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ANTISEIZURE AGENTS & EFFECTS

Group 3 Munyadi, Muneeslaxmi Singh, Ruby Austin, Nissy Khader Basha Augustus, Joel Jayabalan, Jerusha Darapastham Finny

Topic Outlines
Introduction

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Drugs Overview
Data Collection Q & A Conclusion

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INTRODUCTION
What is seizure ?
Seizure results from abnormal neuronal discharge in the CNS produced by either focal or generalized disturbances of brain tissue. Seizure results in abnormal phenomena of motor (convulsion), sensory, autonomic, or psychic origin
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INTRODUCTION
Etiology & Mechanism

1. Activity of voltage-gated ion channels ( Na+, K+ & Ca++ channels) 2. Inhibitory (GABA) neurotransmission 3. Excitatory neurotransmission (Glutamate receptors) 4. Alteration of extracellular ion concentration (Potassium, calcium).
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INTRODUCTION
Types of Seizure
A. Partial Seizure
The discharge begins locally, often remains localized. Produce relatively simple symptoms w/o loss of Consciousness.

B. Generalized Seizure
Involve the whole brain, including the reticular system, producing abnormal electrical activity throughout both hemispheres. Immediate loss of consciousness
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INTRODUCTION
Antiseizure Agents
They are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. The nerve-calming qualities of some of these drugs can also help quiet the burning, stabbing or shooting pain often caused by nerve damage.
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INTRODUCTION
MOA of Antiseizure Agents
1. Prolong inactivation of voltage-dependent Na+ channels in a usedependent fashion. 2. the effectiveness of inhibitory GABA transmission via the GABAA receptor. 3. Inhibition of Ca++ currents through T-type Ca++ channels. 4. Inhibition of excitatory glutamate transmission via ionotropic receptors.

DRUGS OVERVIEW
1. Nicotine
Nicotine is taken by smoking or chewing tobacco. Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant. Release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes stimulation.
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DRUGS OVERVIEW
2. Phenobarbital
Phenobarbital is in a class of medications called barbiturates which is used to control seizures. It is also used to prevent withdrawal symptoms in people who are dependent on another barbiturate medication and are going to stop taking the medication.

It works by slowing activity in the brain.


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DRUGS OVERVIEW
3. Phenytoin
Phenytoin is in a class of medications called anticonvulsants. It is used to control certain type of seizures, and to treat and prevent seizures that may begin during or after surgery to the brain or nervous system. It works by decreasing abnormal electrical activity in the brain.
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DRUGS OVERVIEW
4. Diazepam
Diazepam belongs to a group called benzodiazepines.

Diazepam is used to relieve anxiety, muscle spasms, and seizures and to control agitation caused by alcohol withdrawal.

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DATA COLLECTION (Group 1)


EFFECTS DRUGS ONSET OF ACTION 20 secs 1 min 20 secs DURATION OF ACTION 20 mins 1 min

SEIZURE
Nicotine Phenobarbital + Nicotine +++ ++

SLEEP
-

AROUSAL
+++ ++

Nicotine + Phenobarbital
Nicotine + Phenytoin Nicotine + Diazepam

+
++ ++

+
+++ ++

15 secs
12 secs 10 secs

8 mins
12 mins 15 mins
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DATA COLLECTION (Group 2)


EFFECTS DRUGS ONSET OF ACTION 13 mins 15 mins DURATION OF ACTION 19 mins 25 mins

SEIZURE
Nicotine Phenobarbital + Nicotine + +

SLEEP
++ +

AROUSAL
+++ +

Nicotine + Phenobarbital
Nicotine + Phenytoin Nicotine + Diazepam

+++
++ ++

++
++ ++

++
++ ++

15 mins
15 mins 7 mins

17 mins
17 mins 10 mins
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DATA COLLECTION (Group 3)


EFFECTS DRUGS ONSET OF ACTION Immediate Immediate DURATION OF ACTION 7 mins 1 min

SEIZURE
Nicotine Phenobarbital + Nicotine + +

SLEEP
-

AROUSAL
+++ ++

Nicotine + Phenobarbital
Nicotine + Phenytoin Nicotine + Diazepam

+
+ +

++
+++ ++

30 secs
25 secs 15 secs

3 mins
2 mins 2 mins
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DATA COLLECTION (Group 4)


EFFECTS DRUGS ONSET OF ACTION 1-3 mins Immediate DURATION OF ACTION 7-8 mins 5-7 mins

SEIZURE
Nicotine Phenobarbital + Nicotine + ++

SLEEP
++ ++

AROUSAL
++ +

Nicotine + Phenobarbital
Nicotine + Phenytoin Nicotine + Diazepam

+ +

+++
+++ +++

1-2 mins
40 secs 30 secs

5 mins
2 mins 2 mins
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Q&A
1. Drug of choice for status epilepticus in children and adults? The general principles of management & the initial agents used in the pediatric patients remain same as for adults. Differences between adults and children a. Etiology of status epilepticus in children differ from adults b. Prognosis of status epilepticus is better in children than adults. c. Refractory of status epilepticus in children seems more 16 similar to that in adults

Q&A
Medications class Available routes Intravenous Rectal Sublingual Intramuscular Intravenous Rectal(gel form) Intra muscular Intravenous intramuscular Adverse effects Respiratory depression Hypotension Decreased level of conciousness Respiratory depression Hypotension Decreased level of conciousness Respiratory depression Hypotension Decreased level of conciousness Hypotension QT prolongation Purple glove syndrome Hypotension Cardiac arrythmias Advantages Prepared agent Longer duration of action May have least respiratory depression of its class Slightly faster onset of action Rectal examination is done in children Additional intramuscular route Disadvantages Slightly longer delay in brain uptake Need for refrigeration Short DOA Second line drug is needed Short DOA additional drug is needed Lorazepam

Diazepam

Midazolam

intavenous Phenytoin

Low cost

Adverse effect profile

Fosphenytoin

Intravenous Intramuscular

Possibly fewer adverse effects

Expensive

Intravenous Phenobarbital

Respiratory depression Hypotension Decreased level of conciousness

Long acting

Long half life 17

Q&A
1. Drug of choice for status epilepticus in children and adults?

Initial drug of choice is : IN CHILDREN Lorazepam iv 0.05-0.1mg/kg Or Diazepam iv 0.2-0.5mg/kg Initial drug of choice is : IN ADULTS Lorazepam iv 0.10.15 mg/kg Or Diazepam iv 0.3 mg/kg ,0.50.7 mg/kg recta
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Q&A
2. Give the drugs used to treat seizures. MOA tabulation and specific uses

Carbamazepine Phenobarbital Phenytoin Primidone Valproic acid Lamotrigine


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Q&A
DRUGS
Carbamazepine (Tegretol)

MOA
Carbamazepine stabilizes the inactivated Na channels. This leaves the affected cells less excitable until the drug dissociates. The primary action of phenobarbital is to enhance the inhibitory actions of (GABA) on neurons . Block Na channels, therefore limit repetitive firing of action potentials. Stimulate or increase the action at the GABA receptor. Blocks Na channels, augment the action of GAD, , it restricts GABA-T . Inhibit release of glutamate and aspartate evoked by the Na-channel

SPECIFIC USES
Treating trigeminal neuralgia (a condition that causes facial nerve pain). Prevent withdrawal symptoms in people who are dependent on another barbiturate medication and are going to stop taking the medication. Prevent seizures that may begin during or after surgery to the brain or nervous system. Treatment of tremors, specifically, essential tremor (ET), the most common movement disorder. Treat bipolar disorder. It is also used to prevent migraine headaches . Treat bipolar disorder.

Phenobarbital (Luminal)

Phenytoin (Dilantin)

Primidone (Mysoline)

Valproic Acid (Depakote)

Lamotrigine (Lamictal)

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Q&A
3. MOA of nicotine

Nicotine binds to nicotinic acetylcholine receptors channels open depolarization activate Ca channel dopamine release epinephrine release = vasoconstriction, BP, blood sugar, rate.

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CONCLUSION

Nicotine diminishes the anticonvulsant activity of antiseizure drugs. The combination of both nicotine and antiseizure drugs should be carefully considered as a cause of therapeutic failure in epileptic patients.

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