AKT 4 Kit - A Ray of Hope for Tuberculosis

Overview

AKT-4 kit is an anti-tubercular drug used in the treatment of tuberculosis. It is a medicine acting against mycobacterium tuberculosis that causes tuberculosis. Drugs present in the AKT 4 kit are included in the “lists of essential medicines” in the WHO (world health organization) model. Patients having systemic conditions involving the liver, kidney, or heart are prescribed anti-tubercular drugs by changing the dose; it is to be noted that AKT 4 is not the only ultimate treatment for every patient diagnosed with tuberculosis (TB) disease; however, AKT-4 is the first line standard treatment for TB. The duration of treatment can last up to six months to nine months.

What Is AKT 4?

AKT-4 is a kit containing four drugs in the form of tablets and capsules. They are administered to treat tuberculosis. The following are the four drugs included in the kit:

• Ethambutol hydrochloride - 800 milligrams (mg).

• Isoniazid - 300 mg.

• Rifampicin - 450 mg.

• Pyrazinamide - 750 mg.

All four tablets are administered daily for the entire treatment duration. Treatment duration lasts for six months or nine months, which depends on the clinical condition of the patient.

How Does AKT 4 Work?

• AKT-4 is a combination of four drugs acting against tuberculosis.

• Isoniazid acts on the TB bacteria and prevents the formation of a protective covering.

• Rifampicin acts by inactivating the RNA polymerase, which is a bacterial enzyme utilized by the bacteria to reproduce.

• Pyrazinamide and Ethambutol hydrochloride slow down the growth of TB bacteria.

• All four drugs actively act against mycobacterium tuberculosis and inhibit the growth and progression of the infection.

What Are the Available Doses and Dosages?

Isoniazid: Isoniazid is available in the following forms and dosages:

• Tablets - 50 mg, 100 mg, 300 mg.

• Elixir - 50 mg/mL (milligram per milliliter).

• Injection - 100 mg/mL.

Rifampicin: It is available in the following formulations and dosages:

• Capsule - 150 mg, 300mg.

• Powder.

• Aqueous solution.

Pyrazinamide and Ethambutol: They are available in tablet form:

• Pyrazinamide tablet - 500 mg.

• Ethambutol tablet - 100 mg, 400 mg.

Directions- The medication is better preferred to be taken an hour before the food. It is beneficial to consume the drugs at the same time every day.

Storage- The drugs are stored in a container at room temperature, away from moisture or freezing, or direct sunlight.

Warnings-

• It is not safe to consume alcohol during the treatment period. It causes low blood pressure, chest pain, and increased heart rate.

• Upon taking the AKT-4, the ability to drive is also affected. Rarely it can cause visual impairment, numbness, or tingling sensation in the hands and feet, and hence it is unsafe to drive during the treatment period.

• As the AKT-4 shows harmful effects on the developing child inside the mother's womb, it is unsafe to take the medicine during pregnancy unless prescribed by a doctor.

• Patients with liver ailments should be cautious while taking AKT-4 as dose adjustment will be necessary; it is important to consult a doctor follow-up is done before and after the beginning of the treatment by performing liver function tests.

• Vitamin B6, 25 to 50 mg per day is given along with Isoniazid in patients associated with a high risk of neuropathy.

For Patients:

What Is Tuberculosis?

Tuberculosis is a disease caused by a bacteria called Mycobacterium tuberculosis that mostly affects the lungs. TB spreads through the air from one person to another. Patients suffering from TB are generally the source of infection. Sneeze, cough, or sputum of the infected person can be spread into the air. It is a globally spread infection; many infected people do not develop TB disease. Infected patients showing no symptoms cannot transmit the disease.

What Are the Symptoms of Tuberculosis?

Symptoms of the disease include the following:

• Fever, cough, weight loss, fatigue, pain in the chest, night sweats, and loss of appetite which can range from mild to moderate. People with impaired immunity and the habit of smoking or drinking are at increased risk of TB.

• Symptoms of TB also depend on the type of the disease.

• Pulmonary TB affects the lungs, and extra-pulmonary TB affects organs like the stomach, bones, kidneys, etc.

• Symptoms of extra-pulmonary TB include general symptoms like fever, loss of appetite and weight, and specific affected organ-related symptoms such as the following.

• Back pain and paralysis of lower limbs in the case of bone TB.

• Nausea, diarrhea, vomiting, and malabsorption in TB of the gastrointestinal system.

• Blood in the urine in the case of tuberculosis of the kidney.

When and Why to Take AKT 4?

AKT-4 kit is a medicine prescribed by the doctor. Patients who are diagnosed with tuberculosis are advised treatment with AKT-4 drugs.

How Effective Is AKT 4?

The drug's efficiency can be enhanced by taking it on an empty stomach at a fixed time every day. AKT-4 acts on the Mycobacterium tuberculosis and inhibits and decreases the progression of the tuberculosis infection. Drugs included in the AKT-4 kit show less harmful drug interactions and are also effective against other strains of bacteria such as Mycobacterium leprae and Atypical mycobacteria.

What Are the Side Effects of AKT 4?

Common side effects of the AKT 4 include:

• Nausea.

• Fever.

• Vomiting.

• Dark-colored urine.

• Increased saliva.

• Sweating.

• Rash.

• Increased uric acid in the blood.

• Jaundice (condition occurring due to excessive secretions of the liver that dissolve into fat under the skin causing yellowish discoloration)

• Peripheral neuropathy (damage to the nerves located outside the spinal cord and brain).

Things to Inform Doctors About Before Taking AKT-4

• A thorough medical history is to be told to the doctor.

• Any drugs taken for other systemic health conditions must also be informed.

• Patients suffering from any liver or kidney ailments, breastfeeding, or pregnant women are advised to take AKT 4 with proper caution and consultation.

How to Take AKT 4?

AKT-4 contains three tablets and one capsule, and it is to be taken on an empty stomach before food or two hours after consumption of food. It can be prescribed for six months or nine months.

What Happens When One Skip or Misses Taking the Tablet?

In situations where the dose is missed, taking the medication soon after recollecting must be followed, keeping in mind not to take two doses at once. When one remembers to take the missed dose at the time of the next dose, skip the dose which is missed and take the regular medicine as it will double the dose. The entire course of the treatment should be completed even if the symptoms are subsiding. Discontinuing the treatment suddenly will affect the efficiency of the drug working in the body.

For Doctors:

Dosing:

• Ethambutol, 15 mg per kilogram of body weight is administered once every 24 hours for six or nine months for patients receiving the anti-tubercular treatment for the first time.

• In re-treatment cases, 25 mg per kg is administered once orally every 24 hours.

• Isoniazid 5 mg per kg up to 300 mg daily in a single dose or 15 mg per kg up to 900 mg per day two or three times a week is administered for a period of six to nine months.

• Rifampicin 450 mg orally once every 24 hours is the administered dose for Rifampicin.

• Pyrazinamide is always administered in a dose of 15 to 30 mg/kg once daily. Older regimens included three to four divided doses per day. Another alternative way of administering Pyrazinamide is 50 to 70 mg/kg twice weekly based on the body weight.

Pharmacology of the Drugs:

Clinical Pharmacology of Ethambutol Hydrochloride:

• When Ethambutol hydrochloride of 25 mg/kg is introduced into the body, after two to four hours of administration, it reaches a level of 2 to 5 micrograms/ml in the serum. Administering the drug at the same dose maintains the serum levels. Within 24 hours, the serum levels go undetectable except in patients with renal abnormalities. Erythrocytes’ intracellular concentrations reach peak values, twice that of the plasma, and these levels are maintained throughout the 24 hours.

• Within 24 hours of duration after the administration of oral Ethambutol, 50 percent of the drug dose is initially excreted in the urine. Metabolites account for eight to fifteen percent of the remaining drug dose. The oxidation pathway is taken first by the drug. A part of the remaining dose of nearly 20 mg is excreted through feces. Single daily dose drugs do not show any accumulation of the drug.

Mechanism of Action:

Initial oxidation is the main path of metabolism. Conversion of alcohol to aldehyde (an intermediate product), and then conversion to a dicarboxylic acid. Ethambutol diffuses into the cells that are actively growing, such as tubercle bacilli. This inhibits the synthesis of metabolites, causing cell metabolism impairment, multiplication of cells is prevented along with cell death.

Toxicity:

An increase in the levels of Ethambutol causes optic neuritis (swelling associated with inflammation that damages the optic nerve) with decreased visual activity and color blindness.

Warnings and Precautions:

Ethambutol hydrochloride is not indicated in children below 13 years of age. This is because the safety of the drug in children is not established.

Contraindications:

Ethambutol is contraindicated in patients with known hypersensitivity to the drug. Patients suffering from optic neuritis are also contraindicated from the Ethambutol drug.

Drug Interactions:

Ethambutol hydrochloride, when used alone, caused increased resistance. Ethambutol does not show any cross-resistance with other anti-tubercular drugs.

Pharmacology of Isoniazid:

It is the most effective anti-tubercular drug. It is tuberculocidal for rapidly multiplying bacteria but static for resting bacteria. Isoniazid destroys intracellular bacilli as it penetrates the cells.

Bacteria multiplying in the walls of the cavities are also destroyed. And hence, it is effective against both extracellular and intracellular organisms.

Drug Interactions: Isoniazid, when used alone, Mycobacteria develop resistance to the drug. There is no resistance between Isoniazid and other anti-tubercular drugs.

Mechanism of Action: Isoniazid inhibits the synthesis of mycolic acids, which are the most important components of the mycobacterial cell wall. Isoniazid enters the mycobacteria, where the drug is converted into an active metabolite. This metabolite binds the enzymes necessary for mycolic acid synthesis, and thereby, synthesis of mycolic acid is inhibited.

Pharmacokinetics: Isoniazid is completely absorbed orally and penetrates all the tissues, tubercular cavities, necrotic tissues, and cerebrospinal fluid. It is metabolized by acetylation. The patient's body can show fast or slow acetylators depending on the genetic inheritance, while slow acetylators respond better. The half-life of the drug in slow acetylators is three to five hours, while in fast acetylators it is one hour. Metabolites of Isoniazid are excreted in the urine.

Adverse Effects:

1. Peripheral Neuritis - It is the damage occurring to the nerves present in the outer regions of the brain. This can be avoided by administering prophylactic pyridoxine (10 to 50 mg) along with Isoniazid.

2. Hepatitis - Inflammation of the liver is called hepatitis. The elderly and alcoholics are mostly affected by this condition.

3. CNS Toxicity - Seizures and psychosis can also occur but in rare conditions. Epileptic patients are more prone to the occurrence of these symptoms.

Pharmacology of Rifampicin:

It is a semi-synthetic drug derivative of Rifamycin, which is an antibiotic obtained from streptomyces mediterranei. Rifampicin is a bactericidal virus to Mycobacterium tuberculosis. It also inhibits many gram-positive and gram-negative bacteria. It is the only drug that acts on persisters and is also effective against tubercle bacilli resistant to other drugs and hence can be called a sterilizing agent.

• Drug Interactions: When used alone, Mycobacteria develop resistance to the drug Rifampicin. There is no resistance between Rifampicin and other anti-tubercular drugs. It also accelerates the metabolism of drugs such as oral contraceptives, methadone, hypoglycemics, digitoxin as well as barbiturates.

• Mechanism of Action: Rifampicin binds to DNA-dependent RNA polymerase and inhibits RNA synthesis in the bacteria.

• Pharmacokinetics: It is a well-absorbed drug and has good tissue penetrability that reaches the caseous material, cerebrospinal fluid, and cavities. It also appears in saliva, sweat, and tears. Being a microsomal enzyme inducer, it can be responsible for drug interactions.

Toxicity

• Hepatotoxicity: Patients having liver dysfunction or receiving hepatotoxic drugs should be carefully monitored as it can lead to the death of the patient.

• Gastrointestinal Disturbances: Nausea, vomiting, epigastric distress, diarrhea, and abdominal cramps can occur.

• Flu-Like Syndrome: It is characterized by body aches, chills, fever, and hemolytic anemia.

• CNS Symptoms: Headache, drowsiness, ataxia (disorder affecting the co ordination, speech and balance), dizziness, peripheral neuropathy, confusion with pain and numbness in the extremities, and muscle weakness have been reported.

• Hypersensitivity Reactions: Skin rashes, fever, urticaria, and hemolysis can also occur.

• Staining of Secretions: Rifampicin stains the secretion including, tears, saliva, and sweat, to orange-red color. A soft contact lens can also get stained.

Pharmacology of Pyrazinamide:

It is an anti-tubercular drug that is more active in acidic pH. It is well absorbed in the Gastrointestinal tract and reaches peak concentrations in two hours. Pyrazinamide is distributed in all body tissues, including the cerebrospinal fluid (CSF), lungs, and liver. The half-life of Pyrazinamide is nine to ten hours in patients without any renal or hepatic abnormalities. Hydrolyzation of Pyrazinamide is done in the liver to pyrazinoic acid, which is an active metabolite. Hydroxylation of Pyrazinoic acid to 5-hydroxy pyrazinoic acid is also done, which is the main excretory product. Within 24 hours, 70 percent of the initial dose is eliminated in the urine by glomerular filtration.

Pyrazinamide is bactericidal as well as bacteriostatic against bacteria causing tuberculosis, depending on the drug concentration at the site of infection. The drug is active mainly under acidic pH.

• Contra-Indications of Pyrazinamide: It is contraindicated in patients with severe damage to the liver, patients hypersensitive to the drug previously, and patients suffering from acute gout.

• Warnings: Patient’s serum uric acid and liver function determinations should be a baseline in patients receiving Pyrazinamide for treatment. Close follow-up of patients with increased risk of hepatitis (drug-related hepatitis) and pre-existing liver disease must be maintained. The drug should be discontinued completely when signs of hyperuricemia and hepatocellular damage along with arthritis occur.

• Precautions: Renal excretion of urates is inhibited by Pyrazinamide which results in hyperuricemia. Hyperuricemia is usually asymptomatic, and this condition, when presented along with acute gouty arthritis (condition characterized by sudden onset of pain), Pyrazinamide should be stopped. In patients suffering from diabetes mellitus, Pyrazinamide is used cautiously as the difficulty is higher during management. Resistance of bacteria to Pyrazinamide is not common.

• Adverse Reaction: General adverse reactions, including fever, dysuria, and porphyria, are rarely reported.

• Gastrointestinal Reactions: Dose-related damage to the liver can occur at any time during the course of therapy. Along with hepatotoxicity, gastrointestinal reactions include anorexia, nausea, and vomiting also.

• Hematologic and Lymphatic Reactions: Sideroblastic anemia and thrombocytopenia with hyperplasia increased serum concentrations of iron, and vacuolation of erythrocytes also occurred. Alterations of the blood clotting mechanisms are also reported. Myalgia and arthralgia are frequently reported.

• Toxicity: Toxicity rarely occurs. Toxicity causes abnormal liver functions, which are reduced and brought back to normal by stopping the drug. Clinical monitoring should be continuously done.