PHARMACOLOGY- INTRDOCTION
Drug Interactions
YABIN OFUMBA
Bsc. Med.Ed-mak
Dip. Clinical med.
Dip. HSm
Drug interaction
• This is when the pharmacological action of a drug is
altered by concurrent administration of another drug.
• A drug interaction is a situation in which a substance
(usually another drug) affects the activity of a drug
when both are administered together.
This action can be synergistic (when the drug's effect is
increased) or antagonistic (when the drug's effect is
decreased) or a new effect can be produced that
neither produces on its own.
• Sometimes clinicians allow drug interactions to occur
for better actions, but adverse reactions occur with
drugs having low therapeutic index.
• If a number of drugs are simultaneously given,
or drugs interact with endogenous substances,
one drug can be displaced by another.
• Example includes interaction of sulphonamide
with bilirubin, with the result that bilirubin is
displaced which may cause kernicterus in
babies.
• Drug interactions may create alarming
situations.
• In most cases, monotherapy is preferred but
sometimes drugs need to be given in
combination e.g. in treatment of congestive
cardiac failure, diuretics and vasodilators need
to be combined, or in patients suffering from
malignancy, coma, chemotherapy or
tuberculosis.
Types of drug interactions
1. In Vitro
2. In Vivo
Drugs interactions can occur outside the body, e.g.
1. Incompatibilities of drug in an IV infusion
2. Use of wrong vehicle for infusion:
A) No drug should be added to blood plasma, aminoacid
solutions, fat emulsions, sodium bicarbonate
solution, mannitol solution (mannitol may crystalize) and
to heparin infusion.
B) Mannitol should not be mixed with electrolytes, KCl or
other drugs
Highly acidic solution such as dextrose, or fructorse are
unsuitable as vehicle for sodium and potassium salts of
weakly acidic drugs. Such as sulfonamides, barbiturates,
methicillin and novobiocin
Benzyl penicillin, ampicillin, heparin and aminophylline are
unstable at the pH of these solutions.
Isotonic saline is slightly acidic or neutral and is suitable
vehicle for most drug like phenytoin, diazepam
Drugs interactions outside the body
Most antibiotics become unstable and
deteriorate in large volumes of fluids exceptions
are amphotericin B and erythromycin.
Erythromycin lactobionate is unstable in
electrolyte solution but may be diluted with 5%
dextrose solutions
Amphotericin B should be diluted with 5%
dextrose
Calcium salts should not be added to sodium
bicarbonate
Incompatibilities in syringe
Soluble and protamine zinc insulin: soluble
insulin interacts with excess of zinc and
protamine and its onset of action may be delayed
Drugs interactions outside the body
Barbiturates,, phenytoin, phenothiazine,
frusemide should not be mixed with any other
drug in solution
Penicillin is incompatible with gentamicin,
tetracycline and hydrocortisone
Tetracycline is incompatible with calcium salts
Heparin sodium is incompatible with
gentamicin and hydrocortisone
Thiopentone sodium is incompatible with
succinylcholine
In Vivo
1. Pharmacokinetic Drug Interactions
Differences in plasma levels of a drug
achieved by a given dose of that drug.
2. Pharmacodynamic Drug Interactions
Differences in pharmacological effects
produced by a given plasma level of a drug
Pharmacokinetic Drug Interactions
Interactions Affecting Absorption
Drugs + Epinephrine (vasodilator –effective drug levels not achieved)
Chelation / Adsorption; Tetracycline + Ca++
Cholestyramine (adsorption) + Cardiac Glycosides
Sucralfate adsorbs, cannot give other drugs
Altered Intestinal Motility with Atropine + Acetaminophen
Metoclopramide (prokinetic) + Cimetidine (anti ulcer) (increased gastric
emptying, less drug absorbed)
Inhibition of Absorption by Phenytoin and oral contraceptives + Folic acid
Influence of Diet/ Food in Stomach: Fatty Meal
Griseofulvin has increased absorption with fatty meal ( Also with Coartem)-
pH Dependent Absorption
Weak acidic drugs e.g. NSAIDS
Weak basic drugs
Interactions Affecting Distribution
• Competition for Plasma Protein Binding in Sulfisoxazole
and Bilirubin (may lead to kernicterus)- sulfonamide is
thought to displace bilirubin from its albumin-binding
sites in plasma leading to an elevation of
plasma bilirubin, which crosses the blood-brain barrier,
reaches central neurons to cause kernicterus.
• Displacement from Tissue Binding Sites in
Methotrexate + Aspirin (efficacy decreased, increased
levels of methotrexate) so aspirin is stopped before
treatment otherwise may cause methotrexate toxicity
Interactions Affecting Metabolism
Enzyme inducers –adverse effects, therapeutic failure,
diminished response
Interactions Affecting Excretion
• Probenecid with penicillin and methotrexate
• Aspirin with methotrexate
• Agents that alkalinize urine –weak acid
poisoning, sodium bicarbonate given
• Agents that acidify urine
Pharmacodynamic Drug Interactions
Receptor site down regulation or upregulation
1. Synergism
Sulfamethoxazole & Trimethoprim
Levodopa with Carbidopa
2. Antagonism
Rifampicin and Cloxacillin
Protamine and Heparin
3. Combined Toxicity
Ethanol with opioids, barbiturates and benzodiazepi
nes
Drug Antagonism
– Effects of two drugs is less than the sum of drugs acting
separately
• 1+1 = 0
• Summation/Addition (Enhancement of drug effect)
1+1=2
– Response elicited by combined drugs is equal to the
combined response of the individual drugs.
• Synergism 1+1=3
– Response elicted by combined drugs is greater than the
combined responses of the individual drugs.
• Potentiation 0+1=2
– A drug which has no effect enhances the effect of a second
drug.
10/20/2023
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