Hemorrhagic Stroke Medication

Updated: Apr 22, 2019
  • Author: David S Liebeskind, MD, FAAN, FAHA, FANA; Chief Editor: Andrew K Chang, MD, MS  more...
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Medication

Medication Summary

Medications used in the treatment of acute stroke include anticonvulsants such as diazepam, to prevent seizure recurrence; antihypertensive agents such as labetalol, to reduce blood pressure (BP) and other risk factors for heart disease; and osmotic diuretics such as mannitol, to decrease intracranial pressure in the subarachnoid space.

As previously mentioned, the treatment and management of patients with acute intracerebral hemorrhage depends on the cause and severity of the bleeding. However, there is currently no effective targeted therapy for hemorrhagic stroke.

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Anticonvulsants, Other

Class Summary

Benzodiazepines are commonly used to control seizure activity and recurrence. Agents such as lorazepam and diazepam are often used acutely, in combination with either phenytoin or fosphenytoin loading.

Diazepam (Diastat, Diazemuls, Valium)

Diazepam controls active seizures by modulating the postsynaptic effects of gamma-aminobutyric acid type A (GABA-A) transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic system, the thalamus, and hypothalamus, to induce a calming effect. It also acts as an effective adjunct for the relief of skeletal muscle spasm caused by upper motor neuron disorders.

Diazepam should be augmented by longer-acting anticonvulsants, such as phenytoin or phenobarbital, because it rapidly distributes to other body fat stores.

Lorazepam (Ativan)

Lorazepam is a short-acting acting benzodiazepine with a moderately long half-life. It has become the drug of choice in many centers for treating active seizures.

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Anticonvulsants, Hydantoins

Class Summary

Anticonvulsants prevent seizure recurrence and terminate clinical and electrical seizure activity. These agents are used routinely to avoid seizures that may be induced by cortical damage.

According to the American Heart Association/American Stroke Association (AHA/ASA) 2010 guidelines for management of spontaneous intracranial hemorrhage, treatment with antiepileptic drugs is indicated for those patients with clinical seizures or with electroencephalographic (EEG) seizure activity accompanied by a change in mental status. [1] Prophylactic use of anticonvulsants is controversial and should be used judiciously, if at all.

Phenytoin (Dilantin)

Phenytoin may act in the motor cortex, where it may inhibit spread of seizure activity, as well as in the brainstem centers responsible for the tonic phase of grand mal seizures. All doses should be individualized. The antiepileptic effect of phenytoin is not immediate. Concomitant administration of an intravenous benzodiazepine will usually be necessary to control status epilepticus. In addition, a larger dose before retiring should be administered if the dose cannot be divided equally.

Fosphenytoin (Cerebyx)

Fosphenytoin is a diphosphate ester salt of phenytoin that acts as water-soluble prodrug of phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.

To avoid the need to perform molecular-weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express the dose as phenytoin sodium equivalents. Although fosphenytoin can be administered intravenously or intramuscularly, the intravenous route is the route of choice and should be used in emergency situations.

The antiepileptic effect of phenytoin, whether given as fosphenytoin or parenteral phenytoin, is not immediate. Concomitant administration of an intravenous benzodiazepine will usually be necessary to control status epilepticus.

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Beta Blockers, Alpha Activity

Class Summary

Beta blockers are used to reduce BP and risk factors for heart disease. They are first-line agents for acute BP reduction in hemorrhagic stroke, but they are second-line agents for stroke prevention. Selective beta blockers obstruct access to beta-1 receptors more than they do to beta-2 receptors; nonselective beta blockers obstruct access to beta-1 and beta-2 receptors.

Labetalol (Trandate)

Labetalol blocks beta1-, alpha-, and beta2-adrenergic receptor sites to decrease BP. It is administered as a 5-20 mg intravenous bolus over 2 minutes, then as a continuous infusion at 2 mg/min (not to exceed 300 mg/dose).

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Beta Blockers, Beta-1 Selective

Class Summary

Beta blockers are used to reduce BP and risk factors for heart disease. They are first-line agents for acute BP reduction in hemorrhagic stroke, but they are second-line agents for stroke prevention. Selective beta blockers obstruct access to beta-1 receptors more than they do to beta-2 receptors; nonselective beta blockers obstruct access to beta-1 and beta-2 receptors.

Esmolol (Brevibloc)

Esmolol is an ultra-short-acting agent that selectively blocks beta-1 receptors with little or no effect on beta-2 receptor types. This drug is particularly useful in patients with elevated arterial pressure, especially if surgery is planned, and its short half-life of 8 minutes allows for titration and quick discontinuation, if necessary.

Esmolol is also useful in patients at risk for experiencing complications from beta blockade, particularly those with reactive airway disease, mild to moderate left-ventricular dysfunction, and/or peripheral vascular disease.

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Vasodilators

Class Summary

Vasodilators lower BP through direct vasodilation and relaxation of the vascular smooth muscle. They are used more for BP lowering in refractory situations.

Hydralazine (Apresoline)

Hydralazine decreases systemic resistance through direct vasodilation of arterioles and is used to treat hypertensive emergencies. The use of a vasodilator will reduce the stroke volume ratio (SVR), which, in turn, may allow forward flow, improving cardiac output. Hydralazine is typically not a first-line agent, because of its side-effect profile.

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Calcium Channel Blockers

Class Summary

Calcium channel blockers are used to lower BP by relaxing the blood vessels and increasing the amount of blood and oxygen that is delivered to the heart, while reducing the heart’s workload. In acute situations, intravenous calcium channel blockers are frequently used to control BP. These are first-line agents for long-term BP control in stroke patients (along with thiazides, ACEIs, and angiotensin receptor blockers [ARBs]).

Nicardipine (Cardene, Cardene IV, Cardene SR)

Nicardipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery and reduces myocardial oxygen consumption.

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Angiotensin-converting Enzyme Inhibitors

Class Summary

ACEIs prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. These are first-line agents for emergent and long-term BP control in hemorrhagic stroke patients.

Enalapril (Vasotec)

Enalapril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion. It helps to control BP and proteinuria.

Ramipril (Altace)

Ramipril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.

Lisinopril (Zestril)

Lisinopril prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion.

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Angiotensin Receptor Blockers

Class Summary

ARBs may be used as an alternative to ACEIs in patients who develop adverse effects, such as a persistent cough.

Losartan (Cozaar)

Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of the renin-angiotensin system than ACEIs do. In addition, it does not affect the response to bradykinin and is less likely to be associated with cough and angioedema.

Candesartan (Atacand)

Candesartan blocks vasoconstriction and the aldosterone-secreting effects of angiotensin II. It may induce a more complete inhibition of the renin-angiotensin system than ACEIs do. In addition, it does not affect response to bradykinin and is less likely to be associated with cough and angioedema.

Valsartan (Diovan)

Valsartan produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower BP by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses.

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Diuretics, Thiazide

Class Summary

Thiazide diuretics inhibit sodium and chloride reabsorption in the distal tubules of the kidney, resulting in increased urinary excretion of sodium and water.

Hydrochlorothiazide (Microzide)

Hydrochlorothiazide inhibits the reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as potassium and hydrogen ions.

Chlorthalidone (Diuril)

Chlorthalidone inhibits the reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as potassium and hydrogen ions.

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Diuretics, Osmotic Agents

Class Summary

Osmotic diuretics, such as mannitol, may be used to decrease intracranial pressure in the subarachnoid space. As water diffuses from the subarachnoid space into the intravascular compartment, pressure in the subarachnoid compartment may decrease.

Mannitol (Osmitrol)

Mannitol reduces cerebral edema with the help of osmotic forces. It also decreases blood viscosity, resulting in reflex vasoconstriction and lowering of intracranial pressure.

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Analgesics, Other

Class Summary

Because hyperthermia may exacerbate neurologic injury, these agents may be given to reduce fever and relieve pain.

Acetaminophen (Tylenol, FeverAll, Aspirin Free Anacin)

Acetaminophen reduces fever, maintains normothermia, and reduces headache.

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Hemostatics

Class Summary

Vitamin K is used to promote the formation of clotting factors. Phytonadione can overcome the competitive block produced by warfarin and other related anticoagulants. A fresh frozen plasma (FFP) infusion followed by oral vitamin K should be given without delay in the emergency department to manage warfarin-related intracranial hemorrhage.

Vitamin K1 (phytonadione; vitamin K, Mephyton, AquaMephyton)

Phytonadione can overcome the competitive block produced by warfarin and other related anticoagulants. Vitamin K3 (menadione) is not effective for this purpose. There is a delay of the clinical effect for several hours while liver synthesis of the clotting factors is initiated and plasma levels of clotting factors II, VII, IX, and X are gradually restored.

Phytonadione should not be administered prophylactically and is used only if evidence of anticoagulation exists. The required dose varies with the clinical situation, including the dose and duration of action of the anticoagulant ingested. Intravenous phytonadione is recommended for life-threatening bleeding, including intracerebral hemorrhage complicating warfarin therapy, although it carries a small risk of anaphylaxis.

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Blood Components

Class Summary

These agents are indicated for the correction of abnormal hemostatic parameters.

Fresh frozen plasma

Plasma, the fluid component of blood, contains the blood's soluble clotting factors. FFP is created by separating plasma from a unit of blood and freezing it for use in patients with blood-product deficiencies.

Platelets

Platelets are fragments of large bone marrow cells found in the blood that play a role in blood coagulation. A single random donor unit of platelets per 10 kg is administered in adults when the platelet count drops below 50,000/µL.

Prothrombin complex concentrate (Bebulin VH, Profilnine SD)

Prothrombin complex concentrate (PCC) is a mixture of vitamin K-dependent clotting factors found in normal plasma that replaces deficient clotting factors, provides an increase in plasma levels of factor IX, and can temporarily correct a coagulation defect in patients with factor IX deficiency. PCC is usually reserved for situations in which volume overload is a concern.

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Antidotes, Other

Class Summary

Protamine is used to neutralize the effects of anticoagulants.

Protamine

Protamine sulfate forms a salt with heparin and neutralizes its effects. The dosage administered is dependent on the amount of time that has passed since heparin was given.

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Vasopressin-Related

Class Summary

These agents improve bleeding time and hemostasis.

Desmopressin acetate (DDAVP, Stimate)

Desmopressin releases von Willebrand protein from endothelial cells. It improves bleeding time and hemostasis in patients with mild and moderate von Willebrand disease without abnormal molecular forms of von Willebrand protein. It is effective in uremic bleeding. Tachyphylaxis usually develops after 48 hours, but the drug can be effective again after several days.

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