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Pharmacy Clinic
Drug Interactions
Drug-drug interactions are changes in a drug's effects caused by another drug taken during the same time period
It occurs when the effect of one drug is changed by the presence of another drug, food, drink, or by environmental chemical agents
The net effect of the combination between different medications may be;
Interaction of potential clinical significant; is when the a therapeutic combination could lead to an unexpected change or complication in the condition of
the patient.
Duplication: When two drugs with the same effect are taken, their therapeutic effects and their side effects may be intensified. Duplication may occur
when a person inadvertently takes two drugs, usually over-the-counter drugs, that have the same active ingredient. For example, a person may take a
cold remedy and a sleep aid, both of which contain diphenhydramine, or a cold remedy and a pain reliever, both of which contain acetaminophen
Opposition (Antagonism): Two drugs with opposing actions can interact, thereby reducing the effectiveness of one or both
For example, nonsteroidal anti-inflammatory drugs, (NSAIDs, such as ibuprofen, which are taken to relieve pain, may cause the body to retain salt and
fluid; diuretics, such as hydrochlorothiazide and furosemide, help rid the body of excess salt and fluid. If a person takes both types of drug, the NSAID
may reduce the diuretic's effectiveness
Certain beta-blockers (such as propranolol), taken to control high blood pressure and heart disease, counteract beta-adrenergic stimulants, such as
albuterol, taken to manage asthma
Alteration: One drug may alter how the body absorbs, distributes, metabolizes, or excretes another drug. Some drugs affect the P-450 enzyme system
in the liver (which inactivates many drugs) and may cause another drug to be inactivated more quickly or more slowly than usual. For example, by
increasing the activity of P-450 enzymes, barbiturates such as phenobarbital cause the anticoagulant warfarin to be inactivated more quickly and thus to
be less effective when taken during the same time period
Some drugs affect the rate at which the kidneys excrete another drug. For example, large doses of vitamin C supplements increase the urine's acidity
and thus may change the rate of excretion and activity of certain drugs. For example, the rate of excretion may be decreased for acidic drugs such as
aspirin but may be increased for basic drugs such as pseudoephedrine
Clinical significance
Not all drug interactions are clinically significant or cause an adverse effect. In some cases, interacting drugs can be prescribed for patients as long as
the patient is given proper instructions and is compliant. For example, cimetidine and an antacid might be prescribed to the patient, but the patient
should be instructed not to take both medications at the same time.
Combination drug therapy can have beneficial effects
Drug combinations are used to improve the therapeutic objective or to decrease adverse events
Some examples include:
a. Trimethoprim and sulfamethoxazole-a combination antibiotic for increased efficacy in urinary tract infections
b. Amoxicillin and clavulanate potassium-a combination containing a beta-lactamase inhibitor (clavulanate) to inhibit the breakdown of amoxicillin
c. Hydrochlorothiazide and enalapril containing a combination diuretic and antihypertensive to minimize potassium excretion
Some drug-food and drug-drug interactions are utilized for their beneficial effects
a. Saquinavir is given with food to increase its bioavailability through enhanced absorption
b. Probenecid inhibits renal tubular secretion of penicillin, therefore prolonging the plasma half-life of the antibiotic
The likelihood of a drug interaction can be classified as follows:
a. Established-a drug interaction supported by well proven clinical studies
b. Probable-a drug interaction that is very likely but might not be proven clinically
c. Suspected-a drug interaction that might occur; some data might be available
d. Possible-a drug interaction that could occur; limited data is available
e. Unlikely-a drug interaction that is doubtful; no good evidence of an altered clinical effect
is available
Two types of interactions;
Adverse interaction; the outcome may be harmful, either by;
Increasing the efficacy or toxicity of drug, e.g.; pts taking monoamino oxidate inhibitors, may experience an acute and life threatening hypertension
crises if they eat tyramine rich food
Decreasing the efficacy of the drug; e.g.; pts on warfarine given rifampicin will need an increase in the dose of warfarine to maintain adequate effect
It is often difficult to detect an interaction, because;
Many drugs which are known to interaction in some patients, simply fail to do so in others
Patients apparently tolerate adverse interactions, remarkably well
Physicians accommodate the effects without consciously recognizing that what they are seeing is the result of an interaction
I. Pharmacokinetic Interactions
Are those which can affect the processes by which the drugs are absorbed, distributed, metabolized, and excreted
Drug absorption interaction
Most of the interactions which go on the gut results in reduced rather than increased absorption
Some times changes only in the absorption rate, others in the total amount of drug absorbed
For drugs which are given on a multiple dose regimen (e.g oral anticoagulants) the rate of absorption is usually unimportant provided the total amount
of drug absorbed is not markedly altered
For drugs which are given as single doses, and extended to be absorbed rapidly (hypnotics or analgesics); a reduction in the rate of absorption may
result in failure to achieve adequate serum level
e.g; administration of anti cholinergic drugs leads to a reduction in the GIT motility, so the rate of absorption of drugs absorbed in the intestine is
reduced, while the extent of there absorption is increased.
It occurs when the effect of one drug is changed by the presence of another drug, food, drink, or by environmental chemical agents
The net effect of the combination between different medications may be;
- Synergism or additive effect of one or more drugs
- Antagonism of effect one or more drugs
- Alteration of effect of one or more drugs
- Production of idiosyncratic effects
Interaction of potential clinical significant; is when the a therapeutic combination could lead to an unexpected change or complication in the condition of
the patient.
Duplication: When two drugs with the same effect are taken, their therapeutic effects and their side effects may be intensified. Duplication may occur
when a person inadvertently takes two drugs, usually over-the-counter drugs, that have the same active ingredient. For example, a person may take a
cold remedy and a sleep aid, both of which contain diphenhydramine, or a cold remedy and a pain reliever, both of which contain acetaminophen
Opposition (Antagonism): Two drugs with opposing actions can interact, thereby reducing the effectiveness of one or both
For example, nonsteroidal anti-inflammatory drugs, (NSAIDs, such as ibuprofen, which are taken to relieve pain, may cause the body to retain salt and
fluid; diuretics, such as hydrochlorothiazide and furosemide, help rid the body of excess salt and fluid. If a person takes both types of drug, the NSAID
may reduce the diuretic's effectiveness
Certain beta-blockers (such as propranolol), taken to control high blood pressure and heart disease, counteract beta-adrenergic stimulants, such as
albuterol, taken to manage asthma
Alteration: One drug may alter how the body absorbs, distributes, metabolizes, or excretes another drug. Some drugs affect the P-450 enzyme system
in the liver (which inactivates many drugs) and may cause another drug to be inactivated more quickly or more slowly than usual. For example, by
increasing the activity of P-450 enzymes, barbiturates such as phenobarbital cause the anticoagulant warfarin to be inactivated more quickly and thus to
be less effective when taken during the same time period
Some drugs affect the rate at which the kidneys excrete another drug. For example, large doses of vitamin C supplements increase the urine's acidity
and thus may change the rate of excretion and activity of certain drugs. For example, the rate of excretion may be decreased for acidic drugs such as
aspirin but may be increased for basic drugs such as pseudoephedrine
Clinical significance
Not all drug interactions are clinically significant or cause an adverse effect. In some cases, interacting drugs can be prescribed for patients as long as
the patient is given proper instructions and is compliant. For example, cimetidine and an antacid might be prescribed to the patient, but the patient
should be instructed not to take both medications at the same time.
Combination drug therapy can have beneficial effects
Drug combinations are used to improve the therapeutic objective or to decrease adverse events
Some examples include:
a. Trimethoprim and sulfamethoxazole-a combination antibiotic for increased efficacy in urinary tract infections
b. Amoxicillin and clavulanate potassium-a combination containing a beta-lactamase inhibitor (clavulanate) to inhibit the breakdown of amoxicillin
c. Hydrochlorothiazide and enalapril containing a combination diuretic and antihypertensive to minimize potassium excretion
Some drug-food and drug-drug interactions are utilized for their beneficial effects
a. Saquinavir is given with food to increase its bioavailability through enhanced absorption
b. Probenecid inhibits renal tubular secretion of penicillin, therefore prolonging the plasma half-life of the antibiotic
The likelihood of a drug interaction can be classified as follows:
a. Established-a drug interaction supported by well proven clinical studies
b. Probable-a drug interaction that is very likely but might not be proven clinically
c. Suspected-a drug interaction that might occur; some data might be available
d. Possible-a drug interaction that could occur; limited data is available
e. Unlikely-a drug interaction that is doubtful; no good evidence of an altered clinical effect
is available
Two types of interactions;
- Adverse interactions
- Beneficial interactions
Adverse interaction; the outcome may be harmful, either by;
Increasing the efficacy or toxicity of drug, e.g.; pts taking monoamino oxidate inhibitors, may experience an acute and life threatening hypertension
crises if they eat tyramine rich food
Decreasing the efficacy of the drug; e.g.; pts on warfarine given rifampicin will need an increase in the dose of warfarine to maintain adequate effect
It is often difficult to detect an interaction, because;
Many drugs which are known to interaction in some patients, simply fail to do so in others
Patients apparently tolerate adverse interactions, remarkably well
Physicians accommodate the effects without consciously recognizing that what they are seeing is the result of an interaction
I. Pharmacokinetic Interactions
Are those which can affect the processes by which the drugs are absorbed, distributed, metabolized, and excreted
Drug absorption interaction
Most of the interactions which go on the gut results in reduced rather than increased absorption
Some times changes only in the absorption rate, others in the total amount of drug absorbed
For drugs which are given on a multiple dose regimen (e.g oral anticoagulants) the rate of absorption is usually unimportant provided the total amount
of drug absorbed is not markedly altered
For drugs which are given as single doses, and extended to be absorbed rapidly (hypnotics or analgesics); a reduction in the rate of absorption may
result in failure to achieve adequate serum level
e.g; administration of anti cholinergic drugs leads to a reduction in the GIT motility, so the rate of absorption of drugs absorbed in the intestine is
reduced, while the extent of there absorption is increased.