Pharm - Pharmacological Therapy Of Stroke

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.

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.

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.

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.

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.

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.

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

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.

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)

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.