Unit 11 Neuro Flashcards
A 9-year-old child is having learning difficulties at school. He has brief lapses of awareness with eyelid fluttering that occur every 5-10 min. Electroencephalogram (EEG) studies reveal brief 3-Hz spike and wave discharges appearing synchronously in all leads. Which drug would be effective in this child without the disadvantages of excessive sedation or tolerance development?
(A) Clonazepam (B) Ethosuximide (C) Gabapentin (D) Felbamate (E) Phenobarbital.
The answer is (B) Ethosuximide
This child suffers from absence seizures, and 2 of the drugs listed are effective in this seizure disorder. Clonazepam is effective but exerts troublesome CNS-depressant effects, and tolerance develops with chronic use. Ethosuximide is not excessively sedating, and tolerance does not develop to its antiseizure activity. Valproic acid (not listed) is also used in absence seizures. The answer is B.
Which statement concerning the proposed mechanisms of action of anticonvulsant drugs is inaccurate?
(A) Diazepam facilitates GABA-mediated inhibitory actions
(B) Ethosuximide selectively blocks potassium ion (K +) channels in thalamic neurons
(C) Phenobarbital has multiple actions, including enhancement of the effects of GABA, antagonism of glutamate receptors, and blockade of sodium ion (Na +) channels
(D) Phenytoin prolongs the inactivated state of the Na + channel
(E) Zonisamide blocks voltage-gated Na + channels).
The answer is (B)
Ethosuximide selectively blocks potassium ion (K +) channels in thalamic neurons
The mechanism of action of phenylsuccinimides such as ethosuximide involves blockade of T-type Ca2+ channels in thalamic neurons. Ethosuximide does not block K + channels, which in any case would be likely to result in an increase (rather than a decrease) in neuronal excitability. The answer is B.
Which drug used in management of seizure disorders is most likely to elevate the plasma concentration of other drugs administered concomitantly?
(A) Carbamazepine (B) Clonazepam (C) Gabapentin (D) Valproic acid (E) Vigabatrin
The answer is (D) Valproic acid
With chronic use, carbamazepine induces the formation of hepatic drug-metabolizing enzymes (as do phenobarbital and phenytoin). This action may lead to a decrease in the plasma concentration of other drugs used concomitantly. Valproic acid, an inhibitor of drug metabolism, can increase the plasma levels of many drugs, includingcarbamazepine, lamotrigine, phenobarbital, and phenytoin. Benzodiazepines (including clonazepam and diazepam), as well as gabapentin and vigabatrin, have no major effects on the metabolism of other drugs. The answer is D.
A young female patient suffers from absence seizures. Which of the following statements about her proposed drug management is NOT accurate?
(A) Ethosuximide and valproic acid are preferred drugs
(B) Gastrointestinal side effects are common with ethosuximide
(C) She should be examined every 2 or 3 mo for deep tendon reflex activity
(D) The use of valproic acid in pregnancy may cause congenital malformations
(E) Weight gain is common in patients on valproic acid
The answer is (C)
She should be examined every 2 or 3 mo for deep tendon reflex activity
Ethosuximide and valproic acid are preferred drugs in absence seizures because they cause minimal sedation. However, valproic acid causes gastrointestinal distress and weight gain and is potentially hepatotoxic. In addition, its use in pregnancy has been associated with teratogenicity (neural tube defects). Peripheral neuropathy, including diminished deep tendon reflexes in the lower extremities, occurs with the chronic use of phenytoin, not valproic acid. The answer is C.
Which statement concerning the pharmacokinetics of antiseizure drugs is accurate?
(A) Administration of phenytoin to patients in methadone maintenance programs has led to symptoms of opioid overdose, including respiratory depression
(B) Although ethosuximide has a half-life of approximately 40 h, the drug is usually taken twice a day
(C) At high doses, phenytoin elimination follows first-order kinetics
(D) Valproic acid may increase the synthesis of porphyrins
(E) Treatment with vigabatrin reduces the effectiveness of oral contraceptives
The answer is B
Although ethosuximide has a half-life of approximately 40 h, the drug is usually taken twice a day
The enzyme-inducing activity of phenytoin has led to symptoms of opioid withdrawal, presumably because of an increase in the rate of metabolism of methadone. Monitoring of plasma concentration of phenytoin may be critical in establishing an effective dosage because of nonlinear elimination kinetics at high doses. Valproic acid has no effect on porphyrin synthesis. Vigabatrin does not affect the metabolism of oral contraceptives. Twice -daily dosage of ethosuximide reduces the severity of adverse gastrointestinal effects. The answer is B.
With chronic use in seizure states, the adverse effects of this drug include coarsening of facial features, hirsutism, and gingival hyperplasia.
(A) Carbamazepine (B) Felbamate (C) Phenytoin (D) Phenobarbital (E) Valproic acid
The answer is (C) Phenytoin
Common adverse effects of phenytoin include nystagmus, diplopia, and ataxia. With chronic use, abnormalities of vitamin D metabolism, coarsening of facial features, gingival overgrowth , and hirsutism may also occur. The answer is C.
Abrupt withdrawal of antiseizure drugs can result in increases in seizure frequency and severity. Withdrawal is most easily accomplished if the patient is being treated with
(A) Carbamazepine (B) Diazepam (C) Ethosuximide (D) Phenobarbital (E) Phenytoin
The answer is (C) Ethosuximide
Dose tapering is an important principle in antiseizure drug withdrawal. As a rule, withdrawal from drugs used for absence seizures is easier than withdrawal from drugs used for partial and tonic-clonic seizures. Withdrawal is most difficult in patients who have been treated with barbiturates and benzodiazepines. The answer is C.
The mechanism of antiseizure activity of carbamazepine is
(A) Block of sodium ion channels (B) Block of calcium ion channels (C) Facilitation of GABA actions on chloride ion channels (D) Glutamate receptor antagonism (E) Inhibition of GABA transaminase
The answer is A Block of sodium ion channels
The mechanism of action of carbamazepine is similar to that of phenytoin, blocking sodium ion channels. Ethosuximide blocks calcium channels; benzodiazepines and barbiturates facilitate the inhibitory actions of GABA; topiramate may block glutamate receptors; and vigabatrin inhibits GABA metabolism. The answer is A.
Which statement about phenytoin is accurate?
(A) Displaces sulfonamides from plasma proteins
(B) Drug of choice in myoclonic seizures
(C) Half-life is increased if used with phenobarbital
(D) Isoniazid (INH) decreases steady-state blood levels of phenytoin
(E) Toxic effects may occur with only small increments in dose
The answer is (E) Toxic effects may occur with only small increments in dose
Sulfonamides can displace phenytoin from its binding sites, increasing the plasma-free fraction of the drug. Induction of liver drug-metabolizing enzymes by phenobarbital results in a decreased half-life of phenytoin, and isoniazid increases plasma levels of phenytoin by inhibiting its metabolism. Because of the dose-dependent elimination kinetics of phenytoin, some toxicity may occur with only small increments in dose. The answer is E.
A young male patient suffers from a seizure disorder characterized by tonic rigidity of the extremities followed in 15-30 s of tremor progressing to massive jerking of the body. This clonic phase lasts for 1 or 2 min, leaving the patient in a stuporous state. Of the following drugs, which is most suitable for long-term management of this patient?
(A) Carbamazepine (B) Clonazepam (C) Ethosuximide (D) Felbamate (E) Tiagabine
The answer is A Carbamazepine
This patient is suffering from generalized tonic-clonic seizures. For many years, the drugs of choice in this seizure disorder have been carbamazepine or phenytoin or valproic acid. However, many newer drugs are also effective, including gabapentin, lamotrigine, levetiracetem, topiramate, and zonisamide. Clonazepam and ethosuximide are not effective in this type of seizure disorder. Fosphenytoin is available for parenteral use in the management of status epilepticus. Tiagabine is approved for adjunctive use only in partial seizures. The answer is A.
Bradykinesia has made drug treatment necessary in a 60-year-old male patient with Parkinson’s disease, and therapy is to be initiated with levodopa.
1) Regarding the anticipated actions of levodopa, the patient would not be informed that
(A) A netlike reddish to blue discoloration of the skin is a possible side effect
(B) Dizziness may occur upon standing up
(C) He should take the drug in divided doses to avoid nausea
(D) The drug will probably improve his symptoms for a period of time but not indefinitely
(E) Uncontrollable muscle jerks may occur
The answer is A netlike reddish to blue discoloration of the skin is a possible side effect
In prescribing levodopa, the patient should be informed about adverse effects, including gastrointestinal distress, postural hypotension, and dyskinesias. It is reasonable to advise the patient that therapeutic benefits cannot be expected to continue indefinitely. Livedo reticularis (a netlike rash) is an adverse effect of treatment with amantadine. The answer is A
Bradykinesia has made drug treatment necessary in a 60-year-old male patient with Parkinson’s disease, and therapy is to be initiated with levodopa.
2) The prescribing physician will (or should) know that levodopa
(A) Causes less severe behavioral side effects if given together with a drug that inhibits hepatic dopa decarboxylase
(B) Fluctuates in its effectiveness with increasing frequency as treatment continues
(C) Prevents extrapyramidal adverse effects of antipsychotic drugs
(D) Protects against cancer in patients with melanoma
(E) Has toxic effects, which include pulmonary infiltrates
The answer is B: Fluctuates in its effectiveness with increasing frequency as treatment continues
Levodopa causes less peripheral toxicity but more CNS or behavioral side effects when its conversion to dopamine is inhibited outside the CNS. The drug is not effective in antagonizing the akinesia, rigidity, and tremor caused by treatment with antipsychotic agents. Levodopa is a precursor of melanin and may activate malignant melanoma. Use of levodopa is not associated with pulmonary dysfunction. The answer is B.
Which statement about ropinirole is accurate?
(A) Effectiveness of the drug in Parkinson’s disease requires its metabolic conversion to an active metabolite
(B) It should not be administered to patients taking antimuscarinic drugs
(C) Ropinirole causes less mental disturbances than levodopa
(D) Ropinirole specifically activates the dopamine D3 receptor subtype
(E) Warfarin may enhance the actions of ropinirole
The answer is E: Warfarin may enhance the actions of ropinirole
Ropinirole is a dopamine D2 receptor activator and does not require bioactivation . Confusion, delusions, and hallucinations occur more frequently with dopamine receptor activators than with levodopa. The use of dopaminergic agents in combination with antimuscarinic drugs is common in the treatment of parkinsonism. Ropinirole is metabolized by hepatic CYP1A2, and its plasma levels may be increased by other substrates of this enzyme including caffeine and warfarin. The answer is E.
A patient with parkinsonism is being treated with levodopa. He suffers from irregular, involuntary muscle jerks that affect the proximal muscles of the limbs. Which of the following statements about these symptoms is accurate?
(A) Coadministration of muscarinic blockers prevents the occurrence of dyskinesias during treatment with levodopa
(B) Dyskinesias are less likely to occur if levodopa is administered with carbidopa
(C) Other drugs that activate dopamine receptors can exacerbate dyskinesias in a patient taking levodopa
(D) The symptoms are likely to be alleviated by continued treatment with levodopa
(E) The symptoms are usually reduced if the dose of levodopa is increased
The answer is C: Other drugs that activate dopamine receptors can exacerbate dyskinesias in a patient taking levodopa
The form and severity of dyskinesias resulting fromlevodopa may vary widely in individual patients. Dyskinesias occur in up to 80% of patients receiving levodopa for long periods. With continued treatment, dyskinesias may develop at a dose of levodopa that was previously well tolerated. Muscarinic receptor blockers do not prevent their occurrence. They occur more commonly in patients treated with levodopa in combination with carbidopa or with other dopamine receptor agonists. The answer is C.
A 51-year-old patient with parkinsonism is being maintained on levodopa-carbidopa with adjunctive use of low doses of entacapone, but continues to have off-periods of akinesia. The most appropriate drug to “rescue” the patient but that will only provide temporary relief is
(A) Apomorphine (B) Benztropine (C) Carbidopa (D) Ropinirole (E) Selegiline
The answer is A: Apomorphine
Apomorphine, via subcutaneous injection, is used for temporary relief of off-periods of akinesia (“ rescue”) in parkinsonian patients on dopaminergic drug therapy. Pretreatment with the antiemetic trimethobenzamide for 3 days is essential to prevent severe nausea. The answer is A.
