Term
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Definition
Barbiturates- seizures/sedatives
-"tals", phenobarbital
Benzodiazepines
-"pams', diazepam
Benzodiazepine-like drugs
-zolpidem |
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Term
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Definition
Barbiturate
MOA - potentiate/amplifies the actions of GABA (gamma-amino-butyric acid), and directly mimic GABA
Pharmacokinetics - variety of differences between each drug, allows for different clinical applications
Indications - Seizures, Sedatives, Anesthesia, off label for alcohol withdrawal |
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Term
| Barbiturate adverse effect profile |
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Definition
CNS Depression (respiratory)
-paradoxical in pediatrics
Cardiovascular
-sedative doses can cause lower BP and HR
-toxic doses cause profound hypotension and shock
Physical Dependence/Tolerance
-EtOH, benzodiazepines, barbiturates
-Tolerance to therapeutic effect, not respiratory depression
***CYP-450 Inducers*** |
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Term
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Definition
| Benzodiazepines MOA - potentiate/amplifies the actions of GABA (gamma-amino-butyric acid), does NOT directly mimic GABA Pharmacokinetics - variety of differences between each drug, allows for different clinical applications Indications -Anxiety, GAD, Insomnia, Seizure Disorders, Muscle Spasms, Alcohol Withdrawal, Peri-Operative (anesthesia, conscious sedation) |
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Term
| Barbiturate key differences |
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Definition
-Classified as ultra-short, short to intermediate, long acting
-ultra-short methohexital- see this in induction
-secobarbital- sedative for insomnia
-phenobarbital- seizures |
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Term
| Benzodiazepine key differences |
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Definition
-Classified as short, intermediate, long acting
-onset (fast or slow)
-Metabolites (lorazepam has none) |
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Term
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Definition
-acts as depressant in the CNS
-reduce anxiety by acting in the limbic system
-promote sleep by acting on cortical areas
-induce muscle relaxation through effects on supraspinal motor areas
-acts on hippocampus and cerebral cortex and this is why we see confusion, and anterograde amnesia |
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Term
| Benzodiazepine adverse effect profile |
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Definition
-Paradoxical effects- insomnia, anxiety, rage
-Abuse potential, controlled substance
-respiratory depression with high dose (IV) combined with other drugs
-cardiovascular- profound hypotension (IV)
REVERSAL AGENT
flumazenil (Romazicon®) |
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Term
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Definition
Misc anxiolytic drug
MOA - Exact mechanism is unknown. Has NO BZD properties. The drug has high affinity for serotonin receptors and lower affinity for dopamine receptors/
Pharmacokinetics - anxiolytic effects develop slowly- initial response~ 1 week, peak effect 4 weeks
Indications -Generalized Anxiety Disorder (interestingly, only meant for short term use - 1 year), NOT for immediate relief or PRN use, off-label use to augment antidepressants
Adverse effects -well tolerated (dizziness, headache, nausea), paradoxical nervousness/excitement, very little risk or no risk for suicide |
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Term
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Definition
-does have some CYP metabolism - avoid Grapefruit juice, levels can be increased by CYP inhibitors
-not a controlled substance
-no abuse potential
-no CNS depression
-no immediate response |
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Term
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Definition
Benzodiazepine like Drugs
MOA - different molecular structure vs benzos, but same MOA, they act as agonists at the benzodiazepine1 receptor (BZ1)
Pharmacokinetics - rapid onset, long enough duration to last throughout the night
Indications - Insomnia, Difficulty Falling Asleep (DFA), Difficulty Maintaining Sleep (DMS)--exception is zaleplon- Sonata®-short acting
Adverse effects - Same as seen with benzodiazepines, hangover effect, drowsiness, CNS depression, complex sleep-related behaviors |
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Term
| Benzodiazepine-like drug considerations |
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Definition
-Controlled Substances (C-IV), low potential for dependence, tolerance and abuse
-Long Term Use?, typically meant for 2-3 weeks (Lunesta® is approved for long term use) |
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Term
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Definition
melatonin/melatonin agonists
MOA -melatonin - hormone produced by pineal gland to regulate circadian rhythm
ramelteon- melatonin1 receptor agonist
Pharmacokinetics - rapid onset (Can't use for DMS)
Indications -Insomnia, Difficulty Falling Asleep (DFA), Chronic insomnia
Adverse effects - relatively safe drugs- very few adverse effects (1 case report of reversible psychosis when large amount was ingested during the day), No rebound insomnia seen |
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Term
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Definition
Simple (no loss of consciousness)
Complex (consciousness impaired)
Secondarily Generalized |
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Term
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Definition
Absence
Myoclonic
Tonic
Tonic-Clonic
Atonic
Infantile Spasms |
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Term
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Definition
I. Partial
II. Generalized
III. Unclassified
IV. Status epilepticus |
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Term
| 4 main mechanisms of action of antiepileptic drugs |
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Definition
-Blocking of Na+ influx
-Blocking of Ca++ influx
-Antagonizing glutamate activity
-Enhancing GABA activity |
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Term
| Antiepileptic drug selection |
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Definition
(monotherapy first)
-Trial Perioid
-Monitoring Drug Levels (adherence, adverse effects)
-Titrate down to lowest effective dose
-ABRUPT DISCONTINUATION CAN CAUSE SEIZURES- COMPLIANCE! |
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Term
| Antiepileptic drug boxed warning |
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Definition
Warning about increased suicidal thoughts/behavior
-based on 199 placebo controlled studies (43,892 patients)
-AED's vs placebo (0.43%-0.22%) |
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Term
| Antiepileptics - Traditional vs. Newer Generation drugs |
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Definition
Traditionals
-Used for decades- well documented and studied
-Higher risk for developing fetus
-Hepatic enzyme involvement (drug-drug!)
Newer Generation
-May have less risk for developing fetus
-Less drug-drug interactions |
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Term
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Definition
Traditional antiepileptics-hydantoins
MOA - selective inhibition of sodium channels
Pharmacokinetics - non-linear, saturable kinetics; narrow therapeutic index; enzyme inducer
Indications - All types of seizures except absence
Drug of choice in adults and older children, Cardiac dysrhythmias, Status epilepticus
Adverse effects - Hirsutism; Skin Rash*; Sedation*; Gingival Hyperplasia; 20% patients, folic acid supplementation and good oral hygiene; Teratogenic!- Pregnacy Category D; Neurologic Effects- Nystagmus, Ataxia, diplopia; BOXED WARNING: Too rapid infusion can cause dysrhythmias/hypotension ***Narrow therapeutic index - 10-20 mcg/mL***
Well known enzyme inducer - oral contraceptives, warfarin |
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Term
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Definition
Stevens Johnson Syndrome
Toxic Epidermal Necrolysis
The condition appears to be mainly caused by drugs. Early catching and discontinuation of the offending drug is essential |
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Term
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Definition
PS PORCS
P-phenytoin
S- Smoking
P- phenobarbital
O- oxcarbazepine
R- rifampin
C- carbamazepine
S- St. Johns wort (an over the counter herbal supplement) |
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Term
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Definition
PACMAN loves grapefruit juice
P- Protease Inhibitors
A- Azole antifungals
C-cimetidine
M- Macrolides
A- Amiodarone
N- Non-DHP calcium channel blockers
Grapefruit Juice |
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Term
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Definition
Traditional antiepileptics - barbiturates
MOA - potentiate/amplifies the actions of GABA (gamma-amino-butyric acid), and directly mimic GABA (prolongs duration of channel opening)
Pharmacokinetics - variety of differences between each drug, allows for different clinical applications
Indications - Seizures (phenobarbital), Sedatives, off label for alcohol withdrawal
Adverse effects -
Can cause fetal malformations
CNS Depression (respiratory)
-paradoxical in pediatrics
Cardiovascular
-sedative doses can cause lower BP and HR
-toxic doses cause profound hypotension and shock
Physical Dependence/Tolerance
-EtOH, benzodiazepines, barbiturates
-Tolerance to therapeutic effect, not respiratory depression |
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Term
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Definition
Traditional antiepileptics - Iminostilbenes
MOA - Blockade of Na+, possibly Ca++ and K+ channels
Pharmacokinetics - enzyme AUTO inducer
narrow therapeutic index
Indications -Tonic-clonic, simple partial and complex partial seizures, Bipolar disorder, Trigeminal and glossopharyngeal neuralgias
Adverse - Visual effects – nystagmus, blurred vision, diplopia; Ataxia, vertigo, unsteadiness; Headache |
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Term
| carbamazepine considerations |
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Definition
BOXED WARNING: Bone marrow suppression that leads to hematological effects- Aplastic anemia and agranulocytosis
BOXED WARNING: Severe Rash (FDA recommends genetic screening) HLA-B*1502 allele in Asian descent
Teratogenic*- Pregnancy Category DDRUG-DRUG INTERACTIONS
Oral Contraceptives, Warfarin
Grape Fruit Juice- avoid!!!!!
can increase levels by 40% |
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Term
| valproic acid/divalproex sodium/valproate |
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Definition
Traditional antiepileptics
MOA - Blockade of Na+, Ca++ channels AND may potentiate effects of GABA
Pharmacokinetics - hepatic metabolism
Indications - Epilepsy – useful against all types of seizures; Bipolar disorder; Migraine prevention; Lots of off label uses; Adverse effects - Pancreatitis; Fetal Harm; Hepatotoxicity |
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Term
| Valproic acid adverse effect profile |
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Definition
-GI – nausea, vomiting (use enteric coating)
-BOXED WARNING: Hepatotoxicity
-BOXED WARNING: Pancreatitis
-BOXED WARNING: Fetal Harm
-BOXED WARNING: patient with mitochondrial disease increased risk for liver failure
mitochondrial DNA polymerase gamma (POLG) gene (Alpers-Huttenlocher syndrome)
-Teratogenic- Pregnancy Category D
-Risk is 4 times greater than other AEDs
-Neural Tube Defects- 1 in 20 women (vs 1 in 1000 general population)
Spina Bifida
Cleft Palate
Several more |
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Term
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Definition
Newer antiepileptic
MOA - inhibits release of glutamate (an excitatory amino acid) and inhibits voltage-sensitive sodium channels, which stabilizes neuronal membranes
Pharmacokinetics - hepatic metabolism
Indications - Epilepsy, bipolar
Adverse effects - BOXED WARNING: LIFE THREATENING SKIN RASHES***(0.3-0.8% of patients develop these- FATAL?); Pregnancy Category C (When used in pregnancy- cleft lip/palate); N/V, diplopia, blurred vision; Higher risk for Suicidal Ideation vs AEDs |
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Term
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Definition
Newer antiepileptic
MOA - Blocks neuronal voltage-dependent sodium channels, enhances GABA(A) activity, antagonizes glutamate receptors
Indications - Epilepsy; Migraines/Cluster Headaches; Off label: weightloss
Adverse effects - weight loss/anorexia; suicidal ideation?; somnolence, dizziness, diplopia; When used in pregnancy-(0.07-1.4%) cleft lip/palate |
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Term
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Definition
| Newer antiepileptic MOA - structurally related to GABA but does NOT bind to GABA receptors. MOA is complex, believe to delay release of excitatory neurotransmitters (involved in epilepsy and nociception) Indications - Epilepsy; Postherpetic neuralgia Off label - Diabetic Neuropathy; Hot Flashes; Post-Op Pain; Restless Legs Syndrome; Social Anxiety Adverse effects - Somnolence, dizziness (caution with CNS depressants) |
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Term
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Definition
Newer antiepileptic
MOA - UNKNOWN!
DOSE - 500-1500 mg BID (efficacy of >3000 mg/day has not been established)
Pharmacokinetics - linear, IV-PO ~1:1, loading doses
Adverse effects - Behavioral Problems; increased BP; CNS depression |
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Term
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Definition
Newer antiepileptic
MOA - stabilizes hyperexcitable neuronal membranes and inhibits repetitive neuronal firing by enhancing the slow inactivation of sodium channels
DOSE - 100-200 mg BID / Loading dose - 200-400 mg or weight-based
Pharmacokinetics - IV-PO ~1:1
Adverse effects - 1%- euphoria; CNS sedation; Prolong PR interval; Ophthalmic:diplopia, nystagmus |
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Term
| Status epilepticus treatment |
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Definition
| BZDs - diazepam and lorazepam most commonly recommended as first line |
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Term
| Considerations of Traditional vs. Newer antiepileptics |
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Definition
ENZYME INDUCTION
ADVERSE EFFECTS
PREGNANCY
MONITORING LEVELS |
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Term
| Narrow therapeutic index drugs |
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Definition
Carbamazepine
Digoxin
Lithium
Phenytoin
Theophylline
Warfarin |
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