thiazide diuretic hydrochlorothiazide: Topics by posavski-obzor.info
Thiazides and thiazide-like diuretics inhibit Na+/Cl− cotransporter located on the apical membrane of the early Nicotinic acid Further SAR work revealed that addition of an amino group to the aromatic ring of bis-sulfonamides decreased. of benzafibrate and nicotinic acid. 2. What are thiazide diuretics and mention the examples with structures. Explain the structure activity relationship of it. 3. FIGURE 2: Pharmacodynamic illustration of the relationship between diuretic dose and . Despite heterogeneity in their structure–activity relationships, which has Bile acid sequestrants and niacin also reduce cardiovascular risk, although.
Meclofenamate Sodium or Meclofenamic Acid Monosodium N- 2, 6-dichloro-m-tolyl anthranilate monohydrate; Benzoic acid, 2-[2, 6- dichloromethylphenyl amino]- monosodium salt. It may be prepared by the Ulman Condensation of o-iodobenzoic acid with 2, 6-dichloro-mtoluidine in the presence of copper-bronze resulting into the formation of meclofenamic acid which on neutralization with equimolar proportion of sodium hydroxide yields meclofenamate sodium.
It possesses analgesic, anti-inflammatory, and antipyretic properties [ 8 ]. It is used for the treatment of acute and chronic rheumatoid arthritis and osteoarthritis. Usual, oral, to mg daily in 3 or 4 equal doses. Meclofenamic acid, N- 2,6-dichloro-m-tolyl anthranylic acid, is synthesized analogous to flufenamic acid, by the reaction of potassium salt of 2-bromobenzoic acid with 2,6-dichloromethylaniline in the presence of copper II bromide in a mixture of N-ethylmorpholine and diglyme.
It is used for the same conditions as flufenamic acid. A synonym for this drug is movens. The 2,6-dichloro derivative of mefenamic acid, as its sodium salt; and exerts its most predominant side effects, such as: It has analgesic, anti-inflammatory and antipyretic actions. It is employed in the treatment of rheumatic disorders and dysmenorrhoea.
It is synthesized by the reaction of 2-chlorobenzoic acid with 3-trifluoromethylaniline in the presence of potassium carbonate and copper filings. Flufenamic acid is used for moderate pain and dysmenorrhea, but it should not be used for more than 1 week due to the possibility of nephrotoxicity, gastrointestinal toxicity, and anemia.
It is frequently used in combination with the anticoagulant warfarin, the effect of which is strengthened when combined with flufenamic acid. Synonyms for this drug are arlef, flexocutan, romazal, and others. It is a trifluoromethyl analogue of anthranilic acid, that exerts its three-in-one pharmacological actions viz. It finds its abundant usage in dysmenorrhoea and various types of rheumatic disorders. However, the exact and precise mechanism of antipyretic action of the N-aryl anthranilic acid structural variants has not yet been established.
Study of Anthranylic Acid Derivatives: Mefenamic Acid and Its Various Analogues
There exists no relationship to lipid plasma distribution, partition coefficient or pKa values of these types of drugs visa-vis their antipyretic activity.
Niflumic acid, trifluoromethyl anilino nicotinic acid, is synthesized either by the reaction of 2-chloronicotinic acid with 3-trifluoromethylaniline, or 2-aminonicotinic acid with 1-bromotrifluoromethylbenzene.
It is used same as mefenamic acid. Synonyms for this drug are actol, flunir, nifluril, and others [ 910 ]. For nonsteroidal anti-inflammatory carboxylic acids such as mefenamic acid or N- 7-chloroquinolyl anthranilic acid [ 11 ], glyceryl esters are claimed to be less irritating.
Alternatively, the ulcerogenicity of indomethacin derivatives was reduced by formation of the ester with glycolic acid [ 12 ] or the peptide with serine [ 13 ].
Another indomethacin- related anti-inflammatory drug, sulindac, is an inactive sulfoxide and becomes only activated after absorption and reduction into the corresponding sulfide. Thus the initial exposure of gastric and intestinal mucosa to the active drug is circumvented. Mefenamic acid in a dose of mg is superior to mg of aspirin as an analgesic and doubling the dose sharply increases its efficacy.
A study examining this drug relative to gastrointestinal bleeding indicated a lower incidence of this side effect than by aspirin. The possibility of blood disorders has prompted limitation of its administration to 7 days.
It is not recommended children or during pregnancy. It has been approved for use in the management of primary dysmenorrhea PD which is thought to be caused by excessive concentrations of prostaglandins and endoperoxides. The most significant side effects are gastroinestinal, including diarrhea 5. Structure Activity Relationship Substitution on the anthranilic acid ring generally reduced the activity.
Substitution on the N-aryl ring can lead to conflicting results. The position of acidic function is critical for activity, anthranilic acid derivatives are active where as meta and para benzoic acid analogues are not. Replacement of carboxylic acid functions with the isosteric tetrazole has little effect on the activity. Mefenamic Acid Warning s: Cardiovascular Risk; Possible increased risk of serious sometimes fatal cardiovascular thrombotic events e.
Risk may increase with duration of use. Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk. Contraindicated for the treatment of pain in the setting of CABG surgery. Serious GI events can occur at any time and may not be preceded by warning signs and symptoms [ 71415 ]. Geriatric individuals are at greater risk for serious GI events [9,].
Uses for Mefenamic Acid: Consider potential benefits and risks of mefenamic acid therapy as well as alternative therapies before initiating therapy with the drug. Treatment of primary dysmenorrhea. Has been used for reduction of fever associated with infection in children; routine use as an antipyretic not recommended because of potential adverse effects.
Mefenamic Acid Dosage and Administration: Administer orally; May be administered in divided doses up to 4 times daily. Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage. Pain Oral For mild to moderate pain in adults, mg initially followed by mg every 6 hours as necessary. Oral For relief of primary dysmenorrhea in adults, mg initially followed by mg every 6 hours as necessary. Adults Pain Oral Duration of therapy usually should not exceed 1 week.
Oral Therapy should not be necessary for more than 2—3 days. Special Populations Hepatic Impairment: Dosage reduction may be required.
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Dosage reduction may be required if used in patients with renal impairment. Use not recommended in patients with preexisting renal disease or substantial renal impairment. Select dosage carefully since may be more likely to have decreased renal function. Cautions for Mefenamic Acid Contraindications: Known hypersensitivity to mefenamic acid or any ingredient in the formulation. Treatment of perioperative pain in the setting of CABG surgery. Active ulceration or chronic inflammation of upper or lower GI tract.
Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events e. Several prototypical NSAIDs also have been associated with increased risk of cardiovascular events [ 42 ]. Information not available on risk associated with mefenamic acid at this time [ 43 ]. Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events except immediately following CABG surgery.
No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIDs. Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.
Use with caution in patients with hypertension; monitor BP. Impaired response to certain diuretics may occur. Fluid retention and edema reported. Caution in patients with fluid retention or heart failure. Serious GI toxicity e. Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAID therapy. Potential for overt renal decompensation. Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist [ 47 ].
Thiazides are mainly used to treat high Thiaz blood pressure. Increasing the dose of diuretic led to progressive hyperuricemia, thus diureticsinduced hyperuricemia seems to be dose dependent [ 9 - 11 ]. Potassium-sparing diuretics, spironolactone is generally considered not to affect serum uric acid level [ 1213 ].
However it has been reported that spironolactone increased serum uric acid levels in the CKD patients [ 14 ], although the mechanism responsible for the increase in uric acid is unclear. Pyrazinamide and nicotinamide Pyrazinamide is an anti-tubeculous agent, and it increases serum uric acid level through decrease in uric acid excretion [ 15 ].
Pyrazinamide is usually administered as a two-month course during treatment of pulmonary tuberculosis, and hyperuricemia is reversible after withdrawal of the agent, therefore hyperuricemia due to pyrazinamide can be managed by observation and does not require withdrawal of the administration [ 16 ]. In the human kidney, uric acid is transported via URAT1 through the apical membrane of the proximal tubular cells, in exchange for organic anions, such as pyrazinoate, nicotinate, and lactate transported towards the tubular lumen.
It has been reported that pyrazinamide reduces the renal secretion of uric acid via activation of the exchange transport of uric acid with pyrazinecarboxylic acid, which is a metabolite of pyrazinamide, through the uric acid transporter URAT1 [ 1718 ].
Moreover, hOATmediated 14C-urate uptake was elevated by an exchange with L-lactate, pyrazinoate, and nicotinate [ 19 ]. The mechanism of increased serum concentration of uric acid by ethambutol administration is not clear, though seems to differ from that of pyrazinamide and diuretics. Nicotinic acid has been used to treat dyslipidemia. Elevated blood levels of uric acid have been noted with nicotinic acid therapy [ 21 ]. Uric acid raising effects of nicotinic acid may occur when the drug is given in therapeutic doses of 1, mg daily or doses of up to six grams.
In addition to URAT1 mediated nicotinate exchanging for uric acid reabsorption, OAT 10 mediated uric acid uptake is also facilitated by exchange with nicotinate, suggesting the molecular evidence of nicotinate-induced hyperuricemia [ 19 ]. High dose lactate infusion 0. During lactate is secreted through URAT1, uric acid is reabsorbed by exchange, causing an elevation of serum uric acid level. In addition to URAT1 mediated lactate exchanging for uric acid reabsorption, OAT 10 mediated uric acid uptake is also facilitated by exchange with lactate, suggesting the molecular evidence of lactateinduced hyperuricemia [ 19 ].
Cyclosporine Cyclosporine A is used as a common immunosuppressant for management of organ transplantation and various autoimmune diseases. Although hyperuricemia is a well-known adverse effect of cyclosporine, tacrolimus also increases serum uric acid level [ 25 ].
On the contrary, azathioprine seems not to affect serum uric acid level. Recently it is revealed that cyclosporine A enhanced uric acid uptake through OAT10, providing molecular evidence for cyclosporine A-induced hyperuricemia [ 19 ] Cyclosporineinduced hyperuricemia is mitigated by concomitant administration of amlodipine or losartan [ 2627 ]. Testosterone Serum uric acid level of man is higher than that of woman, which is attributed to androgen-induced uric acid reabsorptive transport system in the kidney.
Testosterone replacement therapy against females with gender identity disorder increased serum uric acid level, and a positive correlation between increased levels of serum uric acid and serum creatinine. Thus it may be considered that testosterone-induced hyperuricemia is at least partially attributed to an increase in muscle mass, a major source of purine [ 29 ], although uric acid production is not estimated.
Increased Uric Acid Overproduction Uric acid is produced by decomposition and catabolism of purine nucleotides, and external ingestion of purine body. It is endogenously produced by degradation of ATP or increased turnover rate of cell death.
Certain drugs, such as fructose, xylitol, and theophylline can increase uric acid levels in the blood by accelerated purine nucleotide degradation, while certain cytotoxic agents increase uric acid production by an increased turnover rate of cell death.
Fructose Fructose is widely used intravenously as a carbohydrate nutrient. Fructose infusion is indicated in patients requiring fluid replacement and caloric feeding.
It is metabolized more rapidly than dextrose without requiring insulin and thus is used in diabetic patients. It is significantly metabolized to fructosephosphate by fructokinase with an abrupt consumption of adenosine triphosphate ATP and phosphate, and increased activity of AMP deaminase suppressed by phosphate, consequently, degradation of adeninenucleotide is accelerated, hence increasing the synthesis of uric acid Figure 3 [ 30 ].
Fructose also inhibits the excretion of uric acid, apparently by competing with uric acid for access to the transport protein GLUT 9 [ 31 ]. Fructose should be infused at a speed below 0.