Introduction
Some drug-drug interactions cause unwanted morbidity and mortality within small animal medicine.
Several drug-to-drug interactions are incompatible with each other as they can result in a lack of a therapeutic effect or increase in toxicity within the patient.
There are two ways to mix drugs:
What can mixing drugs do to animals?
Pharmaceutical drug interactions are drug interactions that occur before the administration or absorption of a drug. This can occur from the addition of drugs to intravenous fluid preparations within critical care environments. Besides drug mixing, degradation can also occur from changes in temperature or exposure to ultraviolet radiation. This mixing can cause fluctuations in environment and pH thereby leading to the formation of precipitate and the disruption of drug structure and stability.
Pharmacokinetic drug interactions occur within the body of the patient. These interactions occur when one drug alters the disposition of another drug, thereby changing the way it is absorbed, distributed, metabolised and eliminated from the patient. These changes can interfere with hepatic drug clearance, the activity of cytochrome P-450, and many other pathways thereby causing overdosage or decreased pharmaceutical effects from medication.
The most common drug interactions to look out for:
Antibiotics
One of the leading examples of drug-to-drug interactions is the interactions of antibiotics, such as ampicillin, tetracyclines, chloramphenicol, penicillins and amphotericin B when mixed with other drugs.
Aminoglycosides, such as gentamicin and tobramycin when mixed with most other drugs result in the inactivation of both drugs’ pharmaceutical effects.
Fluoroquinolones
Fluoroquinolones notoriously can chelate with metallic compounds. Mineral and vitamin supplements, such as Lixotinic, contain a significant concentration of iron and calcium, which decreases fluoroquinolone concentration by approximately 50%.
Intravenous fluoroquinolones should never be mixed with cation-containing fluid solutions. Cation-containing fluid solutions include:
Antacid compounds
Antacid compounds or H2 compounds such as Cimetidine can suppress stomach acidity. Many oral drugs require a low pH of stomach acidity to become activated. Therefore, in combination with H2 blockers many oral drugs will have decreased absorption, these include antifungal drugs such as ketoconazole and itraconazole.
Cimetidine
Cimetidine decreases the activity of Cytochrome P-450, which can potentially lead to overdosage involving drugs that utilise this enzyme to be cleared. This effects:
It is recommended that H2 blockers are used over cimetidine for patients treated with multiple drugs.
Sucralfate
Sucralfate belongs to an aluminium-containing drug group. Within this group, they can form complexes with other drugs in the gastrointestinal tract, thereby decreasing their pharmaceutical effects. This effects:
Ketoconazole
Ketoconazole and itraconazole are a part of a group of drugs that are activated within acidic pH environments, thereby it is not advised to combine these with:
Ketoconazole also inhibits cytochrome P450 enzyme alongside p-glycoprotein, which decreases the bioavailability and clearance of many drugs. This effects:
The benefit of drug mixing with Ketoconazole:
Cyclosporine can be used alongside Ketoconazole for favourable interactions by interaction with Cyclosporine to lower its dosage in vivo.
Metoclopramide
Metoclopramide is a dopaminergic antagonist and a prokinetic agent, thereby increasing GI motility. This interacts with:
Cisapride
Cisapride is a substrate of CYP3A enzymes, as such, drugs that inhibit CYP3A may increase cisapride concentration which can lead to fatal cardiac arrhythmias. Drugs that inhibit CYP3A include:
Furosemide
Several drug combinations can lead to enhanced furosemide toxicity. These drug combinations include:
Omeprazole
Omeprazole is an inhibitor of P450 enzymes, as such, it may increase the toxicity, of:
Omeprazole can also decrease the absorption of:
Phenobarbital
Phenobarbital is a major P450 inducer in dogs. It increases the metabolism of:
Phenobarbitol causes minimal disturbances to cytochrome P450 in cats, therefore drug-to-drug interactions are minimal in cats.
Clomipramine
Clomipramine can have interactions with monoamine oxidase inhibitors. As such, they interact with:
The metabolism of clomipramine can be inhibited by:
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Nonsteroidal anti-inflammatory drugs can interact with:
Conclusion
When prescribing medication for a patient, it is always vital to double-check what medications they are already on and how these drugs may potentially affect other medications, efficacy and toxicity. Hampering processes within a patient's body can lead to overdosage of medication or decreased pharmaceutical effects, leading to unwanted consequences for the client and clinic. To help with drug-to-drug interactions find below a simplified table introducing drug-to-drug interactions that may affect small animals.