Pharmacology Test 4: Anticonvulsants

Front 1

Convulsion

Back 1

Sudden attack of involuntary muscular contractions and relaxations

Front 2

Seizure

Back 2

Abnormal central nervous system electrical activity

Front 3

Epilepsy

Back 3

A neurological disorder marked by recurrent episodes of disturbed cerebral function characterized by convulsions and seizures

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Causes of Epilepsy

Back 4

1. Genetic
2. Congenital defects
3. Severe head trauma
4. Ischemic injury, tumor
5. Drug abuse
6. Unknown

Front 5

Nerve Cell Communication

Back 5

Glutamate= excitatory (tells the neuron to fire)

GABA= inhibitory (dampens the neuron firing rate)

Front 6

2 Major Types of Seizures (**TEST QUESTION**)

Back 6

1. Partial Seizures= excessive electrical activity in ONE cerebral hemisphere; affects only PART of the body; PRESERVATION of consciousness

2. Generalized Seizures= excessive electrical activity in BOTH cerebral hemispheres; affects the ENTIRE body; LOSS of consciousness

Front 7

Types of Partial (focal) Seizures

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1. Simple
2. Complex

Front 8

Simple Seizure: a type of partial seizure

Back 8

Person may experience range of strange or unusual sensations (motor, sensory, autonomic, psychic)

Front 9

Complex Seizure: a type of partial seizure

Back 9

Loss of awareness at seizure onset; person seems dazed and confused and exhibits meaningless behaviors

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Types of Generalized Seizures

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1. Myoclonic
2. Atonic
3. Tonic Seizures
4. Clonic Seizures
5. Tonic-clonic (Grand-mal)
6. Absence (petit mal)
7. Lennox-Gastaut Syndrome
8. **STATUS EPILEPTICUS**

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Myoclonic Seizure: a type of generalized seizure

Back 11

Brief shock-like muscle jerks generalized or restricted to part of one extremity

Front 12

Atonic Seizure: a type of generalized seizure

Back 12

Sudden loss of muscle tone

Front 13

Tonic Seizure: a type of generalized seizure

Back 13

Sudden stiffening of the body, arms, or legs

Front 14

Clonic Seizure: a type of generalized seizure

Back 14

Rhythmic jerking movements of the arms and legs without a tonic component

Front 15

Tonic-clonic (Grand-mal): a type of generalized seizure

Back 15

Tonic phase, followed by clonic phase

Front 16

Absence (petit mal): a type of generalized seizure

Back 16

Person appears to blank out

Front 17

Lennox-Gastaut Syndrome: a type of generalized seizure

Back 17

Atypical absence, atonic, and myoclonic seizures

Front 18

**STATUS EPILEPTICUS**: a type of generalized seizure

Back 18

Lasts longer than 30 min., or 3 seizures without a normal period in between (may be fatal, emergency room intervention required)

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**SEIZURE FACTS** (TEST QUESTION)

Back 19

- Seizures are not usually life-threatening
- Brain almost always stops seizure on its own
- Breathing may cease for a few seconds
- People don't feel pain during a seizure; may be sore afterward
- Person may be "different" for a while after seizure

Front 20

Treatment for Seizures

Back 20

**Type of seizure determines the choice of drug
- Therapy is aimed at control--NO cure for seizures
- Monotherapy= rare, but best avenue if possible; increase dose gradually until seizures are controlled or adverse effects become unacceptable; multi-drug therapy may be required
- Achieve steady state kinetics
- Monitor plasma drug levels
- Avoid sudden withdrawal

Front 21

Mechanisms of Action: 3 Main Categories (**TEST QUESTION on categories**)

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1. Limit sustained, repetitive firing of a neuron, by promoting the inactivated state of voltage-gated Na+ channels
2. Enhancement of GABA-mediated synaptic inhibition (pre or post synaptic)
3. Limit activation of voltage-gated Ca2+ channels known as the T-current

Front 22

Na+ Channel Drugs

Back 22

- Phenytoin
- Carbamazepine
- Oxcarbazepine
**VALPROIC ACID- all 3 MOAs
- Lamotrigine- inhibit glutamate release
- Topiramate- enhances GABA actions, and antagonist at NMDA receptors
**ZONISAMIDE**- all 3 MOAs
- Lidocaine- last choice in emergency room situation

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Na+ Channel Drugs-Indications: Typical

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1. Partial
2. Tonic-clonic

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Na+ Channel Drugs-Indications: Atypical

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1. Phenytoin- all except absence
2. **Valproic acid**- all types of seizures
3. Lamotrigine and Topiramate- Lennox Gastaut syndrome
4. **Zonisamide**- all types of seizures
5. Lidocaine- status epilepticus only

Front 25

Na+ Channel Drugs-Contraindications

Back 25

1. Carbamazepine- absence serizures, myoclonic seizures, blood and liver disorders

2. Valproic acid- liver disease

3. Lamotrigine- myoclonic seizures

4. Topiramate- history of kidney stones

Front 26

Na+ Channel Drugs: Adverse Effects of Typical Drugs

Back 26

- weight gain
- hirsutism
- acne
- tremor
- ankle edema
- nervousness
- weight loss
- impaired cognition

Front 27

Na+ Channel Drugs: Adverse Effects of Atypical Drugs

Back 27

**Phenytoin- gingival hyperplasia
- Carbamazepine- decreases thyroid hormone levels
- Lamotrigine- rash

Front 28

Na+ Channel Drugs: Drug Interactions

Back 28

1. Typical= decrease other drug concentrations thru liver P450 enzyme induction
2. Atypical= Zonisamide- phenytoin and carbamazepine decreases half-life by half

Front 29

**Enhancement of GABA Inhibition** (TEST QUESTION)

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1. Increase duration of GABAa-activated Cl- channel opening

2. Increase frequency of GABAa-activated Cl- channel openning

3. Inhibition of GABA transporter (GAT-1)

Front 30

**GABA Drugs** (TEST QUESTION)

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1. Barbiturates= increase the DURATION of GABAa-activated Cl- channel opening (Phenobarbital and Primidone)
2. Benzodiazepines= increase the FREQUENCY of GABAa-activated Cl- channel opening
3. Tiagabine= inhibition of GABA transporter (GAT-1)- reduces uptake of GABA by neurons and glial cells

Front 31

Barbiturate: Indications

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1. Typical= partial seizures; tonic-clonic seizures
2. Atypical= phenobarbital-status epilepticus and infant seizures

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Barbiturate: Contraindications

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1. Phenobarbital- absence seizures
2. Primidone- history of polyphoria

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Barbiturate: Adverse Effects

Back 33

- agitation and confusion in the elderly
- worsening of pre-existing hyperactivity and aggressiveness in children
- sexual side effects
- physical dependence

Front 34

Barbiturate: Drug Interactions

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- other CNS depressants
- Phenytoin increases conversion of primidone to phenobarbital

Front 35

Benzodiazepine: Indications

Back 35

1. Clonazepam- long-term use for Lennox-Gastaut syndrome, myoclonic, atonic, and absence seizures
2. Clorazepate- long-term use for partial seizures
3. Diazepam- tonic-clonic and status epilepticus
4. Lorazepam- status epilepticus; FIRST CHOICE in an EMERGENCY SITUATION

Front 36

Benzodiazepine: Contraindications

Back 36

- all for individuals with narrow angle glaucoma
- Diazepam- children under 9 years old

Front 37

Benzodiazepine: Adverse Effects

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- hypotonia
- dysarthria
- muscle incoordination
- behavioral disturbance- aggression, hyperactivity, irritability, and difficulty concentrating

Front 38

Tiagabine

Back 38

1. Indications: partial seizures
2. Contraindications: absence seizures
3. Adverse Effects: asthenia and abdominal pain
4. Drug Interactions: blood levels decreased by CBZ, phenytoin, phenobarbital, and primidone

Front 39

**ETHOSUXIMIDE**

Back 39

1. Ca2+ Channel Blocker
2. MOA: reduces low threshold Ca2+ currents (T currents) in thalamic neurons
3. **Indications: ABSENCE SEIZURES**
4. Contraindications: partial and tonic-clonic seizures
5. Adverse Effects: psychotic behavior, blood abnormalities, persistent headaches, anorexia, hiccups, erythema multiforme, Steven-Johnson syndrome, Lupus-like syndrome

Front 40

Other/Unknown MOA

Back 40

- Gabapentin
- Pregabalin
- Levetiracetam
- Magnesium chloride
- Paraldehyde

Front 41

Gabapentin and Pregabalin

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1. MOA: may be a GABA agonist and/or v-g Ca2+ channel inhibitor
2. Indications: partial and generalized seizures
3. Contraindications: myoclonic and absence seizures
4. Adverse Effects: weight gain, ankle edema, irritability, behavioral problems in children, and movement disorders

Front 42

Levetiracetam

Back 42

1. MOA: binding affinity to Synaptic Vesicle Protein 2A correlates with its anticonvulsant activity, blocks Ca2+ channel N-currents, and modulates GABA channel currents
2. Indications: partial and myoclonic seizures
3. Contraindications: renal dysfunction
4. Adverse Effects: asthenia, infection, and behavioral problems in children

Front 43

Magnesium Chloride

Back 43

Used for magnesium deficiency seizures

Front 44

Paraldehyde

Back 44

Used for alcohol withdrawal seizures

Front 45

Summary of the 3 Main Categories MOA

Back 45

1. Limit sustained, repetitive firing of a neuron, by promoting the inactivated state of voltage-gated Na+ channels- Na+ channel blockers
2. Enhancement of GABA-mediated synaptic inhibition (pre- or post-synaptic)- increase DURATION of Cl- channel opening, increase FREQUENCY of Cl- channel opening, and inhibit GABA reuptake
3. Limit activation of voltage-gated Ca2+ channels known as the T-current- Ca2+ channel blockers

Front 46

Drugs of Choice and Alternatives for Primary Generalized Tonic-Clonic (Grand Mal) Seizures

Back 46

1. Drugs of Choice:
- Phenytoin
- Carbamazepine
- Oxcarbazepine
**VALPROIC ACID**
2. Alternatives:
- Lamotrigine
- Topiramate
**ZONISAMIDE**
- Levetiracetam
- Primidone
- Phenobarbital
- Diazepam

Front 47

Drugs of Choice and Alternatives for Partial, Including Secondarily Generalized Seizures

Back 47

1. Drugs of Choice:
- Phenytoin
- Carbamazepine
- Oxcarbazepine
**VALPROIC ACID**
2. Alternatives:
- Lamotrigine
- Topiramate
**ZONISAMIDE**
- Levetiracetam
- Primidone
- Phenobarbital
- Gabapentin
- Pregabalin
- Tiagabine

Front 48

Drugs of Choice and Alternatives for Absence (Petit Mal) Seizures

Back 48

1. Drugs of Choice:
- Ethosuximide
**VALPROIC ACID**
2. Alternatives:
- Clonazepam
**ZONISAMIDE**

Front 49

Drugs of Choice and Alternatives for Atypical Absence, Myoclonic, and Atonic Seizures

Back 49

1. Drug of Choice:
**VALPROIC ACID**
2. Alternatives:
- Clonazepam
**ZONISAMIDE**
- Topiramate