MDT- A necessary evil

1. MULTI-DRUG THERAPY
The less is more.

2. WHAT ARE DRUG INTERACTIONS?
● Drug interaction occur when a substance (may or may not be another drug) reacts
with a drug.
● This drug-drug interaction may cause you to experience an unexpected side effect.
● For example, mixing a drug you take to help you sleep (a sedative) and a drug you
take for allergies (an antihistamine) can slow your reactions and make driving a car
or operating machinery dangerous.
● Drug interactions fall into three broad categories:
● Drug-drug interactions (POLYPHARMACY) occur when two or more drugs react
with each other. This drug-drug interaction may cause you to experience an
unexpected side effect.
● For example, mixing a drug you take to help you sleep (a sedative-diazepam) and a
drug you take for allergies (an antihistamine-diphenhydramine) can slow your
reactions and make driving a car or operating machinery dangerous.
● Drug-food/beverage interactions result from drugs reacting with foods or beverages.
● For example, mixing alcohol with some drugs(alprazolam) may cause you to feel
tired or slow your reactions.
● Drug-condition interactions may occur when an existing medical condition makes
certain drugs potentially harmful.
● For example, if you have high blood pressure you could experience an unwanted
reaction if you take a nasal decongestant.

3. WHAT IS MULTIDRUG THERAPY?
● Multiple drug therapy is the concurrent use of multiple medications. It can be
associated with:
1. the prescription and use of too many or unnecessary medicines
2. at dosages or frequencies higher than therapeutically essential.
● It is generally observed practice in the geriatric population or in people having
no. of chronic illness.
● Older people have higher rates of chronic illness and are more likely to be
taking multiple medications. Polypharmacy increases the risk of adverse drug
events such as:
1. Falls, confusion and functional decline.
2. Changes in physiology and social and physical circumstances contribute to
the risk of adverse drug events.
3. Older people are more likely to experience poor vision, hearing and memory
loss and have altered metabolic rates, such as declining renal function.
● Adverse reactions may go undetected because symptoms may mimic problems
associated with older age such as forgetfulness, weakness or tremor.
● Adverse reactions may also be misinterpreted as a medical condition and lead
to the prescription of additional drugs.

4. WHY IS MDT A NECESSARY EVIL?
MDT is unavoidable in patients having chronic diseases. Respective
medicines are required to be taken for treatment of the
particular diseases the patient has. It is an effective way to keep
the diseases in check. MDT poses a problem when:
● The pharmacist is unaware of the full medical profile of the
patient
● Self medication by the patient. Example: casual intake of
antacids
● Medication being provided to the patient without prescription
Example: antibiotics
● Confusing information or lack of information provided to the
patient.

5. HOW DOES MDT CAUSE DRUG INTERACTION?
AND IT’S EFFECT
● Dug interaction can alter the pharmacokinetics or
pharmacodynamics.
● PHARMACOKINETICS:
● Chemical interactions
a)Oral bioavailability
b)Gastric emptying
● Absorption
● Presystemic elimination
● Protein binding interactions
● Altered metabolism

6. CHEMICAL INTERACTIONS
● Drugs can react physically or chemically with
each other before they are administered to the
patient or in case of oral preparations before
they are absorbed.
● Example-oral tetracycline chelates thecations
calcium,magnesium,aluminium
● or iron resulting in a cation-tetracycline
complex that cannot be absorbed.

7. ORAL BIOAVAILABILITY
● This can be divided into interactions affecting gastric emptying, drug absorption
and presystemic elimination.
● Gastric emptying: It is slowed down when we administer drugs like antacids,
anticholinergics, narcotics. This can be disadvantageous in case when drugs that
are acid labile (eg:levodopa) are taken along.
● Absorption:Most drugs are absorbed in the small intestine by passive diffusion.
● Some drugs eg oral neomycin,antineoplastic drugs can damage the intestinal
absorptive surface and potentially result in decreased absorption of other drugs.
● Antacids decrease absorption of drugs that require low pH eg: ketoconazole,
quinolones.
● Presystemic elimination: Drugs have the capacity to be absorbed, metabolised or
extracted during transit across the intestinal epithelium into the portal circulation
and during the first pass through the liver.This is phenomenon is called
presystemic elimination or First pass effect effect.
● Drugs subject to significant presystemic elimination and consequently low
bioavailability include propranolol, metoprolol, chlopromazine, labetalol,
amitriptyline,imipramine, felodipine and morphine.These drugs can compete with
each hence increasing each other’s bioavailability eg chlopromazine and
propranolol

8. PROTIEN BINDING INTERACTIONS
● Drugs that are highly bound in plasma are potentially
subject to displacement from their carrier proteins by
another drug with affinity for the same protein.
● When another highly bound drug is added, competitive
displacement may occur, resulting in a transient
increase in free concentration of the index drug.
●Example- phenytoin displaces warfarin; aspirin
displaces methotrexate.
● This displacement is only likely to cause a clinically
significant effect if the index drug has:
1. a small volume of distribution
2. narrow therapeutic index
3. rapid onset of action

9. ALTERED METABOLISM
● Certain drugs are enzyme inhibitors or enzyme inducers i.e. they can
inhibit the release of metabolizing enzyme or enhance the release of
metabolizing enzyme respectively.
● Enzyme inhibition: The magnitude of inhibition effect in an individual is
variable because it depends on the specific enzyme or enzymes inhibited
and the quantitative importance of that pathway in overall clearance of
the index drug.
● Example - Terbinafine decreases metabolism of tricyclic
antidepressants.Azole antifungals(itraconazole) decreases metabolism of
calcium channel blockers
● This varies from competitive inhibition to irreversible inactivation.
Irreversible inactivation leads to the longest lasting effects.
● Enzyme induction: Enzyme induction can enhance the metabolism of the
inducing agent-(auto induction) and/or a variety of other drugs and some
endogenous compounds eg thyroxin, cortisol and bilirubin.
● Induction can be associated with marked increases in the clearance of the
index drug, resulting in loss of efficacy. Examples: Rifampicin has been
implicated as a cause of Failure of effect of oral contraceptives.

10. PHARMACODYNAMICS
● In pharmacodynamic interactions, the effects of one
drug are changed by the 2nd drug at its site of action.
● Can involve competition for specific sites but can also
be indirect and involve interference with physiological
systems
1. Synergistic/Additive interactions
2. Antagonistic interactions

11. SYNERGISTIC INTERACTIONS
● Occur when 2 drugs with similar pharmacological
effects are given together.
● Examples-antidepresants, antiepileptic,
antihistamines when given together lead to
excessive drowsiness.
• Example –quinidine-digoxin interaction;when quinidine is
given to patients receiving digoxin,two to three fold increase
in steady state levels of digoxin occurs.Various mechanisms
involved may be explained by the inhibition of the p-
glycoprotein efflux transporter by quinidine.

12. ANTAGONISTIC INTERACTIONS
● This occurs when a drug with agonist action at a
particular receptor site interacts with an antagonist at
that site.
● Example;- Specific antagonists may be used to reverse
the effect of another drug at a specific receptor site eg
opioid antagonist-Naloxone, Benzodiazepine
antagonist-Flumazenil
• Example- Drugs with arrythmogenic potential
eg antiarrythmics, neuroleptics, tricyclic
antidepressants and those producing
electrolyte imbalances eg diuretics can lead to
ventricular arrthymias and should be avoided

13. MANAGE POLYPHARMACY
● Prevention- Avoid prescribing for minor, non-specific or self-limiting
complaints. Only prescribe when there is good evidence of likely
efficacy as well as a strong need for the medication.
● Regular medication review- An accurate drug history is essential for
patients on multiple medicines. This is best achieved when the
medication review is done in the patient’s home. Alternatively ask the
patient to bring in all their medicines (prescribed and non-prescribed).
● A review includes assessing appropriateness and ongoing need for
therapy, adverse effects and interactions, the dosage regime and
formulations, and also compliance.
● Non-pharmacological approaches -Use lifestyle measures whenever
possible either as an adjunct or instead of medications.
● Communication- Talk with the patient about their concerns,
expectations, difficulties in using the medications and their ability to
follow the medication regimen.
● Discuss changes to the medication regimen with the patient’s other
health care providers.
● Simplify- Reduce the regimen to essential drugs. Consider fewest
possible dosage intervals and dose reduction where appropriate. Limit
use of optional, trivial and placebo medications.

14. PREVENT DRUG INTERACTIONS
● Document all drugs including herbal preparations,
OTC,recreational drugs that the patient is taking.
● Understand the pharmacokinetics and pharmocodynamics
of the drugs given, keeping in mind the important
mechanisms of drug interactions.
● Minimize the number of drugs given to any patient and try
to ensure that the benefits outweigh the risks for each.
● Be particularly vigilant with patients taking low therapeutic
index drugs.
● Whenever a patient’s course deteriorates, look out for a
possible adverse drug interaction. IF the deterioration is due
to drug therapy, it probably is reversible

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