Introduction
As it lowers the amount of aqueous humor in the body, Acetazolamide is the traditional choice of drug for the treatment of glaucoma. Because of its underlying mode of action, it can also be used to treat altitude sickness. The drug causes the body to release bicarbonate. As a result, the urine becomes more alkaline because it contains more bicarbonate. Due to the excretion of the bicarbonate, the blood becomes more acidic. Several processes relate the carbon dioxide levels in the body to how acidic it is, leading to an artificial compensatory mechanism for what the body perceives as too much carbon dioxide. Breathing becomes quicker and more profound as a result of this adjustment. This results in higher oxygen levels in the body, which enhances its capacity to adapt to higher altitude levels.
What Is the Mechanism of Action of Acetazolamide?
Acetazolamide is a carbonic anhydrase inhibitor, which indicates that this medication prevents the breakdown of carbonic acid. This eventually leads to the accumulation of carbonic acid in the body. Given the increased carbonic acid, which has a reversible reaction into bicarbonate and a hydrogen ion, the outcome is lower blood pH (i.e., the blood becomes more acidic).
Red blood cells and the proximal tubule of nephrons contain carbonic anhydrase enzymes. It works to reabsorb chloride, sodium, and bicarbonate. Inhibition of carbonic anhydrase enzyme by Acetazolamide causes salt, bicarbonate, and chloride to be expelled rather than reabsorbed. This also causes extra water to be excreted. The clinical outcomes include a drop in blood pressure (hypotension), decreased intracranial pressure, and decreased intraocular pressure. In addition, excreting bicarbonate makes the blood more acidic. There are compensating mechanisms for elevated blood acidity, such as hyperventilation and aqueous humor levels dropping in the eyes.
The entire excretion process attempts to acidify the urine and reabsorb bicarbonate. By raising the level of salt and bicarbonate in the urine, which alkalinizes the urine, Acetazolamide disrupts the entire process.
How Should Acetazolamide Be Administered in Different Patients?
Patients should drink a lot of water when taking Acetazolamide because excess water is excreted from the body while taking this drug. Tablets in doses of 125 mg, 250 mg, and 500 mg are readily available. These can also be found in medicine dose forms with instant and delayed releases.
It is possible to administer Acetazolamide intravenously (IV). However, it is not advised to administer Acetazolamide intramuscularly (IM).
250 mg to 1000 mg daily is the suggested dosage range for treating glaucoma. However, the dosage will often range from 250 to 500 milligrams daily. The dosage range for treating altitude sickness is 250 mg to 500 mg twice daily. When treating edema, epilepsy, and diuresis in congestive heart failure, lower doses are advised. The typical dosage range for such instances is 250 mg to 375 mg.
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Patients With Renal Impairment: In case of kidney disease, Acetazolamide is not recommended.
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Patients With Hepatic Impairment: In cirrhosis, Acetazolamide is contraindicated due to the possibility of hepatic encephalopathy.
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Pregnancy Considerations: In preclinical research, Acetazolamide usage during pregnancy has not been advised because of teratogenic consequences (harmful effects of the drug on the growth and development of the fetus). However, a study of pregnant individuals with idiopathic intracranial hypertension found no proof of Acetazolamide's adverse effects on the unborn child. Acetazolamide was previously classified as a category C pregnancy medicine and should only be taken during pregnancy if the advantages outweigh the hazards to the unborn child. As a result, doctors should only recommend Acetazolamide when necessary.
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Breastfeeding Considerations: According to data, Acetazolamide doses for mothers of up to 1000 milligrams daily are found in small amounts in milk and are not expected to affect breastfed children adversely. Additionally, several worldwide professional guidelines concur that Acetazolamide and other carbonic anhydrase inhibitors are safe to use while nursing.
What Are the Adverse Health Effects of Acetazolamide Toxicity?
Using Acetazolamide can result in various general and particular side effects.
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Patients frequently experience fatigue, nausea, vomiting, stomach discomfort, and diarrhea.
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Other patients may have tinnitus (ringing sound in the ear), taste changes, diminished libido (sex drive), paresthesia (tingling sensation), dark stools, etc.
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Additionally, Acetazolamide users have reported experiencing depression or developing a metallic or bitter taste in their mouth. There is a chance of experiencing metabolic acidosis and hypokalemia, but it is rare.
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Although rare, kidney stones can also be seen.
What Are the Contraindications Associated With Acetazolamide?
Patients with liver illness or poor liver function should avoid Acetazolamide since it reduces ammonia elimination. In addition, hepatic encephalopathy (a nervous system disorder caused by liver disease) may develop more quickly with Acetazolamide.
Acetazolamide can bring on electrolyte problems. Because of this, people who have hypokalemia (low blood potassium level) should not use it. Similar to how it can lower kidney function, practitioners want to avoid utilizing it on patients with kidney disease or impaired kidney function. Those with hyperchloremic acidosis (acidosis that develops because of an increase in ionic chloride) should not use Acetazolamide.
Although Acetazolamide does not prolong the QTc (corrected for heart rate) interval, those with a prolonged QTc should use caution and check their potassium levels because the medication can lead to hypokalemia. In addition, Acetazolamide should not be used by those with a sulfonamide allergy (such as a sulfa allergy).
If patients on salicylates start taking Acetazolamide, they risk developing toxicity. Additionally, administering Acetazolamide concurrently with sodium bicarbonate therapy increases the incidence of nephrolithiasis (kidney stones) in some patients.
Acetazolamide should not be used by patients using anti-folate medications such as Methotrexate and Trimethoprim. Additionally, patients taking other carbonic anhydrase inhibitors should avoid this drug. Finally, Acetazolamide should not be used by patients with a history of severe rashes since it can cause Stevens-Johnson syndrome (skin reaction) in some patients.
How to Manage Patients With Acetazolamide Toxicity?
Acetazolamide toxicity can cause damage to the central nervous system (CNS) and eventually lead to coma (period of prolonged unconsciousness). A typical Acetazolamide overdose also includes hyperchloremic metabolic acidosis and electrolyte abnormalities. Therefore, clinicians should quickly collect arterial blood gas analysis and serum electrolyte measurements, particularly serum potassium. Because there is no particular known antidote for Acetazolamide, treatment is typically supportive. The use of bicarbonate can usually reverse metabolic acidosis. Acetazolamide may be dialyzable despite its high RBC distribution and plasma protein binding. Dialysis may be beneficial when addressing Acetazolamide overdose exacerbated by acute renal injury.
Although acetazolamide is rarely used in clinical medicine, doctors must be aware of its side effects and limitations. A team consisting of the doctor, nurse, and pharmacist must educate patients on the dosage and uses of the medication and how to report any adverse effects.
Conclusion
Acetazolamide has the potential to cause toxicity when taken in excess dosage. Acetazolamide does not cause any allergic reactions in the body. However, get immediate medical attention if the patient experiences significant adverse reaction symptoms, such as nausea, redness, itching, or swelling.
