Cholera and its Most Common Drug List

Introduction

Cholera refers to acute diarrheal disease caused due to consumption of water and/ food contaminated with bacterium Vibrio cholerae, present in the feces of a person having cholera. It is an intestinal infection, which can be endemic, pandemic and epidemic. The disease is generally mild or without symptoms but can become severe in nearly 5-10% cases. If prompt treatment is not available, the disease has a potential to become fatal within hours, even in previously healthy individuals.

Cholera is often termed a disease of inequality. According to WHO, cholera and poverty maps of the world overlap. Nearly 1.3 to 4 million cases of cholera are reported annually across the globe, out of which 2100 to 143000 cases result in death.^[1]

Adoption of modern sewage and water treatment has helped in virtually erasing cholera from the face of developed world. However, in developing world, the disease is still quite common. The chances of cholera outbreak increases when people live in crowded conditions without proper sanitation in situations of natural disasters, war or poverty.

Symptoms

Cholera is a highly virulent disease which can result in severely acute watery diarrhea. After ingesting contaminated food or water, it might take anywhere between 12 hours to 5 days to develop symptoms. Most people do not develop any symptoms in-spite of being infected. The bacteria are present in their stools for 1 to 10 days after infection, and they continue to shed the bacteria in their environment, potentially infecting others. Some of the symptoms experienced by cholera patients are:

• Sudden diarrhea, having a characteristic rice water appearance.
• Nausea and vomiting
• Dehydration of the body
• Muscle cramps
• Shock

Treatment

Rehydration is the top most priority in treating cholera. Rehydration is achieved in two steps: rehydration and maintenance. Rehydration aims at restoring normal hydration status, which is expected to take nearly 4 hours. By replacing the ongoing loss of fluids due to diarrhea, normal hydration status can be maintained, which is achieved in the maintenance phase. For this, oral route is generally favored, unless the symptoms turn severe. WHO has laid recommendations for replacing fluids in the patients. Through extensive efforts of WHO and UNICEF, oral rehydration solution (ORS) is now readily available over-the-counter in pharmacies in most of the countries worldwide. ORS is known to provide potassium, glucose and bicarbonate to the patient. Patients require regular monitoring of their body fluids and are kept under observation until diarrhea stops or becomes infrequent less in volume.

Another part of treatment is managing the symptoms by using antibiotics. However, this therapy is only an adjunct to rehydration therapy. In severe cases where diarrheal volume is extremely large, antibiotics can help in bringing down the volume and even decrease the time for which the bacteria are excreted. It helps in stopping diarrhea within 48 hours, thereby shortening the duration of hospital stay. It should be noted that no other drugs should be given for treating cholera. Antibiotics should be chosen while keeping the strain of bacteria in consideration in order to provide effective treatment without developing resistant strains.

Also, antibiotic therapy should be initiated as soon as possible, if cholera is suspected. Drugs belonging to classes such as tetracycline, fluoroquinolones, clotrimazoles, chloramphenicol macrolides and penicillin are used for treating cholera. These are described below:

1. Antibiotics

Drugs that inhibit the growth of bacteria or kill them are called antibiotics. Listed below are different types of antibiotics used in cholera patients:

A. Fluoroquinolones: These are the drugs that are used against gram negative bacteria and a few gram-positive bacteria. They act by inhibiting the enzymes topoisomerase IV and topoisomerase II (DNA gyrase) found in the bacteria, which help them in multiplication.

Drug: ciprofloxacin
Brand name: Cipro
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Tablet
Indicated in Pregnancy: No, unless benefits outweigh risks
Alcohol Content: No
Side Effects: Diarrhea, change in urination, bloody stools, confusion, chills, dizziness, headache, hearing loss, nausea, skin rash, vomiting, and yellow eyes.

Drug: norfloxacin
Brand name: Noroxin
The U.S. FDA Status: Discontinued
Dosage Form: Tablet
Indicated in Pregnancy: No, unless benefits outweigh risks
Alcohol Content: No
Side Effects: Chest pain, chills, skin rash, irritability, soreness of mouth, increased sweating, lack of appetite and tiredness

B. Tetracyclines: These drugs are basically bacteriostatic in nature. They do not kill the bacteria, but slow down their growth and multiplication. They inhibit protein synthesis in the bacteria and inhibit their growth.

Drug: doxycycline hyclate
Brand name: Vibramycin
The U.S. FDA Status: Approved
Availability: Prescription
Dosage Form: Capsule
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Bloating, chills, dark urine, decreased appetite, dizziness, fast heartbeat, headache, skin rash, nausea and sore throat

Drug: tetracycline hydrochoride
Brand name: AchromycinV
The U.S. FDA Status: Approved
Availability: Prescription
Dosage Form: Capsule
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Increased sensitivity to sunlight, abdominal pain, headache, loss of appetite and yellowing of skin

Drug: minocycline hydrochloride
Brand name: Minocin
The U.S. FDA Status: Approved
Availability: Prescription
Dosage Form: Injectable
Indicated in Pregnancy: No, unless benefits outweigh risks
Alcohol Content: No
Side Effects: Joint or muscle pain, discoloration of skin, dizziness, swollen tongue and mild nausea

C. Macrolides: These drugs inhibit protein synthesis in bacteria and hence prevent bacterial growth in the body. They do not kill the bacteria but do not allow them to grow. Therefore, their action can be termed as bacteriostatic.

Drug: azithromycin
Brand name: Zithromax
The U.S. FDA Status: Approved
Availability: Prescription
Dosage Form: Injectable
Indicated in Pregnancy: Yes, under strict supervision
Alcohol Content: No
Side Effects: Diarrhea, abdominal pain, loose stools, nausea, vomiting, blistering of skin, swelling, abdominal pain and body aches

D. Aminopenicillins: Transpeptidase is an enzyme that the bacteria require for synthesizing cell wall. Inhibition of this enzyme by aminopenicillins, bacterial cell wall is inhibited, thereby preventing bacterial multiplication.

Drug: ampicillin sodium
Brand name: Ampicillin Sodium
The U.S. FDA Status: Approved
Availability: Prescription only
Dosage Form: Injectable
Indicated in Pregnancy: No, unless benefits outweigh risks
Alcohol Content: No
Side Effects: Skin rash, swelling, eosinophilia, fever, anorexia, vomiting and pain at site of injection

E. Cotrimoxazole: Two antibiotics, trimethoprim and sulphamethoxazole, in a fixed dose combination are called cotrimoxazole. They enhance each other’s action and therefore, are generally given together. DNA synthesis in bacteria requires folic acid, which is also synthesized in-house. These drugs interfere with synthesis of folic acid and inhibit bacterial multiplication.

Drug: sulphamethoxazole and trimethoprim (cotrimazole)
Brand name: Bactrim
The U.S. FDA Status: Approved
Availability: Prescription
Dosage Form: Tablet
Indicated in Pregnancy: No
Alcohol Content: No
Side Effects: Abdominal pain, chills, black stools, headache, diarrhea, itching, nausea, wheezing and sore throat

F. Chloramphenicol: It prevents bacterial protein synthesis and inhibits bacterial cell multiplication.
Drug: chloramphenicol sodium succinate
Brand name: Chloarmphenicol sodium succinate
The U.S. FDA Status: Approved
Availability: Prescription
Dosage Form: Injectable
Indicated in Pregnancy: No, unless benefits outweigh risks
Alcohol Content: No
Side Effects: Pale skin, unusual bleeding, sore throat, confusion, fatigue, eye pain, skin rash and numbness in hands and feet

2. Vaccination

If you are traveling to a cholera affected area, you can get yourself vaccinated. The cholera vaccine contains a live attenuated cholera bacterium that gets replicated in the gut and activates the immune system to build tolerance towards the bacteria. Later, when cholera bacteria enter the body in future, the immune system is capable of killing them and providing immunity against the disease.

The vaccine is available as a single, oral liquid dose which you should take nearly 10 days before your travel date. Two other oral vaccines are available, which contain inactivated or non-live cholera bacteria and require two doses. These vaccines, although being WHO pre-qualified, are not available in the U.S. The single dose vaccine is the only FDA approved vaccine which is especially beneficial if you are visiting on a short notice.

Cholera vaccines do not provide complete protection and should never replace the standard prevention and control measures.

OTC Drugs Used

WHO recommends that apart from oral rehydration solution (ORS) and antibiotics, no other medicines should be given to the patient, with rehydration being the main focus of treatment. It is not recommended to give loperamide and other antidiarrheal medicines, in any case.

ORS is readily available in majority of the city pharmacies and health care facilities across the globe.^[2]