Drug-Drug Interactions Concept Map: An Overview
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| Part 2 - Pharmacodynamic Drug-Drug Interactions |
Generally, drugs may interact with other drugs, food, herbs,
and laboratory results. This concept map focuses on drug-drug interactions
types, mechanisms of interactions, preventive measures, and risk factors along
with a sufficient number of examples of the most common and the most clinically
significant drug-drug interactions.
Here is an overview about our unique “One Picture” on
Drug-drug interactions (DDIs) concept map from Zoom out - Pharmacotherapy.
Definition
The map starts with a definition of drug-drug interactions
which is a situation in which a drug affects the activity of another drug when
they are both administered together.
Types
Pharmacokinetic Interactions
These interactions occur when the precipitant drug
affects the plasma concentration of the object drug through changes in
the absorption, distribution, metabolism or excretion of the object drug.
Absorption Interactions
Mechanisms of DDIs through changes in absorption
It occurs when drug(s) bind to another in
GIT. The map explains the difference between (Adsorption) and (Chelation); the
two mechanisms responsible for drug binding. Drug binding doesn’t usually cause
harmful interactions, as it may be useful clinically. Find out more in the map.
- Changes in Gastrointestinal
Motility
These changes affect what is called Gastric
Emptying Rate (GER) and consequently affects drug absorption rate and/or
extent. Know from the map what GER is and which drugs increase and decrease GER
and drug absorption rate. An interesting example; how pretreatment with propanthelin
enhances digoxin bioavailability? Understand the mechanism as shown in
the map in the form of a flowchart.
- Alteration in Gastrointestinal
pH
The map let you understand the effect of GI pH on weak
acidic and weak basic drugs extent of absorption.
- Effect on Intestinal Flora
See the image below.
It is showing part of the map that concerns intestinal flora effect on drug
absorption. Two examples provided; antibiotics co-administered with digoxin and
co-administered with oral hormonal contraceptives.
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Effect of intestinal flora - Absorption drug interactions
Click to enlarge |
- Alterations in Drug
Metabolism within the Intestinal Wall
Hypertensive crisis caused by
co-administration of tyramine containing food with MAO inhibitors is a clinically
significant drug interaction that is shown as an example in this part of the
map.
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Alteration in drug metabolism within the intestinal wall
Click to enlarge |
Distribution Interactions
Distribution occurs after the absorbed drug enters the
bloodstream. It is carried by plasma proteins to reach its site of action and
exerts its pharmacological effect. Transport plasma proteins are albumin and
alpha1-acid glycoprotein (AAG). Certain diseases and conditions as: liver cirrhosis, renal failure, inflammatory diseases, and pregnancy can change the
serum concentrations of these plasma proteins and consequently affects drug distribution.
Distribution drug-drug interactions can occur through one of
the following mechanisms (explained in the map):
- Displacement.
- Drug-induced decrease in concentration
of binding protein.
Also mentioned in the map, four cases in which the clinical
significance of drug displacement interactions increase.
Metabolism Interactions
Many administered drugs are extensively metabolized in the
liver by hepatic enzymes. The most common among these enzymes are cytochrome
P450 enzymes. Know about these enzymes’ nomenclature, function and other
information through this part of the map.
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Cytochrome P450 nomenclature and function
Click to enlarge |
Cytochrome P450 drug-drug interactions can occur through:
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| CYP450 enzyme inhibition mechanism |
You’ll also find a table with some examples of interacting
drugs through inhibition of cytochrome P450 enzymes.
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| CYP450 enzyme induction mechanism |
There is also a table with some examples of interacting
drugs through inhibition of cytochrome P450 enzymes.
They are drugs that have no therapeutic action until they
are metabolized into active compounds.
As CYP450 enzymes have a role in the activation of prodrugs,
then enzyme inhibitors and inducers can interfere with the activation of
prodrugs. Know more about the possible mechanisms of inhibition or induction of
CYP450 in case of produrgs as losartan and tramadol through this part of the
map.
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Effect of CYP450 inhibitors and inducers on prodrugs
Click to enlarge |
Excretion Interactions
Excretory organs are: the biliary system, the lungs, the
skin, and the kidney which plays the most important role in excretion.
Excretion of drugs by the kidney involves 3 main mechanisms:
In a logical way, the map explains how
glomerular filtration takes place and how nephrotoxic drugs as:
cyclosporine, tacrolimus, non-steroidal anti-inflammatory drugs (NSAIDs),
angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin II receptor
blockers (ARBs) decrease excretion of drugs eliminated by glomerular filtration
resulting in accumulation of these drugs and increased toxicity.
It is an active process (requires ATP) in
which the drug is carried on a certain transporter to be excreted from the
body. Saturation of this process by two drugs competing for the same carrier
proteins causes accumulation of one or both of these drugs. Two examples of
drug-drug interactions due to drugs competing on active tubular secretion are
mentioned in the map. They include: probenecid and cimetidine.
- Passive Tubular
Reabsorption
Here is a glimpse of this part as shown in the map.
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Passive tubular reabsorption - Excretion drug interactions
Click to enlarge |
Then, know how urine alkalinization
results in more reabsorption of basic drugs and increases the excretion of
acidic drugs as methotrexate to prevent or reverse drug toxicity.
Pharmacodynamic Interactions
They occur when a certain drug modulates the pharmacologic
effect of another one without a change in its concentration. Pharmacodynamic
Interactions occur due to one of these mechanisms: additivity, synergism, or
antagonism.
Mechanisms of Pharmacodynamic Interactions
- Additivity
- Synergism
- Antagonism
Detailed explanation and examples are included in the map
Risk factors of DDI
They can be classified into:
- Patient-related risk factors
Details related to patient’s gender, diseases, and age are
stated in the map.
- Drug-related risk factors
In the map, you’ll find more information about:
- Polypharmacy/ Therapeutic
jungle
- Drugs with narrow
therapeutic indices
- Route of drug
administration
- Time-dependent drug-drug
interactions
- Drugs with high first pass
metabolism (FPM)
- Drugs with highly plasma
protein binding
You’ve to remember that these risk factors may increase the
probability and the clinical significance of drug-drug interactions. This part is followed by examples of
clinically significant drug-drug interactions.
Categories/ Classification of DDIs
This part shows you how DDIs are classified according to two
important online drug
interaction checkers. These references are (
Drugs.com) and (
Lexi-comp).
Classification according to Drug.com
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| Drug interactions classification according to Drugs.com |
Classification according to Lexi-comp
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| Drug interactions categories according to lexi-comp |
Tips for preventing DDIs incidence
This is the final part of the map which provides 7 general
tips to prevent and reduce the incidence of drug-drug interactions. The map also contains hints on how to avoid drug interactions caused by changes absorption, distribution, metabolism, and excretion. To know them and to get the full
map, please order below.
I'm sure you'll be surprised by its comprehensive content shown as mini-maps that makes the topic easy for understand and
memorization. Besides its content of more than 40 examples of drug-drug interactions.
We hope you find Drug-drug Interactions Concept Map helpful and we are looking forward to hearing your opinion. This map is available in the following formats:
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Drug-Drug Interactions Concept Map
is written by: May Mehanna, BCPS
Reviewed and edited by Maha Atef, B Pharm.
Last updated on: 21 April 2014
