Nimodipine
Encyclopedia
Nimodipine is a dihydropyridine calcium channel blocker
originally developed for the treatment of high blood pressure. It is not frequently used for this indication, but has shown good results in preventing a major complication of subarachnoid hemorrhage
(a form of cerebral hemorrhage) termed vasospasm
; this is now the main use of nimodipine.
vasospasm
and resultant ischemia
, a complication of subarachnoid hemorrhage
(a form of cerebral bleed), specifically from ruptured intracranial berry aneurysms irrespective of the patient's post-ictus neurological condition. Its administration begins within 4 days of a subarachnoid hemorrhage and is continued for three weeks. If blood pressure
drops by over 5%, dosage is adjusted. There is still controversy regarding the use of intravenous nimodipine on a routine basis.
A 2003 trial (Belfort et al.) found nimodipine was inferior to magnesium sulfate
in preventing seizures in women with severe preeclampsia.
While nimodipine is not used in head injury
currently, it has shown promise in clinical studies. A 2009 study found that patients with severe head trauma who were given nimodipine, via peripheral vein injection, along with the standard procedures had significantly higher cerebral perfusion
pressure and jugular venous oxygen saturation, while intracranial pressure
, jugular lactate
and jugular glucose
were lower. The study concluded that Glasgow outcome score values were higher, and that the cerebral metabolism was improved.
(an antibiotic) or ketoconazole (an antifungal drug).
, flushing and sweating, edema, nausea and other gastrointestinal problems, most of which are known characteristics of calcium channel blockers. It is contraindicated
in unstable angina
or an episode of myocardial infarction
more recently than one month.
While nimodipine was occasionally administered intravenously in the past, the FDA released an alert in January 2006 warning that it had received reports of the approved oral preparation being used intravenously, leading to severe complications; this was despite warnings on the box that this should not be done.
, congestive heart failure
, hyponatremia, decreasing platelet count, disseminated intravascular coagulation, deep vein thrombosis
.
Calcium channel blocker
A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with...
originally developed for the treatment of high blood pressure. It is not frequently used for this indication, but has shown good results in preventing a major complication of subarachnoid hemorrhage
Subarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
(a form of cerebral hemorrhage) termed vasospasm
Vasospasm
Vasospasm refers to a condition in which blood vessels spasm, leading to vasoconstriction. This can lead to tissue ischemia and death . Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to...
; this is now the main use of nimodipine.
Dosage
The regular dosage is 60 mg tablets every four hours. If the patient is unable to take tablets orally, it was previously given via intravenous infusion at a rate of 1–2 mg/hour (lower dosage if the body weight is <70 kg or blood pressure is too low), but since the withdrawal of the IV preparation, administration by nasogastric tube is an alternative.Usage
Because it has some selectivity for cerebral vasculature, nimodipine's main use is in the prevention of cerebralCerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
vasospasm
Vasospasm
Vasospasm refers to a condition in which blood vessels spasm, leading to vasoconstriction. This can lead to tissue ischemia and death . Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to...
and resultant ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
, a complication of subarachnoid hemorrhage
Subarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
(a form of cerebral bleed), specifically from ruptured intracranial berry aneurysms irrespective of the patient's post-ictus neurological condition. Its administration begins within 4 days of a subarachnoid hemorrhage and is continued for three weeks. If blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
drops by over 5%, dosage is adjusted. There is still controversy regarding the use of intravenous nimodipine on a routine basis.
A 2003 trial (Belfort et al.) found nimodipine was inferior to magnesium sulfate
Magnesium sulfate
Magnesium sulfate is a chemical compound containing magnesium, sulfur and oxygen, with the formula MgSO4. It is often encountered as the heptahydrate epsomite , commonly called Epsom salt, from the town of Epsom in Surrey, England, where the salt was distilled from the springs that arise where the...
in preventing seizures in women with severe preeclampsia.
While nimodipine is not used in head injury
Head injury
Head injury refers to trauma of the head. This may or may not include injury to the brain. However, the terms traumatic brain injury and head injury are often used interchangeably in medical literature....
currently, it has shown promise in clinical studies. A 2009 study found that patients with severe head trauma who were given nimodipine, via peripheral vein injection, along with the standard procedures had significantly higher cerebral perfusion
Perfusion
In physiology, perfusion is the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue. The word is derived from the French verb "perfuser" meaning to "pour over or through."...
pressure and jugular venous oxygen saturation, while intracranial pressure
Intracranial pressure
Intracranial pressure is the pressure inside the skull and thus in the brain tissue and cerebrospinal fluid . The body has various mechanisms by which it keeps the ICP stable, with CSF pressures varying by about 1 mmHg in normal adults through shifts in production and absorption of CSF...
, jugular lactate
Lactate
Lactate may refer to:*The act of lactation*The conjugate base of lactic acid...
and jugular glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
were lower. The study concluded that Glasgow outcome score values were higher, and that the cerebral metabolism was improved.
Absorption
In humans, it is administered primarily orally and reaches peak plasma concentrations within one and a half hours. Patients taking enzyme-inducing anticonvulsants have lower plasma concentrations, while patients taking sodium valproate were markedly higher.Metabolism
Nimodipine is metabolized in the first pass metabolism. The dihydropyridine ring of the nimodipine is dehydrogenated in the hepatic cells of the liver, a process governed by Cytochrome P-4503A (CYP3A). This can be completely inhibited however, by troleandomycinTroleandomycin
Troleandomycin is a macrolide antibiotic. It is currently sold in Italy and Turkey.Side effects: It is a CYP3A4 inhibitor....
(an antibiotic) or ketoconazole (an antifungal drug).
Excretion
Studies in non-human mammals using radioactive labeling have found that 40-50% of the dose is excreted via urine. The residue level in the body was never more than 1.5% in monkeys. There were some metabolites of the drug found in the milk of lactating rat subjects.Mode of action
Nimodipine binds specifically to L-type voltage-gated calcium channels. There are numerous theories about its mechanism in preventing vasospasm, but none are conclusive.Contraindications
Nimodipine is associated with low blood pressureHypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
, flushing and sweating, edema, nausea and other gastrointestinal problems, most of which are known characteristics of calcium channel blockers. It is contraindicated
Contraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
in unstable angina
Unstable angina
Unstable angina is a type of angina pectoris that is irregular. It is a type of acute coronary syndrome.It can be difficult to distinguish from non–Q-wave myocardial infarction.-Definition:...
or an episode of myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
more recently than one month.
While nimodipine was occasionally administered intravenously in the past, the FDA released an alert in January 2006 warning that it had received reports of the approved oral preparation being used intravenously, leading to severe complications; this was despite warnings on the box that this should not be done.
Side-effects
The FDA has classified the side effects into groups based on dosages levels at q4h. For the high dosage group (90 mg) less than 1% of the group experienced adverse conditions including itching, gastrointestinal hemorrhage, thrombocytopenia, neurological deterioration, vomiting, diaphoresisDiaphoresis
Diaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions.Diaphoretic is the state of perspiring profusely, or something that has the power to cause increased perspiration....
, congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, hyponatremia, decreasing platelet count, disseminated intravascular coagulation, deep vein thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
.
External links
- Nimotop (manufacturer's website)
- Nimodipine (patient information)