Lecture 10 Flashcards
(27 cards)
Drug Interaction
- It is the modification of the action of one drug by another.
- A drug interaction can result from one or combination
of the 3 mechanisms.
Three Mechanisms of Drug Interactions:
a. Pharmaceutical
b. Pharmacodynamic
c. Pharmacokinetic
Knowing drug interaction is important:
a. judicious use at a time can benefic patients
b. adverse interactions are common and may be
catatrophic → avoidable
Out-patients also often receive many drugs like:
a. several prescribed drugs
b. proprietary OTC drugs
c. alternative remedies
d. lifestyle drugs (social reasons)
Drug interactions can be:
a. useful
b. no consequence (trivial)
c. harmful
Pharmaceutical Interactions
It occurs by either chemical or physical reactions when drugs are mixed.
Pharmacodynamic Interactions
- It occurs when different drugs influence the same
physiological function.
→ e.g., state of alertness or blood pressure - Adding second drug during treatment may be to increase
the effect of the first
→ e.g., alcohol increases sleepiness caused by
benzodiazepenes - Drugs with opposing actions, the result may be to
reduce the effect of the first.
→ e.g., indomethacin (increase blood pressure) + losartan
(antihypertensive drug)
Pharmacokinetic Interactions
It occurs when one drug affects the pharmacokinetics of another.
→ e.g., reducing metabolism or elimination from the body
Useful Interactions: Increased Effects
- Drugs can be used in combination to enhance their effectiveness.
- Drugs targeting different components of the disease mechanism
→ may have additive effects
→ examples:
a. antiplatelet drug + a fibrinolytic → myocardial infarction
b. β2 agonist + glucocorticoid → asthma (bronchodilation and suppress inflammation)
Useful Interactions: Combinations of Antimicrobial Drugs
- Drug resistance via the synthesis of a microbial enzyme
→ degrades antibiotic (e.g., penicillinase-producing staphylococci) - Can be countered by using a combination with the enzyme inhibitor
→ e.g., co-amoxiclav: clavulanic acid (penicillinase inhibitor) + amoxicillin
Tuberculosis is the best example.
Useful Interactions: Increased Efficacy (Pharmacokinetic Profile)
- Imipenem is partly inactivated by a dipeptidase in the kidney.
→ Can be overcome in combination with cilastin (a special renal dipeptidase inhibitor) - Ritonavir + saquinavir → antiretroviral therapy
→ saquinavir inhibits degradation of ritonavir by GI CYP3A and faecal elimination by blocking P-gp.
Useful Interactions: Synergistic Effect
- Several antibacterial combinations are synergistic → more than an additive effect
- Example:
a. Cisplatin + paclitaxel → cancer chemotherapy - Therapeutic effects of drugs are often limited by the activation of a physiological control loop.
→ a low dose of a second drug may interrupt the negative feedback
→ example:
angiotensin-converting enzyme inhibitor (blocks renin-angiotensin system)
+
diuretic (the effect is limited by activation of the renin-angiotensin system)
Useful Interactions: Minimise Side Effect
- Low doses of two drugs may be better tolerated and more effective than larger doses of a single agent.
- Drugs with similar therapeutic effects having opposing metabolic effects
→ the effects can be canceled out when used together
~ For Example: ~
→ a loop diuretic (e.g., furosemide) + a K+-sparing diuretic (e.g., spironolactone)
- Predictable adverse effects can sometimes be averted by using drug combinations.
~ examples: ~
a. isoniazid neuropathy (pyridoxine) → prevented by this vitamin B6
Useful Interactions: Block Acutely
Unwanted Effect
- Drug combinations can be used to block an undesired or toxic effect.
→ example: <—-
a. vitamin K or fresh plasma to reverse the effect of warfarin
Trivial Interactions: Shallow Dose-Response Curves
Graph is in Slide 15, Lectur
Trivial Interactions: Plasma and Tissue Binding Site Interactions
- Drugs that displace one another from binding sites on plasma albumin or α-1 acid glycoprotein (AAG)
or within tissues.
Slide 16 Lecture 10 for more information
Trivial Interactions: Exception of above situation
- A transient increase in free conc. can have devastating consequences.
Example:
→ bilirubin in premature babies having limited metabolising activity
Slide 17
Certain concurrent therapy with steep dose-response curve and serious dose-related toxicity can cause
harm:
a. Warfarin and other anticoagulants
b. anticonvulsants
c. cytotoxic drugs
d. drugs for HIV/AIDS
e. immunosuppressants
f. digoxin and other anti-dysrhythmic drugs
g. oral hypoglycaemic agents
f. xanthine alkaloids (e.g., theophylline)
h. monoamine oxidase inhibitors
Harmful Interactions: Risk of Adverse Drug Interactions
- The frequency of detection of drug interactions will be underestimated for poor therapeutic outcome of a
disease
→ e.g., epileptic patients tend to have higher rate of graft rejection - Better understanding of potential mechanisms causing such interactions can lead to early prediction and
prevention (early-phase drug evaluation.
Harmful Interactions: Severity of Adverse Drug Interactions (can be diverse)
a. unwanted pregnancy (from failure of the contraceptive pill due to concomitant medication)
b. hypertensive stroke (from hypertensive crisis in patients on monoamine oxidase inhibitors)
c. gastrointestinal or cerebral haemorrhage (in patients receiving warfarin)
d. cardiac arrhythmias(e.g., secondary to interactions leading to electrolyte disturbance or prolongation
of the QTc)
e. blood dyscrasias (e.g., allopurinol + azathioprine)
Harmful Interactions: Pharmaceutical Interactions
- Inactivation can occur when drugs are mixed
→ e.g., heparin + gentamicin - Drugs may also interact in the gut lumen
→ e.g.,
a. tetracycline + iron
b. cholestyramine + digoxin
Harmful Interactions: Pharmacodynamic Interactions
-Mostly is a simple mechanism either summation or opposing drug effects with similar or opposing
actions.
-This type of interaction broadly depends on drug effect rather than chemical structure
Example:
a. H1
-blocking antihistamine + alcohol → drowsiness
More examples can be found on slide 22, 23, 24
Harmful Interactions: Pharmacokinetic Interactions (Absorption)
- Drugs influencing gastric emptying can alter the rate or completeness of absorption of a second drug
→e.g., metoclopramide, propantheline - Drugs can interfere with the enterohepatic recirculation of other drugs
→ e.g., failure of oral contraceptive + antibiotics
Harmful Interactions: Pharmacokinetic Interactions (Distribution)
- Interactions that involve only mutual competition for inert protein- or tissue-binding sites seldom give
rise to clinically important effects.
