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Flashcards in Anticonvulsants Deck (46):
1

the goal of anticonvulsants:

is to suppress the rapid and excessive firing of neurons that start a seizure. Failing this, a good anticonvulsant would prevent the spread of the seizure within the brain and offer protection against possible excitotoxic effects that may result in brain damage.

2

Seizures

A seizure is a sudden change in behavior due to abnormal synchronization and excessive electrical activity in the brain.
• During a seizure, neurons may fire as many as 500 times a second, much faster than the normal neuronal firing rate of 80 times a sec.
There are a wide variety of possible seizure presentations depending in large part on which areas of the brain are affected. The site in the brain of the abnormal electrical activity often determines the seizure symptoms that are produced.

3

status epilepticus

a continuous seizure that will not stop without intervention.

4

Seizure triggers

• Certain environmental factors can lead to an increased likelihood of seizures in someone with epilepsy such as:
• Flashing lights
• Sleep deprivation
• Alcohol consumption
• Stress or anxiety
• Illness

5

hypnogogic seizures

Seizures that occur during sleep or at the transition between sleep and wakefulness

6

Non-epileptic seizure causes

• There are dozens of potential causes for non-epileptic seizures such as:
• Space occupying brain lesions
• Head trauma
• Drug side effects, toxicity, withdrawal
• Fever
• Meningitis, encephalitis
• Metabolic/ electrolyte abnormalities

7

simple vs complex seizures

simple seizures (no change in level of consciousness) or complex seizures (change in level of consciousness occurs).

8

partial /focal vs generalized seizures

partial or focal seizure when only one part or side of the body is affected or a generalized seizure when the entire body is affected.

9

Partial seizures

ccur in just one part of the brain.
• Approximately 60 percent of people with epilepsy have focal seizures.

• These seizures are frequently described by the area of the brain in which they originate. For example, someone might be diagnosed with focal frontal lobe seizures or a focal temporal lobe seizure.

10

Simple partial seizures

In a simple partial seizure, the person will remain conscious but experience unusual feelings or sensations that can take many forms.
• The patient may experience sudden and unexplainable feelings of fear, joy, anger, or sadness out of context with stimuli.
• He or she may also experience hallucinations that involve sight, sound, smell, taste, or skin sensation.

11

Complex partial seizures

• In a complex partial seizure, the person
has a change in or loss of consciousness.
• People having a complex partial seizure may display strange, repetitious behaviors such as blinks, twitches, and mouth movements, or motions such as walking in a circle.
• These repetitious movements are called automatisms and these seizures usually last just a few seconds.

12

Absence seizures

• Absence seizures involve an interruption in consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds).
• Slight muscle twitching may also occur.
• These seizures are sometimes referred to as petit mal seizures.


13

Generalized seizures / tonic clonic or grand mal

• Tonic-clonic seizures cause a mixture of symptoms, including stiffening of the body and repeated jerks of the arms and/or legs as well as loss of consciousness.
• Tonic-clonic seizures are sometimes referred to by the term, grand mal seizures.


initial contraction of the muscles (tonic phase) which may involve tongue biting, urinary incontinence and the absence of breathing. This is followed by rhythmic muscle contractions (clonic phase).

14

Status epilepticus

• Status epilepticus refers to continuous seizure activity with no recovery between successive seizures.

• A tonic-clonic seizure lasting longer than 5 minutes (or two minutes longer than a given person's usual seizures) should be considered a medical emergency.


15

Anticonvulsant drugs

• The main mechanism of action of drugs in this class is as follows:
• Sodium channel blockade
• Calcium channel (T-type) blockade
• Potentiate GABA - inhibitory neurotransmission -
• Decrease Glutamate - excitatory neurotransmission

Nearly all AEDs function by decreasing the excitation of neurons (i.e. by blocking fast or slow sodium channels or modulating calcium channels or by enhancing the inhibition of neurons (i.e. by potentiating the effects of inhibitory neurotransmitters like GABA).

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Partial seizures drugs


• Phenytoin/ Dilantin
• Phenobarbital/Phenobarb
• Primidone/ Mysoline

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Absence seizures (Petit mal) drugs

• Ethosuximide/ Zarontin
• Valproic acid/ Depakote
• Clonazepam/ Klonapin

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Generalized tonic clonic seizures (Grand mal seizures) drugs

• Diazepam/ Valium
• Phenytoin/ Dilantin
• Carbamazepine/ Tegretol
• Phenobarbital/ Phenobarb
• Primidone/ Mysoline
• Lamotrigine/ Lamactil
• Levetriacetam/ Keppra
• Topiramate/ Topamax (also used to treat bipolar disorder or to counteract the weight gain associated with numerous antidepressant)

19

Phenobarbital/ Phenobarb

• Class: Barbiturate anticonvulsant
indicaction: focal/partial seizures
• MOA: Enhanced GABA activity
• Char: IV/PO. Relatively slow onset (>30
mins) and very long half life(>50 hrs). May be initial drug of choice in children with seizures. Metabolized by P450 enzymes in liver.


rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus, but a benzodiazepine such as Lorazepam or Diazepam is usually tried first.

20

Phenobarbital/ Phenobarb SE

• Side effects: CNS depression, drowsiness, associated with lowered IQ scores in children undergoing chronic treatment.
• Stimulation of cytochrome P450 enzymes can increase metabolism of other drugs and concurrent phenobarbital use can lower serum concentration of multiple drugs.

21

Primidone/ Mysoline

• Class: Barbiturate anticonvulsant • MOA: Exact MOA unknown but
Phenobarbital is a known metabolite of Primidone so GABA mediated inhibition is considered as chief MOA.
• Indication: All types of seizure disorders except absence seizures.
 Char: PO, metabolized in liver. Plasma half life of Primidone is 10 – 12 hours but half life of its metabolites > 48 hours.

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Primidone/ Mysoline SE

• Side effects: Nausea, anorexia, headache, vertigo, ataxia. Category D – do not use in pregnancy unless life threatening condition.

23

Diazepam/ Valium

• Class: Benzodiazepine anticonvulsant • MOA: Increased sensitivity of GABA
receptor sites to GABA with subsequent increased chloride influx which serves to inhibit CNS synaptic transmission.
• Indication: Grand mal seizures. Status epilepticus. Seldom if ever used as a chronic treatment choice for seizures. Anxiety, panic disorder.

has a slight effect on gamma-aminobutyric acid transaminase activity. It differs insofar from some other anticonvulsive drugs it was compared with.

24

Clonazepam/ Klonopin

• Class: Benzodiazepine anticonvulsant
• MOA: Similar to Diazepam
• Indication: Alternative to Ethosuximide or
Valproic acid for absence seizures. Status
epilepticus.
• Char: PO. Long acting
• Side effects: Drowsiness, altered mentation,
additive with CNS depressants, ***marked abuse potential.*** Tolerance develops.


25

Phenytoin/ Dilantin


• Class: Anticonvulsant
• MOA: Reduces sodium and calcium and
currents across neuronal membranes.
• Indication: Prophylaxis for all types of
seizures except absence seizures.
• Char: PO/IV/IM. Slow onset. Long half
life. Metabolized in liver. Tolerance develops.

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Phenytoin/ Dilantin SE


• Side effects: Nystagmus, ataxia, gingival hyperplasia, possible hepatotoxicity, and possible bone marrow suppression. I.V. administration may cause hypotension and arrythmias.
• Many drugs may alter metabolism and binding of Dilantin and vice-versa. List of concurrent drugs must be noted.

27

Carbamazepine/ Tegretol


• Class: Anticonvulsant
• MOA: Similar to phenytoin in the reduction of sodium and calcium currents across neuronal membranes.
• Indication: Prophylaxis against all types of seizures except absence seizures. Also used to treat chronic pain such as trigeminal neuralgia and post-herpetic neuralgia. Tegretol has also been used in the treatment of schizophrenia and bi-polar disorder.
Char: PO. Induces P450 enzymes in liver.

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Carbamazepine/ Tegretol SE

• Side effects: Vertigo, nausea, vomiting. Possible bone marrow suppression and aplastic anemia (follow blood counts).
• Should never be given to patients on monoamine oxidase inhibitors (NARDIL) as combination potentially increases risk for all of Carbamazepine side effects as well as increased risk for hypertensive crisis.


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Valproic acid/ Depakote


• Class: Anticonvulsant
• MOA: Unknown, enhancement of GABA
transmission has been postulated.
• Indication: All seizure types, particularly in
absence seizures and combined seizure conditions. Also used to treat bipolar disorder and chronic pain syndromes.
• Char: PO/IV. Metabolized in liver, highly protein bound. Additive anti-seizure effects when combined with other anticonvulsants.

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Valproic acid/ Depakote MOA

affect the function of the neurotransmitter GABA in the human brain, making it an alternative to lithium salts in treatment of bipolar disorder. Its mechanism of action includes enhanced neurotransmission of GABA (by inhibiting GABA transaminase which results in increased concentration of GABA).

31

Valproic acid/ Depakote SE

• Side effects: commonly include nausea, insomnia, anxiety. Potential for severe hepatotoxicity. Known to be an antagonist of folic acid. When taken by women who are pregnant, the incidence rates of serious, irreversible birth defects are 3 to 10 times higher than average (anancephaly)

32

Ethosuximide/ Zarontin

• Class: Anticonvulsant
• Indication: Absence seizures
• MOA: Unknown, possibly affects T-type
calcium ion channels
• Char: PO. Metabolized in liver, not protein
bound. Ethosuximide increases phenytoin levels. Ethosuximide is considered the first choice drug for treating absence seizures in part because it is usually less hepatotoxic than Valproic acid.

33

Ethosuximide/ Zarontin SE


• Side effects: Headache, nausea, vomiting, fatigue, ataxia, blurred vision, confusion, skin rashes, insomnia, gingival hyperplasia, notable for possible hepatotoxicity and lupus-like syndrome.

34

Gabapentin/ Neurontin

• Class: Anticonvulsant, atypical analgesic
• MOA: Appears to potentiate GABA and
also affects N-type calcium channels. Gabapentin halts the formation of new synapses
• Indication: Adjunctive treatment of partial
seizures. Also used in chronic pain syndromes such as post-herpetic neuralgia. Migraine headaches.
• Char: Reduce dose with renal dysfunction. Gabapentin absorption decreased by concurrent use of antacids.

35

Gabapentin/ Neurontin SE


• Side effects: Somnolence, dizziness, ataxia, headache and other CNS side effects.
• There have been reports that Gabapentin 1200 mg at bedtime taken for 40 to 60 days has been effective in reducing the withdrawal symptoms and diminishing desire for methamphetamines and/ or cocaine.
• Pfizer has released a successor drug to Gabapentin, called Pregabalin and marketed as Lyrica.

36

Lamotrigine/ Lamactil


• Class: Anticonvulsant
• MOA: Unknown. May stabilize neurons by
decreasing sensitivity to the exicitatory
effects of glutamate and aspartate. • Indication: Tonic-clonic (grand mal)
seizures, complex partial seizures and
seizures resistant to other drug treatments.
• Char: P.O. Metabolized in liver.
• Side effects: dizziness, headache, rashes,
diplopia, somnolence and ataxia.

37

Lamotrigine/ Lamactil
and bipolar I

• Similar to many other anticonvulsant medications, Lamotrigine seems to act as a mood stabilizer.
• In 2003, Lamotrigine became the first drug approved by the FDA for treating type I bipolar disorder since lithium, a drug approved almost 30 years earlier.

38

Levetiracetam/Keppra

• Class: Anticonvulsant
• MOA: Unknown. May stabilize neurons by inhibition of calcium movement through presynaptic calcium channels.
• Indication: Tonic-clonic seizures, complex partial seizures and seizures resistant to other drug treatments. Keppra is also used to treat neuropathic pain.
• Char: P.O. Metabolized in liver.

39

Levetiracetam/Keppra SE

• Side effects: Levetiracetam is generally well tolerated but may cause drowsiness, weakness, unsteady gait, coordination problems, headache, mood changes, nervousness, loss of appetite, vomiting, diarrhea or constipation and rare reports of possible changes in skin pigmentation.

40

My recommendations for choice of seizure medication

• Partial seizures – Phenytoin (Dilantin)
• Grand mal--Phenytoin (Dilantin), Lamotrigine (Lamactil)
• Absence – Ethosuximide (Zarontin)
• Myoclonic – Valproic acid or Clonazepam
• Febrile seizures – anti-pyretic i.e. Ibuprofen
• Status epilepticus – IV Phenobarbital or IV
Diazepam (Valium) or IV Lorazepam (Ativan)

* Because of its longer half-life, Lorazepam is often used in place of Diazepam.

41

For all anticonvulsant medications:

• Begin at low dose and titrate to the desired effect or until limiting side effects develop.
• Follow serum drug levels.
• Switch to another one or possibly two drugs if not effective at maximum dose before switching from monotherapy to 2 or more drugs.
• Always try to taper the drug dosage.
• Never discontinue an anticonvulsant drug abruptly or status epilepticus may be induced.

42

Other treatment options

• Ketogenic diet program
• Vagus nerve stimulator (VNS) (electric impulses to the left vagus nerve in the neck via a lead implanted under the skin)
• Brain neurostimulators
• Surgery – this may be curative, especially when dealing with a space occupying lesion such as a benign brain tumor
• Seizure responsive service pet


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****Drugs for focal (partial) seizures ****



• Phenytoin/ Dilantin
• Phenobarbital/ Phenobarb
• Primidone/ Mysoline

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***Drugs for absence (petit mal) seizures***


• Ethosuximide/ Zarontin

45

***Drugs for generalized/ tonic clonic seizures***


• Lamotrigine / Lamictal
• Levetiracetam/ Keppra
• Topiramate/ Topamax
• Valproate/ Depakote

46

Drugs for status epilepticus



• Lorazepam/ Ativan
• Diazepam/Valium
• Phenytoin/ Dilantin
• Ethosuximide/ Zarontin

Drugs utilized for treating patients in status epilepticus are usually dosed by IV route.