Pharm - Pharmacological Therapy Of Stroke

1. A 63-year-old man suddenly collapsed at home and was brought unconscious to the hospital. Physical examination showed a comatose patient with flaccid paralysis on both left extremities. Vital signs were: blood pressure 132/70 mm Hg, pulse 90 bpm, respirations 8/min. A MRI scan disclosed a complete occlusion of the right internal carotid artery. An emergency therapy was ordered. Which of the following drugs was most likely included in the emergency treatment of this patient?

Aminocaproic acid

Desmopressin

Alteplase

Dabigatran

Lepirudin

Warfarin

Learning objective: describe the therapeutic uses of alteplase in ischemic stroke. Answer: C

The symptoms and signs of the patient suggest that he was most likely suffering from an ischemic stroke due to the occlusion of a cerebral artery. The guidelines of the American Stroke Association indicate that alteplase, administered within 3 hours of onset can reduce the ultimate disability caused by the ischemic stroke.

A, B) These drugs can increase blood coagulability (desmopressin) or inhibit fibrinolysis (aminocaproic acid) and are therefore contraindicated in ischemic stroke.

D, E, F) No studies have clearly demonstrated that emergency treatment with anticoagulants is useful in mitigating the neurological effects of a stroke. However the use of full dose of unfractionated heparin remains controversial despite years of debate and lack of evidence supporting its use.

Explanation

Learning objective: describe the therapeutic uses of alteplase in ischemic stroke. Answer: C

The symptoms and signs of the patient suggest that he was most likely suffering from an ischemic stroke due to the occlusion of a cerebral artery. The guidelines of the American Stroke Association indicate that alteplase, administered within 3 hours of onset can reduce the ultimate disability caused by the ischemic stroke.

A, B) These drugs can increase blood coagulability (desmopressin) or inhibit fibrinolysis (aminocaproic acid) and are therefore contraindicated in ischemic stroke.

D, E, F) No studies have clearly demonstrated that emergency treatment with anticoagulants is useful in mitigating the neurological effects of a stroke. However the use of full dose of unfractionated heparin remains controversial despite years of debate and lack of evidence supporting its use.

2. A 72-year-old man suffered a transient ischemic attack of about 15 min duration. The patient had been suffering from a long standing hypertension presently controlled with losartan. Detailed workup was negative but for a 45% stenosis of the left carotid artery. A chronic treatment with which of the following drugs would be most appropriate to decrease the risk of a further stroke?

Isosorbide mononitrate

Aspirin

Abciximab

Lepirudin

Heparin

Alteplase

Learning objective: describe the main antithrombotic uses of aspirin.
Answer: B
Stroke may be defined as “the rapidly developing loss of brain function due to
disturbance in the blood supply to the brain”.All patients who had an ischemic stroke or a
transient ischemic attack (defined a mini stroke) should receive long term antithrombotic
therapy for secondary prevention. Aspirin was considered the sole first line agent but the
published literature supports the use of clopidogrel as additional first line agent. Aspirin acts
primarily by irreversibly inactivating cyclooxygenase which in turn decrease platelet aggregation
and prevents release of vasoactive substances.
C) Abciximab is a highly effective inhibitors of platelet aggregation but is used only in
emergency therapy of coronary artery disease (unstable angina, MI) or for percutaneous
coronary intervention.
D, E) Anticoagulants are not use for secondary prevention of ischemic stroke. However warfarin
is a first line agent for the primary and secondary prevention of ischemic stroke in patient with
atrial fibrillation.
F) Alteplase is used for the treatment, but not for the secondary prevention, of stroke.

Explanation

Learning objective: describe the main antithrombotic uses of aspirin.
Answer: B
Stroke may be defined as “the rapidly developing loss of brain function due to
disturbance in the blood supply to the brain”.All patients who had an ischemic stroke or a
transient ischemic attack (defined a mini stroke) should receive long term antithrombotic
therapy for secondary prevention. Aspirin was considered the sole first line agent but the
published literature supports the use of clopidogrel as additional first line agent. Aspirin acts
primarily by irreversibly inactivating cyclooxygenase which in turn decrease platelet aggregation
and prevents release of vasoactive substances.
C) Abciximab is a highly effective inhibitors of platelet aggregation but is used only in
emergency therapy of coronary artery disease (unstable angina, MI) or for percutaneous
coronary intervention.
D, E) Anticoagulants are not use for secondary prevention of ischemic stroke. However warfarin
is a first line agent for the primary and secondary prevention of ischemic stroke in patient with
atrial fibrillation.
F) Alteplase is used for the treatment, but not for the secondary prevention, of stroke.

3. A 64-year-old woman was brought to the day hospital because of a sudden onset of slurred speech and weakness of limbs of one hour duration. Medical history of the patient was significant for a long standing asthma, presently treated with inhaled salmeterol. Physical examination and lab tests were negative. A diagnosis was made and an appropriate therapy was ordered which included a drug that acts by blocking platelet ADP receptors. Which of the following drugs was most likely prescribed?

Warfarin

Aminocaproic acid

Alteplase

Clopidogrel

Heparin

Aspirin

Learning objective: explain the mechanism of actions of clopidogrel.
Answer: D
The patient’s symptoms indicate that she was most likely suffering from a transient ischemic
attack. Antiplatelet therapy is the mainstay treatment for stroke recurrence. prevention. The
treatment usually includes aspirin, but clopidogrel can be used when the patient is at risk of
aspirin hypersensitivity, like the asthmatic patient of the present case. Clopidogrel causes an
irreversible inhibition of ADP receptors thereby inhibiting the ADP-mediated platelet
aggregation (A, B, C, E, F) All these drugs do not block platelet ADP receptors.

Explanation

Learning objective: explain the mechanism of actions of clopidogrel.
Answer: D
The patient’s symptoms indicate that she was most likely suffering from a transient ischemic
attack. Antiplatelet therapy is the mainstay treatment for stroke recurrence. prevention. The
treatment usually includes aspirin, but clopidogrel can be used when the patient is at risk of
aspirin hypersensitivity, like the asthmatic patient of the present case. Clopidogrel causes an
irreversible inhibition of ADP receptors thereby inhibiting the ADP-mediated platelet
aggregation (A, B, C, E, F) All these drugs do not block platelet ADP receptors.

4. A 67-year-old man complained to his family physician of frequent palpitations. The man had had an ischemic stroke one month ago and was dismissed from the hospital last week since his neurologic conditions were stable. Drug prescribed on dismission were captopril, lovastatin and aspirin. Heart examination and ECG lead to the diagnosis of atrial fibrillation. Which of the following drugs was most likely added to the therapeutic treatment of this patient?

Losartan

Warfarin

Clopidogrel

Gemfibrozil

Lidocaine

Learning objective: describe the use of warfarin in patients with previous cardioembolic
stroke.
Answer: B
It has been shown that oral anticoagulants are not effective for prevention of stroke relapse but
they are the most effective treatment when previous stroke is associated withatrial fibrillation. In
patients with atrial fibrillation and a recent history of stroke or transient ischemic attack the risk
of recurrence places these patients in one of the highest risk categories known. Warfarin can
give a 50% reduction of this risk. Therefore warfarin (o .dabigatran) should be given to all
patients with previous ischemic stroke, who have persistent or paroxysmal atrial fibrillation.
A, C, D) The patient was already on drugs of these classes so the addition of other drug of the
same classes would be irrational
E) Lidocaine is not effective in supraventricular arrhythmias, like atrial fibrillation.

Explanation

Learning objective: describe the use of warfarin in patients with previous cardioembolic
stroke.
Answer: B
It has been shown that oral anticoagulants are not effective for prevention of stroke relapse but
they are the most effective treatment when previous stroke is associated withatrial fibrillation. In
patients with atrial fibrillation and a recent history of stroke or transient ischemic attack the risk
of recurrence places these patients in one of the highest risk categories known. Warfarin can
give a 50% reduction of this risk. Therefore warfarin (o .dabigatran) should be given to all
patients with previous ischemic stroke, who have persistent or paroxysmal atrial fibrillation.
A, C, D) The patient was already on drugs of these classes so the addition of other drug of the
same classes would be irrational
E) Lidocaine is not effective in supraventricular arrhythmias, like atrial fibrillation.

5. A 53-year-old woman was brought to the hospital because of a sudden unilateral blindness and inability to move the extremities of the contralateral body side. All symptoms disappeared half an hour later. An angiogram revealed a 55% stenosis of the right carotid artery. An appropriate therapy was prescribed. A chronic treatment with which of the following drugs would be appropriate to decrease the risk of further stroke in this patient?

Isosorbide mononitrate

Furosemide

Lovastatin

Esmolol

Alteplase

Gemfibrozil

Learning objective: outline the therapeutic uses of HMG-CoA reductase inhibitors.
Answer: C
The symptoms and signs of the patient indicate that she was most likely suffering from a
transient ischemic attack, a brief episode of neurological disturbance caused by a reduced
blood supply to an area if the brain. A secondary prevention must be considered in every
patient with a previous transient ischemic attack or a previous stroke. Drugs effective in
reducing the risk of stroke include aspirin and statins (in all patients), warfarin (in patients with
atrial fibrillation) and ACE inhibitors or angiotensin antagonists plus a thiazide (in patient with
high blood pressure)
A, B, D, E, F) All these drugs are useless, or even dangerous, in patient at risk of ischemic
stroke.

Explanation

Learning objective: outline the therapeutic uses of HMG-CoA reductase inhibitors.
Answer: C
The symptoms and signs of the patient indicate that she was most likely suffering from a
transient ischemic attack, a brief episode of neurological disturbance caused by a reduced
blood supply to an area if the brain. A secondary prevention must be considered in every
patient with a previous transient ischemic attack or a previous stroke. Drugs effective in
reducing the risk of stroke include aspirin and statins (in all patients), warfarin (in patients with
atrial fibrillation) and ACE inhibitors or angiotensin antagonists plus a thiazide (in patient with
high blood pressure)
A, B, D, E, F) All these drugs are useless, or even dangerous, in patient at risk of ischemic
stroke.

6. A 65-year-old woman suddenly collapsed in the dining room of her home. Upon arrival by ambulance to the emergency department she regained consciousness and complained of severe headache. Physical examination was significant for a stiff neck and a mild mental confusion. A CT scan revealed blood in the subarachnoidal space. Which of the following drugs would be appropriate to prevent the delayed cerebral ischemia in this patient?

Verapamil

Isosorbide mononitrate

Propranolol

Dobutamine

Nicardipine

Clonidine

Learning objective: choose the appropriate drug therapy for a patient with subarachnoid hemorrhage
Answer: E
Subarachnoid hemorrhage should always be considered in patient who presents with headache and syncope. The diagnostic test of choice for this disease is CT scan which has a sensitivity >90%. Delayed ischemic deficit due to vasospasm is the most common cause of morbidity and mortality following subarachnoid hemorrhage. Nicardipine is a calcium channel blocker with some affinity for cerebral blood vessels and is used by IV infusion to prevent delayed cerebral vasospasm associated with subarachnoid hemorrhage.

A) All the other calcium channel blockers lack selectivity for cerebral blood vessel and therefore
are not indicated in subarachnoid hemorrhage.
B, C, D, F) All these drugs are useless or dangerous in subarachnoid hemorrhage

Explanation

Learning objective: choose the appropriate drug therapy for a patient with subarachnoid hemorrhage
Answer: E
Subarachnoid hemorrhage should always be considered in patient who presents with headache and syncope. The diagnostic test of choice for this disease is CT scan which has a sensitivity >90%. Delayed ischemic deficit due to vasospasm is the most common cause of morbidity and mortality following subarachnoid hemorrhage. Nicardipine is a calcium channel blocker with some affinity for cerebral blood vessels and is used by IV infusion to prevent delayed cerebral vasospasm associated with subarachnoid hemorrhage.

A) All the other calcium channel blockers lack selectivity for cerebral blood vessel and therefore
are not indicated in subarachnoid hemorrhage.
B, C, D, F) All these drugs are useless or dangerous in subarachnoid hemorrhage

7. A 56-year-old man hospitalized because of a hemorrhagic stroke was found semiconscious in his bed by the nurse. Shortly thereafter he showed muscle rigidity and opisthotonus followed by jerking movements of his harms and legs. An emergency therapy was planned and a drug was administered IV. Which of the following drugs was most likely given?

Ethosuximide

Lamotigrine

Topiramate

Alteplase

Heparin

Lorazepam

Learning objective: describe the use of lorazepam in stroke-related seizures.
Answer: F
The signs of the patient indicate that he had a tonic-clonic seizure. Seizures may occur in up to
20% of stroke patients and can appear soon after stroke or be related to a rapidly developing
neurologic event such as further infarction, hemorrhage or cerebral edema. Benzodiazepines
(lorazepam, diazepam) are the treatment of choice for a person who is actively seizing,
irrespective to the cause of seizure.
A) Ethosuximide is an anticonvulsant active only against absence seizure.
B, C) These anticonvulsant can be used for chronic treatment of tonic-clonic epilepsy but they
are given orally and cannot be used for emergency therapy of a clonic-tonic attack.
D, E) These drugs are absolutely contraindicated in hemorrhagic stroke.

Explanation

Learning objective: describe the use of lorazepam in stroke-related seizures.
Answer: F
The signs of the patient indicate that he had a tonic-clonic seizure. Seizures may occur in up to
20% of stroke patients and can appear soon after stroke or be related to a rapidly developing
neurologic event such as further infarction, hemorrhage or cerebral edema. Benzodiazepines
(lorazepam, diazepam) are the treatment of choice for a person who is actively seizing,
irrespective to the cause of seizure.
A) Ethosuximide is an anticonvulsant active only against absence seizure.
B, C) These anticonvulsant can be used for chronic treatment of tonic-clonic epilepsy but they
are given orally and cannot be used for emergency therapy of a clonic-tonic attack.
D, E) These drugs are absolutely contraindicated in hemorrhagic stroke.

8. A 61-year-old man was admitted to the hospital because of slurred speech and rapidly progressive paralysis of his left arm. These symptoms lasted for twenty minutes and disappeared rapidly. Vital sings on admission were: Blood pressure 220/110, heart rate 110 bpm, respirations 14/min. Neurologic examination was normal. A doppler exam of his carotid arteries showed 80% stenosis on the left and 40% stenosis on the right. A diagnosis was made and an emergency therapy was prescribed. Which of the following drugs was most likely administer by IV infusion to this patient?

Labetalol

Alteplase

Lovastatin

Clopidogrel

Hydrochlorotiazide

Learning objective: describe the management of a patient with transient ischemic attack and
concomitant severe hypertension.
Answer: A
The symptoms of the patient indicate that he was most likely suffering from a transient ischemic
attack. Since the patient had a severe hypertension, blood pressure should be controlled promptly
to decrease the risk of further stroke. Labetalol given by IV infusion has a fast onset of action and
can reduce blood pressure without causing reflex tachycardia, which is especially useful in this
patient who is already tachycardic.
B) Fibrinolytic drugs are indicated only when there is diagnosis of stroke with persisting neurologic
deficit. They are not indicated in transient ischemic attack.
C, D) These drugs are used chronically to prevent stroke relapse but are not given iv in emergency
situations.

Explanation

Learning objective: describe the management of a patient with transient ischemic attack and
concomitant severe hypertension.
Answer: A
The symptoms of the patient indicate that he was most likely suffering from a transient ischemic
attack. Since the patient had a severe hypertension, blood pressure should be controlled promptly
to decrease the risk of further stroke. Labetalol given by IV infusion has a fast onset of action and
can reduce blood pressure without causing reflex tachycardia, which is especially useful in this
patient who is already tachycardic.
B) Fibrinolytic drugs are indicated only when there is diagnosis of stroke with persisting neurologic
deficit. They are not indicated in transient ischemic attack.
C, D) These drugs are used chronically to prevent stroke relapse but are not given iv in emergency
situations.

9. A 68-year-old man suddenly collapsed at home and was brought unconscious to the hospital. Physical examination showed a comatose patient with spasticity on left limbs. Vital signs were: blood pressure 145/86 mm Hg, pulse 85 bpm, respirations 12/min, temperature 102.7F. A CT scan confirmed the diagnosis of ischemic stroke and an emergency multidrug therapy was started. Which of the following drugs was most likely included in the emergency treatment of this patient?

Nimodipine

Labetalol

Acetaminophen

Warfarin

Lepirudin

Learning objective: describe the treatment of hyperthermia in a patient with ischemic stroke.
Answer: C
Increased body temperature in the setting of acute ischemic stroke is associated with poor
neurological outcome (increased risk of morbidity and mortality), possibly secondary to
increased metabolic demands, enhanced release of neurotransmitters, and increased free
radical production. Because of the negative effects of fever, lowering an acutely elevated body
temperature might improve the prognosis of patients with stroke. Measures include antipyretic
medications like acetaminophen and cooling devices.
A, B ) Antihypertensive drugs should be administered to a patient with stroke only when the
blood pressure is quite high (systolic >185 mm Hg. or diastolic >110 mm Hg).
D, E) No studies have clearly demonstrated that emergency treatment with anticoagulants is
useful in mitigating the neurological effects of a stroke.

Explanation

Learning objective: describe the treatment of hyperthermia in a patient with ischemic stroke.
Answer: C
Increased body temperature in the setting of acute ischemic stroke is associated with poor
neurological outcome (increased risk of morbidity and mortality), possibly secondary to
increased metabolic demands, enhanced release of neurotransmitters, and increased free
radical production. Because of the negative effects of fever, lowering an acutely elevated body
temperature might improve the prognosis of patients with stroke. Measures include antipyretic
medications like acetaminophen and cooling devices.
A, B ) Antihypertensive drugs should be administered to a patient with stroke only when the
blood pressure is quite high (systolic >185 mm Hg. or diastolic >110 mm Hg).
D, E) No studies have clearly demonstrated that emergency treatment with anticoagulants is
useful in mitigating the neurological effects of a stroke.

10. A 66-year-old woman, admitted to the hospital with an ischemic stroke, received an appropriate therapy which included low dose of aspirin. Which of the following statements best explains why aspirin is given at a low dose to prevent platelet aggregation?

Higher doses would cause a longer inhibition of prostacyclin synthesis

Higher doses would cause an unacceptable high risk of adverse effects

Low doses also cause blockade of platelet ADP receptor

Low doses favor the adhesion of platelet to vascular endothelium

Higher doses favor the rupture of atherosclerotic plaques in the coronaries.

Learning objective: explain why the antiplatelet action of aspirin may disappear when
higher does are given.
Answer: A
Cyclooxygenase blockade reduces both the platelet-mediated production of TA2, which promotes
aggregation, and the endothelial cells-mediated production of prostacyclin (PGI2) which inhibits
aggregation. However endothelial cells produce new cyclooxygenase in a matter of hours while the
anuclear platelets cannot manufacture the enzyme. Therefore the low dose used is sufficient for
causing an inhibition of TA2 production that last for the life of the platelets. Higher doses are
potentially less efficacious, because of a longer inhibition of prostacyclin production that would
cause an increase in platelet. It has been shown that doses of 75 to 325 mg/day are the best for
inhibition of platelet aggregation with minimal depletion of prostacyclin
B, C, D, E) (see explanation above)

Explanation

Learning objective: explain why the antiplatelet action of aspirin may disappear when
higher does are given.
Answer: A
Cyclooxygenase blockade reduces both the platelet-mediated production of TA2, which promotes
aggregation, and the endothelial cells-mediated production of prostacyclin (PGI2) which inhibits
aggregation. However endothelial cells produce new cyclooxygenase in a matter of hours while the
anuclear platelets cannot manufacture the enzyme. Therefore the low dose used is sufficient for
causing an inhibition of TA2 production that last for the life of the platelets. Higher doses are
potentially less efficacious, because of a longer inhibition of prostacyclin production that would
cause an increase in platelet. It has been shown that doses of 75 to 325 mg/day are the best for
inhibition of platelet aggregation with minimal depletion of prostacyclin
B, C, D, E) (see explanation above)