Actions of Emodopan in details
Pharmacology: Emodopan HCl can stimulate α, β and Emodopan receptors. At infusion rates of 0.5-2 mcg/kg/min, Emodopan receptors are selectively activated and blood pressure either does not change or decreases slightly. The most important effects are renal and mesenteric vasodilatation. Renal plasma flow, glomerular filtration rate and sodium excretion usually increases. At infusion rates of 2-10 mcg/kg/min, β-receptors are activated and cardiac output and systolic blood pressure increase. The total peripheral resistance is relatively unchanged because peripheral vasoconstriction (α effect) and muscle vasodilatation (β effect). At infusion rates >10 mcg/kg/min, α receptors are activated, causing vasoconstriction, and both systolic and diastolic pressure increase.
Emodopan does not cross the blood-brain barrier and so does not activate receptors in the brain.
Pharmacokinetics: Absorption: The steady state blood levels following IV infusion have not been determined in any species, nor has the time for these to be achieved.
Distribution: Emodopan is widely distributed in the body.
Protein-Binding: No information is available for humans or animals (however, Emodopan is rapidly metabolized and excreted).
Metabolism: Emodopan is metabolized in the liver, kidneys and plasma and the metabolites are excreted by the kidneys. The major routes of metabolism are deamination by monoamine oxidase and formation of methylated and reduced derivatives by cathechol-o-methyl transferase.
On infusion of 14C labeled Emodopan into humans, it was found that approximately 75% of the infused Emodopan was rapidly converted into metabolites of Emodopan and 25% was synthesized into noradrenaline and its metabolic products. Only a trace of unlabeled adrenaline was detected. The principal metabolite of Emodopan was 3-methoxy-4-hydroxy phenylethanol (18.6% of an infused dose) and the principal metabolites of noradrenaline were normetanephrine and 3-4-dihydroxy-mandelic acid.
Excretion: Ninety-seven percent of the infused dose of 14C labeled Emodopan appeared in urine as metabolites. The metabolites of both Emodopan and noradrenaline appear to be at least partially secreted (70% of an infused dose has been found to be secreted per 10 min infusion period). The degree of active excretion of Emodopan is about the same for adrenaline and noradrenaline and is inhibited by probenecid.
Onset of Action: Five minutes, with a duration of action <10 min (in patients receiving MAOIs, the duration of action may be as long as 1 hr).
Half-Life: Approximately 2 min after an IV bolus (due to rapid metabolism and excretion).
Clinical implication of pharmacokinetic data: Emodopan should be given by continuous infusion because of the rapid metabolism and excretion of the drug.
How should I take Emodopan?
Emodopan injection is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.
Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when Emodopan is injected.
Your breathing, blood pressure, oxygen levels, kidney function, and other vital signs will be watched closely while you are receiving Emodopan.
To be sure Emodopan is helping your condition and not causing harmful effects, your blood cells and kidney function may need to be tested often. Do not miss any follow-up visits to your doctor for blood or urine tests.
Emodopan administration
Emodopan injection is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.
Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when Emodopan injection is injected.
Your breathing, blood pressure, oxygen levels, kidney function, and other vital signs will be watched closely while you are receiving Emodopan injection.
To be sure this medication is helping your condition and not causing harmful effects, your blood cells and kidney function may need to be tested often. Do not miss any follow-up visits to your doctor for blood or urine tests.
Emodopan pharmacology
Emodopan is a natural catecholamine formed by the decarboxylation of 3,4-ihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves.
Emodopan produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve ending.
Emodopan’s onset of action occurs within five minutes of intravenous administration, and with Emodopan’s plasma half-life of about two minutes, the duration of action is less than ten minutes. If monoamine oxidase (MAO) inhibitors are present, however, the duration may increase to one hour. The drug is widely distributed in the body but does not cross the blood-brain barrier to a significant extent. Emodopan is metabolized in the liver, kidney, and plasma by MAO and catechol-O-methyltransferase to the inactive compounds homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid. About 25% of the dose is taken up into specialized neurosecretory vesicles (the adrenergic nerve terminals), where it is hydroxylated to form norepinephrine. It has been reported that about 80% of the drug is excreted in the urine within 24 hours, primarily as HVA and its sulfate and glucuronide conjugates and as 3,4-dihydroxyphenylacetic acid. A very small portion is excreted unchanged.
The predominant effects of Emodopan are dose-related, although actual response of an individual patient will largely depend on the clinical status of the patient at the time the drug is administered. At low rates of infusion (0.5-2 mcg/kg/min) Emodopan causes vasodilation that is presumed to be due to a specific agonist action on Emodopan receptors (distinct from alpha- and beta-adrenoceptors) In the renal, mesenteric, coronary, and intracerebral vascular beds. At these Emodopan receptors, haloperidol is an antagonist. The vasodilation in these vascular beds is accompanied by increased glomerular filtration rate, renal blood flow, sodium excretion, and urine flow. Hypotension sometimes occurs. An increase in urinary output produced by Emodopan is usually not associated with a decrease in osmolarity of the urine.
At intermediate rates of infusion (2-10 mcg/kg/min) Emodopan acts to stimulate the beta1-adrenoceptors, resulting In improved myocardial contractility, increased SA rate and enhanced impulse conduction in the heart. There is little, if any, stimulation of the beta2-adrenoceptors (peripheral vasodilation). Emodopan causes less increase in myocardial oxygen consumption than isoproterenol, and its use is not usually associated with a tachyarrhythmia. Clinical studies indicate that it usually increases systolic and pulse pressure with either no effect or a slight increase in diastolic pressure. Blood flow to the peripheral vascular beds may decrease while mesenteric flow increased due to increased cardiac output. At low and intermediate doses, total peripheral resistance (which would be raised by alpha activity) is usually unchanged.
At higher rates of infusion (10-20 mcg/kg/min) there is some effect on alpha-adrenoceptors, with consequent vasoconstrictor effects and a rise in blood pressure. The vasoconstrictor effects are first seen in the skeletal muscle vascular beds, but with increasing doses they are also evident in the renal and mesenteric vessels. At very high rates of infusion (above 20 mcg/kg/min), stimulation of alpha-adrenoceptors predominates and vasoconstriction may compromise the circulation of the limbs and override the dopaminergic effects of Emodopan, reversing renal dilation and natriuresis.
Dextrose provides a source of calories. Dextrose is readily metabolized, may decrease losses of body protein and nitrogen promotes glycogen deposition and decreases or prevents ketosis if sufficient doses are provided.
References
- NCIt. "Dopamine: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Dopamine: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Emodopan are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Emodopan. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
