# A drug has a narrow therapeutic window.
# A drug has serious, dose-dependent toxicity.
# The change in the serum drug is at least 30%.
There are two basic types of interactions:
# Pharmacokinetic (what the body on drugs): occurs when changes in the absorption, distribution, metabolism and excretion of a drug. For example, P-glycoprotein is a membrane transport pump found in many areas of the body, including the GI tract, blood-brain barrier and the kidneys, the distribution of drugs into the tissue. It looks like a nightclub bouncer, the prevention of certain drugs, the membrane (ie in the bloodstream from the gut or the blood-brain barrier). Inhibition of P-glycoprotein by a medicine to facilitate the entry of certain drugs into the tissue.
# Pharmacodynamic (drugs, which means the body): You may be additive effects of two drugs - for example, simultaneous Metoprolol and verapamil therapy will slow the heart rate.
There are two major types of drug metabolism (both occur primarily in the liver):
Phase I reactions (cytochrome P450 enzyme system):
There are over 100 different P450 families and these enzymes are responsible for metabolizing both endogenous and exogenous substances. The major P450 systems used in drug metabolism are shown in the pie chart below. CYP 3A4 is the most common enzyme system in interaction.
Phase II reactions:
Acetylation, methylation, glucuronidation, sulfation.
Overall, the goal of drug metabolism is a relatively nonpolar and polar substance, thus facilitating their excretion in urine. Phase I reactions, it is an oxygen-share situation on the drug molecule (oxidation-reduction type of reaction). Then, a phase II reaction to act on this matter, and in the process, stick to a polar side group. The drug will be easier on the kidneys.
Below are some commonly used medications in the P450 are:
CYP # 450-inhibitors:
Clarithromycin, erythromycin, protease inhibitors (nelfinavir, ritonavir, indinavir), amiodarone, Fluvoxamine, fluoxetine, paroxetine, diltiazem, verapamil, itraconazole, ketoconazole, isoniazid (2C9), fluoroquinolones, quinidine.
# CYP 450 inducers:
rifampin, phenobarbital, phenytoin, carbamazepine, isoniazid (2E1).
# CYP 450 substrates:
Theophylline, amitriptyline, phenytoin, phenobarbital, propafenone, cyclosporine, tacrolimus, clarithromycin, erythromycin, quinidine, Alprazolam, Diazepam, Triazolam, ritonavir, indinavir, saquinavir, amlodipine, nifedipine, Felodipine, Verapamil, Diltiazem, clozapine.
Source:
Drugs and medicines, a practical guide for the safe use of common drugs in the adult, S Hui and D. Hamilton, Second Edition
"The true polypharmacy is the skillful combination of measures."
Sir William Osler. The treatment of diseases. Brit Med J
1909; 2:185-9.
Written by Raj Padwal, by Dawna Gilchrist, Dayle Strachan and Jeff Whissell
