Recent

  • Show all results for ""

🎧 New: AI-Generated Podcasts Turn your study notes into engaging audio conversations. Learn more

Neuro pharm
138 Questions
10 Views

Neuro pharm

Created by
@YouthfulPorcupine

Podcast Beta

Play an AI-generated podcast conversation about this lesson

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

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    More Quizzes Like This

    Challenge Your Pharmaceutical Calculation Skills with this Carbamazepine Supposi...
    3 questions

    Challenge Your Pharmaceutical Calculation Skills with this Carbamazepi...

    HilariousTeal avatar
    HilariousTeal
    Carbamazepine Quiz
    64 questions

    Carbamazepine Quiz

    IndulgentChaparral avatar
    IndulgentChaparral
    Pharmacology of Carbamazepine
    10 questions

    Pharmacology of Carbamazepine

    SparklingDahlia avatar
    SparklingDahlia
    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser