Mood disorder and Antiepileptic Drug Questions

A 26 year old with a PMH of an unknown mood disorder comes to clinic with a headache. He has the following labs. WBC: 2.2 Hb: 14 Platelets: 334 Creatine 0. 3 Which drug is responsible for these adverse drug reactions? A) Lithium B) Valproic Acid C) Lamotrigine D) Carbamazepine E) SSRI

D) Carbamazepine Low WBC = Agranulocytosis Other SE's of Carbamazepine SIADH Very Potent P450 inducer

Ethosuximide is most commonly associated with which of the following side effects? A. Diplopia B. Gastrointestinal distress C. Steven-Johnson syndrome D. Weight gain

B. Gastrointestinal distress is the most common side effect associated with ethosuximide. Patients may experience nausea, vomiting, abdominal cramping, and diarrhea. A. Diplopia is more often associated with lamotrigine than ethosuximide. In rare cases, ethosuximide has been reported to cause myopia. C. In rare cases, ethosuximide has been associated with Stevens-Johnson syndrome (SJS). However, SJS is uncommon and gastrointestinal distress is a far more common adverse effect of ethosuximide. D. Weight gain is not a typical feature of ethosuximide administration. In contrast, valproate is known to increase appetite and cause weight gain.

A 30 year old with a PMH of an unknown mood disorder comes to clinic with a headache. He has the following labs. WBC: 11 Hb: 14 Platelets: 334 Creatine 1.9 Which drug is responsible for these adverse drug reactions? A) Lithium B) Valproic Acid C) Lamotrigine D) Carbamazepine E) Oxcarbazepine

A) Lithium increases creatine if from kidney damage

A 30 year old with a PMH of an unknown mood disorder comes to clinic with a non specific symptoms. He has the following labs. WBC: 11 Hb: 14 Platelets: 86 Creatine 0.4 Which drug is responsible for these adverse drug reactions? A) Lithium B) Valproic Acid C) Lamotrigine D) Carbamazepine E) Oxcarbazepine

B) Valproic Acid Low platelets = Thrombocytopenia

A 22 year old with a PMH of an unknown mood disorder comes to clinic with a non specific symptoms. He has the following labs. AST: 110 ALT: 104 Lipase: normal Amylase: normal Which drug is responsible for these adverse drug reactions? A) Lithium B) Valproic Acid C) Lamotrigine D) Carbamazepine E) Oxcarbazepine

B) Valproic Acid increase of LFT's

A 22 year old with a PMH of an unknown mood disorder comes to clinic with a non specific symptoms. He has the following labs. AST: 22 ALT: 16 Lipase: High Amylase: High Which drug is responsible for these adverse drug reactions? A) Lithium B) Valproic Acid C) Lamotrigine D) Carbamazepine E) Oxcarbazepine

B) Valproic Acid Hepatotoxicity but have normal LFT's

Topiramate and valproate can both be used for which other indication besides both being broad spectrum antiepileptic agents? A. Cluster headache acute treatment B. Cluster headache prophylaxis C. Migraine headache prophylaxis D. Tension headache treatment

C. Migraine headaches are pulsating headaches which may occur with auras, photophobia, and phonophobia. Both topiramate and valproate are used for prophylaxis against migraine headaches. Amitriptyline, venlafaxine, and beta blockers can also be used to prevent migraine headaches.

Before initiating a patient on carbamazepine, you warn your patient about its most common side effects of dizziness, lethargy, and double vision. You also discuss other rare but more serious side effects for which the drug has black box warnings. One of these is aplastic anemia. What other black box warning should you also warn your patient about? A) serious dematologic reactions B) gingival hyperplasia C) hepatic failure D) hirsutism E) mania

A) It has been estimated that 1 to 6 per 10,000 new users of carbamazepine develop potentially fatal dermatologic reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome. The highest risk for these reactions is in patients with the HLA-B 1502 inherited allelic variant of the HLA-B gene E) Carbamazepine & other antiepileptics are actually indicated for the treatment of mania in patients suffering from bipolar disorder

A 17-year-old young man is brought to the emergency department after suffering from an apparent seizure. A friend who witnessed the episode states that the patient began acting strange immediately before suffering a series of convulsions. His right arm had began shaking before he fell to the ground and experienced a tonic-clonic seizure for several minutes. During the seizure he turned pale, suffered from urinary incontinence, and bit his tongue severely. Afterwards he had no memory of the events he suffered from during the seizure, but recalled having a strange feeling of "deja vu" before he lost consciousness. Shortly after obtaining his medical history, a neurology consult performed an EEG, which revealed focal epileptiform discharges in the patient's left temporal lobe. The patient stated that he had suffered from a head injury several months ago after being thrown off his bike when he hit a storm drain. He was not wearing a helmet. A diagnosis of a focal-onset seizure evolving into a bilateral convulsive seizure (also refered to as a secondarily generalized tonic-clonic seizure) was made. Based on this diagnosis, which of the following drugs would be the most appropriate choice for treating this seizure disorder, due to its ability to block Na channels in a frequency-dependent manner A) carbamazepine B) diazepam C) ethosuximide D) gabapentin E) phenobarbital

A Carbamazepine blocks Na channels in a frequency or rate-dependent manner, a mechanism that can prevent the development and spreading of high frequency discharges from an epileptic focus B) Diazepam is a benzodiazepine that does not block Na channels at therapeutic doses. It is not used for the prevention of partial or generalized seizures. C) Ethosuximide is not a Na channel blocker, and it has another primary indication as an antiepileptic. D) Dabapentin's pharmacology is still poorly understood, it is not a Na channel blocker. Current evidence supports two likely mechanisms of action: 1) it binds to a subunit of N-type Ca channels, interfering with Ca channel trafficing, and decreasing Ca entry across the presynaptic membrane; resulting in a reduction in glutamate release; & 2) increasing brain levels of GABA, the major inhibitory neurotransmitter in the CNS. It is considered an adjunct drug in the treatment of epilepsy, and is not indicated as an initial drug of choice for partial or generalized seizures E) Barbiturates are generally not drugs of first choice for long term management in adults, or young adults, because of their sedative side effects. Barbiturates also act primarily by enhancing the effect of GABA on GABA-A channels at lower doses, and only affect Na channels at high doses

You are initializing treatment of a man suffering from a focal-onset seizure with 300 mg/day phenytoin. A blood sample confirms a steady-state plasma level of 9 ug/ml. However, lack of adequate seizure control requires a dosage elevation. If his daily drug dosage were doubled, what would be the most likely change in his drug plasma level? A) double his previous plasma level B) less than doubled C) more than doubled D) no change due to zero order clearance

A) Phenytoin has dose-dependent clearance due to progressive saturation of its hepatic metabolism by cyt P-450 at normal therapeutic plasma levels, and ~10 ug/ml is considered the minimal effective plasma concentration for seizure control. Due to saturation of its metabolism, even small increases in maintenance dosage can cause large, unpredictable increases in plasma drug concentrations, which increases the risk of adverse effects such as ataxia, nystagmus, confusion, gingival hyperplasia, hirsuitism (and the list goes on). In addition, other drugs that either inhibit or induce P-450 can produce marked changes in phenytoin plasma levels

Which of the following patients should be treated with ethosuximide? A. 10-year-old boy with 3 Hz spike-and-wave complexes seen on electroencephalogram B. 12-year old girl with multiple delta waveforms seen on electroencephalogram during sleep C. 13-year old boy with multiple beta waveforms on electroencephalogram while focusing on a problem-solving task D. 16-year-old girl with startle myoclonus and periodic sharp waves seen on electroencephalogram

A. Absence seizures are characterized by 3 Hz spike-and-wave complexes on EEG. Absence seizures can be treated with 1st) ethosuximide, 2nd) lamotrigine, and 3rd) valproate. B. Delta waveforms are typically seen during stage N3 non-REM sleep. This is a normal waveform and should not be treated with medication. C. Beta waveforms are usually seen on EEG during times of mental activity and concentration as well as during REM sleep. This is a normal waveform and should not be treated with medication. D. Startle myoclonus and periodic sharp waves on EEG are consistent with Creutzfeldt-Jakob disease (CJD). There is currently no known treatment for CJD

Ethosuximide is indicated for which of the following seizure types? A. Absence seizures B. Complex partial seizures C. Simple partial seizures D. Status epilepticus

A. Absence seizures are the only indication for ethosuximide administration and is the first line therapy for absence seizures. Patients who cannot tolerate or who fail treatment with ethosuximide may be treated with valproate or lamotrigine. B. Ethosuximide is not used to treat complex partial seizures. A broader spectrum agent like valproate can be useful for treating complex partial seizures. C. Ethosuximide is a narrow spectrum antiepileptic drug and is only approved for treatment of absence seizures. Carbamazepine and valproate may be used to treat simple partial seizures. D. Ethosuximide is not used to treat status epilepticus. Benzodiazepines and phenytoin should be used to treat status epilepticus.

A woman with bipolar disorder treated with lithium presents to clinic complaining of increased urinary frequency and excessive thirst. Hemoglobin A1c is 4.3 and fasting plasma glucose is 86 mg/dL. What underlying pathology is most likely responsible for her symptoms? A. Decreased ability to concentrate urine B. Depletion of antidiuretic hormone C. Hypothyroidism D. Insulin resistance

A. Around 20% of patients who take lithium chronically will develop nephrogenic diabetes insipidus (DI). As a result of taking lithium, patients become less responsive to antidiuretic hormone (ADH) despite normal or elevated levels of ADH. Clinically, patients present with polydipsia and polyuria due to inability to concentrate urine. B. Central diabetes insipidus (DI) is caused by decreased production of antidiuretic hormone (ADH). Central DI is often caused by trauma or malignancy involving the pituitary gland. Lithium is associated with nephrogenic DI rather than central DI. C. Lithium is known to cause hypothyroidism. However, hypothyroidism is more often characterized by fatigue, weight gain, constipation, and dry skin rather than urinary frequency and polydipsia. This patient most likely has nephrogenic diabetes insipidus secondary to chronic lithium use. D.Type 2 diabetes mellitus can present with polyuria and polydipsia. Patients with type 2 diabetes have insulin resistance, elevated hemoglobin A1c (> or =6.5%) and elevated fasting plasma glucose (> or =126 mg/dL) which this patient does not have. This patient most likely developed nephrogenic diabetes insipidus as a result of taking lithium.

Which of the following INCORRECTLY pairs an antiepileptic drug with its associated adverse effect? A. Ethosuximide - Tremor B. Ethosuximide - Fatigue C. Lamotrigine - Rash D. Valproate - Tremor

A. Ethosuximide is not typically associated with development of tremors. Ethosuximide most commonly causes gastrointestinal distress and fatigue. B. Fatigue is known to occur with ethosuximide use. In fact, many antiepileptic agents (e.g. topiramate, gabapentin and levetiracetam) are known to cause fatigue, sedation and somnolence. C. Lamotrigine may cause a relatively benign drug rash. However, in rare cases patients can develop Stevens-Johnson syndrome, a potentially life-threatening condition. D. Tremor is one of the known side effects associated with use of valproate. Other side effets include gastrointestinal distress, weight gain, alopecia, pancreatitis, and hepatotoxicity.

A man with bipolar disorder treated with lithium presents to his psychiatrist with complaints of weight gain, fatigue, cold intolerance and dry skin. Which of the following laboratory studies would most likely show an abnormality? A. Thyroid stimulating hormone B. Prothrombin time C. Serum sodium D. Testosterone

A. Lithium is known to cause hypothyroidism. This patient is most likely to have an elevated TSH and decreased T3 and T4 serum levels. Patients with lithium induced hypothyroidism should be treated with T4 and may continue to take lithium. B. Prothrombin time (PT) is used to monitor the extrinsic coagulation pathway. PT and the international normalized ratio (INR) are routinely monitored in patients taking warfarin, but are not useful for monitoring lithium levels. C. Lithium can cause hypernatremia secondary to nephrogenic diabetes insipidus. However, this patient's clinical symptoms are more consistent with hypothyroidism. D. Male testosterone levels often decline with age. Decreased testosterone may lead to fatigue and weight gain. Lithium is not known to influence testosterone.

Which of the following side effects is NOT commonly associated with lithium toxicity? A. Anuria B. Diarrhea C. Nausea D. Tremor

A. Polyuria and polydipsia (not Anuria) are the most common side effects of lithium therapy. Lithium can cause nephrogenic diabetes insipidus and impair the ability to adequately concentrate urine. Up to 70% of patients on chronic lithium therapy develop symptoms of excessive urination and thirst as a result of excreting too much dilute urine. B. Lithium therapy often causes symptoms of gastrointestinal distress including diarrhea, nausea and vomiting, especially in the first few month after initiating treatment. C. Nausea, vomiting, and diarrhea are all symptom of acute lithium toxicity caused by medication overdose. Dehydration, NSAIDs, thiazide diuretics and ACE inhibitors are all known to increase the serum concentration of lithium. Because lithium has a narrow therapeutic index, even a slight increase in serum drug level can cause toxic reactions. Patients with lithium overdose should be treated with hydration to increase renal clearance of the lithium ion. In severe cases, hemodialysis may be used to remove circulating lithium ions. D. Tremor is a common side effect of lithium therapy. Lithium-induced tremor often presents as a coarse, symmetrical hand tremor and may develop in either the early or late stages of treatment. Patients treated with lithium may also develop ataxia, hypothyroidism and weight gain. Note that patients with chronic lithium toxicity are more likely to present with neurological symptoms, whereas patients with acute lithium toxicity are more likely to present with gastrointestinal symptoms.

A child is taken to the emergency department by her parents after developing a fever and a painful rash. She was recently diagnosed with absence seizures and started on an antiepileptic drug. Physical exam is notable for desquamating lesions on the trunk and mucosal ulcerations in the mouth. Which of the following antiepileptic drug is she most likely taking? A. Lamotrigine B. Levetiracetam C. Lithium D. Topiramate

A. This child is likely suffering from Stevens-Johnson syndrome (SJS), which is characterized by fever and desquamating rash involving the oral mucosa. Although many anticonvulsant medications have been reported to cause SJS, carbamazepine, phenytoin and lamotrigine are the most strongly associated with SJS. B. Levetiracetam is used to treat partial as well as tonic clonic seizures, but is not likely to be used to treat absence seizures. Although levetiracetam has been implicated to cause Stevens-Johnson syndrome in rare cases, lamotrigine is much more strongly associated with Stevens-Johnson syndrome. C. Lithium is a mood stabilizer and is not used to treat absence seizures. Lithium is also not known to cause Stevens-Johnson syndrome. D. Topiramate is not associated with increased risk of developing Stevens-Johnson syndrome The following medications are most strongly associated with increased risk of developing Stevens-Johnson syndrome: lamotrigine, carbamazepine, allopurinol, phenytoin and sulfa drugs

A 43-year-old woman is referred to a neurologist after three episodes of focal seizures. She has a past medical history of angle-closure glaucoma, migraines, and chronic insomnia. Her BMI is 37. She inquires about topiramate because she recently saw the drug in a television advertisement. Why is topiramate not an appropriate antiepileptic drug for this patient? A. Patient has angle-closure glaucoma B. Patient has insomnia C. Patient has migraines D. Patient has obese habitus

A. Topiramate is a known to cause secondary acute angle closure glaucoma. If possible, topiramate should be avoided in patients who already have primary angle closure glaucoma. B. Topiramate can lead to somnolence and may be useful in a patient suffering from insomnia. Insomnia is not a contraindication to using topiramate. C. Topiramate is indicated for the treatment for partial seizures, tonic clonic seizures as well as migraine prophylaxis. Migraines are not a contraindication for using topiramate. D. Topiramate is known to result in weight loss and can be useful in treating seizure patients who are overweight or obese. This patient's BMI is not a contraindication to using topiramate.

Both lithium and valproate _______. A. Are known teratogens B. Have anticonvulsant activity C. Serum drug levels are affected by thiazide diuretics D. Undergo hepatic metabolism

A. Valproate and lithium are both mood stabilizers used to treat bipolar disorder. Additionally, both drugs are known teratogens. Taking lithium during pregnancy increases the risk of Ebstein's anomaly. Valproate exposure during gestation is also associated with a number of fetal abnormalities, including neural tube defects and facial dysmorphisms. B. Valproate is considered a broad spectrum antiepileptic drug and can also be used to treat bipolar disorder. Lithium can also be used to treat bipolar disorder but has no known efficacy against seizures. C. Thiazide diuretics impair renal clearance of the monovalent lithium ion and increase serum lithium levels. Serum valproate concentration, in contrast, is not affected by thiazide diuretics. D. Valproate undergoes metabolism in the liver. Lithium is not metabolized and is excreted as an ion by the kidneys.

Patients started on valproate therapy should have which of the following lab values routinely monitored? A. Liver function tests B. Serum creatinine C. Urine glucose D. White blood cell count

A. Valproate is known to cause fatal hepatotoxicity, especially within the first six months of administration. Patients prescribed valproate should have liver function tests drawn before starting the medication and these values should be closely monitored especially in the first few months after initiating therapy. B. Valproate does not undergo renal excretion and does not require dose adjustment in the setting of renal disease. There is no need to routinely check serum creatinine in patients taking valproate. C. Valproate is not associated with derangements in glucose levels. There is no need to monitor urine glucose levels in patients taking valproate. D. Valproate is not associated with leukopenia or leukocytosis so routine monitoring of the white blood cell count specifically is not necessary. However, valproate is known to cause thrombocytopenia so patients should be monitored with a complete blood count.

A patient suffering from a seizure disorder is diagnosed by EEG to be suffering from a type of generalized seizure known to be caused by the abnormal activation of thalamic T-type Ca channels that produce a neuronal bursting activity that interferes with the transmission of sensory signals to the cortex necessary for staying awake. This abnormal bursting pattern results in a state of unconsciousness or sleep. Which of the following drugs is selective for treating this particular seizure disorder because it selectively blocks the channel subtype responsible for causing it? A) carbamazepine B) ethosuximide C) lamotrigine D) phenytoin E) pregabalin

B) Ethosuximide is a selective T-type Ca channel blocker. This is what makes it a drug specifically effective against absence seizures (it is not indicated for other types of seizures) A and D) Carbamazepine and Phenytoin are Na channel blockers C) Lamotrigine's major therapeutic effect appears to be block of Na channels. However there is evidence that it can also block N- and P/Q type Ca channels as well. Although it has some efficacy against absence attacks, it is not known to block T-type Ca channels. Since it's not a selective T-type Ca channel blocker, its not the best answer E) Pregabalin is a structural analog of GABA that nevertheless does not bind to GABA receptors. It has a mechanism of action similar to gabapentin. It does not target T-type Ca channels

A girl with absence seizures who was prescribed ethosuximide returns to her neurologist for follow up. She complains of an itchy rash all over the body. Her parents say that she has been experiencing nausea, headache, and fatigue ever since starting ethosuximide. Which alternative medication may be used to treat this patient? A. Carbamazepine B. Lamotrigine C. None, as ethosuximide is the only medication used to treat absence seizures D. Vigabatrin

B. Lamotrigine and valproate are both broad spectrum antiepileptic agents with efficacy against absence seizures and can be used to treat patients who do not tolerate ethosuximide. Ethosuximide is known to cause gastrointestinal distress, nausea, fatigue, headaches, and urticarial rash A. Carbamazepine is known to exacerbate absence seizures and should not be used in this patient. Carbamazepine is used as first line treatment for partial seizures. C. Although ethosuximide is the preferred medication for treatment of absence seizures, lamotrigine and valproate may also be used to treat absence seizures. D. Vigabatrin is known to exacerbate absence seizures and should not be used in this patient. Vigabatrin is indicated for focal seizures.

Which of the following medications cannot be used to treat acute mania in a patient with bipolar disorder? A. Haloperidol B. Lamotrigine C. Quetiapine D. Valproate

B. Lamotrigine is a broad spectrum antiepileptic agent which can also be used as a mood stabilizer for patients with bipolar disorder. Lamotrigine can be used as maintenance therapy for bipolar disorder but should not be used to treat episodes of acute mania. A. Haloperidol is a first generation antipsychotic which can be used in the setting of acute mania. A combination of lithium or valproate plus an antipsychotic can be administered to patients with bipolar disorder suffering from acute mania. C. Quetiapine is a second generation antipsychotic which can be used to treat acute mania. Second generation antipsychotics are associated with fewer anticholinergic side effects and less risk of extrapyramidal symptoms when compared with first generation antipsychotics. D. Valproate is a broad spectrum antiepileptic agent which can also be used to treat bipolar disorder. Valproate can be used to treat acute mania and can be used as maintenance therapy.

Which of the following statements regarding lithium is most accurate? A. Lithium circulates as an electrically neutral molecule B. Lithium is exclusively excreted by the kidneys C. Lithium is primarily absorbed in the distal nephron D. NSAIDs increase renal clearance of lithium

B. Lithium is a small cation and is exclusively excreted by the kidneys. Thus, serum levels of lithium are determined by renal function, especially the glomerular filtration rate. Patients with decreased renal function or patients taking drugs which impair renal filtration may need adjustments in lithium dosage to avoid toxicity. A. Lithium circulates in the blood as a small monovalent cation (Li+) similar to sodium ion (Na+). Lithium is not metabolized, and is excreted intact by the kidneys. C. The majority of lithium reabsorption occurs in the proximal convoluted tubules; virtually no lithium reabsorption occurs in the distal nephron. D. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase and decrease production of prostaglandins, thereby reducing glomerular filtration rate and impairing renal excretion of lithium. NSAIDs use should be carefully monitored as it may increase serum lithium to toxic levels.

Which of the following INCORRECTLY pairs an antiepileptic drug with its associated side effect? A. Lamotrigine - Diplopia B. Levetiracetam - Hyperphagia C. Topiramate - Sedation D. Valproate - Tremor

B. The most common side effect associated with levetiracetam, and most other antiepileptic medications, is somnolence. Levetiracetam is also known to cause a loss of appetite (anorexia), not hyperphagia, as well as agitation, irritability and mood changes. A. Lamotrigine can be associated with diplopia, nausea and somnolence. Lamotrigine is also known to cause drug rash, and in rare cases may cause Stevens-Johnson syndrome. C. Topiramate is associated with significant risk of sedation and drowsiness. Topiramate is also known to cause weight loss, confusion, cognitive slowing, and nephrolithiasis. D. Valproate is known to cause gastrointestinal upset, weight gain, tremor, pancreatitis, and in rare cases, fatal hepatotoxicity.

All of the following agents are known to inactivate sodium channels EXCEPT: A. Lamotrigine B. Levetiracetam C. Topiramate D. Valproate

B. The precise mechanism of action of levetiracetam is not well known. Some studies have found that levetiracetam can inhibit presynaptic calcium channels as well as modulate GABA and glutamate transmission. Levetiracetam is not known to inactivate sodium channels. A. Lamotrigine stabilizes neuronal membranes by inactivating voltage gated sodium channels. Additionally, lamotrigine inhibits release of the excitatory neurotransmitter glutamate. C. Topiramate blocks neuronal sodium channels to prevent high frequency firing. Topiramate also increases transmission of the inhibitory neurotransmitter GABA while antagonizing transmission of the excitatory neurotransmitter glutamate . D. Valproate has several mechanisms of action, including inactivation of sodium channels. Valproate also inhibits GABA degradation by inhibiting the enzyme GABA transaminase.

A patient who has been on combination therapy with carbamazepine and gabapentin continues to have occassional seizures, and the decision is made to add phenytoin to the daily drug regimen. What effect, if any, would this concomitant therapy be expected to have on drug plasma levels compared to patients on monotherapy alone? A) gabapentin plasma levels would be increased B) higher than normal phenytoin plasma levels C) lower than normal phenytoin plasma levels D) no difference compared to patients on monotherapy

C) Carbamazepine is metabolized primarily by CYP 3A4, but is a wide spectrum inducer of several P-450 isoforms (3A4, 1A2, 2B6, 2C9 & 2C19), including the P-450 isozymes that metabolize phenytoin (CYP 2C9 and CYP 2C19). The enzyme-inducing effect of carabamazepine pretreatment will result in lower than expected phenytoin plasma levels at steady state. The other answer options are false. Gabapentin (an amino acid) is not metabolized, and is excreted unchanged in the urine

A 25 year old with a PMH of an unknown mood disorder comes to clinic with a painful rash on face and mucous membranes. Which drug is responsible for these adverse drug reactions? A) Lithium B) Valproic Acid C) Lamotrigine D) Carbamazepine E) Oxcarbazepine

C) Lamotrigine is only drug on this list to cause Steven Johnson Syndrome

A 2nd grade teacher notices that one of her students, a 7-year-old girl has been having 5-10 second staring spells several times a day while in class. During these spells, the girl exhibits small amplitude hand motions, and yet becomes fully alert immediately afterwards. When examined by a neurologist, the young girl's EEG shows a 3 second spike-wave pattern in all leads while experiencing a similar staring spell. What would be a drug of first choice for treating this patient's seizure disorder? A) carbamazepine B) diazepam C) ethosuximide D) phenobarbital E) phenytoin

C) This patient has an absence seizure, and ethosuximide is a drug of choice for this seizure type. At least two other drugs are also effective against absence seizures - valproate and clonazepam. Valproate (like ethosuximide) is non-sedating, but clonazepam is sedating and tolerance to its effects develop over time. Lamotrigine and topiramate may also be effective. A) Carbamazepine is not known to be effective against this type of seizure. It would not be a good drug of first choice B) Diazepam is indicated for short term treatment of a different type of seizure D) Phenobarbital is fairly sedating, and is not known to be effective against this type of seizure. It would not be a good drug of first choice. E) Phenytoin is not known to be effective against this type of seizure, and would not be a good drug of first choice.

Which of the following features is NOT associated with absence seizures? A. Automatisms B. Loss of awareness C. Postictal state D. Spike-wave complexe

C. A postictal state refers to the period following a generalized seizure in which patients regain consciousness but continue to experience lethargy and confusion. This typically lasts between 5 to 30 minutes. Unlike tonic-clonic seizures, absence seizures are not associated with a postictal state A. Automatisms refer to brief, repetitive movements or behaviors that occur below the level of consciousness during a seizure. Examples include snapping, tapping, or chewing. Although not unique to absence seizures, automatisms are typical of the condition. B. Absence seizures are characterized by temporary loss of awareness. Patients are temporarily unaware of their surroundings despite often having open eyes and staring behavior. D. Absence seizures are characterized by 3 hertz spike-wave complexes on electroencephalography.

Which of the following statements regarding carbamazepine is most accurate? A. Carbamazepine is a second generation antipsychotic B. Carbamazepine is not effective in treating acute mania C. Carbamazepine is used as maintenance treatment for bipolar disorder D. Carbamazepine may increase the risk of seizures

C. Carbamazepine is an antiepileptic medication and can also be used for acute and maintenance treatment of bipolar disorder. Carbamazepine, phenytoin, phenobarbital and gabapentin are all considered narrow spectrum antiepileptic agents. A. Carbamazepine is an anticonvulsant, not an antipsychotic medication. Second generation antipsychotic medications include olanzapine, quetiapine and risperidone. B. Carbamazepine can be used for treating acute mania in patients with bipolar I disorder. Carbamazepine can also be used as maintenance treatment for bipolar disorder. D. Carbamazepine is an anticonvulsant effective in treating partial seizures as well as tonic-clonic seizures. Carbamazepine is associated with Stevens-Johnson syndrome, agranulocytosis and induction of the cytochrome P450 system.

Which of the following findings would be expected in a patient with Ebstein's anomaly? A. Atrialization of the left ventricle B. Bicuspid aortic valve C. Malformation of the tricuspid valve D. Ventricular septal defect

C. Ebstein's anomaly is a congenital cardiac malformation that is frequently associated with maternal lithium use during pregnancy. Ebstein's anomaly is characterized by atrialization of the right ventricle, atrial septal defect, and malformation of the tricuspid valve. A. Ebstein's anomaly involves atrialization of the right ventricle, not the left ventricle. Because the tricuspid valve is displaced caudally, the right atrial is enlarged. As a result, the upper portion of the right ventricle is "atrialized". B. There is an increased incidence of bicuspid aortic valve in patients with Turner syndrome. Patients with Turner syndrome also have increased risk of coarctation of the aorta. There is no increased risk of bicuspid aortic valve in patients with Ebstein's anomaly. D. Ebstein's anomaly is most frequently associated with atrial septal defect rather than ventricular septal defect. Auscultation of a patient with atrial septal defects reveals a fixed split S2.

Ethosuximide prevents absence seizures by inhibiting _____ located in the _____. A. GABA transaminase; medulla oblongata B. Calcium channels; frontal cortex C. Calcium channels; thalamus D. Sodium channels; hypothalamus

C. Ethosuximide inhibits thalamic T-type calcium channels. These channels would normally lead to rhythmic burst discharges of thalamic neurons. Ethosuximide acts to prevents signal propagation and thus prevent absence seizures. A. Ethosuximide does not inhibit GABA transaminase and does not act on neurons in the medulla oblongata. Vigabatrin, another narrow spectrum antiepileptic, does inhibit the enzyme GABA transaminase. B. Ethosuximide does inhibit calcium channels in the thalamus, but not in the frontal cortex. D. Ethosuximide does not inhibit sodium channels, nor does it act at the hypothalamus. Multiple other antiepileptic drugs do inactivate sodium channels, including valproate and lamotrigine

Valproate is a broad spectrum antiepileptic agent with many indications. Which of the following is NOT an indication for using valproate? A. Bipolar disorder B. Focal seizures C. Generalized anxiety disorder D. Juvenile myoclonic epilepsy

C. Selective serotonin reuptake inhibitors (SSRI) or serotonin norepinephrine reuptake inhibitors (SNRI) are used as first line treatment for generalized anxiety disorder. Benzodiazepines may also be used in this acute setting to abort an anxiety attack. Valproate is not used to treat generalized anxiety disorder. A. Valproate, lithium, carbamazepine, lamotrigine, and antipsychotic medications are all considered mood stabilizers and can be useful in the treatment of bipolar disorder. B. Valproate is considered a broad spectrum antiepileptic agent because it can be used to treat both focal (partial) seizures as well as generalized seizures. Valproate treats seizures by increasing levels of the inhibitory neurotransmitter GABA in the central nervous system as well as inactivating neuronal sodium channels. D. Valproate is used as a first line treatment for juvenile myoclonic epilepsy, the most common generalized seizure disorder in children.

Which of the following medications is known to increase serum lithium levels? A. Acetaminophen B. Aripiprazole C. Hydrochlorothiazide D. Valproate

C. Thiazide diuretics, including chlorthalidone and hydrochlorothiazide, increase serum lithium levels by reducing renal clearance of lithium. Angiotensin converting enzyme (ACE) inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) are also known to increase lithium levels. Patient taking thiazides, ACE inhibitors or NSAIDs who are also taking lithium should be carefully monitored for lithium toxicity. A. Acetaminophen is an antipyretic and analgesic medication which does not affect the serum concentration of lithium. NSAIDs, on the other hand, impair renal clearance of lithium via a reduction in the glomerular filtration rate. B. Aripiprazole is an atypical antipsychotic used to treat bipolar disorder, schizophrenia and Tourette syndrome. Aripiprazole is not known to affect serum lithium levels. D. Valproate, or valproic acid, can be used to treat bipolar disorder as well as epilepsy. Valproate is not known to increase circulating levels of lithium.

A father mentions that his son is often reprimanded for inattentiveness during class. His teacher states that he frequently stares out the window and does not appear to hear any verbal requests to pay attention for approximately 30 seconds at a time. Other than these occasional episodes, the child is always well behaved, friendly and does not appear to have hearing or learning difficulties. How should you address this father's concern? A. Referral for hearing test B. Referral to psychiatry for evaluation of conduct disorder C. Send for electroencephalography testing D. Start therapy for attention-deficit hyperactivity disorder

C. This child appears to have normal hearing, normal attention span and proper behavior except during short episode "staring spells." Absence seizures are characterized by sudden momentary lapse in awareness often lasting less than a minute and are accompanied by staring, blinking, or clonic jerks. An EEG can be used to diagnose absence seizures which manifest as 3 Hz spike-and-wave complexes. A. Hearing disorder and visual impairment are often underdiagnosed in school aged children and can lead to learning difficulties. However, this patient only appears to have hearing loss during staring episodes which is more consistent with temporary loss of consciousness during absence seizures rather than true hearing impairment. B. Conduct disorder is characterized by extreme and aggressive antisocial behaviors (e.g. animal abuse, property destruction) This boy does not have any behaviors concerning for conduct disorder and should be evaluated for absence seizures instead. D. Attention-deficit hyperactivity disorder is characterized by impulsive behavior and inability to pay attention for a sustained period of time in more than one setting. This child only appears to be affected temporarily in school and does not seem to have impulsive behavior or hyperactivity. An EEG test to evaluate for absence seizures is more likely to help this patient.

Which of the following adverse effects is NOT usually associated with valproate? A. Nausea B. Tremor C. Urolithiasis D. Weight gain

C. Valproate does not typically cause urolithiasis. Instead, urolithiasis is a known side effect that can occur with use of topiramate. A. Gastrointestinal upset including nausea, vomiting and diarrhea may be caused by valproate. B. Valproate is known to precipitate tremors in a small subset of patients. Valproate is also associated with hepatotoxicity and pancreatitis. D. Valproate can cause increased appetite and significant weight gain. Patients should be counseled on this potential side effect and develop strategies to maintain a healthy weight. Topiramate, another broad spectrum antiepileptic drug, is associated with weight loss.

Fetuses exposed to valproate in utero are at an increased risk for developing which of the following defects? A. Ebstein's anomaly B. Hypoplastic nails C. Neural tube defects D. Sensorineural hearing loss

C. Valproate is a known teratogen and should be prescribed with caution to women of childbearing age. Exposure to valproate during pregnancy is associated with increased risk of fetal neural tube defects including meningocele and spina bifida. A. Ebstein's anomaly is characterized by a displaced tricuspid valve resulting in atrialization of the right ventricle. Ebstein's anomaly is a congenital heart defect associated with maternal lithium use, not valproate use. B. Hypoplastic fingernails and toenails are congenital nail defects associated with exposure to phenytoin, not valproate. D. Aminoglycosides, amphotericin B, and cisplatin are known to cause ototoxicity and should not be prescribed to pregnant women. Sensorineural hearing loss is not associated with valproate. Fetuses exposed to valproate in utero have an increased risk of developing neural tube defects.

Which of the following best characterizes the mechanism of action of lamotrigine? A. Activation of neuronal sodium channels B. Blockade of thalamic calcium channels C. Inactivation of voltage-gated sodium channels D. Inhibition of GABA transaminase

C. Lamotrigine inactivates voltage-gated sodium channels in order to prevent excitatory neuronal depolarization. Lamotrigine is a broad spectrum antiepileptic drug which can be used to treat partial as well as generalized seizures. Lamotrigine is used as a second line therapy for absence seizures. A. Lamotrigine inactivates voltage-gated sodium channels, thereby impairing sustained high-frequency neuronal firing. B. Ethosuximide blocks T-type Ca2+ channels in the thalamus. Lamotrigine does not block thalamic calcium channels. D. Vigabatrin is known to inhibit GABA transaminase, the enzyme responsible for degradation of GABA. This inhibition leads to elevated levels of GABA in the central nervous system. Lamotrigine does not inhibit GABA transaminase.

A 32-year-old man with a history of epilepsy is brought into the emergency department suffering from a tonic-clonic seizure that has lasted for more than 30 minutes. His blood pressure is 200/105 mm Hg, pulse 135/min, rectal body temp 37.6oC. He is placed on his side to prevent aspiration, and to allow drainage of saliva and mucus. An i.v. line is established using normal saline. A blood sample is taken for analysis of blood electrolytes, glucose, and a toxicology screen for pro-convulsant drugs. Which anticonvulsant drug should be given immediately to treat his seizure? A) ethosuximide B) gabapentin C) lamotrigien D) lorazepam

D) This patient is suffering from status epilepticus. Both diazepam and lorazepam have been found to be most effective in treating this seizure subtype. They act primarily by enhancing the inhibitory effects of GABA on GABA-A receptors, which causes a chloride mediated membrane hyperpolarization that inhibits neuronal firing. The other drugs listed are not indicated for this clinical situation A) Ethosuximide is primarily effective against absence seizures due to its specificity in blocking T-type Ca channels. It would not be very effective in this clinical situation B) Gabapentin is considered an adjunct drug for treating several different types of seizures, and would not be a drug of first choice for this patient with a long lasting, and potentially life-threatening tonic-clonic seizure C) This patient is suffering from a potentially life threatening tonic-clonic seizure. Lamotrigien is considered effective against focal or partial seizures, or as add-on therapy when monotherapy with a different drug does not provide adequate seizure control. It would not be a drug of first choice for this patient

Several of the commonly used drugs for treating epilepsy are associated with significant side effects or risks for serious toxicity. For example, valproate has 3 black box warnings. Which of the following most accurately summarizes these 3 warnings? A) aplastic anemia, agranulocytosis, Stevens-Johnson syndrome B) ataxia, sedation, cognitive impairment C) gingival hyperplasia, hirsuitism, nystagmus D) hepatotoxicity, pancreatitis, spina bifida

D) hepatotoxicity, pancreatitis, spina bifida are the 3 black box warnings for valproate A) aplastic anemia, agranulocytosis, Stevens-Johnson syndrome are the 3 black box warnings for carbamazepine B) ataxia, sedation, cognitive impairment are side effects associated with for phenobarbital and diazepam C) gingival hyperplasia, hirsuitism, nystagmus are the 3 black box warnings for phenytoin

Your patient's seizure disorder is well controlled by carbamazepine once his dosage is adjusted to produce a steady-state plasma level of ~9 ug/ml. Two months later he develops an upper respiratory infection, for which he is prescribed a 14-day regimen of clarithromycin, a macrolide antibiotic. Five days later the symptoms associated with his infection have cleared, but he now complains of being tired, dizzy and having blurred vision. What is the best explanation for these new symptoms? A) decreased carbamazepine plasma levels B) increased macrolide plasma levels C) late-onset carbamazepine syndrome D) macrolide-induced inhibition of P-450

D) macrolide-induced inhibition of P-450 Clarithromycin ( & erythromycin) are inhibitors of Cyp 3A4, the enzyme responsible for metabolism of carbamazepine. This patient's symptoms are consistent with increased side effects associated with elevated plasma levels of carbamazepine A) A reduction of carbamazepine plasma levels would not be expected to produce lethargy, dizziness and double vision B) Macrolide side effects would include problems with balance, hearing or signs of kidney failure, but not lethargy, or double vision.

Which of the following findings is NOT consistent with lithium-induced diabetes insipidus? A. Low urine specific gravity B. No rise in urine osmolality upon water deprivation testing C. Polyuria D. Reduced serum level of antidiuretic hormone

D. Chronic lithium use may cause nephrogenic diabetes insipidus (NDI). Patients with NDI often have normal or elevated levels of antidiuretic hormone (ADH), but the nephrons do not respond appropriately. In contrast, central diabetes insipidus is caused by a disruption of pituitary storage and release of ADH and thus is characterized by decreased levels of of ADH.

A man presents to the emergency department with severe epigastric pain radiating to the back. He has epilepsy for which he is taking valproate. He was initially treated with topiramate but it was not effective at controlling his seizures. He was recently hospitalized for severe cellulitis and treated with clindamycin. CT of the abdomen shows retroperitoneal fat stranding and enlargement of the pancreatic head. What is the most likely cause of this patient's condition? A. Nosocomial infection B. Past exposure to topiramate C. Recent treatment with clindamycin D. Use of valproate

D. Epigastric abdominal pain in a patient with positive radiological findings is diagnostic for acute pancreatitis. Acute pancreatitis may be caused by alcohol use, trauma, hypercalcemia, autoimmune disease, gallstones as well as certain medications such as protease inhibitors, sulfa drugs, corticosteroids, diuretics and valproate. Based on this patient's past medical history, valproate is the most likely causative agent.

A boy presents to the neurologist after a brief episode at school in which he was reportedly unresponsive, staring inattentively out the window. In the past he has also experienced generalized convulsions with loss of consciousness and periods of subsequent confusion. Which of the following agents is best suited to treat this child? A. Ethosuximide B. Gabapentin C. Phenytoin D. Valproate

D. The boy in the vignette above appears to be experiencing absence seizures. In addition, he also has separate episodes consistent with generalized tonic-clonic seizures. Valproate is a broad spectrum antiepileptic drug that is effective against focal, and many types of generalized seizures, including generalized tonic clonic and absence seizures. Therefore, valproate is the best agent to treat and manage this child's seizure episodes. A. Ethosuximide is useful for treating absence seizures, but it has limited utility apart from this indication. The drug is a very narrow spectrum antiepileptic agent and would not be appropriate in this child, as he suffers from multiple different forms of seizure activity. B. Gabapentin is a narrow spectrum antiepileptic drug useful for treating partial or secondarily generalized seizures. It is also commonly used to treat neuropathic pain, such as that associated with diabetic neuropathy. Gabapentin is not effective in treating absence seizures. C. Phenytoin is a narrow spectrum antiepileptic. It is administered in the treatment of focal and generalized tonic-clonic seizures, but not absence seizures.

A patient is diagnosed with having both absence seizures and concomitant generalized tonic-clonic seizures. Which of the following would be most effective in treating both types of seizures, yet not have significant sedating side effects? A) ethosuximide B) phenobarbital C) gabapentiin D) phenytoin E) valproate

E) valproate The other answer options are either not indicated for treating absence seizures (e.g. gabapentin, phenytoin, phenobarbital), are sedating (phenobarbital), or are effective only against absence seizures (ethosuximide). Many patients with absence seizures eventually develop tonic-clonic seizures, and require a change in therapy