Types of Drug Interactions
Drug interactions are often classified as either pharmacodynamic or
pharmacokinetic interactions. Pharmacodynamic interactions include those
that result in additive or antagonistic pharmacological effects. Pharmacokinetic
interactions involve induction or inhibition of metabolizing enzymes in the liver or
elsewhere, displacement of drug from plasma protein binding sites, alterations
in gastrointestinal absorption, or competition for active renal secretion.
The frequency and prevalence of interactions is dependent upon the number
of concomitant medications and the complexity of the regimens. The prevalence
is also dependent upon other variables, such as patient adherence, hydration
and nutritional status, degree of renal or hepatic impairment, smoking and
alcohol use, genetics and drug dosing. Additionally, some patients may exhibit
evidence of a particular drug interaction, while others with the same drug
combination do not.
Pharmacodynamic interactions
This type of interaction will not be addressed in this reference, since these
should be reasonably easy to predict, knowing the pharmacology of any
given drug.
Pharmacokinetic interactions
Interactions Resulting from Alterations in Gastrointestinal Absorption
The rate and extent of drug absorption after oral administration may be grossly
altered by other agents. Absorption of a drug is a function of the drug’s ability to
diffuse from the lumen of the gastrointestinal tract into the systemic circulation.
Changes in intestinal pH may profoundly affect drug diffusion as well as
dissolution of the dosage form. For example, the absorption of ketoconazole
is reduced by the co-administration of antacids or H
famotidine) that reduce the extent to which the ketoconazole tablet is dissolved.
Formation of insoluble complexes by a process known as chelation is another
mechanism by which a drug interaction may lead to reduced oral absorption.
For example, fluoroquinolones (e.g. ciprofloxacin) and divalent metal ions
(such as calcium and iron) form an insoluble complex that results in reduced
absorption of both the antibiotic and the metal ion. Interactions that decrease
the rate of drug absorption may be of little importance, since the overall extent
of absorption may remain unaltered.
2-blockers (e.g. ranitidine, Interactions Resulting from Alterations in Metabolizing Enzymes
The liver is the major, though not exclusive, site for drug metabolism. Other sites
include the kidney and the lining of the gastrointestinal tract. The two main types
of hepatic drug metabolism are phase I and phase II reactions. Phase I oxidative
reactions are the initial step in drug biotransformation, and are mediated by the
cytochrome P-450 (CYP) system. This complex superfamily of enzymes has been
subclassified into numerous enzymatic subfamilies. The most common CYP
subfamilies include CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4.
These enzymes may be induced or inhibited by other agents, thereby leading
to an increase or decrease in the metabolism of the primary drug. Phase II
reactions occur following Phase I reactions. In this process, drug metabolites
are converted into more water-soluble compounds that can be more easilyeliminated by the kidneys
Patients with acute renal failure, chronic kidney disease (CKD) or those treated
with dialysis or kidney transplantation are frequently prescribed numerous
medications. Drugs of many therapeutic classes are used to treat the underlying
diseases leading to CKD, such as diabetes mellitus and hypertension, while
others are used to control or treat the common complications of CKD, such
as anemia, renal bone disease and lipid disorders. Dialysis patients often are
prescribed 10 to 12 medications. With such a large number of medications, there
is an increased risk for drug interactions. The accompanying table has been
prepared as a reference regarding the most clinically significant drug
interactions that might occur, together with an indication of the possible
consequence. This table should be used as a general guideline.
Sometimes information is known about one specific drug within a certain drug
class, while additional information is not known about other agents within the
same therapeutic category. Clinicians must be aware of this possibility and use
their best judgement when prescribing or assessing drug therapy.
تعليقات
إرسال تعليق