Drug Drills, CNS Drugs Flashcards
Which type of seizure(s) does carbamazepine treat?
Simple Partial seizures
Complex Partial seizures
Tonic-Clonic seizures
Which type of seizure(s) does phenobarbital treat?
Partial seizures
Generalized Tonic-Clonic seizures
Which type of seizure(s) does phenytoin treat?
Partial seizures
Generealized Tonic-Clonic Seizures
p.155
Which type of seizure(s) does valproic acid treat?
Partial seizures
Tonic-Clonic Seizures
Absence Seizures
Which traditional anti-seizure drug(s) can be used to treat all major seizure types?
Valproic Acid
Which newer anti-seizure drug can be used to treat all major seizure types?
Lamotrigine
Which type of seizure(s) does gabapentin treat?
Partial Seizures
Which type of seizure(s) do topiramate treat?
Partial Seizures
Tonic-Clonic Seizures
Which type of seizure(s) does felbamate treat?
Parital Seizures
Which type of seizure(s) does ethosuximide treat?
Absence Seizures
Which anti-seizure drug(s) are associated with an increase in suicidal thoughts and behaviors?
Topiramate
Lamotrigine
Which anti-seizure drug(s) decrease effectiveness of oral contraception?
Carbamazepine Phenytoin Phenobarbital Topiramate Lamotrigine
(Caribbean Pirates Pillage Treasure Loudly)
Which anti-seizure drug(s) is absolutely contraindicated during pregnancy?
Valproic acid
Which supplement should be taken throughout pregnancy before and in conjunction with anti-seizure medication?
Folic Acid
Which class of anti-seizure medication has greater risks to developing fetus (traditional or newer)?
Traditional
Which class of anti-seizure medication is less expensive (traditional or newer)?
Traditional
Which class of anti-seizure medication has greater drug/drug interactions (traditional or newer)?
Traditional
Which class of anti seizure medication has fewer side effects (traditional or newer)
Newer
Which class of anti-seizure medication has fewer drug/drug interactions (traditional or newer)
Newer
Which class of anti-seizure medication is safer during pregnancy (traditional or newer)?
Newer
Which class of anti-seizure medication is generally better tolerated (traditional or newer)?
Newer
What is the drug of choice for treating tonic-clonic seizures in adults and older children?
Phenytoin
What is the drug of choice for treating tonic-clonic seizures in young children?
Carbamazepine
Does Phenytoin have a narrow or broad therapeutic range?
Narrow (must be maintained between 10-20 micrograms/ml)
Potential serious adverse effects of Phenytoin
Gingival hyperplasia
DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), associated with HLA-B* 1502 mutation
Stevens-Johnson Syndrome
Hirsutism
Which demographic group is at highest risk for Stevens-Johnson as an adverse effect of Phenytoin?
Asian Decent
Related to HLA-B* genetic mutation
Which genetic mutation is responsible for a higher risk for Stevens-Johnson Syndrome and Toxic Epidermal Necrolyisis (TEN) in patients taking Phenytoin?
HLA-B* 1502
Can Phenytoin be prescribed to pregnant women?
Only if a safer anti-seizure medication can not produce necessary seizure control
Phenytoin is a teratogen–associated with cleft palate, heart malformations, fetal hydantoin syndrome and other physical deformities
What is the risk to newborns of mothers who took Phenytoin during pregnancy.
Bleeding tendencies–related to decreased synthesis of Vitamin K dependent clotting factors.
What is the half-life of Phenytoin?
Initially short
Extends up to 60 hours with prolonged use.
Can Phenytoin be given to breastfeeding women?
Yes
Phenytoin Black Box Warning
Related to IV use only
Hypotension and Cardiac Dysrhythmias
Phenytoin Drug Interactions
Oral Contraceptives (decreased effectiveness)
Warfarin (decreased effectiveness)
Glucocorticoids: anti-inflammatory and immunosuppressives (decreased effectiveness)
Drugs that increase Phenytoin Levels: Diazepam Cimetidine Alcohol Valproic Acid
Drugs that decrease Phenytoin Levels:
Carbamazepine
Phenobarbital
Alcohol
CNS Depressants-Add to CNS effects of Phenytoin
Enteral tube feedings-Decrease Phenytoin absorption
Is Phenytoin used as monotherapy or adjunct therapy?
Monotherapy
Which anti-seizure drug is converted to Phenytoin when metabolized?
Fosphenytoin
When is Fosphenytoin used?
Generalized tonic-clonic seizures
Partial Seizures
*When oral Phenytoin can not be used
What is half-life of Carbamazepine?
Decreases as therapy progresses.
40hours during initial phase of treatment
Decreases to about 15 hours
What time of day should Carbamazepine be administered?
Night time to decrease CNS effects
Common Adverse Effects of Carbamazepine?
Visual disturbances (nystagnus, blurred vision, diplopia) Ataxia Vertigo Unsteadiness Headache
Decrease with continued used
Potential Serious Adverse Effects of Carbamazepine?
Bone marrow suppression causing: Leukopenia Anemia Thrombocytopenia *Don't withdraw use unless severe white count drop Fatal Aplastic Anemia
Hepatic Failure
Renal Failure
Monitoring requirements for Carbamazepine?
CBC prior to treatment and periodically during treatment
Signs of hematologic abnormalities associated with Carbamazepine use?
Fever Sore throat Pallor Weakness Infection Easy Bruising Petechiae
Black Box Warning for Carbamazepine?
Risk for serious skin reactions (SJS & TEN), strongly associated with HLA-B* 1502 variant primarily in people of Asian decent.
Aplastic anemia and agranulocytosis is rare but possible.
*Genetic screening recommended by FDA prior to prescribing
Can Carbamazepine be used in pregnancy?
Only if benefits of seizure control are deemed to outweigh risks to fetus.
Teratogenic.
2.6 fold increase for neural tube defects.
What electrolyte imbalance is associated with Carbamazepine?
Hyponatremia.
Dose dependent, drug inhibits renal excretion of water
Carbamazepine drug reactions?
Oral contraceptives (decreased effect) Warfarin (decreased effect)
Phenytoin & Phenobarbital (decreases effects of Carbamazepine)
Carbamazepine food reactions?
Grapefruit juice
Increases peak and trough levels by 40%
Is Carbamazepine used as monotherapy or adjunct therapy?
Monotherapy
Is Valproic Acid used as monotheray or adjunct therapy?
Monotherapy
What anti-seizure medication is considered a first-line drug for all partial and generalized seizures?
Valproic Acid
Common side effects fo Valproic Acid?
Minimal sedation and cognitive impairment
GI effects most common (minimized with enteric-coated product)
Possible serious adverse effects of Valproic Acid?
Hepatotoxicity
Pancreatitis
Black Box warning for Valproic Acid?
Fatal hepatic failure
(young children, patents with mitochondrial disease are at increased risk)
Fatal, rapidly increasing pancreatitis has occurred (nausea, vomiting, anorexia, abdominal pain)
HIGHLY teratogenic. Neonates may have major congenital malformations and decreased mental capacity.
Contraindications for Valporic Acid
Use in children under 2 years in conjunction with other drugs
Preexisting liver dysfunction
Pregnancy
Monitoring requirements for Valporic Acid
Liver function at baseline and periodically throughout treatment.
Valporic Acid ok in breastfeeding women?
Yes
Drug interactions with Valproic Acid?
Pheonobarbital (increases level of Phenobarbital up to 40%, causing increased CNS effects)
Phenytoin (increased free Phenytoin leading to Phenytoin toxicity)
Topiramate (increases risk of hyperammonemia)
Antibiotics–Meropenem & Imipenem/Cilastatin (reduce levels of Valporic Acid)
What anti-seizure medication is devoid of significant adverse effects and interactions?
Ethosuximide
What is the drug of choice for absence seizures?
Ethosuximide
Does Ethosuximide have a short or long half life?
Long
Allows for once a day dosing but twice daily dosing is better tolerated
is Phenobarbital used as monotherapy or adjunct therapy?
Monotherapy
Phenobarbital half life long or short?
Long…4 days
Allows for once daily dosage
Requires 2-3 weeks to reach plateau plasma levels
How is Phenobarbital initially dosed to overcome time required for drug to reach plateau plasma levels?
Loading doses given for first 4 days
double dosage
What ages is Phenobarbital appropriate for?
All ages
Common side effects of Phenobarbital?
Lethargy, depression, learning impairment can be significant. Drowsiness is most common.
Confusion in older adults
Hyperexcitability in children.
Absolute contraindications for Phenobarbital?
1). Porphyria, personal or family history
Porphyria is a group of liver disorders that cause porphyrins to build up in the body, negatively affecting the skin or nervous system.
2). Significant respiratory compromise
Effects of Phenobarbital toxicity?
Moderately excessive dosing: nystagmus and and ataxia
Severe: Generalized CNS depression
Phenobarbital drug interactions?
Induces CYP drug-metabolizing enzymes, so can increase metabolism (decrease effectiveness) of ORAL CONTRACEPTIVES and others.
Other CNS depressants (intensify)
Valproic Acid-competes with phenobarbital for drug metabolizing enzymes, increasing plasma levels of phenobarbital by approximately 40% (requires dose reduction of phenobarbital when used together).
Phenobarbital safe in pregnancy?
No
Phenobarbital safe for elderly?
No
Phenobarbital safe for breastfeeding?
No
Phenobarbital safe with history of drug abuse?
No
What type of seizure(s) does Oxcarbazepine (Trileptal) treat?
Partial Seizures
Is Oxcarbazepine used as monotherapy or adjunct therapy?
Both
Monotherapy for children >/= 4
Adjunct therapy for children < 2
Potentially serious adverse effects of Oxcarbazepine?
Hyponatremia, esp with diuretics
SJS, TEN
Multi-organ hypersensitivity reactions
*Loss of bone density with long term use
Drug-drug interactions with Oxcarbazepine?
Phenytoin (increases phenytoin levels, decrease oxcarbazepine levels)
Valporic Acid & Phenobarbital-decreases levels of oxcarbazepine
Sodium depleting drugs (diuretics)-increase risk of hyponatremia
Oral contraceptives-decreased effect
Alcohol-increases CNS depression
Is Lamotrigine (Lamictal) used as monotherapy or adjunct therapy?
Both
Monotherapy for children > 16 with partial seizures who are converting from another seizure med
Adjunct in adults and children > 2
Lamotrigine (Lamictal) is a preferred drug for treating which type of seizure?
Absence
Lamotrigine (Lamictal) common adverse effects?
dizziness, diplopia (double vision), blurred vision, nausea, vomiting and headache
Potential serious adverse effects of Lamotrigine (Lamictal)?
SJS, TEN and DRESS
Risk increases with Valporic Acid
**Stop immediately if pt develops a rash
Blood dycrasias
Aseptic Meningitis (rare but serious)
Black box warning for Lamotrigine (Lamictal)?
Serious skin reactions such as SJS, TEN
Fatalities reported
Lamotrigine (Lamictal) drug interactions?
CYP enzymes-DRAMATICLLY effects half life of Lamotrigine.
Inducers (other AEDs)-decrease Lamotrigine half life to 10 hours
Inhibitors Increases-half life to about 60 hours
Estrogens-lower Lamotrigine Levels
Progestins-lowered by Lamotrigine levels
Is Gabapentin used as monotherapy or adjunct therapy?
Both
FDA approval is ONLY for ADJUNCTIVE therapy for partial seizures
Also used as monotherapy for partial seizures
Is Topiramate (Topamax) used as monotherapy or adjunct therapy?
Both
Monotherapy of adults and children >10 for:
Partial seizures
Primary generalized tonic-clonic seizures
Adjunctive in adults and children > 2 years old for:
Partial seizures
Primary generalized tonic-clonic seizures (Lennox-Gastaut syndrome)
Common adverse effects of Topiramate?
Somnolence, dizziness, ataxia, nervousness, diplopia, nausea, anorexia, weight loss
Potential Adverse Effects of Topiramate?
Metabolic acidosis (manifested by hyperventilation)
Rapid blindness
Hypohidrosis (reduced sweating), decreases exercise tolerance r/t to risk of hyperthermia
Higher risk of suicide
Is Topiramate safe in pregnancy?
No
Drug-Drug interactions with Topiramate?
Phenytoin & Carbamazepine can decrease levels of Topiramate.
Phenytoin may increase the level of Topiramate
Valproic Acid-Increases risk for hyperammonemia
Is Felbamate (felbatol) used as monotherapy or adjunct therapy?
Both
Mono & Adjunct in adults for partial seizures
Adjunct for children with Lennox-Gastaut syndrome
Black box warning for Felbamate (felbatol)
Aplastic anemia-up to 70% of useres
Acute Liver failure-rare but serious when it occurs (liver transplants required)
Common adverse effects of Felbamate (felbatol)
GI disturbances, CNS effects
More common with adjunct use
Drug-drug Interactions of Felbamate (felbatol)
Most other anti-seizure drugs
Is Pregabalin (Lyrica) used as monotherapy or adjunct therapy?
Adjunct for partial seizures
Potential serious adverse effects of Pregabalin (Lyrica)
Hypersensitivity
Rhabdomyolysis (muscle breakdown)
Abuse potential
Reproductive risks (male and female)
Can Pregabalin (Lyrica) be used in Pregnancy?
No
Drug-Drug interactions with Pregabalin (Lyrica)?
Alcohol
Benzos
Opioids and other CNS depressants
**does not appear to interfere with other antiseizure drugs
Is Levetiracetam (Keppra) used as monotherapy or adjunct therapy?
Adjunct for:
Myoclonic seizures in adults and adolescents 12 and older.
Partial-onset seizures in adults and kids 4 and older
Primary generalized tonic-clonic seizures in adults and kids 6 and older.
Potential serious adverse effects of Levetiracetam (Keppra)
Renal injury
Common side effects of Levetiracetam (Keppra)
Minimal, generally very well tolerated
Drug-drug interactions with Levetiracetam (Keppra)
None known
Which AED is particularly sensitive to very small dosage changes, producing disproportionately large changes in serum drug levels?
Phenytoin (Dilantin)
Which AED is considered the drug of choice for treating all types of seizures in adults and older children?
Phenytoin (Dilantin)
Which AED is a derivative of carbamazepine and shares most common features with it?
Oxcarbazepine (Trileptal)
True or False: Pregnancy test should be administered prior to starting AED therapy?
True
Monitoring requirments with Carbamazepine?
CBC w/diff LFT Renal Screen HLA-B* in Asian decent Assess for Rash
Contraindication for Carbamazepine?
Hx of bone marrow suppression or preexisting hematologic abnormalities
HLA-B* 1502 Allele increases the risk for SJS or TEN
Felbamate is contraindicated for patients with what condition (s)
Anemia
Hepatic impariment
Gabapentin should be used cautiously in which patients?
History of drug use Renal impairment (dose adjustments may be required)
Lacosamide is not recommended for which patients?
Those with cardiac conduction disorders
Those who take drugs that can prolong PR interval
History of drug dependency or abuse
Oxcarbazepine may worsen which two preexisting conditions?
Osteopenia & Osteoporosis
Phenobarbital is contraindicated in which patients?
Personal or family history of porphyria
Patients with marked anemia
Patients with marked liver impairment
Patients with significant respiratory disease
Phenytoin can worsen what preexisting conditions?
Atrioventricular block
Bradycardia
What are the contraindications for Valproic Acid
Significant hepatic dysfunction
Children under 3 who are taking other antiseizure drugs
Pregnancy unless LAST resort
What is the drug of choice for treating absence seizures?
Ethosuximide
Which AED is generally devoid of significant adverse effects and drug-drug interactions?
Ethosuximide
which AED is nearly identical in structure to Phenobarbital?
Primidone
Is Primadone used as monotherapy or adjunct therapy?
Primarily adjunct, usually with Phenytoin or carbamazepine.
Treats tonic-clonic seizures
Simple Partial seizures
Complex Partial Seizures
What type of seizure(s) does Primadone treat?
Tonic-clonic seizures
Simple Partial seizures
Complex Partial Seizures
Common Side effects of Primidone?
Sedation, ataxia, dizziness during initial use
Confusion in older adults
Hyperexcitability in children
Absolute contraindication for Primidone?
Acute intermittent porphyria
Potential serious adverse effects of Primidone?
Acute psychosis, leukopenia, thrombocytopenia, systemic lupus (all rare but possible)
Drug-Drug interactions with Primidone?
Same as Phenobarbital
CYP inducing so can decrease the effectiveness of Warfarin and oral contraceptives
CNS Depressants (enhances effect)
Is Tiagabine used as monotherapy or adjunct therapy?
ONLY adjunct therapy for:
Partial seizures in patients at least 12 years old
What kind of seizure(s) does Tiagabine treat?
Partial seizures in patients at least 12 years old
Common adverse effects of Tiagabine?
Generally well tolerated
dizziness, somnolence, asthenia, nausea, nervousness, tremor
Dose-related cognitive effects
Potential serious effects of Tiagabine?
Can cause seizure with off-label use
Drug-drug interactions with Tiagabine?
Phenytoin, Phenobarbital, and Carbamazepine (all induce drug-metabolizing enzymes) will decrease levels of Tiagabine
Is Zonisamide used for monotherapy or adjunct therapy?
Adjunct for Partial seizures in adults
What kind of seizure(s) does Zonisamide treat?
Partial seizures in ADULTS
Potential Serious side effects of Zonisamide?
Severe psychiatric effects (severe depression, suicide attempts)
Hypersensitivity reactions-SJS, TEN, fulminant hepatic necrosis
Kidney stones
Metabolic acidosis
Hypohidrosis (decreased sweating) & hyperthermia
Drug-Drug Interactions with Zonisamide?
CYP inducers (including St. John’s wort) can reduce the half-life to 27 hours or less
CYP inhibitors & Protease Inhibitors slow the metabolism and intensify/prolong Zonisamide effects
Grapefruit juice slows metabolism
Tiagabine is not recommended for patients with which preexisting condition?
Hepatic Impairment
What antibiotic chemical family is Zonisamide the same as?
Sulfonamide antibiotics
What are contraindications for use of Zonisamide?
Sulfa allergy
Conditions that contribute to metabolic acidosis
What term refers to a group of movement disorders of CNS origin characterized by heightened muscle tone, spasm & loss of dexterity?
Spasticity
What are the most common causes of spasticity?
Multiple sclerosis (MS) and cerebral palsy (CP)
Which 3 drugs relieve spasticity by actions through the CNS?
Baclofen
Diazepam
Tizanidine
Which drug relieves spasticity by acting directly on the skeletal muscle?
Dantrolene
Baclofen, indication for use?
Spasticity related to MS and some spinal cord injuries
Baclofen MOA?
Acts within the spinal cord to suppress hyperactive reflexes involved in the regulation of muscle movement.
Is not a direct muscle relaxant
Does not decrease muscle strength
Reduce the discomfort of spasticity and increases performance.
Common adverse effects of Baclofen?
CNS and GI
Can baclofen be abruptly withdrawn?
No-does not cause physical dependence but the abrupt withdrawal of oral dosages can cause visual hallucinations, paranoid ideation, and seizures
Drug-drug interactions with Baclofen?
Other CNS depressants-increases CNS depressive effects
Drugs that contribute to increased urinary retention
Possible serious adverse effects of Baclofen?
Urinary retention
Patients with what preexisting conditions should be cautiously prescribed Baclofen?
Benign Prostatic hypertrophy
Patients taking drugs that increase urinary retention
Patients with hx of schizophrenia or other psychiatric illnesses
What is the only benzodiazepine labeled for treating spasticity?
Diazepam
Diazepam MOA?
Acts in CNS to suppress spasticity.
Does not directly affect skeletal muscle
Common Adverse effects of Diazepam
Sedation-minimize by using low doses initially
What drug directly acts on skeletal muscle to treat spasticity?
Dantrolene
Dantrolene MOA?
Makes skeletal muscle less able to contract by suppressing the release of calcium from the sarcoplasmic reticulum.
**has minimal effect on contraction of smooth muscle and cardiac muscle.
Dantrolene indications for use?
Relieves spasticity associated with MS, CP & spinal cord injury.
Management of muscle contraction and rigidity associated with malignant hyperthermia
Suppression of spasticity by Dantrolene has what effect on skeletal muscle strength?
Dantrolene reduces muscle strength which may reduce overall function rather than improve function.
**Risk-benefit analysis is necessary for treatment.
How long does it take to determine if treatment of spasticity with Dantrolene will be beneficial?
45 days
Black box warning for Dantrolene
Fatal hepatotoxicity, especially at higher doses even with short-term use.
May be asymptomatic so baseline liver function should be obtained along with frequent monitoring during treatment.
What action should be taken to decrease the risk of hepatotoxicity from treatment with Dantrolene?
Use the lowest possible effective dose
Frequent monitoring (as the patient may be asymptomatic)
Common adverse effects of Dantrolene?
Muscle weakness, drowsiness, and diarrhea are the most common
Less common adverse effects are dysphagia, hoarseness, nausea, vomiting, and ERECTILE DYSFUNCTION
What is the term for the involuntary contraction of a muscle or muscle group which is often painful and reduces the ability to function?
Muscle Spasm
What two groups of medicines are used to treat acute muscle spasms?
Analgesics
Centrally acting muscle relaxants
Cyclobenzaprine MOA?
Centrally acting skeletal muscle relaxant. The primary action is in the brain stem and causes reduction of tonic motor activity,
Cyclobenzaprine indications for use?
Relief of muscle spasm and associated pain
What is considered the most effective drug for the relief of muscle spasm and its associated pain?
Cyclobenzaprine
Cyclobenzaprine (Flexeril) adverse effects?
CNS depressive symptoms:
drowsiness, dizziness, fatigue-most intense early in treatment
ANTICHOLINERGIC effects (mostly dry mouth, blurred vision, photophobia, urinary retention, and constipation.
What class of drugs is Cyclobenzaprine (Flexeril) similar to?
Tricyclic antidepressants
Potential serious adverse effects of Cyclobenzaprine (Flexeril)?
Cardiac rhythm disturbances similar to those of tricyclic antidepressants
*Primarily sinus tachycardia and significant conduction delays.
Cyclobenzaprine (Flexeril) Drug-drug interactions?
MAO inhibitor antidepressants (must wait two weeks after MAO inhibitor discontinued to prevent risk of serotonin sickness)
SSRIs-risk of serotonin sickness
SNRIs-risk of serotonin sickness
tricyclic antidepressants-risk of serotonin sickness
Alcohol & other CNS depressants
What is the indication for use for Tizanidine (Zanaflex)
relief of Spasticity
Potential serious adverse reaction of Tizanidine (Zanaflex)?
Liver damage
Potential serious adverse effect of metaxalone (Skelaxin)
Liver damage
Potential serious adverse effect of Chlorzoxazone (Lorzone)
Hepatitis and potentially fatal hepatic necrosis.
Risk generally greater than benefit with this drug
Chlorzoxazone (Lorzone) indication for use?
Muscle relaxant
Potential adverse effects of Chlorzoxazone?
Urine orange to purple-red
Methocarbamol indication for use?
Muscle relaxant
Methocarbamol contraindications for use?
Seizure disorder
Methocarbamol adverse effects?
Urine becomes brown, black, or dark green (dose-related, harmless)
Which muscle relaxants have significant anticholinergic effects?
Cyclobenzaprine
Orphenadrine
Potential adverse effects of Tizanidine
dry mouth, hypotension, hallucinations, and psychotic symptoms
Hypotension
*When discontinuing the drug, may need to taper to prevent hypertension
Contraindication for Carisoprodol?
Intermittent porphyria
What side effects are common among all centrally acting muscle relaxants?
CNS depression
Risk for physical dependence
Which drugs for the treatment of muscle spasms and spasticity are NOT approved for use in children?
Chlorzoxazone,
Orphenadrine
Tizanidine
Is Cyclobenzaprine safe for pregnant women?
Generally, yes
Is Diazepam safe for pregnant women?
No, it is a teratogen
Can drugs for muscle spasms and spasticity be safely taken by breastfeeding women?
No-can cause injury to infants
What drugs for muscle spasms and spasticity are listed in the Beers Criteria as potentially inappropriate for older adults?
Carisoprodol Chlorzoxazone Cyclobenzaprine Metaxalone Methocarbamol Orphenadrine