Carbonic anhydrase inhibitors drugs

Urinary bladder Carbonic anhydrase inhibitors Drugs that affect urinary pH... 

The final example of a novel process development formulation involves a semi-solid ophthalmic gel containing a carbonic anhydrase inhibitor drug for the treatment of glaucoma. It is administered to the patient by extruding the gel from an ophthalmic tube into the conjunctival sac of the eye. The drug had a very low aqueous solubility. It was necessary to reduce the particle size of the drug to less than 10 pim and suspend it in a very thick carbomer gel vehicle, to increase the residence time of the gel and maximise corneal permeation. The formulation details are given below ... 

Adverse reactions associated with short-term therapy with carbonic anhydrase inhibitors are rare. Long-term use of these drug s may result in fever, rash, paresthesia... 

If a carbonic anhydrase inhibitor is being given for absence or nonlocalized epileptic seizures, the nurse assesses the patient at frequent intervals for the occurrence of seizures, especially early in therapy and in patients known to experience seizures at frequent intervals. If a seizure does occur, the nurse records a description of the seizure in the patient s chart, including time of onset and duration. Accurate descriptions of the pattern and the number of seizures occurring each day helps the primary health care provider plan future therapy and adjust drug dosages as needed. 

Local side effects include burning, stinging, itching, foreign body sensation, dry eyes, and conjunctivitis. Brinzolamide may have a lower incidence of these side effects since the drug is in a neutral pH solution. Dorzolamide has been reported to cause irreversible corneal decompensation. Taste abnormalities have been reported with each agent. Both topical carbonic anhydrase inhibitors are sulfonamides and are contraindicated in patients with history of sulfonamide hypersensitivity.10,13... 

Not all drugs contain functional groups that lend themselves readily to prodrug derivatization. A case in point is the carbonic anhydrase inhibitors such as acetazolamide, ethoxzolamide, and methazolamide. Although the amino functional group of their sulfonamide moiety can be methylated, the resulting analogs... 

Carbonic anhydrase inhibitors such as acetazolamide act in the proximal tubule. These drugs prevent the formation of H+ ions, which are transported out of the tubular epithelial cell in exchange for Na+ ions. These agents have limited clinical usefulness because they result in development of metabolic acidosis. 

The answer is c. (Hardman, pp 6917 693 J Acetazolamide is a carbonic anhydrase inhibitor with its primary site of action at the proximal tubule of the nephron. Acetazolamide promotes a urinary excretion of Na, K, and bicarbonate There is a decrease in loss of Cl ions The increased excretion of bicarbonate makes the urine alkaline and may produce metabolic acidosis as a consequence of the loss of bicarbonate from the blood. None of the other diuretic drugs promote a reduction in the excretion of the Cl ion... 

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production and is therefore indicated in glaucoma to reduce the intraocular pressure. Salbutamol is a selective, short-acting beta2-agonist used as a bronchodilator in asthma. Tolbutamide is a short-acting sulphonylurea used in type 2 (non-insulin dependent) diabetes mellitus. Chlorpromazine is an aliphatic neuroleptic antipsychotic drug used in schizophrenia. Zafirlukast is a leukotriene-receptor antagonist that is indicated in the prophylaxis of asthma but should not be used to relieve acute severe asthma. 

Diuretics are drugs that increase secretion of excess water and salt that accumulates in tissues and urine. An excess qnantity of intercellnlar flnid is formed in the organism as a result of an inability of the kidneys to release sodinm ions fast enongh to ensure that a sufficient quantity of water is excreted along with them. Therefore, efficacy of a diuretic depends first and foremost on its ability to release sodinm ions from the body, since they are accompanied by an osmotically eqnivalent amonnt of water that is released from interstitial fluids. The exceptions are dinretics classified as carbonic anhydrase inhibitors. 

Acetazolamide is an aromatic sulfonamide used as a carbonic anhydrase inhibitor. It facilitates production of alkahne urine with an elevated biocarbonate, sodium, and potassium ion concentrations. By inhibiting carbonic anhydrase, the drug suppresses reabsorption of sodium ions in exchange for hydrogen ions, increases reflux of bicarbonate and sodium ions and reduces reflux of chloride ions. During this process, chloride ions are kept in the kidneys to cover of insufficiency of bicarbonate ions, and for keeping an ion balance. Electrolytic contents of fluid secreted by the kidneys in patients taking carbonic anhydrase inhibitors are characterized by elevated levels of sodium, potassium, and bicarbonate ions and a moderate increase in water level. Urine becomes basic, and the concentration of bicarbonate in the plasma is reduced. 

Drugs that may interact with carbonic anhydrase inhibitors include cyclosporine, primidone, salicylates, and diflunisal. 

Drugs that may affect aspirin include activated charcoal, ammonium chloride, ascorbic acid or methionine, antacids and urinary alkalinizers, carbonic anhydrase inhibitors, corticosteroids, and nizatidine. Drugs that may be affected by aspirin include alcohol, ACE inhibitors, anticoagulants (oral), beta-adrenergic blockers, heparin, loop diuretics, methotrexate, nitroglycerin, NSAIDs, probenecid and sulfinpyrazone, spironolactone, sulfonylureas and exogenous insulin, and valproic acid. 

Hypersensitivity to sulfonamides or chemically related drugs (eg, sulfonylureas, thiazide and loop diuretics, carbonic anhydrase inhibitors, sunscreens with PABA, local anesthetics) pregnancy at term lactation infants less than 2 months of age (except in congenital toxoplasmosis as adjunct with pyrimethamine) porphyria salicylate hypersensitivity. 

Dorzolamide (Trusopt) [Carbonic Anhydrase Inhibitor, Sul-fonamide/Glaucoma A9ent] Uses Glaucoma Action Carbonic anhydrase inhibitor Dose 1 gtt in eye(s) tid Caution [C, ] Contra Component sensitivity Disp Soln SE Irritation, bitter taste, punctate k atitis, ocular all gic Rxn EMS t Effects W/ oral carbonic anhydrase inhibitors, salicylates EMS Drug is absorbed systemicaUy OD May cause electrolyte disturbances (K) and acidosis monitor ECG... 

Memantine (Namenda) [Anti Alzheimer Agent/NMDA Receptor Antagonist] Uses Mod/ evere Alzheimer Dz Action N-methyl-D-aspartate recqjtor antagonist Dose Target 20 mg/d, start 5 mg/d, t 5 mg/d to 20 mg/d, wait >1 wk before t dose use doses if >5mg/d Caution [B, /-] Hqjatic/mild-mod renal impair Disp Tabs, sol SE Dizziness Interactions t Effects W amantadine, carbonic anhydrase inhibitors, dextromethorphan, ketamine, Na bicarbonate t effects W/ any drug, herb, food that alkalinizes urine EMS Use NaHCOs w/ caution OD May cause restlessness, hallucinations, drowsiness, and fainting symptomatic and supportive... 

Sulfasalazine is contraindicated in individuals with hypersensitivity to salicylates, sulfonamides, sulfonylureas, and certain diuretics (furosemide, thiazides, and carbonic anhydrase inhibitors). Because it can cause kernicterus, sulfasalazine is contraindicated in infants and children under 2 years of age. Sulfasalazine passes into breast milk and is therefore contraindicated for nursing mothers. Similarly, pregnant women near term should not use this drug, although it appears to be the safest of the DMARDs during early pregnancy. 

A variety of thiophene-fused 1,2-thiazines have been prepared as carbonic anhydrase inhibitors for the treatment of glaucoma <2002JME888, 2000BMC957>. The drug brinzolamide (under the trade name Azopt ) 24 has recently been approved by the FDA. 

Several examples of non-oxicam-type 1,2-thiazine-containing small molecule enzyme inhibitors have been disclosed. The landmark work in this area involves the antiepileptic drug sulthiame 10, first discovered and approved for use over 30 years ago. Interest in this carbonic anhydrase inhibitor has been renewed by recent work on its efficacy in treatment of both childhood benign and focal epilepsies <2002MI469>. 

The development of sulfonamide carbonic anhydrase inhibitors was based on the observation that antibacterial sulfanilamides produce alkaline urine. This discovery led to the development of acetazolamide (8.29), a thiadiazole derivative. It is not an ideal drug because it promotes K+ excretion and causes a very high urine pH. Since chloride ions are not excreted simultaneously, systemic acidosis also results. Much more useful are the chlorothiazide (8.30) derivatives, which are widely used as oral diuretic drugs. These compounds differ from one another mainly in the nature of the substituent on C3 ... 

S. P. Gupta (2003). Quantitative structure-activity relationships of carbonic anhydrase inhibitors. Prog. Drug Res. 60 171-204. 

It is noteworthy that sulfanilamide structural modifications have led to other valuable classes of drugs already discussed, including the hypoglycemic sulfonylureas and the diuretic carbonic anhydrase inhibitors. 

Other drugs, such as verapamil, caffeine, theophylline, osmotic diuretics, carbonic anhydrase inhibitors, or aminophylline, can increase lithium excretion, possibly dropping plasma levels below the therapeutic threshold ( 329). Further, if doses are increased to compensate for this effect, care must be taken to readjust the lithium downward when these concomitant agents are reduced or discontinued. 

The carbonic anhydrase inhibitors are well absorbed after oral administration. An increase in urine pH from the HC03 diuresis is apparent within 30 minutes, is maximal at 2 hours, and persists for 12 hours after a single dose. Excretion of the drug is by secretion in the proximal tubule S2 segment. Therefore, dosing must be reduced in renal insufficiency. 

Acidosis predictably results from chronic reduction of body HC03 stores by carbonic anhydrase inhibitors (Table 15-2) and limits the diuretic efficacy of these drugs to 2 or 3 days. Unlike the diuretic effect, acidosis persists as long as the drug is continued. 

Loop diuretics selectively inhibit NaCI reabsorption in the TAL. Because of the large NaCI absorptive capacity of this segment and the fact that the diuretic action of these drugs is not limited by development of acidosis, as is the case with the carbonic anhydrase inhibitors, loop diuretics are the most efficacious diuretic agents currently available. 

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