Drug-drug Interactions Concept Map | Pharmacokinetic Drug Interactions | Pharmacodynamic Drug Interactions

Drug-Drug Interactions Concept Map: An Overview

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Part 1 - Pharmacokinetic Drug-Drug Interactions
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Pharmacodynamic_drug_drug_interactions_zoom_out_pharmacotherapy
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
  • Drug Binding
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):
  1. Displacement.
  2. 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:
  • Enzyme Inhibition
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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.
  • Enzyme Induction
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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.

Prodrugs
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:
  • Glomerular Filtration
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.
  • Active Tubular Secretion
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

  1. Additivity
  2. Synergism
  3. 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:
  1.           Polypharmacy/ Therapeutic jungle
  2.           Drugs with narrow therapeutic indices
  3.           Route of drug administration
  4.           Time-dependent drug-drug interactions
  5.           Drugs with high first pass metabolism (FPM)
  6.           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

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