Anticonvulsants

Front 1

the 3 stages of seizures

Back 1

Focal discharge
Spread,
Termination

Front 2

What is the prevalance of epilepsy:

Back 2

1-2%

Front 3

Simple or complex partial seizure?: Various manifestations, depending upon the affected brain region. Key feature is preservation of consciousness

Back 3

simple partial seizures

Front 4

Simple or complex partial seizure: Localized onset followed by widespread discharges (usually bilateral) Presents with complex behavior, impairment of consciousness. Most arise from the temporal lobe; Almost always involve limbic system.

Back 4

Complex partial seizures

Front 5

What kind of generalize seizures presents with major convulsions (tonic body muscle spasms followed by synchronous clonic jerking). Prolonged depression of all central functions after seizures, post-ictal depression)

Back 5

Tonic-clonic (Grand mal)

Front 6

This type of generalized seizures presents with sudden onset, abrupt cessation (usually less than 10 secs. Brief Loss of consciousness, sometimes with motor involvement. Occur in childhood and often disappear later if well-controlled. Characteristic 3 Hz spike and wave EEG

Back 6

Absence (Petit mal)

Front 7

Seizure spread depends on action potentials (______ channels) and release of excitatory neurotransmitters, mostly (_____ and _______ channels) It is prevented by inhibitory neurotransmitters, especially ______.

Back 7

Seizure spread depends on action potentials SODIUM channels and release of excitatory neurotransmitters, mostly GLUTAMATE (excitatory) and CALCIUM channels. It is prevented by inhibitory neurotransmitters, especially GABA.

Front 8

True or False: genetic mutations of channels or receptors are associated with rare familial epilepsy syndromes

Back 8

True

Front 9

These type of drugs are generally effective against partial seizures and generalized tonic clonic seizures

Back 9

Sodium Channel blockers (i.e. phenytoin, carbamzepine, Lamotrigine)

Front 10

These specifically bind to and prolong the inactivated state of voltage activated sodium channels

Back 10

Sodium Channel blockers (i.e. phenytoin, carbamzepine, Lamotrigine)

Front 11

these type of drugs inhibit high frequency seizure activities without affecting normal action potentials

Back 11

Sodium Channel blockers (i.e. phenytoin, carbamzepine, Lamotrigine)

Front 12

These type of drugs have the side effects of nystagmus, diplopia and ataxia

Back 12

Sodium Channel blockers (i.e. phenytoin, carbamzepine, Lamotrigine)

Front 13

These are the only 2 sodium channel blockers that are not effective against petite mal seizures

Back 13

Phenytoin, carbamzepine.

Front 14

With drugs that enhance GABA neurotransmission. What are the 3 drugs that increase synaptic GABA levels (presynaptic) What are their mechanisms of action?

Back 14

Valproic acid (inhibits two GABA degrading enzymes - GABA transaminase "GABA-T". 2) Tiagabine (reduces neuronal reuptake of GABA by inhibiting GAT-1 **GABA transporter**) 3) Gabapentin (increases GABA release)

Front 15

With drugs that enhance GABA neurotransmission. What are the GABA(A) Receptor modulators (post synaptic)?

Back 15

Barbiturates (phenobarbital) and benzodiazepines (diazepam and lorazepam) Bind to GABA(A) receptors (distinct to GABA binding sites) and enhance GABA-mediated chloride influx (usually Cl-comes in or potassium leaves- for hyperpolarization in general)) (increase membrane hyperpolarization)

Front 16

Name 3 drugs that are calcium channel blockers

Back 16

Ethosuximide and Valproic acid (These 2 inhibit "T-type" Calcium channels that are enriched in thalamic neurons and involved in the generation of rhythmic action potentials responsible for absence seizures), and Lamotrigine (inhibits another type "High-voltage activated" of calcium channels.

Front 17

Name 3 drugs that decrease glutamate neurotransmission, but these drugs have other anticonvulsant mechanisms as well

Back 17

Valproic acid, topiramate, and Lamotrigine.

Front 18

What should you treat status epilepticus with?

Back 18

Benzodiazepines: lorazepam or diazepam.

Front 19

What is the pure petit mal drug

Back 19

Ethosuximide

Front 20

What drug combo (3) all induce a variety of cytochrome P450 enzymes: increase metabolism of each other

Back 20

Carbamazepine, pheytoin, phenobarbital

Front 21

What drug combo (4) decrease the plasma concentration of oral contraceptives (increases pregnancy)

Back 21

carbamazepine, phenytoin, phenobarbital, lamotrigine

Front 22

What drug combo (2) increases the plasma concentration of warfarin - bleeding problem

Back 22

phenytoin and warfarin

Front 23

What drug inhibits some CYP enzymes: increases the plasma concentration of phenytoin, carbamazepine and phenobarbital

Back 23

Valproic aicd

Front 24

( I didn't understand this concept because it said this in two different areas in the book) 1: What drug combo yields high protein binding OR 2: What reduces serum protein binding of phenytoin?

Back 24

1) Phenytoin and valproic acid. 2) valproic acid

Front 25

True or False, most anticonvulsants increase the likelihood of birth defects and you should try to withdraw drugs atleast 6 months before pregnancy.

Back 25

True

Front 26

Where does phenytoin bind to and what does it prolong?

Back 26

voltage gated sodium channels, inactivated state

Front 27

What are the acute toxicities and long term side effects of pheyntoin

Back 27

nystagmus, ataxia, diplopia. LT: gingival hyperplasia, hirsutism, teratogen.

Front 28

1. Very similar 3D structure and mechanism of
action as phenytoin.
2. Considered the drug of choice for controlling partial seizures and generalized tonic- clonic seizures.
3. Induces microsomal CYP enzymes
V. Specific Drugs

4. Diplopia and ataxia are the most common dose- related side effects. Skin rash (hypersensitivity reaction) is also common.
Serious hematological conditions including aplastic anemia (depletion of red blood cells due to bone marrow suppression: 1/200,000) and agranulocytosis (1 / 75,000) rarely occur.
5. Also used for pain control (initially marketed for trigeminal neuralgia)

Back 28

Carbamazepine (tegretol)

Front 29

1. Binds to allosteric regulatory site on the GABAA receptor and enhances GABA mediated Cl- influx
2. Induces microsomal enzymes
3. Its long plasma t1/2 (about 100 hr) simplifies maintenance of a fairly constant blood level.
V. Specific Drugs
C. Phenobarbital
4. Though less sedating than other barbiturates, it frequently causes sedation at efficacious doses.
5. Inexpensive, relatively low toxicity: most commonly prescribed in many developing countries.

Back 29

Phenobarbital

Front 30

1. Used for status epilepticus (emergency situation): intravenous lorazepam (Ativan®) or
diazepam (Valium®) 2. Not used for long-term therapies (tolerance)

Back 30

Benzodiazepines

Front 31

1. Blocks T type calcium channels
2. Particularly effective for absence (pure petit mal drug) and lacks the hepatotoxicity of valproate: the drug of choice for absence seizure
3. The most common adverse effect is gastric distress: idiosyncratic side effects are extremely rare.

Back 31

Ethosuximide

Front 32

1. First drug effective against both absence and
tonic-clonic seizures.
2. Discovered by accident – it was the “placebo” liquid in animal studies.
3. Blocks sodium channels and T type calcium channels. Also increases synaptic GABA concentration by inhibiting GABA turnover in neurons.
V. Specific Drugs
F. Valproic acid
4. Hepatotoxicity is a major concern (including a rare but severe fulminant hepatitis, especially < 2yr old)
5. Reduces serum protein binding of some drugs (e.g. phenytoin).
6. Inhibits CYP enzymes: increases plasma concentration of phenobarbital and phenytoin
7. Teratogen: spina bifida

Back 32

Valproic Acid

Front 33

1. Structurally similar to GABA, but has no effect on GABA-receptors.

GABA
V. Specific Drugs
G. Gabapentin
2. Appears to increase GABA-transmission by unknown mechanism (modify GABA release?).
3. Well tolerated.
4. Not metabolized by the liver : no known drug interaction

Back 33

Gabapentin

Front 34

1. Mechanism of action:
(a) Blocks voltage sensitive sodium channels. (b) Inhibits calcium channels. (c) Inhibits glutamate release.
2. Broader spectrum: even absence
3. Adverse effects include diplopia, skin rash (hypersensitivity reaction that may be life threatening in up to 2% of pediatric patients)

Back 34

Lamotrigne

Front 35

1. Mechanism of action:
(a) Inhibits sodium channels. (b) Modulates GABAA receptors. (c) Blocks glutamate receptors.
2. Broader spectrum: even absence 3. Also useful for preventing migraine headaches.

Back 35

Topiramate

Front 36

1. Blocks reuptake of GABA into nerve terminals
and glia by inhibiting GABA transporter, GAT-1. 2. Side effects: generally mild.

Back 36

Tiagabine

Front 37

The two drugs that covers all the mechanism of actions and has effect on all types of seizures.

Back 37

Valproic Acid and Topiramate

Front 38

you get the side effects of diplopia, and ataxia, an)..can be used for pain control (initially marketed for trigeminal neuralgia)

Back 38

Carbamazepine

Front 39

What is the drug of choice for controlling partial seizures and generalized tonic-clinic seizures

Back 39

Carbamazepine

Front 40

Which drug has concern for hepatotoxicity?

Back 40

Valproic acid

Front 41

This drug can cause spina bifida, or can cause to be a teratogen

Back 41

Valproic Acid