Drug Interactions of Antibiotics
Antibiotic drug interactions gain lots of importance as they can cause clinically significant adverse effects
Reasons for antibiotic and other drug interactions
1. Antibiotics are widely used drugs
2. Most of the antibiotics have potential effect on metabolizing enzymes, which are responsible for the drug levels in the blood.
3. As infections are mostly related to pre-existing illnesses, ex: bronchitis or diabetes, patients are likely to be taking other medications.
Different antibiotics and their drug interactions:
The prototype of the group was erythromycin, other macrolides are clarithromycin and azithromycin
: There are several different mechanisms by which macrolides interact with other drugs
1. The most common mechanism involves the affect of macrolide on the cytochrome P 450 (CYP) enzymatic system. Macrolides are oxidized by CYP3, thereby inhibiting the enzymes by forming an inactive enzyme/ metabolite complexes. These interactions of enzymes will lead to decreased metabolism of any concurrent drugs which are cleared by this route.
2. The other mechanisms include (1)interfering with gut bacteria affecting availability of drug locally and (2) complexation.
These groups of drugs are involved in a wide range of interactions; most commonly used systemic antifungals are traizoles, imidazoles and griseofulvin
These are potent inhibitors of CYP3A, this means that any drugs given concurrently, that are highly metabolized by CYP3A, may show substantial increase in concentration.
These are board spectrum antibiotics, but now-a-days these are less widely used because of bacterial resistance. However it is a drug of choice for chlamydial infections.
This involves the formation of poorly absorbed chelates with metallic cations. The concurrent use of antacids containing aluminum, bismuth, calcium or magnesium can markedly reduce absorption of tetracyclines to the point where efficacy is lost. The interactions seen between tetracyclines and milk are due to the formation of chelates of calcium and tetracycline.
This group includes cinoxin, ciprofloxacin, levofloxacin, naldixic acid, norfloxacin and ofloxacin. Quinolines are used in the treatment of infectious diseases such as respiratory and urinary infections, GIT infections and sexually transmitted diseases.
The two main mechanism of drug interaction with quinolines are absorption interactions and interactions involving hepatic metabolism.
1. Mg, Al, Ca, Fe and other drugs have shown reduced absorption of various quinolines due to formation of insoluble drug cationic chelates in GIT.
2. Quinolines have shown inhibition of the enzyme CYP1A and caused reduced hepatic metabolism of co-administred drugs such as theophylline and caffeine.
Pencillins and Cephalosporin's:
These are two widely used group of antibiotics having some serious drug interactions.
1. Penicillin causes an increase in the anticoagulant affect of warfarin due to its effect on clotting system. Very rare cases of decreased warfarin affects have also occurred with some Pencillins.
2. Cephalosporins also acts as anti-coagulants because it acts as Vitamin K antagonist, so the risk of bleeding may be increased in patients treated with warfarin and cephalosporin.
Antibiotics and Oral Contraceptives:
Several cases of contraceptive failure have been reported due to concurrent use of combined oral contraceptives and pencillins and tetracyclines
The mechanism is local action of antibiotics in the gut reduces the activity of those bacteria that normally act on conjugation of estrogen which is secreted into the bile. This then leads to reduction in the amount of conjugated, estrogen for reabsorption and leads to a drop in the level of circulating estrogen. The net result may be an unwanted pregnancy.
1. The Pharmaceutical Journal, Volume 261; Nov 14th 1998. Pg no: 779- 783.