Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
111 Cards in this Set
- Front
- Back
|
What is epilepsy |
Epilepsy is a common neurological disorder USUALLY CHRONIC characterized by REPEATED SEIZURE OR CONVULSION, and usually EPISODES OF UNCONSCIOUSNESS OR AMNESIA. |
|
|
what is a seizure |
A seizure is a TRANSIENT(INTERMITTENT) CHANGE in behavior, emotions, motor function or sensation which results from DISORDERED, SYNCHRONOUS, RHYTHMIC AND HIGH FREQUENCY FIRING of a certain population of neurons in the body. |
|
|
How common is epilepsy |
It is the THIRD most common neurological disorder in the world and it is MORE COMMON IN CHILDREN than in adults |
|
|
Classification of epilepsy |
(a) Focal (Partial) seizures(b) Generalized seizures |
|
|
What are partial seizures and secondarily generalized seizures |
In partial seizures, the abnormal electrical discharges start in a localized area of the brain. Focal seizures are located in just one area of the brain. This discharge may remain localized or spread to other parts of the brain and the seizurebecomes generalized (secondarily generalized seizures). |
|
|
What are generalized seizures |
Generalized seizures affect both sides of the brain. In generalized seizures, the seizure is generalized from the onset (i.e primary generalizedseizures), starting in the whole brain or spread from the small area (focus) to the whole brain and spinal cord. (Secondary generalized seizures) |
|
|
Types of generalized seizures |
1) Absence seizures, sometimes called petit mal seizures, can cause rapid blinking or a few seconds of staring into space.2) Tonic-clonic seizures, also called grand mal seizures, can make a person Cry out. Lose consciousness.Fall to the ground. Have muscle jerks or spasms. |
|
|
Types of partial seizures |
1) Simple focal seizures affect a small part of the brain. These seizures can cause twitching or a change in sensation, such as a strange taste or smell. CONSCIOUSNESS NOT IMPAIRED2) Complex focal seizures can make a person with epilepsy confused or dazed. The person will be unable to respond to questions or direction for up to a few minutes. WITH IMPAIRMENT OF CONSCIOSNESS3) Secondary generalized seizures begin in one part of the brain, but then spread to both sides of the brain. In other words, the person first has a focal seizure, followed by a generalized seizure. |
|
|
Forms of generalized seizures |
These words are used to describe generalized seizures:Tonic: Muscles in the body become stiff.Atonic: Muscles in the body relax.Myoclonic: Short jerking in parts of the body.Clonic: Periods of shaking or jerking parts on the body. |
|
|
Conditions associated with the appearance of epileptic seizures |
Brain tumors, meningitis, childhood fever , metabolic toxins, infection and degenerative disease of the cerebral circulation. Epileptic seizures may also be a toxicmanifestation of the action of the stimulants and certain other drugs |
|
|
Idiopathic and symptomatic epilepsy |
In most cases, epileptic seizures may be labelled "idiopathic" if the aetiology is unknown or "symptomatic" if it is secondary to anidentifiable condition such as illicit drug use, tremor, hypoglycaemia, alcohol withdrawal etc. |
|
|
What is the first line drug for use in partial and general epilepsy |
PHENYTOIN (PHT) |
|
|
Side effects of phenytoin |
Nausea and vomiting, rash, blood dyscrasias, headaches, vitamin K and folate deficiencies, loss of libido, hormonal dysfunction, and bone marrow hypoplasia are among the most common adverse effects associated with PHT. |
|
|
How does phenytoin adversely affect pregnancy |
When given during pregnancy, PHT,like other AEDs, can cause cleft palate, cleft lip, congenital heart disease, slowed growth rate,and mental deficiency in the offspring. |
|
|
Other side effects of phenytoin |
1) Gingival hyperplasia and coarsening of the facial features in women makes its use less desirable than other agents that block Na channel (e.g. CBZ). 2) PHT causes central nervous system (CNS) and systemic adverse effects. CNS effects occur particularly in the cerebellum and the vestibular system, causing ataxia and nystagmus.3) PHT is not a generalized CNS depressant; however, some degree of drowsiness and lethargyIs present, without progressing to hypnosis. |
|
|
Long term use of phenytoin can cause |
Osteoporesis |
|
|
Why does phenytoin have the greatest problem with drug interaction |
1) its highly protein-bound( >90%) nature 2) its use of P-450 enzymes for metabolism |
|
|
Drugs that have variable effects on the phenytoin levels |
Carbemazapine and phenobarbitone |
|
|
Drugs that lower phenytoin levels |
Vigabatrin (VGB) and Amiodarone |
|
|
Phenytoin elevates the levels of these drugs |
Chloramphenicol and quinidine |
|
|
What is fosphenytoin |
Fosphenytoin sodium is a PRODRUG intended for parenteral administration. |
|
|
What is the active metabolite of fosphenytoin |
Phenytoin |
|
|
Advantages of Fosphenytoin over PHT |
1) it is better tolerated and safer 2) it can be infused 3 times faster than IV PHT can |
|
|
Where is Fosphenytoin indicated |
In ADULTS with partial or generalized seizures where SHORT-TERM parenteral administration is indicated |
|
|
Fosphenytoin is completely bioavailable after |
IM administration |
|
|
What metabolized Fosphenytoin to PHT |
Phosphatases |
|
|
Excretion of fosphenytoin |
It is not excreted in the urine |
|
|
Side effects of Fosphenytoin |
Cardiovascular depression and hypotension may occur with fosphenytoin but to a lesserextent than with PHT. Severe burning, itching, and/or paresthesia mainly in the groin area,have been associated with this drug. The discomfort may be improved by lowering the infusion rate or temporary discontinuation. Hepatic or hemopoietic adverse reactions, like those seen with PHT, also may occur. |
|
|
Disadvantage of Fosphenytoin over PHT |
It is more expensive |
|
|
Why is carbemazepine (CBZ) one of the most widely used AEDs in the world |
It is highly effective and well tolerated |
|
|
MOA of action of CBZ |
Like PHT, CBZ's mechanism of action is to block sustained high-frequency repetitive firing (SHFRF) of action potentials in the epileptic focus and preventing their spread. This isaccomplished by reducing the amplitude of sodium dependent-action potential throughprolongation of the inactivated state of the Na channel |
|
|
How is the absorption of CBZ like |
It is slow and erratic and varies from with patients |
|
|
Half life of CBZ in adults and children |
5-26hrs and 3-32 hours |
|
|
How is the absorption of OXC |
It is absorbed almost completely on oral administration and can be taken with food. IT ALSO READILY PASSES THE BBB |
|
|
What is responsible for the pharmacological effects of OXC |
Its active metabolite 10-monohydroxy metabolite(MHD) |
|
|
CONTRAINDICATIONS of OXC |
do not take with contraceptives. It reduces their efficacy |
|
|
Side effects of OXC |
Somnolence, headache, dizziness, rash, hyponatremia, weight gain, gastrointestinal (GI) disturbances, and alopecia are the most commonly reported adverse effects. |
|
|
What is Eslicarbazepine acetate |
It is a PRODRUG that is activated to ESLICARBAZEPINE |
|
|
another name for Eslicarbazepine acetate |
Aptiom |
|
|
What is Eslicarbazepine |
It is a major active metabolite of oxcarbazepine |
|
|
Application of Eslicarbazepine |
It is used as an adjunct or monotherapy for PARTIAL-ONSET SEIZURES in adults and children |
|
|
Side effects of Eslicarbazepine |
Dizziness, somnolence, nausea, headache, diplopia |
|
|
Side effects of Eslicarbazepine |
Dizziness, somnolence, nausea, headache, diplopia |
|
|
Applications of Valproate |
It is the drug of choIce in idiopathic generalized epilepsy and is also approved for the treatment ofpartial seizures. It is the drug of choice for juvenile myoclonic epilepsy. In addition, it is a first-line drug in photosensitive epilepsy andLennox-Gastaut Syndrome. It is a second choice in the treatment of infantile spasms. |
|
|
MOA of valproate |
VPA has been shown to blockvoltage-dependent sodium channels at therapeutically relevant concentrations. VPA enhances GABA function, but this effect is observed only at high Concentrations. There is also evidence that VPA at clinically relevant but slightly higher concs. may inhibit T-calcium channels. |
|
|
How is VPA absorbed |
It is absorbed rapidly with a bioavailability of close 100 percent |
|
|
Advantage of VPA |
It is well tolerated, with only 2% of patients discontinuing treatment because of adverseeffects, and has no significant effect on the cardiovascular system. |
|
|
Side effects of VPA |
nausea, vomiting, tremor, sedation,confusion, irritability, and weight gain. Severe sedation or even coma may result. Hair loss or curling of hair mayoccur. VPA has adverse endocrine effects. including insulin resistance and change in sex hormone levels causing anovulatory cycles, amenorrhea, and polycystic ovary syndrome. The most serious idiosyncratic adverse effect is hepatotoxicity. This is observed mainly inpatients younger than 2 years and with polytherapy. Hepatic failure from VPA is extremelyrare in adulthood. Metabolic etfects frominterference in mitochondrial metabolism include hypocarnitinemia, hyperglycinemia, and hyperammonemia |
|
|
What is Lamotrigine |
LamotrigineLamotrigine (LTG) is a triazine compound that is chemically unrelated to any of the otherAEDS. It was developed as an antifolate agent.on the basis of a theory that the mechanism ofSome AEDs is related to their antifolate property. |
|
|
MOA of Lamotrigine |
LTG's major mechanism of action is blocking voltage-dependent sodium-channelconductance. It has been found to inhibit depolarization of the glutaminergic presynapticmembrane, thus inhibiting the release of glutamate. It has a weak antifolate effect that is unrelated to its anti seizure efficacy. ma neunre lated to its ant ise izure efficacy. |
|
|
Side effects of LTG |
Unlike most AEDs, LTG produces few CNS side effects. Rash is the main concern. Severe rash (more common in children taking VPA) may develop and lead to Stevens-Johnson syndrome, which may be fatal. Other commonly reported adverse reactions are headache, blood dyscrasias, ataxla, diplopia, GI disturbance, psychosis, tremor, hypersensitivity reactions, somnolence, and insomnia. |
|
|
Indications of LTG |
The excellent side-effect profile and lack of significant CNS toxicity make this one oI the preferred choices in treating elderly patients. It is also the preferred drug for pregnant patients. It is also the preferred drug for pregnant patients. |
|
|
What effect does VPA have on LTG |
Combinationtherapy with VPA enhances the antiepileptic effect; however, it also increases the chances ofdeveloping allergic skin reactions. |
|
|
Advantage of zonisamide |
It is preferred clinically because of the ease of patient tolerance, degree of seizure reduction, long half-life, and lack of drug interactions with other AEDs. |
|
|
Application of zonisamide |
as adjunctive therapy for patients with partial seizures who are 12 years or older. |
|
|
MOA of ZNS |
The major mechanism of action of ZNS is a reduction of neuronal repetitive firing by blocking sodium channels and preventing neurotransmitter release. It also exerts influence onT-type calcium channels and prevents the influx of calcium. In addition, ZNS exhibitsneuroprotective effects through free radical scavenging. |
|
|
Adverse effects of ZNS |
dizziness anorexia, headacheataxia, confusion, speech abnormalities, mental slowing, irritability, tremor, and weight gain, somnolence and fatigue. |
|
|
What reduces the adverse reactions of ZNS |
gradual administration |
|
|
Application of lacosamide |
Partial-onset seizures |
|
|
MOA of lacosamide |
Lacosamide has a novel mechanism of action of modulation of Voltage- gated sodium channels by selective enhancement of slow inactivation. This effect may be relativeiyselective for neurons involved in a seizure activity in which the persistence of sodiumCurrents is more pronounced. Lacosamide does not affect AMPA, kainate, NMDA, GABAAGABAB, Or various dopaminergic, serotoninergic, adrenergic. muscarinic, or cannabinoidreceptors and does not block potassium or calcium currents. |
|
|
Bioavailability of lacosamide |
Close to 100 percent and it is not affected by food |
|
|
Adverse effects of lacosamide |
Commonly reported adverse reactions include dizziness, headache, nausea, and diplopia.Lacosamide has been labeled pregnancy category C because it has produced developmental toxicity (increased embryo fetal and perinatal mortality, growth deficit). |
|
|
Why is topiramate special |
It is structurally different from other AEDs. It is derived from D-fructose and was initially developed as an antidiabetic drug |
|
|
Applications of topiramate |
Drug-resistant generalized epilepsy and migraine headaches |
|
|
MOA of topiramate |
Topiramate has multiple mechanisms of action. It exerts an inhibitory effect on sodiumconductance, decreasing the duration of spontaneous bursts and the frequency of generatedaction potentials, enhances GABA by unknown mechanisms, inhibits the AMPA subtype glutamate receptor, and is a weak inhibitor of carbonic anhydrase. |
|
|
Side effects of topiramate |
ataxia, impairment of concentration,confusion, dizziness, fatigue, paresthesia in the extremities, somnolence, anorexia,disturbance of memory, depression, agitation, and slowness of speech. The drug causes weight loss inmany patients. The weight loss appears to be related to appetite suppression.As a carbonic anhydrase inhibitor, topiramate also has a propensity to cause renal calculi. Therefore, patients should be encouraged to drink plenty of fluids. |
|
|
How do calcium channels work |
Calcum channels function as the "pacemakers " of normal rhythmic brain activity. This isparticularly true of the thalamic neuron. The influx of calcium currents in the resting stateproduces a partial depolarizat ion of the membrane, facilitating the development of an action potential after rapid depolarization of the cell. |
|
|
Application of the calcium channel blockers |
AEDs that inhibit these T-calcium channels areparticularly useful for controlling absence seizures. |
|
|
What is the calcium channel blocker AED |
Ethosuximide |
|
|
MOA of ETS |
Ethosuximide blocks voltage-dependentcalcium channels especially those which mediate currents in thalamic neurons. |
|
|
Application of ETS |
absence seizure |
|
|
Why is the use of ethosuximide limited |
It has very narrow specificity of clinical activity |
|
|
Side effects of ETS |
Most of the side etfects are dose related and consists ofgastrointestinal irritation (nausea, vomiting, anorexia), and CNS effect(drowsiness,lethargy, euphoria, dizziness, headache and hiccough). A variety of blood dyscrasias have been reported. rashes and Stevens-Johnson syndrome have also been associated withits usage. |
|
|
What is GABA |
Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the CNS.GABA has 2 types of receptors: A and B. |
|
|
What can enhance the GABA system |
The GABA system can be enhanced by binding directly to GABA-A receptors, by blocking prësynaptic GABA uptake, by inhibiting themetabolism of GABA by GABA transaminase, and by increasing the synthesis of GABA. |
|
|
MOA of GABA |
When GABA binds to a GABA-A receptor, the passage of chloride, a negatively charged ion, into the cell is facilitated via chloride channels. This influx of chloride ion increases thenegativity of the cell (i.e, a more negative resting membrane potential). This causes the cell tohave greater difficulty reaching the action potential. |
|
|
How can antiepileptic drugs act to facilitate the action of GABA |
Several Antiepileptic drugs may act to facilitate the actions of GABA ether by:1)Modulating transmission through chloride channel (GABA receptor agonist)2) Inhibiting GABA metabolism (degradation) by blocking GABA transaminase (eg,vigabatrin (VGB), resulting in increased accumulation of GABA at the postsynapticreceptors.3) Inhibiting the reuptake of GABA (uptake blocker) into the presynaptic terminal (eg,tiagabine (TGB). |
|
|
What are the GABA receptor agonist |
1) Benzodiazepines-lorazepam, diazepam, clonazepam, clobazam 2) barbiturates - phenobarbital, primidone |
|
|
Which Benzodiazepines are used in treating epilepsy |
Lorazepam, diazepam, clonazepam and clobazam |
|
|
What is special about lorazepam and diazepam |
The first 2 drugs are used mainly for emergency treatment of seizures because of their quick onset of action, availability in intravenous (IV) forms, and strong anticonvulsanteffects. Their use for long-term treatment is limited because of the development of tolerance. |
|
|
MOA of the Benzodiazepines |
The primary action of the benzodiazepines as AEDs is to enhance GABA inhibitory activity through interaction with GABA-A receptor at the BDZ binding site. Also, BDZ can block voltage dependent sodium channels. |
|
|
What is special about clobazam |
Clobazam has a 1.5 substitution instead of the usual 1,4-diazepine. This change results in an 80% reduction in its anxiolytic activity and a 10-fold decrease in its sedative effects.
|
|
|
MOA of clobazam |
In addition to its agonist action-at the GABA-A receptor, clobazam may affect voltage sensitive conductance of calcium ions and the function of sodium channels. |
|
|
Why does clobazam have no IM or IV Preparations |
It is relatively insoluble in water |
|
|
What is the metabolite of clobazam |
Norclobazam( N-desmethylclobazam) |
|
|
Side effects of clobabzam |
Essentially, the adverse effects of clobazam are similar to those of other benzodiazepines.The most common effect is sedation. Other adverse effects include dizziness, ataxia, blurredvisian, diplopia, irritability, depression, muscle fatigue, and weakness.
|
|
|
Structure of clonazepam |
It is a 1,4-substituted benzodiazepine |
|
|
Mode of administration of clonazepam and diazepam |
IV or rectally |
|
|
Indications of clonazepam |
It is employed in the treatment of all types of myoclonus and is useful inpatients with concomitant anxiey disorder. It is also effective in generalized convulsions. It is very effective in the emergency treatment of status epilepticus. |
|
|
MOA of clonazepam |
Clonazepam has higher affinity for the GABA-A receptor site than diazepam and binds to GABA-A receptors that don't bind with other benzodiazepines. It may have some action on sodium-channel conductance.
|
|
|
Side effects of clonazepam |
Clonazepam's major adverse effect is sedation, even at low doses. Clonazepam has the typical adverse effects benzodiazepines (eg, ataxia, hyperactivity, restlessness, irritability, depression, cardiovascular or respiratory depression). Children and infants may have hypersalivation. |
|
|
Why is clonazepam used by pediatricians |
Children tolerate thismedication much better than adults do |
|
|
Which barbiturates are used in the treatment of epilepsy |
Phenobarbital and primidone |
|
|
General method of action of the barbiturates |
They bind to the barbiturate-binding site of the benzodiazepine receptor yo affect the duration of chloride channel opening. |
|
|
Why are barbiturates second line drugs |
They have significant adverse effects. |
|
|
Classes of AED |
In all, there are 4 major classes sodium channel blockers, T-calcium current inhibitors, gamma-amino butyric acid (GABA) enhancers, glutamate blockers, and drugs with unknown mechanisms of action. |
|
|
What is the purpose of sodium channels |
They are responsible for the firing of an action potential by an axon |
|
|
What are the three states a sodium channel can exist in dynamically |
CLOSED STATE: During which the channel activation gate is closed and sodium ion cannot pass through the channel. OPEN OR ACTIVE STATE: During which the channel activation_gate opens rapidly following depolarization and sodium ion enters freely. INACTIVATED STATE: During which the channel inactivation gate closes preventing furtherentry of sodium ions into the cell. |
|
|
method of action of Na channel blockers |
During an action potential, these channels exist in the active state and allow the intlux ofsodium ions. Once the activation or stimulus is terminated, a percentage of these sodiumchannels become inactive for a period known as the REFRACTORY PERIOD. AEDs that target thesodium channels prevent the return of these channels to the active state by stabilizing them inthe inactive state. In doing so, they prevent high-frequency repetitive firing of the neuron. |
|
|
EXAMPLES OF NA CHANNEL BLOCKERS |
(Pheny and Fosphenytoin, carbemazepine. Ox and Esli carbazepine, Zoni and Laco samide, Valproate, Lamotrigine and Topiramide) |
|
|
Indications of phenytoin |
phenytoin (PHT) has been one of the most commonly used first-line or adjunctive treatments for partial and generalized seizures, Lennox-Gastautsyndrome, status epilepticus, and childhood epileptic syndromes. |
|
|
Phenytoin isn't used for |
lt is not indicated for myoclonic and absence seizures. |
|
|
Phenytoin isn't used for |
lt is not indicated for myoclonic and absence seizures. |
|
|
MOA of phenytoin |
It nas a stabilizing effect on excitable membrane of many cells including neurons. At therapeutic concentrations, it blocks sustained high-frequency repetitive firing (SHFRF) of action potentials. This is accomplished by reducing the amplitude of sodum dependent- action potential through prolongation of the inactivated state of the Na channel. |
|
|
Pharmacokinetics of phenytoin |
Following oral administration, PHT absorption is slow but complete and occurs in the duodenum; oral bioavailability is approximately 95%, and peak level after oral administrationreached in approximately 4-12 hours. It is 70-95% bound to plasma protein, and ismetabolized in the liver by the hepatic P-450 mixed oxidase system. A number of minor metabolites are formed, but none of them is active (i.e , they have no antiepileptic properties). Excretion is through the kidneys. Elimination half-life is 7-42hours (average 24 hrs). Food and diseases of the small intestines alter PHT absorption. |
|
|
Drugs that have variable effects on the phenytoin levels |
Carbemazapine and phenobarbitone |
|
|
Side effects of carbamazepine |
The major disadvantages of CBZ are transient adverse dose-related effects at initiation oftherapy and occasionai toxicity. Potential dose-related adverse effects include dizziness, diplopia, nausea, ataxia, and blurred vision. Rare idiosyncratic adverse effects include aplastic anaemia, agranulocytosis, thrombocytopenia, and Stevens-Johnson syndrome.Asymptomatic elevation of liver enzymes is observed commonly during the course of therapy1n 5-10% of patients. Rarely, severe hepatotoxic effects can occur |
|
|
What is the PRODRUG of CBZ |
Oxcarbazepine |
|
|
Advantages of oxcarbazepine |
It was developed in aattempt to maintain the benefits of CBZ while avoiding its AUTOINDUCTION AND DRUG INTERACTION PROPERTIES. This property decreases the problem associated with drug interactionswhen used in combination with other drugs. |
|
|
Why is OXC safer than CBZ |
It does not produce the epoxide metabolite which is responsible for the adverse effects reported with CBZ |
|
|
MOA of OXC |
like CBZ it blocks the neuronal sodium channel during sustained rapid repetitive firing |
