Neuro pharm
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Questions and Answers

What is the primary route of administration for carbamazepine?

  • Topical
  • Oral (correct)
  • Intravenous
  • Sublingual

    • What is the effect of carbamazepine on its own metabolism?

  • It has no effect on its own metabolism
  • It induces its own metabolism (correct)
  • It inhibits its own metabolism
  • It slows down its own metabolism

    • Which of the following medications is NOT affected by carbamazepine's induction of metabolism?

  • Antipsychotics
  • Cimetidine (correct)
  • Valproic acid
  • Oral contraceptives

    • What is a common side effect of carbamazepine?

    <p>Sedation</p> Signup and view all the answers

    Which of the following is a rare but serious side effect of carbamazepine?

    <p>Aplastic anemia</p> Signup and view all the answers

    What is the percentage of carbamazepine that is bound to protein?

    <p>80%</p> Signup and view all the answers

    What is the range of time it takes for carbamazepine to reach its peak concentration after oral administration?

    <p>2-6 hours</p> Signup and view all the answers

    What is the primary site of metabolism for carbamazepine?

    <p>Liver</p> Signup and view all the answers

    What is the half-life of carbamazepine?

    <p>8-24 hours</p> Signup and view all the answers

    What type of seizures is carbamazepine used to treat?

    <p>Partial and generalized seizures</p> Signup and view all the answers

    What is the primary mechanism by which carbamazepine and phenytoin affect the plasma concentration of ESLICARBAMAZEPINE?

    <p>Enzyme induction</p> Signup and view all the answers

    Which of the following patient populations is contraindicated for ESLICARBAMAZEPINE therapy?

    <p>Patients with 2nd and 3rd degree AV block</p> Signup and view all the answers

    What is the primary route of elimination for ESLICARBAMAZEPINE?

    <p>Renal excretion</p> Signup and view all the answers

    What is the percentage of ESLICARBAMAZEPINE that is bound to plasma proteins?

    <p>40%</p> Signup and view all the answers

    What is the percentage of ethosuximide excreted unchanged in urine?

    <p>25%</p> Signup and view all the answers

    What is the primary mechanism of action of ethosuximide?

    <p>Decreasing calcium conductance in thalamic nuclei</p> Signup and view all the answers

    What is a rare but serious side effect of ethosuximide?

    <p>Bone marrow suppression</p> Signup and view all the answers

    What is the half-life of ethosuximide?

    <p>20-60 hours</p> Signup and view all the answers

    What type of seizures is ethosuximide typically used to treat?

    <p>Absence (petit mal) seizures</p> Signup and view all the answers

    What is the primary elimination route for felbamate?

    <p>Renal excretion of unchanged drug</p> Signup and view all the answers

    What is a major concern when co-administering felbamate with phenytoin?

    <p>Inhibition of phenytoin metabolism</p> Signup and view all the answers

    What is a crucial laboratory test to monitor in patients receiving felbamate therapy?

    <p>C &amp; D</p> Signup and view all the answers

    What is a potential interaction between felbamate and valproic acid?

    <p>Inhibition of valproic acid metabolism</p> Signup and view all the answers

    What is the half-life of felbamate?

    <p>20 hours</p> Signup and view all the answers

    What is the half-life of gabapentin?

    <p>6 hours</p> Signup and view all the answers

    What is the mechanism of action of gabapentin?

    <p>Inhibition of calcium channels</p> Signup and view all the answers

    What is a common side effect of gabapentin?

    <p>Sedation and GI disturbances</p> Signup and view all the answers

    What is the protein binding of gabapentin?

    <p>0%</p> Signup and view all the answers

    What is gabapentin used to treat?

    <p>Seizures, anxiety, panic, and major depression</p> Signup and view all the answers

    What is the primary mechanism of action of Lacosamide?

    <p>Inhibiting voltage-gated sodium channels</p> Signup and view all the answers

    What is the primary use of Lacosamide?

    <p>Partial onset seizures</p> Signup and view all the answers

    What is the bioavailability of Lacosamide?

    <p>Almost 100%</p> Signup and view all the answers

    What is a common side effect of Lacosamide?

    <p>All of the above</p> Signup and view all the answers

    What percentage of Lacosamide is bound to plasma proteins?

    <p>20%</p> Signup and view all the answers

    What is the mechanism of lamotrigine?

    <p>stabilizes voltage-gated sodium channels</p> Signup and view all the answers

    What is the effect of phenytoin, phenobarbital, and carbamazepine on lamotrigine's half-life?

    <p>Decreases it by 50%</p> Signup and view all the answers

    What is a rare but serious side effect of lamotrigine?

    <p>Stevens-Johnson's syndrome</p> Signup and view all the answers

    What is the percentage of lamotrigine that is bound to protein?

    <p>50%</p> Signup and view all the answers

    What is the use of lamotrigine?

    <p>For partial onset and generalized seizures</p> Signup and view all the answers

    What is the primary mechanism of action of LEVETIRACETAM?

    <p>Inhibition of the release of neurotransmitters from calcium channels</p> Signup and view all the answers

    What is the characteristic of LEVETIRACETAM's protein binding?

    <p>Minimal protein binding</p> Signup and view all the answers

    What type of seizures is LEVETIRACETAM typically used to treat?

    <p>Partial and general convulsive seizures</p> Signup and view all the answers

    What is a common side effect of LEVETIRACETAM?

    <p>Sedation</p> Signup and view all the answers

    What is the characteristic of LEVETIRACETAM's metabolism?

    <p>Minimal hepatic metabolism</p> Signup and view all the answers

    What is the primary mechanism of action of PERAMPANEL?

    <p>Selective noncompetitive antagonism of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors</p> Signup and view all the answers

    What percentage of PERAMPANEL is bound to protein?

    <p>95%</p> Signup and view all the answers

    What is the elimination half-life of PERAMPANEL?

    <p>110 hrs</p> Signup and view all the answers

    What is the primary route of elimination for PERAMPANEL?

    <p>Liver metabolism and fecal excretion</p> Signup and view all the answers

    What is a black box warning for PERAMPANEL?

    <p>Suicide or homicidal thoughts</p> Signup and view all the answers

    Which of the following is the mechanism of phenobarbital?

    <p>A &amp; C</p> Signup and view all the answers

    What percentage of phenobarbital is eliminated through pH-dependent renal excretion?

    <p>25%</p> Signup and view all the answers

    What is a rare but serious side effect of phenobarbital?

    <p>All of the above</p> Signup and view all the answers

    What is the effect of phenobarbital on the metabolism of other drugs?

    <p>Induction of hepatic enzymes</p> Signup and view all the answers

    What is the primary use of phenobarbital?

    <p>Treatment of all seizure types except non-convulsive generalized seizures</p> Signup and view all the answers

    What is the primary mechanism of action of phenytoin in regulating neuronal excitability?

    <p>Regulating sodium and calcium transport</p> Signup and view all the answers

    What is the therapeutic concentration of phenytoin in the plasma?

    <p>10-20 mcg/mL</p> Signup and view all the answers

    What is a potential side effect of phenytoin in patients with diabetes?

    <p>Hyperglycemia</p> Signup and view all the answers

    What is the characteristic of phenytoin's protein binding?

    <p>90% bound to protein</p> Signup and view all the answers

    What is the primary elimination route for phenytoin?

    <p>Hepatic metabolism</p> Signup and view all the answers

    What is the primary site of accumulation for Stiripentol?

    <p>Cerebellum and medulla</p> Signup and view all the answers

    What is the protein binding rate of Stiripentol?

    <p>99%</p> Signup and view all the answers

    What is the half-life of Stiripentol?

    <p>10-15 hours</p> Signup and view all the answers

    What is a major concern when prescribing Stiripentol?

    <p>Neutropenia</p> Signup and view all the answers

    What is the primary mechanism of action of Stiripentol?

    <p>Increasing GABA activity</p> Signup and view all the answers

    What is the primary mechanism of action of Tiagabine?

    <p>Potent inhibitors of GABA reuptake</p> Signup and view all the answers

    What is the protein binding percentage of Tiagabine?

    <p>95%</p> Signup and view all the answers

    What is the half-life of Tiagabine?

    <p>5-8 hours</p> Signup and view all the answers

    What is a common side effect of Tiagabine?

    <p>All of the above</p> Signup and view all the answers

    What is the primary use of Tiagabine?

    <p>Adjunct therapy for partial seizures</p> Signup and view all the answers

    What is a unique feature of topiramate's pharmacokinetics?

    <p>Minimal protein binding</p> Signup and view all the answers

    Which of the following is a mechanism of action of topiramate?

    <p>Inhibition of voltage-gated sodium and calcium channels</p> Signup and view all the answers

    What is a potential side effect of topiramate?

    <p>Nephrolithiasis</p> Signup and view all the answers

    What is a therapeutic use of topiramate?

    <p>Treatment of essential tremor</p> Signup and view all the answers

    What is a unique feature of topiramate's mechanism of action?

    <p>Inhibition of glutamate and carbonic anhydrase</p> Signup and view all the answers

    What is the primary mechanism of action of valproic acid?

    <p>Affects voltage-gated sodium channels</p> Signup and view all the answers

    What is the range of time it takes for valproic acid to reach its peak concentration after oral administration?

    <p>1-4 hours</p> Signup and view all the answers

    What is a rare but serious side effect of valproic acid in children under 2?

    <p>Hepatotoxicity</p> Signup and view all the answers

    What is the percentage of valproic acid that is bound to protein?

    <p>85%</p> Signup and view all the answers

    What is the mechanism by which valproic acid affects the plasma concentration of phenytoin and phenobarbital?

    <p>Inhibits hepatic enzymes</p> Signup and view all the answers

    What is the effect of vigabatrin on the GABA transaminase enzyme?

    <p>Irreversible inhibition of GABA transaminase enzyme</p> Signup and view all the answers

    What is a significant side effect of vigabatrin that can be permanent?

    <p>Visual loss</p> Signup and view all the answers

    What is the primary use of vigabatrin in pediatric patients?

    <p>Monotherapy for infantile spasms</p> Signup and view all the answers

    How does vigabatrin affect the metabolism of other medications?

    <p>It has no effect on the metabolism of other medications</p> Signup and view all the answers

    What is necessary when dosing vigabatrin in patients with renal impairment?

    <p>Dose reduction is necessary</p> Signup and view all the answers

    What percentage of zonisamide is bound to protein?

    <p>50%</p> Signup and view all the answers

    What is the half-life of zonisamide?

    <p>50-70 hours</p> Signup and view all the answers

    What is a side effect of zonisamide?

    <p>Anorexia</p> Signup and view all the answers

    What is a mechanism of action of zonisamide?

    <p>GABA enhancement</p> Signup and view all the answers

    What is a unique feature of zonisamide?

    <p>It is a carbonic anhydrase inhibitor</p> Signup and view all the answers

    What is the mechanism of action of benzodiazepines?

    <p>Increasing chloride permeability and leading to cellular hyperpolarization</p> Signup and view all the answers

    What is the primary effect of benzodiazepines on neurons?

    <p>Hyperpolarization</p> Signup and view all the answers

    What is the result of benzodiazepines binding to GABA receptors?

    <p>Increased chloride permeability</p> Signup and view all the answers

    What is the effect of benzodiazepines on the nervous system?

    <p>Relaxation</p> Signup and view all the answers

    What is the general effect of benzodiazepines on GABA receptors?

    <p>Agonizing GABA receptors</p> Signup and view all the answers

    What is the peak absorption time for clonazepam when administered orally?

    <p>2-4 hours</p> Signup and view all the answers

    What is the primary concern when discontinuing clonazepam therapy?

    <p>Generalized seizures activity</p> Signup and view all the answers

    What is the percentage of protein binding for clonazepam?

    <p>50%</p> Signup and view all the answers

    What is the half-life of clonazepam?

    <p>30-40 hours</p> Signup and view all the answers

    What is the typical use of clonazepam in seizure therapy?

    <p>First-line for myoclonic seizures</p> Signup and view all the answers

    What is the primary use of diazepam?

    <p>Managing status epilepticus and local anesthetic induced seizures</p> Signup and view all the answers

    What is the half-life of diazepam?

    <p>27-48 hours</p> Signup and view all the answers

    What is a common side effect of diazepam?

    <p>Sedation</p> Signup and view all the answers

    What is the maximum dose of diazepam?

    <p>30mg</p> Signup and view all the answers

    How is diazepam administered for seizures?

    <p>Intravenously, every 10-15 minutes</p> Signup and view all the answers

    What is the primary use of lorazepam?

    <p>Status epilepticus and seizure clusters</p> Signup and view all the answers

    What is the duration of lorazepam's antiepileptic activity?

    <p>Longer than diazepam</p> Signup and view all the answers

    What is the primary side effect of lorazepam?

    <p>Sedation</p> Signup and view all the answers

    How is lorazepam metabolized?

    <p>In the liver without active metabolites</p> Signup and view all the answers

    What is the half-life of lorazepam?

    <p>8-25 hours</p> Signup and view all the answers

    What is the primary indication for the use of Clobazam?

    <p>Complex partial, tonic-clonic, and myoclonic seizures</p> Signup and view all the answers

    What is the primary mechanism of Clobazam's metabolism?

    <p>Metabolized by liver to active metabolites</p> Signup and view all the answers

    What is a common side effect of Clobazam?

    <p>Sedation (much less effect than other benzodiazepines)</p> Signup and view all the answers

    What is an important consideration when discontinuing Clobazam?

    <p>Gradual discontinuation is recommended</p> Signup and view all the answers

    What is the approximate half-life of Clobazam?

    <p>16-18 hours</p> Signup and view all the answers

    What percentage of an orally administered levodopa dose is rapidly decarboxylated to dopamine in the liver?

    <p>95%</p> Signup and view all the answers

    What is the primary reason for combining levodopa with a peripheral decarboxylase inhibitor?

    <p>To inhibit the conversion of levodopa to dopamine in the periphery</p> Signup and view all the answers

    What is the primary mechanism by which domperidone is effective in treating nausea and vomiting associated with levodopa therapy?

    <p>It does not cross the blood-brain barrier and blocks dopamine receptors in the periphery</p> Signup and view all the answers

    What is the primary metabolic fate of dopamine in the brain?

    <p>It is converted to 3,4 dihydroxyphenylacetic acid</p> Signup and view all the answers

    What is the primary reason for the abrupt discontinuation of levodopa therapy being contraindicated?

    <p>It can cause an increase in Parkinsonian symptoms</p> Signup and view all the answers

    What is the primary mechanism by which levodopa exerts its therapeutic effect in Parkinson's disease?

    <p>It is converted to dopamine in the brain, which replenishes dopamine stores</p> Signup and view all the answers

    What is the primary cause of orthostatic hypotension in patients taking levodopa?

    <p>Increased alpha and beta stimulation from dopamine, epinephrine, and norepinephrine</p> Signup and view all the answers

    What is the primary dietary factor that is necessary for the continued action of COMT to metabolize dopamine?

    <p>Methionine</p> Signup and view all the answers

    What is a common side effect of Levodopa therapy that develops within 1-4 months of treatment in 50% of patients?

    <p>Abnormal involuntary movements</p> Signup and view all the answers

    Why should high protein meals be avoided when taking Levodopa?

    <p>To prevent amino acid interference with Levodopa transport to the brain</p> Signup and view all the answers

    What is a potential complication of sudden withdrawal of Levodopa therapy?

    <p>Parkinsonism-hyperpyrexia syndrome</p> Signup and view all the answers

    Which of the following medications can antagonize the effects of dopamine and should not be administered to patients with Parkinson's?

    <p>All</p> Signup and view all the answers

    What is the effect of pyridoxine on the efficacy of Levodopa?

    <p>It abolishes the efficacy of Levodopa by enhancing pyridoxine dependent dopa decarboxylase metabolism</p> Signup and view all the answers

    What is the characteristic of the interaction between anticholinergics and Levodopa?

    <p>Anticholinergics work synergistically with Levodopa</p> Signup and view all the answers

    What is the effect of nonspecific MOAI on Levodopa therapy?

    <p>It interferes with the inactivation of catecholamines, including dopamine, and can exaggerate the peripheral effects of Levodopa</p> Signup and view all the answers

    What is a potential complication of Levodopa therapy?

    <p>All of the above</p> Signup and view all the answers

    What is the primary mechanism by which COMT inhibitors, such as tolcapone and entacapone, increase the effectiveness of levodopa therapy?

    <p>By inhibiting the conversion of levodopa to dopamine in the peripheral nervous system</p> Signup and view all the answers

    What is the primary advantage of synthetic dopamine agonists, such as pramipexole and ropinirole, compared to levodopa?

    <p>They do not require transformation or facilitated transport across the blood-brain barrier</p> Signup and view all the answers

    What is the primary mechanism of action of anticholinergic medications, such as trihexyphenidyl and benztropine, in the treatment of Parkinson's disease?

    <p>They reduce the activity of the excitatory neurotransmitter acetylcholine</p> Signup and view all the answers

    What is the primary advantage of MAO-B enzyme inhibitors, such as selegiline and rasagiline, compared to other medications used to treat Parkinson's disease?

    <p>They do not affect the metabolism of norepinephrine</p> Signup and view all the answers

    What is the primary mechanism by which amantadine improves symptoms in Parkinson's disease?

    <p>It promotes the release of dopamine and slows its reuptake</p> Signup and view all the answers

    What is the primary difference between peripheral decarboxylase inhibitors, such as carbidopa and benserazide, and COMT inhibitors, such as tolcapone and entacapone?

    <p>The location of their action in the body</p> Signup and view all the answers

    What is the primary advantage of using a combination of levodopa and a peripheral decarboxylase inhibitor, such as carbidopa and levodopa (Sinemet), compared to using levodopa alone?

    <p>It reduces the peripheral side effects of levodopa</p> Signup and view all the answers

    What is the primary risk associated with abrupt discontinuation of synthetic dopamine agonists, such as pramipexole and ropinirole?

    <p>Parkinsonism-hyperpyrexia syndrome</p> Signup and view all the answers

    Study Notes

    Carbamazepine Uses

    • Used to treat partial and generalized seizures
    • Also used to treat trigeminal and glossopharyngeal neuralgia

    Pharmacokinetics

    • Available in oral form only
    • Peak concentration reached in 2-6 hours
    • 80% bound to protein
    • Half-life of 8-24 hours
    • Metabolized in the liver to active metabolites

    Metabolism and Interactions

    • Induces its own metabolism, requiring possible dosage increase after 2-4 weeks
    • Induces metabolism of oral contraceptives, valproic acid, corticosteroids, anticoagulants, and antipsychotics
    • Metabolism inhibited by cimetidine, propoxyphene, diltiazem, verapamil, isoniazid, and erythromycin

    Side Effects

    • Common: sedation, vertigo, diplopia, nausea, and vomiting
    • Rare: aplastic anemia, thrombocytopenia, neutropenia, jaundice, oliguria, hypertension, and cardiac dysrhythmia

    Carbamazepine

    • Used to treat partial and generalized seizures
    • Also used to treat trigeminal and glossopharyngeal neuralgia
    • Administered orally only
    • Peak concentration reached in 2-6 hours
    • Highly protein-bound (80%)
    • Half-life of 8-24 hours
    • Undergoes hepatic metabolism to produce some active metabolites

    Eslicarbazepine

    • Used to treat partial-onset seizures
    • Pharmacokinetics:
      • Administered orally
      • Peaks in 2-4 hours
      • 40% bound to protein
      • 90% excreted through the kidneys
    • Common side effects:
      • Nausea and vomiting (N/V)
      • Diarrhea
      • Fatigue
      • Dizziness
    • Contraindications:
      • Patients with 2nd and 3rd degree AV block
    • Interactions:
      • Carbamazepine and phenytoin reduce its plasma concentration through enzyme induction

    Ethosuximide

    • Indicated as the drug of choice for treating absence (petit mal) epilepsy, specifically when toni-clonic seizures are not present.
    • Administered orally, with a peak concentration reached in 1-7 hours.
    • Excreted via two routes: 25% remains unchanged in urine, while the remainder is metabolized by the liver.
    • Half-life of the drug ranges from 20-60 hours.
    • Common side effects include:
      • Nausea and vomiting (N/V)
      • Lethargy
      • Dizziness
      • Ataxia
      • Photophobia
      • Hyponatremia
    • Rare but significant side effect: bone marrow suppression.
    • Mechanism of action: decreases calcium conductance in thalamic nuclei.

    Felbamate

    • Used to treat intractable epilepsy
    • Pharmacokinetics:
      • Mostly excreted unchanged by the kidneys
      • Half-life: 20 hours
      • Protein binding: 25%
    • Major side effects:
      • Aplastic anemia
      • Hepatotoxicity
    • Monitoring requirements:
      • Blood counts
      • Liver function
    • Interactions with other medications:
      • Carbamazepine and phenytoin decrease felbamate's plasma concentration
      • Felbamate is a potent inhibitor of P450 enzymes
      • Slows metabolism of:
        • Phenytoin
        • Phenobarbital
        • Valproic acid

    Gabapentin

    • Used to treat seizures, anxiety, panic, and major depression, although it has limited efficacy for seizures
    • Has a half-life of 6 hours
    • Does not bind to proteins (0% protein binding)
    • Common side effects include sedation and gastrointestinal disturbances

    Mechanism of Action

    • Works by inhibiting calcium channels, rather than binding to GABA receptors
    • Although it is an analog of GABA, it does not interact with GABA receptors

    Partial Onset Seizures Medication

    • Pharmacokinetics:
      • Peak concentration reached in 2-5 hours
      • Almost 100% bioavailability
      • 20% of the drug binds to plasma proteins

    Side Effects

    • Gastrointestinal:
      • Nausea (N)
      • Vomiting (V)
      • Diarrhea
    • Neurological:
      • Headaches
      • Itching
    • Cardiovascular:
      • Postural hypotension
      • Dysrhythmias (abnormal heart rhythms)

    Mechanism of Action

    • Inhibits voltage-gated sodium channels
    • Stabilizes hyperexcitable neurons

    Lamotrigine

    • Half-life: 25 hours
    • Protein binding: 50%

    Clinical Use

    • Indication: partial onset and generalized seizures

    Adverse Effects

    • Common: headache, nausea and vomiting (N/V), diplopia, ataxia, tremor
    • Rare but serious: Steven-Johnson's syndrome

    Pharmacological Mechanism

    • Stabilizes voltage-gated sodium channels

    Drug Interactions

    • Decreased half-life (by 50%): phenytoin, phenobarbital, and carbamazepine
    • Increased half-life (to 60 hours): valproic acid

    Levetiracetam

    • Used to treat juvenile myoclonic epilepsy, partial seizures, and general convulsive seizures, including tonic-clonic seizures
    • Pharmacokinetics:
      • Not metabolized by the liver (hepatic metabolism)
      • Minimal binding to proteins
    • Common side effects:
      • Sedation
      • Anxiety
      • Headache
    • Mechanism of action:
      • Binds to calcium channels
      • Reduces release of neurotransmitters

    Perampanel

    • Used to treat partial onset and generalized tonic-clonic seizures

    Pharmacokinetics

    • 95% bound to plasma proteins
    • Elimination half-life: 110 hours
    • Metabolized primarily in the liver
    • Excreted: 70% in feces, 30% in urine

    Side Effects

    • Black box warning: increased risk of suicide or homicidal thoughts
    • Other side effects: vertigo, slurred speech, irritability, aggression, fatigue, and euphoria

    Mechanism of Action

    • Works by selective noncompetitive antagonism of AMPA receptors

    Phenobarbital

    • Effective against all seizure types except non-convulsive generalized seizures.
    • Oral absorption is nearly 100%.
    • Peak concentration is reached in 12-18 hours.
    • 50% protein binding.
    • Elimination occurs through:
      • 25% pH-dependent renal excretion.
      • 75% hepatic metabolism.

    Side Effects

    • Sedation.
    • Irritability.
    • Hyperactivity.
    • Depression.
    • Confusion.
    • Rash.
    • Megaloblastic anemia.
    • Osteomalacia.
    • Nystagmus.
    • Ataxia.
    • Abnormal collagen deposits, manifesting as Dupuytren's contracture.
    • Congenital malformations when given during pregnancy.

    Mechanism of Action

    • Postsynaptic potentiation of GABA.
    • Inhibition of glutamate, leading to prolonged duration of chloride channel opening.

    Clinical Notes

    • 2nd line drug due to cognitive and behavioral side effects.
    • Induces hepatic enzymes, speeding up metabolism of many lipid-soluble drugs.

    Phenytoin

    • Used to treat partial and generalized seizures
    • Available in both oral and intravenous (IV) forms

    Pharmacokinetics

    • Therapeutic concentration: 10-20 mcg/mL within 20 minutes
    • High therapeutic index with minimal sedation
    • 90% bound to plasma proteins
    • Half-life: 9-40 hours
    • Metabolized by the liver (98%)
    • First-order elimination at plasma concentrations above 10 mcg/mL

    Adverse Effects

    • Nystagmus
    • Ataxia
    • Diplopia
    • Vertigo
    • Peripheral neuropathy
    • Gingival hyperplasia
    • Acne
    • Hirsutism
    • Fetal hydantoin syndrome (if taken during pregnancy)
    • Rash
    • Hyperglycemia and glycosuria (due to inhibition of insulin secretion)
    • Megaloblastic anemia
    • Hepatic toxicity

    Mechanism of Action

    • Regulates sodium and calcium transport, decreasing neuronal excitability
    • Precipitates in solutions with pH

    STIRIPENTOL

    • Used to treat Dravet syndrome

    Pharmacokinetics

    • Rapidly crosses Blood-Brain Barrier (BBB)
    • Accumulates in medulla and cerebellum
    • 99% protein binding
    • Half-life of 10-15 hours

    Side Effects

    • Weight loss
    • Loss of appetite
    • Somnolence
    • Ataxia
    • Hypotonia
    • Neutropenia
    • Nausea and Vomiting (N/V)
    • Sleep disorders
    • Hyperexcitability

    Additional Notes

    • Increases GABA activity
    • Requires White Blood Cell (WBC) monitoring

    Tiagabine

    • Used as an adjunct therapy for treating partial seizures
    • Has a high protein binding capacity of 95%
    • Exhibits a half-life of 5-8 hours
    • Undergoes hepatic metabolism
    • Common side effects include:
      • Dizziness
      • Aphasia
      • Tremor
      • Mental depression
    • Acts as a potent inhibitor of GABA reuptake

    Topiramate Overview

    • Used to treat partial, generalized tonic-clonic, and absence seizures, as well as migraines, bulimia, and essential tremor.

    Pharmacokinetics

    • Topiramate has minimal protein binding.
    • Does not affect P450 enzymes.

    Adverse Effects

    • Sedation is a possible side effect of topiramate.
    • Dizziness is a potential side effect.
    • Ataxia can occur as a side effect.
    • Nephrolithiasis is a possible side effect.

    Mechanism of Action

    • Topiramate inhibits voltage-gated sodium channels.
    • Inhibits voltage-gated calcium channels.
    • Inhibits glutamate.
    • Weakly inhibits carbonic anhydrase.

    Valproic Acid

    • Indicated for treatment of all primary generalized seizures, with greater efficacy on convulsive seizures than nonconvulsive seizures
    • Administered orally, with peak plasma concentrations reached in 1-4 hours
    • Highly protein-bound, with 85% of the drug bound to plasma proteins
    • Half-life of 7-17 hours, with hepatic metabolism to active metabolites

    Side Effects

    • Gastrointestinal (GI) upset
    • Weight gain
    • Tremor
    • Thrombocytopenia (low platelet count)
    • Hepatotoxicity, particularly in children under 2 years old
    • Sedation
    • Ataxia (coordination and balance problems)

    Pharmacological Interactions

    • Affects voltage-gated sodium channels
    • Can displace phenytoin and diazepam from protein binding sites
    • Inhibits hepatic enzymes necessary for metabolism of phenytoin and phenobarbital

    VIGABATRIN

    • Used to treat refractory complex partial seizures and as monotherapy for infantile spasms in infants.
    • Not bound to proteins, which affects its distribution and interaction with other drugs.
    • Undergoes minimal metabolism, which means it is primarily excreted in its original form.

    Side Effects

    • Can cause permanent visual loss, making it essential to monitor visual acuity.
    • Common side effects include fatigue, anemia, and somnolence.
    • Patients should be aware of these potential side effects and report them to their doctor.

    Pharmacological Mechanism

    • Irreversibly inhibits the GABA transaminase enzyme, leading to increased GABA concentrations.
    • Dose adjustments are necessary for patients with renal impairment to prevent accumulation and toxicity.

    Zonisamide

    • Used as an adjunct for partial and secondary generalized seizures
    • Metabolized in the liver
    • 50% protein binding
    • Half-life: 50-70 hours
    • Side effects:
      • Sedation
      • Dizziness
      • Ataxia
      • Anorexia
      • Mania
      • Nephrolithiasis
    • Mechanism of action:
      • Inhibits calcium channels
      • Enhances GABA (gamma-aminobutyric acid) activity

    Clonazepam Usage

    • Used to treat myoclonic seizures, often as an addition to other drug therapies or as a first-line treatment

    Pharmacokinetics

    • Rapidly absorbed into the bloodstream when taken orally, with peak levels reached within 2-4 hours
    • IV administration produces rapid effects on the central nervous system
    • 50% bound to plasma proteins
    • Extensively metabolized
    • Half-life of 30-40 hours

    Side Effects

    • Sedation
    • Ataxia (loss of muscle coordination)
    • Behavioral disturbances
    • Hyperactivity
    • Irritability
    • Difficulty concentrating
    • Depression
    • Increased secretions

    Important Considerations

    • Abrupt discontinuation may precipitate generalized seizures activity

    Diazepam

    • Used as a mainstay for treating status epilepticus and local anesthetic-induced seizures
    • Administered at a dose of 0.1mg/kg IV every 10-15 minutes until seizure activity is suppressed
    • Has a half-life of 27-48 hours
    • Undergoes metabolism to form active metabolites
    • Common side effect is sedation
    • Maximum dose is 30 mg

    Lorazepam

    • Used to treat status epilepticus and seizure clusters
    • Available in oral and IV forms
    • Has a half-life of 8-25 hours
    • Metabolized in the liver, but does not produce active metabolites
    • Common side effect is sedation
    • Has a longer duration of antiepileptic activity compared to diazepam due to slow redistribution

    Antiepileptic Drugs

    • Diazepam: used for status epilepticus and local anesthetic-induced seizures; pharmacokinetics: half-life 27-48 hours, metabolism to active metabolites; side effects: sedation; max dose 30mg.

    Carbamazepine

    • Uses: partial and generalized seizures, trigeminal and glossopharyngeal neuralgia
    • Pharmacokinetics: oral only, peak 2-6 hours, 80% protein binding, half-time 8-24 hours, hepatic metabolism to active metabolites
    • Notes: induces its own metabolism, may require dosage increase, induces metabolism of oral contraceptives, valproic acid, corticosteroids, anticoagulants, and antipsychotics; inhibited by cimetidine, propoxyphene, diltiazem, verapamil, isoniazid, and erythromycin

    Eslicarbazepine

    • Use: partial-onset seizures
    • Pharmacokinetics: oral administration, peak 2-4 hours, 40% protein bound, 90% renal excretion
    • Side effects: N/V, diarrhea, fatigue, dizziness
    • Notes: contraindicated in patients with 2nd and 3rd degree AV block; carbamazepine and phenytoin reduce plasma concentration through enzyme induction

    Ethosuximide

    • Use: drug of choice for absence (petit mal) epilepsy without tonic-clonic seizure
    • Pharmacokinetics: oral administration, peak 1-7 hours, 25% excreted unchanged in urine with remainder metabolized by liver, half-time 20-60 hours
    • Side effects: N/V, lethargy, dizziness, ataxia, photophobia, hyponatremia, and bone marrow suppression (rare)
    • Notes: works by decreasing calcium conductance in thalamic nuclei

    Felbamate

    • Use: intractable epilepsy
    • Pharmacokinetics: mostly excreted unchanged by the kidneys, half-life 20 hours, 25% protein binding
    • Major side effects: aplastic anemia, hepatotoxicity
    • Notes: requires monitoring of blood counts and liver function; carbamazepine and phenytoin decrease plasma concentration; felbamate is a potent inhibitor of P450 enzymes and can slow metabolism of phenytoin, phenobarbital, and valproic acid

    Gabapentin

    • Use: seizures (limited efficacy), anxiety, panic, and major depression
    • Pharmacokinetics: half-life 6 hours, 0% protein binding
    • Side effects: sedation and GI disturbances
    • Notes: analog of GABA but does not bind to GABA receptors, probably works by inhibition of calcium channels

    Other Antiepileptic Drugs

    • Lamotrigine: stabilizes voltage-gated sodium channels; pharmacokinetics: half-life 25 hours, 50% protein binding
    • Levetiracetam: binds to calcium channels and reduces release of neurotransmitters; pharmacokinetics: no hepatic metabolism and minimal protein binding
    • Perampanel: selective non-competitive antagonist of AMPA receptors; pharmacokinetics: 95% protein bound, elimination half-life 110 hours
    • Phenobarbital: postsynaptic potentiation of GABA and inhibition of glutamate; pharmacokinetics: oral absorption nearly 100%, protein binding 50%, 25% elimination by pH-dependent renal excretion and 75% hepatic
    • Phenytoin: regulates sodium and calcium transport; pharmacokinetics: oral and IV administration, high therapeutic index with minimal sedation, 90% protein bound, 9-40 hour half-life
    • Stiripentol: increases GABA activity; pharmacokinetics: rapidly crosses BBB and accumulates in medulla and cerebellum, 99% protein binding, 10-15 hour half-life
    • Tiagabine: potent inhibitor of GABA reuptake; pharmacokinetics: 95% protein binding, 5-8 hour half-life
    • Topiramate: inhibits voltage-gated sodium and calcium channels and glutamate; pharmacokinetics: minimal protein binding and does not affect P450 enzymes
    • Valproic acid: affects voltage-gated sodium channels; pharmacokinetics: oral administration, peaks in 1-4 hours, 85% protein binding, half-time 7-17 hours
    • Vigabatrin: irreversible inhibition of GABA transaminase enzyme; pharmacokinetics: not protein bound and undergoes very little metabolism
    • Zonisamide: calcium inhibition and enhancement of GABA; pharmacokinetics: hepatic metabolism, 50% protein binding, 50-70 hour half-life

    Clobazam

    • Used to treat complex partial seizures, tonic-clonic seizures, and myoclonic seizures
    • Metabolized by the liver to produce active metabolites
    • Half-life of 16-18 hours
    • Known for causing sedation, but to a lesser extent compared to other benzodiazepines
    • Important to discontinue gradually to avoid withdrawal symptoms

    Levodopa in Parkinson's Treatment

    • Levodopa is the cornerstone of symptomatic treatment for Parkinson's disease.
    • It is a precursor to dopamine that crosses the blood-brain barrier (BBB) and is converted to dopamine by aromatic-L-amino-acid decarboxylase.
    • Levodopa replenishes dopamine stores within the basal ganglia.

    Pharmacokinetics

    • Requires frequent dosing due to a half-life of 1-3 hours.
    • Beneficial effect typically diminishes 5-10 years after treatment initiation.
    • Abrupt discontinuation can result in a quick return of Parkinson's symptoms and Parkinsonism-Hyperpyrexia syndrome.

    Administration

    • Usually given with a peripheral decarboxylase inhibitor (carbidopa or benserazide) to maximize entrance into the brain before conversion.

    Metabolism

    • 95% of an orally administered dose is rapidly decarboxylated to dopamine with initial passage through the liver.
    • Inhibition of peripheral decarboxylase enzyme increases the fraction available for cross through the BBB.
    • Most metabolites are converted to dopamine, with some to norepinephrine and epinephrine.
    • Further metabolism of dopamine yields 3,4-dihydroxyphenylacetic acid.
    • Dietary methionine is necessary for continued action of COMT to metabolize.

    Side Effects

    • Nausea and hypotension are common side effects within the first weeks of therapy.
    • Long-term effects include dyskinesia, mobility changes, confusion, and psychosis.
    • Excessive dopamine can lead to side effects.
    • N/V occurs in up to 80% of patients and reflects action of dopamine on the CRTZ.
    • Domperidone is the most effective treatment for N/V and does not cross the BBB.
    • Other dopamine antagonists that cross the BBB (e.g., prochlorperazine, metoclopramide, and promethazine) must be avoided in patients with Parkinson's.

    Cardiac Side Effects

    • Alpha and beta stimulation from increased dopamine, epinephrine, and norepinephrine.
    • Flushing of the skin, orthostatic hypotension (30% of patients), and cardiac dysrhythmias.

    Abnormal Involuntary Movements

    • Develop within 1-4 months of therapy in 50% of patients.
    • Tolerance does not develop to this side effect.
    • Includes movements such as rocking of the arms, legs, or trunk, irregular respiratory movements, facial tics, and grimacing.

    Interactions and Contraindications

    • High protein meals should be avoided because amino acids can interfere with transport of Levodopa to the brain.
    • Sudden withdrawal can result in a neuroleptic malignant-like disorder characterized by rigidity, pyrexia, autonomic instability, and decreased LOC.
    • Other complications may include aspiration pneumonia, pulmonary embolism, venous thrombosis, renal failure, and death.

    Psychiatric Disturbances

    • May reflect progression of the disease or from pharmacologic therapy and usually begins with a nocturnal pattern.
    • Drug interactions may occur with the use of Levodopa therapy.
    • Antipsychotics such as butyrophenones and phenothiazines can antagonize the effects of dopamine and should not be administered to patients with Parkinson's.
    • Droperidol and Metoclopramide can also interfere with dopamine activity.
    • Nonspecific MOAI interfere with inactivation of catecholamines, including dopamine, and can exaggerate the peripheral effects of levodopa.
    • Anticholinergics work synergistically with levodopa, but in large doses may interfere with levodopa absorption within the GI tract.
    • Pyridoxine can abolish the efficacy of levodopa by enhancing pyridoxine-dependent dopa decarboxylase metabolism of levodopa prior to entry within the CNS.

    Peripheral Decarboxylase Inhibitors

    • Carbidopa or benserazide are used with levodopa to prevent metabolism before entering the CNS
    • These inhibitors don't cross the BBB and have no effect when used alone
    • They reduce peripheral side effects of levodopa therapy but don't affect abnormal involuntary movements or psychiatric disturbances
    • Examples of combinations include Sinemet and Madopar

    Catechol-O-Methyltransferase (COMT) Inhibitors

    • COMT inhibitors (tolcapone and entacapone) increase plasma concentrations of levodopa or carbidopa by 10-15%
    • Side effects include induced dyskinesias, nausea and vomiting, hepatotoxicity (tolcapone), rhabdomyolysis (tolcapone), and orange urine (entacapone)

    Synthetic Dopamine Agonists

    • Examples include pramipexole, ropinirole, rotigotine, and bromocriptine
    • These drugs don't require transformation or facilitated transport across the BBB
    • Side effects include visual and auditory hallucinations, hypotension, dyskinesia, pleuropulmonary fibrosis, erythromelalgia, vertigo, and N/V
    • Abrupt discontinuation can result in parkinsonism-hyperpyrexia syndrome

    Anticholinergics

    • Examples include trihexyphenidyl and benztropine
    • They blunt the effects of acetylcholine and are primarily used to treat tremor
    • Side effects include hallucinations, confusion, sedation, mydriasis, cycloplegia, adynamic ileus, and urinary retention

    Amantadine

    • Antiviral used for influenza A prophylaxis that also improves Parkinson's disease symptoms by unknown mechanisms
    • It may increase dopamine release and slow its reuptake, as well as promote anticholinergic effects and antagonize glutamate & NMDA
    • Has better effects on skeletal muscle rigidity and bradykinesia than anticholinergic drugs
    • Side effects include ankle edema, livedo reticularis of the legs, confusion, psychosis, and potential cardiac failure

    Monoamine Oxidase Type B (MAO-B) Enzyme Inhibitors

    • Examples include selegiline, rasagiline, and safinamide
    • MAO-B enzyme blockade increases the half-time of dopamine within the CNS
    • Selegiline doesn't affect norepinephrine metabolism and thus doesn't result in life-threatening potentiation of its effects
    • Side effects include confusion, depression, paranoia, and insomnia
    • Rasagiline and safinamide carry a theoretical risk of serotonin syndrome, and tyramine avoidance is recommended

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