic Considerations Treatment goal and treatment options Neurosurgery (best success rate) Vagal nerve stimulation Ketogenic diet Diagnosis and drug selection Drug evaluation

Epilepsy: Therapeutic Considerations:

Epilepsy: Therapeutic Considerations Monitoring plasma drug levels Promoting patient adherence Withdrawing antiepileptic drugs Suicide risk – antiepileptic drugs

Classification of Antiepileptic Drugs:

Classification of Antiepileptic Drugs Two major categories Traditional antiepileptic drugs (AEDs) Phenytoin, carbamazepine, valproic acid, and others Newer AEDs Oxcarbazepine, gabapentin, zonisamide, and others

Phenytoin (Dilantin):

Phenytoin (Dilantin) Partial and tonic-clonic seizures Mechanism of action: selective inhibition of sodium channels Varied oral absorption Half-life: 8 to 60 hours

Slide 11:

Fig. 24-1. Relationship between dose and plasma level for phenytoin compared with most other drugs. A, Within the therapeutic range, small increments in phenytoin dosage produce sharp increases in plasma drug levels. This relationship makes it difficult to maintain plasma phenytoin levels within the therapeutic range. B, Within the therapeutic range, small increments in dosage of most drugs produce small increases in drug levels. With this relationship, moderate fluctuations in dosage are unlikely to result in either toxicity or loss of therapeutic effects.

Phenytoin (Dilantin):

Phenytoin (Dilantin) Adverse effects Nystagmus Sedation Ataxia Diplopia Cognitive impairment Gingival hyperplasia Skin rash Effects in pregnancy Cardiovascular effects

Phenytoin (Dilantin):

Phenytoin (Dilantin) Drug interactions Decreases the effects of oral contraceptives, warfarin, and glucocorticoids Increases levels of diazepam, isoniazid, cimetidine, alcohol, and valproic acid

Carbamazepine (Tegretol):

Carbamazepine (Tegretol) Uses Epilepsy Bipolar disorder Trigeminal and glossopharyngeal neuralgias Adverse effects Neurologic effects: nystagmus, ataxia Hematologic effects: leukopenia, anemia, thrombocytopenia Birth defects Hypo-osmolarity Dermatologic effects: rash, photosensitivity reactions

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Valproic Acid (Depakene, Depakote, Depacon):

Valproic Acid (Depakene, Depakote, Depacon) Uses Seizure disorders Bipolar disorder Migraine Adverse effects GI effects Hepatotoxicity: liver failure Pancreatitis Teratogenic effects

Ethosuximide:

Ethosuximide Drug of choice for absence seizures Generally devoid of significant adverse effects and interactions Initially may cause drowsiness, dizziness, and lethargy

Phenobarbital:

Phenobarbital Uses Epilepsy (partial and generalized tonic-clonic seizures) Promotes sleep and sedationa

Newer Antiepileptic Drugs:

Newer Antiepileptic Drugs Gabapentin Lamotrigine Levetiracetam Oxcarbazepine Tiagabine Topiramate Zonisamide

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Slide 21:

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Management of Generalized Convulsive Status Epilepticus:

Management of Generalized Convulsive Status Epilepticus Continuous series of tonic-clonic seizures Goals of treatment Maintain ventilation Correct hypoglycemia Terminate seizures IV benzodiazepines (lorazepam or diazepam)

Chapter 25:

Chapter 25 Drugs for Muscle Spasm and Spasticity

Drugs for Muscle Spasm and Spasticity:

Drugs for Muscle Spasm and Spasticity Two groups of drugs that cause skeletal muscle relaxation One group for localized muscle spasm Other group for spasticity Most produce their effects through actions in the CNS (except dantrolene). Groups are not interchangeable.

Drugs for Muscle Spasm and Spasticity:

Drugs for Muscle Spasm and Spasticity Muscle spasm: involuntary contraction of muscle or muscle group Causes Epilepsy Hypocalcemia Pain syndromes: adult and chronic Trauma: localized skeletal muscle injury

Drug Therapy of Muscle Spasm:

Drug Therapy of Muscle Spasm Treatment of spasm Physical measures Immobilization of affected muscle Cold compresses Whirlpool baths Physical therapy

Drug Therapy of Muscle Spasm:

Drug Therapy of Muscle Spasm Treatment of spasm Drug therapy Analgesic anti-inflammatory (aspirin) Centrally acting muscle relaxants Diazepam Tizanidine

Centrally Acting Muscle Relaxants:

Centrally Acting Muscle Relaxants Mechanism of action (MOA) unclear – may result from sedative properties of the drugs Diazepam MOA through enhancing effects of GABA Tizanidine MOA through agonist action at presynaptic alpha 2 receptors

Centrally Acting Muscle Relaxants:

Centrally Acting Muscle Relaxants Therapeutic use Relieve local muscle spasm Decrease local muscle pain Increase range of motion No studies to indicate superiority of one drug over another

Centrally Acting Muscle Relaxants:

Centrally Acting Muscle Relaxants Adverse effects Generalized CNS depression Hepatic toxicity Tizanidine (Zanaflex) and metaxalone (Skelaxin) can cause damage. Chlorzoxazone (Paraflex) can cause hepatitis and necrosis. Physical dependence Abstinence syndrome

Drugs for Spasticity:

Drugs for Spasticity Spasticity Movement disorders of CNS origin Most common causes: multiple sclerosis and cerebral palsy Characteristics include: Heightened muscle tone Spasm Loss of dexterity

Three Drugs for Spasticity:

Three Drugs for Spasticity Baclofen (Lioresal) Acts in the CNS Diazepam (Valium) Acts in the CNS Dantrolene (Dantrium) Acts directly on smooth muscle

Baclofen (Lioresal):

Baclofen (Lioresal) Mechanism Acts in the spinal cord Suppresses hyperactive reflexes Mechanism unknown May mimic the action of GABA on spinal neurons

Baclofen (Lioresal):

Baclofen (Lioresal) Therapeutic uses Multiple sclerosis, spinal cord injury, cerebral palsy NOT with stroke Decreases flexor and extensor spasms Suppresses resistance to passive movement No direct effect on skeletal muscle

Baclofen (Lioresal):

Baclofen (Lioresal) Adverse effects No antidote for overdose Gradual withdrawal over 1 to 2 weeks Abrupt intrathecal withdrawal – risk for rhabdomyolysis CNS depressant GI symptoms (nausea, constipation) Urinary retention

Diazepam (Valium):

Diazepam (Valium) Member of the benzodiazepine family (see Chapter 34) The only one labeled to treat spasticity Mechanism Acts in the CNS Mimics action of GABA Adverse effect Sedation

Dantrolene (Dantrium):

Dantrolene (Dantrium) Mechanism Acts directly on skeletal muscle Suppresses the release of calcium from the sarcoplasmic reticulum (SR) Therapeutic uses Spasticity associated with multiple sclerosis, cerebral palsy, spinal cord injury Malignant hyperthermia Potentially fatal condition caused by succinylcholine and general anesthetics

Dantrolene (Dantrium):

Dantrolene (Dantrium) Adverse effects Hepatic toxicity Muscle weakness Drowsiness Diarrhea Acne-like rash

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