Actions of Metoclopramide Hydrochloride in details
The action of the drug on the human body is called Pharmacodynamics in Medical terminology. To produce its effect and to change the pathological process that is happening the body and to reduce the symptom or cure the disease, the medicine has to function in a specific way. The changes it does to the body at cellular level gives the desired result of treating a disease. Drugs act by stimulating or inhibiting a receptor or an enzyme or a protein most of the times. Medications are produced in such a way that the ingredients target the specific site and bring about chemical changes in the body that can stop or reverse the chemical reaction which is causing the disease.
sponsored
S(-)Metoclopramide Hydrochloride is a β1-selective blocker. Metoclopramide Hydrochloride has an insignificant membrane stabilizing effect and does not display partial agonistic activity.
Pharmacology: Pharmacodynamics: Metoclopramide Hydrochloride is a β1-selective β-blocker ie, it blocks β1-receptors at doses much lower than those needed to block β2-receptors. S-Metoclopramide Hydrochloride is an active enantiomer of racemic Metoclopramide Hydrochloride which has been shown to have higher binding affinity for β1-adrenergic receptors. The mechanism of antihypertensive effect of β-blocking agent has not been elucidated. However, several possible mechanisms have been proposed: (1) Competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites leading to decreased cardiac output; (2) a central effect leading to reduced central sympathetic outflow to the periphery; and (3) inhibition of renin release from the juxtaglomerular apparatus in kidneys.
Metoclopramide Hydrochloride interferes less with insulin release and carbohydrate metabolism than do nonselective β-blockers. Metoclopramide Hydrochloride interferes much less with the cardiovascular response to hypoglycaemia than do nonselective β-blockers.
Pharmacokinetics: S-Metoclopramide Hydrochloride is almost completely absorbed after oral administration. Maximum plasma concentration is achieved in approximately 7 hrs. Metoclopramide Hydrochloride exhibits stereoselective pharmacokinetics and undergoes oxidative metabolism in the liver. Majority of an oral dose can be recovered in the urine.
Significant reduction in systolic and diastolic blood pressure was noticed at 7 days of S(-)Metoclopramide Hydrochloride therapy in 1 randomized control clinical trial (SMART study).
How should I take Metoclopramide Hydrochloride?
Take Metoclopramide Hydrochloride exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.
Take the medicine at the same time each day.
Metoclopramide Hydrochloride should be taken with a meal or just after a meal.
A Metoclopramide Hydrochloride tablet can be divided in half if your doctor has told you to do so. The half tablet should be swallowed whole, without chewing or crushing.
While using Metoclopramide Hydrochloride, you may need frequent blood tests at your doctor's office. Your blood pressure will need to be checked often.
If you need surgery, tell the surgeon ahead of time that you are using Metoclopramide Hydrochloride.
You should not stop using Metoclopramide Hydrochloride suddenly. Stopping suddenly may make your condition worse.
If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.
Store Metoclopramide Hydrochloride at room temperature away from moisture and heat.
Metoclopramide Hydrochloride administration
Administration of drug is important to know because the drug absorption and action varies depending on the route and time of administration of the drug. A medicine is prescribed before meals or after meals or along with meals. The specific timing of the drug intake about food is to increase its absorption and thus its efficacy. Few work well when taken in empty stomach and few medications need to be taken 1 or 2 hrs after the meal. A drug can be in the form of a tablet, a capsule which is the oral route of administration and the same can be in IV form which is used in specific cases. Other forms of drug administration can be a suppository in anal route or an inhalation route.
sponsored
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Take Metoclopramide Hydrochloride at the same time every day.
Metoclopramide Hydrochloride should be taken with food or just after a meal.
A Metoclopramide Hydrochloride tablet can be divided in half if your doctor has told you to do so. The half tablet should be swallowed whole, without chewing or crushing. Chewing or crushing the pill could cause too much of the drug to be released at one time.
Do not skip doses or stop taking Metoclopramide Hydrochloride without first talking to your doctor. Stopping suddenly may make your condition worse.
Your blood pressure will need to be checked often. Visit your doctor regularly.
If you need surgery, tell the surgeon ahead of time that you are using Metoclopramide Hydrochloride.
Metoclopramide Hydrochloride is only part of a complete program of treatment for hypertension that may also include diet, exercise, and weight control. Follow your diet, medication, and exercise routines very closely if you are being treated for hypertension.
If you are being treated for high blood pressure, keep using this medication even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medication for the rest of your life.
Store at room temperature away from moisture and heat.
Metoclopramide Hydrochloride pharmacology
Pharmacokinetics of a drug can be defined as what body does to the drug after it is taken. The therapeutic result of the medicine depends upon the Pharmacokinetics of the drug. It deals with the time taken for the drug to be absorbed, metabolized, the process and chemical reactions involved in metabolism and about the excretion of the drug. All these factors are essential to deciding on the efficacy of the drug. Based on these pharmacokinetic principles, the ingredients, the Pharmaceutical company decides dose and route of administration. The concentration of the drug at the site of action which is proportional to therapeutic result inside the body depends on various pharmacokinetic reactions that occur in the body.
sponsored
Mechanism of Action
Metoclopramide Hydrochloride is a beta1-selective (cardioselective) adrenergic receptor blocking agent. This preferential effect is not absolute, however, and at higher plasma concentrations, Metoclopramide Hydrochloride also inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature.
Metoclopramide Hydrochloride has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at plasma concentrations much greater than required for beta-blockade. Animal and human experiments indicate that Metoclopramide Hydrochloride slows the sinus rate and decreases AV nodal conduction.
The relative beta1-selectivity of Metoclopramide Hydrochloride has been confirmed by the following: (1) In normal subjects, Metoclopramide Hydrochloride is unable to reverse the beta2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, Metoclopramide Hydrochloride reduces FEV1 and FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta1-receptor blocking doses.
Hypertension: The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity.
Angina Pectoris: By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, Metoclopramide Hydrochloride reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris.
Heart Failure: The precise mechanism for the beneficial effects of beta-blockers in heart failure has not been elucidated.
Pharmacodynamics
Clinical pharmacology studies have confirmed the beta-blocking activity of Metoclopramide Hydrochloride in man, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia.
The relationship between plasma Metoclopramide Hydrochloride levels and reduction in exercise heart rate is independent of the pharmaceutical formulation. Beta1-blocking effects in the range of 30 to 80% of the maximal effect (approximately 8 to 23% reduction in exercise heart rate) correspond to Metoclopramide Hydrochloride plasma concentrations from 30 to 540 nmol/L. The relative beta1‑selectivity of Metoclopramide Hydrochloride diminishes and blockade of beta2-adrenoceptors increases at plasma concentration above 300 nmol/L.
In five controlled studies in normal healthy subjects, extended-release Metoclopramide Hydrochloride succinate administered once a day, and immediate-release Metoclopramide Hydrochloride administered once to four times a day, provided comparable total beta1-blockade over 24 hours (area under the beta1-blockade versus time curve) in the dose range 100 to 400 mg. In another controlled study, 50 mg once daily for each product, extended-release Metoclopramide Hydrochloride succinate produced significantly higher total beta1-blockade over 24 hours than immediate-release Metoclopramide Hydrochloride. For extended-release Metoclopramide Hydrochloride succinate, the percent reduction in exercise heart rate was relatively stable throughout the entire dosage interval and the level of beta1-blockade increased with increasing doses from 50 to 300 mg daily.
A controlled cross-over study in heart failure patients compared the plasma concentrations and beta1-blocking effects of 50 mg immediate-release Metoclopramide Hydrochloride administered t.i.d., and 100 mg and 200 mg extended-release Metoclopramide Hydrochloride succinate once daily. Extended-release Metoclopramide Hydrochloride succinate 200 mg once daily produced a larger effect on suppression of exercise-induced and Holter-monitored heart rate over 24 hours compared to 50 mg t.i.d. of immediate-release Metoclopramide Hydrochloride.
In other studies, treatment with Metoclopramide Hydrochloride succinate produced an improvement in left ventricular ejection fraction. Metoclopramide Hydrochloride succinate was also shown to delay the increase in left ventricular end-systolic and end-diastolic volumes after 6 months of treatment.
Although beta-adrenergic receptor blockade is useful in the treatment of angina, hypertension, and heart failure there are situations in which sympathetic stimulation is vital. In patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. In the presence of AV block, beta-blockade may prevent the necessary facilitating effect of sympathetic activity on conduction. Beta2-adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients.
Pharmacokinetics
The peak plasma levels following once-daily administration of extended release Metoclopramide Hydrochloride succinate are reduced by 50 to 75% on average compared to a corresponding dose of immediate-release Metoclopramide Hydrochloride tartrate, both when administered once daily or in divided doses. At steady state the average bioavailability of Metoclopramide Hydrochloride following administration of Metoclopramide Hydrochloride succinate, across the dosage range of 50 to 400 mg once daily, was reduced by 25% relative to the corresponding single or divided doses of immediate-release Metoclopramide Hydrochloride tartrate. The bioavailability of Metoclopramide Hydrochloride shows a dose-related, although not directly proportional, increase with dose. The exposure (Cmax and AUC) of Metoclopramide Hydrochloride succinate extended-release capsule are similar to that of TOPROL-XL® tablet.
Absorption
Plasma levels following oral administration of Metoclopramide Hydrochloride tablet approximate 50% of levels following intravenous administration, indicating about 50% first-pass metabolism. Peak plasma concentration of Metoclopramide Hydrochloride is attained at 10 hours following administration of Metoclopramide Hydrochloride succinate extended-release capsule.
Effect of food
Compared to fasted state administration, high-fat, high-calorie meal (54.3% fat, 15.6% proteins and 30.1% carbohydrates) did not have a significant effect on the absorption of Metoclopramide Hydrochloride succinate extended-release capsule.
200 mg Metoclopramide Hydrochloride succinate extended release capsule administered under fasting conditions to healthy adults by sprinkling the entire contents on one-tablespoon (15 mL) of applesauce did not significantly affect Tmax, Cmax, and AUC of Metoclopramide Hydrochloride.
Distribution
About 12% of the drug is bound to human serum albumin.
Metoclopramide Hydrochloride crosses the blood-brain barrier and has been reported in the CSF in a concentration 78% of the simultaneous plasma concentration.
Elimination
Elimination is mainly by biotransformation in the liver, and the plasma half-life ranges from approximately 3 to 7 hours.
Metabolism
Metoclopramide Hydrochloride is a racemic mixture of R- and S- enantiomers, and is primarily metabolized by CYP2D6. When administered orally, it exhibits stereoselective metabolism that is dependent on oxidation phenotype.
Excretion
Less than 5% of an oral dose of Metoclopramide Hydrochloride is recovered unchanged in the urine; the rest is excreted by the kidneys as metabolites that appear to have no beta-blocking activity.
Following intravenous administration of Metoclopramide Hydrochloride, the urinary recovery of unchanged drug is approximately 10%.
Specific Populations
Pediatric Patients
The pharmacokinetic profile of Metoclopramide Hydrochloride succinate was studied in 120 pediatric hypertensive patients (6 to 17 years of age) receiving doses ranging from 12.5 to 200 mg once daily. The pharmacokinetics of Metoclopramide Hydrochloride were similar to those described previously in adults. Age, gender, race, and ideal body weight had no significant effects on Metoclopramide Hydrochloride pharmacokinetics. Metoclopramide Hydrochloride apparent oral clearance (CL/F) increased linearly with body weight. Metoclopramide Hydrochloride pharmacokinetics have not been investigated in patients < 6 years of age.
Drug Interactions
CYP2D6
Metoclopramide Hydrochloride is metabolized predominantly by CYP2D6. In healthy subjects with CYP2D6 extensive metabolizer phenotype, coadministration of quinidine 100 mg, a potent CYP2D6 inhibitor, and immediate-release Metoclopramide Hydrochloride 200 mg tripled the concentration of S-Metoclopramide Hydrochloride and doubled the Metoclopramide Hydrochloride elimination half-life. In four patients with cardiovascular disease, coadministration of propafenone 150 mg t.i.d. with immediate-release Metoclopramide Hydrochloride 50 mg t.i.d. resulted in steady-state concentration of Metoclopramide Hydrochloride 2- to 5-fold what is seen with Metoclopramide Hydrochloride alone. Extensive metabolizers who concomitantly use CYP2D6 inhibiting drugs will have increased (several-fold) Metoclopramide Hydrochloride blood levels, decreasing Metoclopramide Hydrochloride's cardioselectivity.
Alcohol
An in vitro dissolution study was conducted to evaluate the impact of alcohol (5, 10, 20 and 40%), on the extended-release characteristics of Metoclopramide Hydrochloride succinate extended-release capsules. The in vitro study showed that about 89% of the total Metoclopramide Hydrochloride succinate dose was released at 2 hour at the highest alcohol level (40%), and about 17% of total drug was released at 2 hour with 5% alcohol. Alcohol causes a rapid release of Metoclopramide Hydrochloride succinate from the extended-release capsules that may increase the risk for above events associated with Metoclopramide Hydrochloride succinate extended-release capsules. Consumption of alcohol is not recommended when taking Metoclopramide Hydrochloride succinate extended-release capsules 25 mg, 50 mg, 100 mg and 200 mg.
Pharmacogenomics
CYP2D6 is absent in about 8% of Caucasians (poor metabolizers) and about 2% of most other populations. CYP2D6 can be inhibited by several drugs. Poor metabolizers of CYP2D6 will have increased (several-fold) Metoclopramide Hydrochloride blood levels, decreasing Metoclopramide Hydrochloride's cardioselectivity.
References
DailyMed. "METOPROLOL FUMARATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
NCIt. "Metoprolol Fumarate: 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).
NCIt. "Metoclopramide: 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).
Reviews
The results of a survey conducted on ndrugs.com for Metoclopramide Hydrochloride 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 Metoclopramide Hydrochloride. 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
Consumer reported administration
No survey data has been collected yet
Consumer reviews
There are no reviews yet. Be the first to write one!
