Hydralazine
Encyclopedia
Hydralazine is a direct-acting smooth muscle
relaxant used to treat hypertension
by acting as a vasodilator primarily in arteries and arterioles. By relaxing vascular smooth muscle
, vasodilators act to decrease peripheral resistance, thereby lowering blood pressure
and decreasing afterload.
However, this only has a short term effect on blood pressure, as the system will reset to the previous, high blood pressure necessary to maintain pressure in the kidney necessary for natriuresis. The long term effect of antihypertensive drugs comes from their effects on the pressure natriuresis curve.
levels, decreasing the action of the second messenger IP3
, limiting calcium release from the sarcoplasmic reticulum of smooth muscle. This results in an vessel relaxation. It dilates arterioles more than veins.
It recently has been identified as a nitric oxide
donor.
Activation of hypoxia-inducible factors has been suggested as a mechanism.
stimulation of the heart (the baroreceptor reflex). The sympathetic stimulation may increase heart rate and cardiac output
, and in patients with coronary artery disease may cause angina pectoris or myocardial infarction
. Hydralazine may also increase plasma
renin
concentration, resulting in fluid retention. In order to prevent these undesirable side-effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., propranolol) and a diuretic
.
Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential hypertension
. However, hydralazine is the first-line therapy for hypertension in pregnancy, with methyldopa
.
nerve sheaths, acrolein may be a factor in the development of multiple sclerosis
. Hydralazine, a known scavenger of acrolein, was found to reduce myelin damage and significantly improve behavioral outcomes in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis
).
Patients given hydralazine over a period of six months may develop a lupus
-like syndrome or other immune-related diseases that, in general, are reversible with withdrawal. Hydralazine is differentially acetylated by fast and slow acetylator phenotypes, hence incidence of lupus-like disease in slow acetylators.
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
relaxant used to treat hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
by acting as a vasodilator primarily in arteries and arterioles. By relaxing vascular smooth muscle
Vascular smooth muscle
Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels.Vascular smooth muscle contracts or relaxes to both change the volume of blood vessels and the local blood pressure, a mechanism that is responsible for the...
, vasodilators act to decrease peripheral resistance, thereby lowering 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...
and decreasing afterload.
However, this only has a short term effect on blood pressure, as the system will reset to the previous, high blood pressure necessary to maintain pressure in the kidney necessary for natriuresis. The long term effect of antihypertensive drugs comes from their effects on the pressure natriuresis curve.
Mechanism of action
Hydralazine increases guanosine monophosphateGuanosine monophosphate
Guanosine monophosphate, also known as 5'-guanidylic acid or guanylic acid and abbreviated GMP, is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside guanosine. GMP consists of the phosphate group, the pentose sugar ribose, and the nucleobase...
levels, decreasing the action of the second messenger IP3
Inositol triphosphate
Inositol trisphosphate or inositol 1,4,5-trisphosphate , together with diacylglycerol , is a secondary messenger molecule used in signal transduction and lipid signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell...
, limiting calcium release from the sarcoplasmic reticulum of smooth muscle. This results in an vessel relaxation. It dilates arterioles more than veins.
It recently has been identified as a nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
donor.
Activation of hypoxia-inducible factors has been suggested as a mechanism.
Clinical use
Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex sympatheticSympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
stimulation of the heart (the baroreceptor reflex). The sympathetic stimulation may increase heart rate and cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
, and in patients with coronary artery disease may cause angina pectoris or 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...
. Hydralazine may also increase plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
concentration, resulting in fluid retention. In order to prevent these undesirable side-effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., propranolol) and a diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
.
Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
. However, hydralazine is the first-line therapy for hypertension in pregnancy, with methyldopa
Methyldopa
Methyldopa is an alpha-adrenergic agonist psychoactive drug used as a sympatholytic or antihypertensive. Its use is now mostly deprecated following the introduction of alternative safer classes of agents...
.
Pre-clinical research
Multiple sclerosis: Due to its ability to damage myelinMyelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
nerve sheaths, acrolein may be a factor in the development of multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. Hydralazine, a known scavenger of acrolein, was found to reduce myelin damage and significantly improve behavioral outcomes in a mouse model of multiple sclerosis (experimental autoimmune encephalomyelitis
Experimental autoimmune encephalomyelitis
Experimental autoimmune encephalomyelitis, sometimes Experimental Allergic Encephalomyelitis is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system...
).
Side effects
Common side-effects include:- DiarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
- Compensatory tachycardiaTachycardiaTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
due to baroreceptor reflex ->Angina - HeadacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
- Loss of appetiteAnorexia (symptom)Anorexia is the decreased sensation of appetite...
- NauseaNauseaNausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
or vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose... - DepressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
- Pounding heartbeatPalpitationA palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...
- Vitamin B6Vitamin B6Vitamin B6 is a water-soluble vitamin and is part of the vitamin B complex group. Several forms of the vitamin are known, but pyridoxal phosphate is the active form and is a cofactor in many reactions of amino acid metabolism, including transamination, deamination, and decarboxylation...
deficiency - Drug-Induced Lupus ErythematosusDrug-induced lupus erythematosusDrug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response producing symptoms similar to those of SLE...
- ANCA-associated Vasculitis - Generally MPO-ANCA positive
Patients given hydralazine over a period of six months may develop a lupus
Lupus
Lupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...
-like syndrome or other immune-related diseases that, in general, are reversible with withdrawal. Hydralazine is differentially acetylated by fast and slow acetylator phenotypes, hence incidence of lupus-like disease in slow acetylators.