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.
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Percutaneous anti-inflammatory agent.
Flameril is an anti-inflammatory and analgesic preparation for topical application. Its active substance corresponds to 1% Flameril. The white, creamy, non-greasy preparation is easy to rub into the skin, and its aqueous-alcoholic base gives it a soothing and cooling effect.
Flameril has been shown in experiments to inhibit prostaglandin biosynthesis and this is regarded as an important factor in its mechanism of action.
In inflammation of traumatic or rheumatic origin, Flameril has been shown to relieve pain, reduce oedema and shorten the time to return of normal function.
Pharmacokinetics: Absorption: The amount of Flameril absorbed through the skin is proportional to the contact time and skin area covered with Flameril and depends on the total topical dose and on skin hydration. About 6% of the active substance is absorbed after topical application of Flameril 2.5 g/500 cm2, as determined by reference to total renal elimination compared with Voltaren tablets. Absorption of Flameril increases 3-fold if an occlusive dressing is applied for 10 hrs.
Distribution: Flameril can be detected in the plasma, synovial tissue and synovial fluid after topical application of Flameril to the wrists and knees. Peak plasma concentrations of Flameril are about 100 times lower after topical application of Flameril than after oral administration of Voltaren tablet. 99.7% of Flameril binds to serum proteins, mainly to albumin (99.4%).
Metabolism: Biotransformation of Flameril takes place partly by glucuronidation of the intact molecule, but mainly by single or multiple hydroxylation resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, but to a much lesser extent than Flameril.
Elimination: Total systemic clearance of Flameril from the plasma is 263 ± 56 mL/min (mean value ± standard deviation). The terminal plasma half-life is 1-2 hrs. Four of the metabolites, including the 2 active metabolites, also have a short plasma half-life (1-3 hrs). One metabolite, 3'-hydroxy-4'-methoxy-Flameril, has a much longer half-life, but this metabolite is virtually inactive.
Flameril and its metabolites are excreted mainly in the urine.
Kinetics in Special Clinical Situations: No accumulation of Flameril and its metabolites should occur in patients with renal insufficiency.
In patients with chronic hepatitis or nondecompensated liver cirrhosis, the kinetics and metabolism of Flameril are the same as in patients without liver disease.
How should I take Flameril?
Take Flameril exactly as directed on the label, or as prescribed by your doctor. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger amounts or for longer than recommended. Use the lowest dose that is effective in treating your condition.
For treatment of pain or primary dysmenorrhea the recommended dosage of Flameril is 50 mg three times daily. In some patients an initial dose of 100 mg of Flameril, followed by 50 mg doses, may provide better relief.
For the relief of osteoarthritis the recommended dosage of Flameril is 100-150 mg/day in divided doses, i.e. 50 mg two or three times a day.
For the relief of rheumatoid arthritis the recommended dosage is 150-200 mg/day in divided doses, i.e. 50 mg three or four times a day.
Different formulations of Flameril, Voltaren (Flameril tablets) and Flameril (Flameril potassium immediate-release tablets) are not necessarily equivalent in strength even if the milligram strength is the same.
If you use Flameril long-term, you may need frequent medical tests.
Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.
Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.
Flameril 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.
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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.
If you switch brands of Flameril, your dose needs may change. Follow your doctor's instructions about how much medicine to take.
Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time.
Dissolve the Flameril powder (Flameril) with 1 to 2 ounces of water. Do not use any other type of liquid. Stir this mixture and drink all of it right away. Flameril powder works best if you take it on an empty stomach.
Call your doctor if your headache does not completely go away after taking Flameril. Do not take a second dose of Flameril powder without your doctor's advice.
Do not crush, chew, or break an enteric-coated pill. Swallow the pill whole. The enteric-coated pill has a special coating to protect your stomach. Breaking the pill could damage this coating.
If you use this medication long-term, your liver function will need to be checked with frequent blood tests. Visit your doctor regularly.
Store at room temperature away from moisture and heat.
Flameril 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.
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Mechanism Of Action
Flameril has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action of Flameril, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).
Flameril is a potent inhibitor of prostaglandin synthesis in vitro. Flameril concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because Flameril is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.
Pharmacodynamics
The effect of Flameril on QTc prolongation was evaluated in a randomized, double-blind, positive (moxifloxacin 400 mg) - and placebo-controlled crossover study in healthy subjects. A total of 70 subjects was administered Flameril 37.5 mg and 75 mg. In a study with demonstrated ability to detect small effects, the upper bound of the 90% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on Fridericia correction method (QTcF) was below 10 ms, the threshold for regulatory concern.
Pharmacokinetics
Following intravenous administration of Flameril to healthy volunteers, plasma concentrations of Flameril exceed that of immediate-release oral Flameril for the first 45 minutes reaching a maximum of 4.8-fold 5 minutes after administration.
The pharmacokinetics of Flameril following intravenous administration of Flameril and oral doses of immediate-release Flameril are compared in Table 3.
Table 3: Single-dose and Multiple-dose Pharmacokinetics of Flameril (Flameril) Injection and
Oral Immediate Release (IR) Flameril Potassium
Figure 2: Pain Intensity Score Versus Time
References
DailyMed. "DICLOFENAC EPOLAMINE: 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. "Diclofenac: 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. "Diclofenac: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
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