!Neuropharm Antiepileptics Flashcards
Benzodiazepines first line
Acute status epilepticus
Benzodiazepines second line indications
Eclampsia seizures
Can also be used for alcohol detoxification
Suffix of benzodiazepines
Pam
Examples of benzodiazepines
Diazepam, lorazepam, triazolam, temazepam, oxazepam, midazolam, and chlordiazepoxide
How do benzodiazepines work
Bind to the BZd site not he GABAa Cl channels, leading to increased frequency of the Cl channel opening . Leading to neuronal membrane hyperpolarization and decrease in CNS excitability
Side effects of benzodiazepines
Decreased REM sleep
CNS depression
Dependence
How do you treat a benzodiazepine overdose
Flumazenil
Why do benzodiazepines treat status epilepticus first line
Fast acting , strong, and potent anticonvulsant drugs
Midazolam
IV used to induce anesthesia
Also cause relaxation
Causes anterograde amnesia
Benzodiazepine and anxiety
Acute use as anxiolytics
Not used one term due to risk of dependence
Benzodiazepines and eclampsia
Second line if magnesium sulfate is contraindicated.
Benzodiazepines and detoxification
Treat alcohol detox to prevent withdrawal symptoms
What benzodiazepines treat alcohol detox
Diazepam and chlorodiazepoxide
What are the two suffix of benzodiazepine
Zelma Zola’s
Name a benzodiazepine without the usual suffix
Chlorodiazepexide
How do diazepine work
Bind GABAA Cl receptor complex
Leads to Cl channel opening and increased frequency, yielding a higher chloride conductance
Causes neuronal membrane hyperpolarization and decreased CNS excitation
Sleep and benzodiazepines
Decrease REM but also sleep more
Benzodiazepine and CNS depression
ESP when combined with alcohol and other drugs
Alcohol binds GABAA like benzodiazepines
Benzodiazepine overdose
Dangerous
Espicially in combination with alcohol, barbiturates, opioids or tricyclics antidepressants
Symptoms of benzodiazepine overdose
CNS depression and intoxication with impaired balance, ataxia,and slurred speech
Respiratory distress, coma
Treat benzodiazepine overdose
Supportive care and flumazenil
How does flumazenil work
Benzodiazepine receptor antagonist which reverses the effects of benzodiazepine by competitive inhibition at the benzodiazepine binding site on the GABA receptor
Barbiturates
Barb in name
Wide range of uses and side effects
Indication for barbiturates
Seizure (simple and complex partial seizures as well), generalized tonic-clonic seizures
Thiopental barbiturate
Fast acting medication used for anesthesia induction
How do barbituates work
Potentiating GABAa, leading to increased chloride channel opening duration.leading to decreased neuronal firing.
Barbiturates increase the ____of chloride channel opening, whereas benzodiazepines increase __ of chloride channel opening
Duration
Frequency
Side effects of barbiturates
Sedation, grogginess
Respiratory and cardiac depression, which can progress to respiratory arrest and low blood pressure in patients who overdose or recreationally use barbiturates
CNS depression
If take with ethanol-additive adverse effects
Induce cytochrome P450 enzyme complex and may affect the metabolism of other medications
Examples of barbiturates
Barb Phenobarbital Pentobarbital Secobarbital Anesthetic thiopental
Exception to barb name barbiturate
Thiopental-an anesthetic
Indications for barbiturate
Seizure control and anesthesia induction
What barbiturate use for seizure treatment -epilepsy, simple and complex seizures and generalized tonic-clonic seizures
Phenobarbital
Nick name of IV injected thiopental
Truth serum bc patients divulge sensitive information
Barbiturates : by increasing CL channel opening duration, __ __ is decreased
Neuronal firing
Barbiturates often mimic __
Ethanol
Can lead to severe cardiovascular depression
(Respiratory arrest and low bp in patients who abuse these drugs)
What happens when barbiturates increase p450
Clearance of such drugs from blood also increased. Therefore barbiturates can shorten the effects of other administered drugs making them less effective
Phenobarbital
Treat seizures acting onGABA receptors to inhibit excitatory neuronal firing
Side effect phenobarbital
CNS depression , drowsiness, fatigue, ataxia , paradoxical excitement
Why should you check blood levels of the drug
To avoid overdose
Huge concern with phenobarbital
High potential for recreational abuse with phenobarbital
Other use for phenobarbital
CNS depression is what it does
Daytime sedation and induction of sleep and anesthesia
Ataxia from phenobarbital
High doses
Also show nystagmus
Paradoxical excitement with phenobarbital
Espicially kids
Can get hyperactivity or “paradoxical excitement”
Important to ensure a calm environment
Phenytoin
Antiepileptic medication used to treat generalized tonic clonic (grand mal) seizures and during status epilepticus.
How does phenytoin work
Blocking sodium channel activation in neuronal membranes leading to an inhibition of glutamate release and resultingly, enhanced GABA release
Phenytoin is categorized as and also has use as a class IB ___ medication
Antiarrhythmic
Side effects phenytoin
Teratogenic-fetal hydantoin syndrome Induces cytochrome p45- Decreases folate levels-megaloblastic anemia Drug induced lupus Neurological symptoms Hirsutism-women who use it one term Gingival hyperplasia
Indications for phenytoin
2nd line-status epilepticus (when benzodiazepines fail)
1st line-generalized tonic-clonic (grand mal) seizures
MOA phenytoin
Blocks Na channel activation on neuronal cell membrane
Increases sodium channel inactivation
Decreasing lux of sodium ions across the Neuronal membrane
Limits spread of seizure activity and reducing propagation
Also stabilizes the threshold against hyperexcitability caused by excessive stimulation or environmental changes
As a consequence of blocking na channel activation, phenytoin inhibits ___ release from excitatory presynaptic neurons and enhances __ release
Glutamate
GABA
Teratogen effects of phenytoin
Fetal hydantoin syndrome
What is fetal hydantoin syndrome
Intrauterine growth restriction, microcephalic, craniofacial deformities, developmental delay
How does phenytoin cause microcytic megaloblastic anemia
Decreases folate levels
What do patients with drug induced lupus from phenytoin have
Anti histone antibodies
__ use of phenytoin can lead to peripheral neuropathy whale ataxia and diplopia can be seen with __ use of phenytoin
Chronic
Acute
Long term use of phenytoin may lead to women with facial hair, ___
Hirsutism
What percent of patients taking phenytoin have gingival hyperplasia
50
Valproic acid (valproate)
Anticonvulsant and mood stabilizing drug that works by increasing GABA concentration and blocking Na channels
Indications for valproic acid
Epilepsy, bipolar, migraine prophylaxis
How does valproic acid work
Increases GABA by inhibiting the enzyme GABA transaminase, which acts to break down GABA
Also valproic acid decreases repetitive neuronal firing by blocking what
Voltage gated Na channels
Side effects valproic acid
GI distress
Hepatotoxic
Pancreatitis
Who should not have valproic acid
Pregnant women-teratogenic and a folate antagonist and can lead to neural tube defects
First line valproic acid
Tonic-clonic seizures and can also be used for absence, myoclonic and partial seizure treatment
Bipolar and valproic acid
Totally
Migraine prophylaxis and valproic acid
Totally
Valproic acid MOA
Increases GABA concentration by inhibiting GABA transaminase, an enzyme which acts to break down GABA
Blocks voltage gated Na channels
Suppressing repetitive neuronal activity preventing Na influx though fast channels
Side effects valproic acid
VALPROATE Vomiting Alopecia Liver toxicity Pancreatitis/pancytopenia Retain fat (weight gain Oedema (edema) Appetite increase Tremor Enzyme inhibitor (P450)
Manage liver with valproic acid
Check AST/ALT before and during treatment
Pancytopenia valproic acid
Blood dyscrasias like anemia, leukopenia, and thrombocytopenia
Do a CBC found regularly
Valproic acid and p450 inhibitor
Increase circulating amounts of other medications that would normally be metabolized
Liver disease patients-dosage decrease
Topiramate
Epilepsy drug used in the treatment of partial seizures, and generalized tonic-clonic seizures
What is the most common cause to prescribe topiramate
Migraine prophylactic
Topiramate potentials __. What does this do
GABA, augmenting its Action on the GABAa receptor.
Topiramate also induces a block of _ channel
Coltage gated Na
Side effects topiramate
Kidney stones, weight loss and sedation
Indications for topiramate
Seizure control
Migraine prophylaxis
Can topiramate be used for weight loss
Yup and its FDA approved when combined with phentermine
Carbamazepine
Anticonvulsant drug used as a first line agent against seizure and trigeminal neuralgia
Also a mood stabilizer in bipolar
How does carbamazepine work
Blocking Na channel activation, stabilizing channels in an inactivated state, in a mechanism similar to phenytoin
Side effects carbamazepine
SJS-dangerous hypersensitivity reaction affecting skin and mucous membranes
Hepatotoxicity-affecting the glutathione pathway
Blood dsycrasias-anemia and agranulocytosis
Inducer of cytochrome p450
Teratogen -neural tube defects /other birth defects
First line indications for carbamazepine
Simple and complex partial seizures
Trigeminal neuralgia
Second line carbamazepine
Neuropathic pain syndromes
Tonic-clonic generalized seizures
Mood stabilizer
How does carbamazepine work
Stabilizing the inactivated state of voltage gated sodium channels, leaving cells less excitable and decreasing conductance.
Similar mechanism to phenytoin
SJS
Hypersensitivity complex involving the skin and mucous membranes
Carbamazepine and cytochrome p450
Increasing metabolism and reducing half life
May also accelerate clearance of other drugs
Teratogen carbamazepine
Spina bifida, craniofacial abnormalities, Cardiovascular and urinary tract anomalies
Carbamazepine and hepatotoxicity
Bc causes disturbance in glutathione metabolism which may occur as a result of accumulated toxic metabolites
Can be fatal , but rapidly reversed by stopping therapy
Carbamazepine and blood dyscrasias
Rare side effect of carbamazepine includes blood dyscrasias such as agranulocytosis and aplastic anemia
Lamotrigine
Anticonvulsant medication used to treat simple ad complex partial seizures, as well as generalized tonic-clonic seizures Mood stabilizing (bipolar type I)
Off label indications for lamotrigine
Neuropathic, migraine and personality disorders
How does lamotrigine work
Block voltage sensitive Na channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of glutamate and aspartate , which are excitatory aa (glutamate is a precursor to GABA)
Side effects lamotrigine
SJS
What is the effect of lamotrigine blocking voltage gated Na channels
Modulated presynaptic transmitter release of glutamate and aspartate, which are excitatory aa
Ethosuximide
Anticonvulsant medication used to treat absence seizures, or petit mal seizures, which are mostly seen in school age kids
First line indication for ethosuximide
Neurological disorder, and is preferred over similar drugs bc it does not cause hepatotoxicity
MOD ethosuximide
Blocking thalmic t type ca channels leading to decreased neuronal transmission
Side effects ethosuximide
SJS
First line ethosuximide
Absence seizure treatment (petit mal seizures) and is preferred over other agents bc it does not cause hepatotoxicity
T type channels
Blocked by ethosuximide
They serve peacemaking functions in both central neurons and support calcium signaling and are also involved int he modulation of firing patterns of neurons
Side effects ethosuximide
SJS
Fatigue
Diarrhea
