Drug Interactions Flashcards
A drug interaction occurs when:
The effects of one drug are altered by the co-administration of another drug, herbal medicine, food, drink, or other environmental agents.
Why is it difficult to obtain an accurate estimate of the incidence of drug interactions?
1) Unawareness
2) Under reporting
Which patients suffer from much greater rejection rates of transplants?
Epileptic patients (due to drug interactions)
Which patients are susceptible to drug interactions?
1) Poly-pharmacy
2) Hepatic or renal disease
3) Long-term therapy for chronic diseases: (epilepsy, diabetes, patients in intensive care, transplant patients, etc.)
4) More than one prescriber
5) Critically ill and elderly patients (altered homeostatic mechanisms)
6) Elderly patients
Drug interactions can be:
1) Useful
2) No consequence
3) Harmful
How can drug interactions be useful?
1) Increased therapeutic effect
2) Minimize adverse effects
3) Block acutely an adverse effect (antidote)
Imipenem deactivation can be countered with which drug?
Cilastatin
Isoniazid neuropathy can be prevented by:
Pyridoxine (B6)
What are some severe adverse drug interactions?
1) Unwanted pregnancy
2) Stroke
3) GI or cerebral hemorrhage
4) Cardiac arrhythmias
5) Blood dyscrasias
Which 2 drugs can cause blood dyscrasias?
Allopurinol and azathioprine
What are the mechanisms of drug interactions?
1) Chemical
2) Pharmacodynamic
3) Pharmacokinetic
Chemical drug interactions happen by:
Mixing drugs together outside of the body
Give some examples of chemical drug interactions:
1) Inactivation of heparin with gentamicin
2) Inactivation of heparin with hydrocortisone
3) Inactivation of gentamicin with hydrocortisone
4) Inactivation of penicillin with hydrocortisone
5) Aminoglycosides and penicillins inactivate each other
6) Diazepam can be precipitated by infusion fluids, and adsorbs to the plastic of IV bags and tubing
7) Phenytoin can be precipitated by infusion fluids
What are some examples of pharmacodynamic drug interactions?
1) Drowsiness caused by an H1-blocking antihistamine and alcohol
2) β-blockers and verapamil may precipitate heart failure, heart block, and asystole in patients with SVT
3) Antihypertensive drugs may be less effective with use of NSAIDs
4) Warfarin and aspirin may cause excessive bleeding
5) Combined diuretics
6) Potassium-sparing diuretics with potassium supplements and/or ACEi.
7) Antagonistic interactions
Why are antihypertensive drugs less effective with use of NSAIDs?
1) Inhibition of biosynthesis of vasodilator prostaglandins in the kidney
2) Sodium and water retention
Warfarin mode of action?
Inhibits the coagulation cascade
Aspirin mode of action?
Inhibits platelet function
Aspirin may predispose to ___ by direct irritation and by inhibition of PGE2 biosynthesis in the gastric mucosa.
Gastric bleeding
Give an example of interruption of physiological control loops.
β-blocking drugs with insulin mask insulin-induced hypoglycemia symptoms
Combined diuretics can cause:
1) Excessive intravascular fluid depletion
2) Electrolyte loss
3) “Pre-renal” renal failure
Thiazide and loop diuretics commonly cause:
Hypokalemia = digoxin toxicity (because of increased binding of digoxin to plasma membrane Na+/K+ -ATPase)
β2-Agonists (salbutamol) may reduce:
The plasma potassium concentration
Potassium-sparing diuretics with potassium supplements and/or ACEi may cause:
Hyperkalemia
___ is one of the most common
causes of fatal adverse drug reactions.
Hyperkalemia
The bronchodilator action of selective β2-agonists will be antagonized by:
β-blockers
The opioid antagonist __blocks actions of opioids.
Naloxone
___ blocks the action of benzodiazepines.
Flumazenil
___ blocks the action of oral anticoagulants (warfarin).
Vitamin K
___ antagonizes the action of antipsychotics.
Levo-Dopa
Neuroleptics and tricyclic antidepressants (TCAs) given with drugs producing electrolyte imbalance (diuretics) may cause:
Ventricular arrhythmias
Drugs that prolong the QT interval can cause:
Fatal polymorphic ventricular tachycardia (torsade de pointes).
Selective serotonin reuptake inhibitors and MAOIs can cause:
Serotonin syndrome
___ is an antibacterial with MAOI activity.
Linezolid
MAOIs can prevent metabolism of __ in the gut.
Tyramine
Tyramine is found in:
Cheese and red wine
What affects absorption of drugs?
1) Changes in gastric pH due to drugs
2) Some drugs within the GIT form chelates that are not absorbed
Which drugs aren’t absorbed when GI pH is changed?
1) Aspirin
2) Itraconazole
___ and ___ can complex with iron and antacids containing calcium, magnesium, and aluminum.
Tetracyclines; Fluoroquinolones
___ are often co-prescribed with calcium supplements for treatment of osteoporosis and they reduce the bioavailability of each other, leading to therapeutic failure.
Bisphosphonates
What are some examples of adsorbents?
1) Charcoal
2) Kaolin (Clay)
What are some examples of anion-exchange resins?
1) Cholestyramine
2) Colestipol
Drugs that affect the rate of gastric emptying can affect absorption of other drugs absorbed in:
The upper part of the small intestine
Drugs with anticholinergic effects decrease:
Gut motility and gastric emptying
What are some drugs with anticholinergic effects?
1) TCAs
2) Phenothiazines
3) Antihistamines
Opioids inhibit gastric emptying and reduce the absorption rate of __, without affecting
the extent of absorption.
Paracetamol
Anticholinergics reduce the bioavailability of __, as a result of increased metabolism in
the intestinal mucosa.
Levodopa
Metoclopramide increases gastric emptying and increases the absorption rate of:
1) Paracetamol
2) Propranolol
3) Mefloquine
4) Lithium
5) Cyclosporine
Drugs that inhibit P glycoprotein such
as ___ may increase bioavailability of
___, and thus its toxicity.
Verapamil; Digoxin
___ may cause a malabsorption syndrome causing reduced absorption of drugs
Neomycin
___ reduces absorption of co-administered fat soluble drugs and vitamins.
Orlistat
Orlistat mechanism of action?
Inhibition of pancreatic lipases
What is the most important target of drug interactions?
Metabolism
Which is faster: Enzyme induction or enzyme inhibition?
Enzyme inhibition
What does enzyme inhibition depend on?
The presence of high-enough concentration of the inhibiting drug at the metabolic site.
If you give a drug, then inhibit the enzyme that metabolizes it, what will happen?
Reduced drug metabolism = increase in its steady-state
concentration.
Enzyme inhibition is __-related
Dose
The enzyme inhibition effect will be seen faster when the inhibitor half-life is __(short/long), and will be delayed for drugs with __(short/long) half-lives.
Short; long
Enzyme interactions are most likely to affect drugs with __(wide/narrow) therapeutic ranges
Narrow
Which drugs are more likely to be affected by enzyme interactions?
1) Theophylline
2) Phenytoin
3) Cyclosporine
4) Oral anticoagulants
Erythromycin is an inhibitor of ___.
CYP3A4
Carbamazepine is metabolized by:
CYP3A4
Can carbamazepine be given with erythromycin?
No, because Erythromycin will inhibit CYP3A4 leading to increased carbamazepine concentration
Which fruit is an inhibitor of CYP3A4?
Grapefruit
Which drugs shouldn’t be given with grapefruit?
1) Carbamazepine
2) Nifedipine
3) Felodipine
What does the PPI lansoprazole inhibit?
CYP2C19
Clopidogrel is a pro-drug activated by which enzyme?
CYP2C19
What will happen if you give lansoprazole and clopidogrel together?
Decreased effectiveness of clopidogrel due to inhibition of CYP2C19
6-mercaptopurine is a metabolite of:
Azathioprine
___ is responsible for inactivation of 6-mercaptopurine.
Xanthine oxidase
Allopurinol inhibits:
Xanthine oxidase
Phenytoin is metabolized by:
CYP450
Isoniazid is an inhibitor of:
CYP450
Warfarin is metabolized by:
CYP450
Sulfonamides are inhibitors of:
CYP450
Warfarin should not be given with:
Sulfonamides
Phenytoin should not be given with:
Isoniazid
Phenelzine is a:
Non-selective monoamine oxidase inhibitor
Non-selective monoamine oxidase inhibitors potentiate the action of:
Indirectly acting amines such as tyramine
Clinically important impairment of drug metabolism may also result indirectly from ___ rather than enzyme inhibition.
Hemodynamic effects
___ is metabolized in the liver and the hepatic extraction ratio is high.
Lidocaine
Which drugs reduce hepatic blood flow?
1) Negative inotropes
2) β-blockers
3) H2-blockers
Which drugs are the most powerful enzyme inducers?
1) Rifampicin
2) Antiepileptic drugs
a) Barbiturates
b) Phenytoin
c) Carbamazepine
Which drug can induce its own metabolism (autoinduction)?
Carbamazepine
Which enzyme inducers are nondrugs?
1) Cigarette smoking
2) Chronic alcohol use
3) The herb St John’s wort
Rifampicin has a ____(short/long) half-life.
Short
Phenytoin has a ____(short/long) half-life.
Long
The enzyme induction effect develops over several days or weeks because it requires:
New protein synthesis
How long will an enzyme induction effect persist after withdrawing the drug?
Same time it takes to develop in the first place
Inducers with ___(long/short) half-lives will induce metabolism more rapidly than those with ___(long/short) half-lives because they reach
steady-state concentrations more rapidly.
Short; Long
Enzyme induction is __-dependent.
Dose
Enzyme induction means increase in:
Drug metabolism
Enzyme induction usually results in ___(increased/reduced) pharmacological effect of the affected drug.
Reduced
Why is Saint John’s Wort given?
For depression
Which medications will fail if given with Saint John’s Wort?
1) Cyclosporine
2) Tacrolimus
3) HIV-protease inhibitors
4) Irinotecan
5) Imatinib
If the drug has active metabolites (or pro-drug), induction ___(decreases/increases) its pharmacological effect.
Increases
The dose of the drug may need to be ___(increased/decreased) in the presence of the inducer to attain the therapeutic effect.
Increased
You need to be careful when stopping an inducer if taking another drug. Why?
Enzymes go down, which means slower drug metabolism = we have to lower the drug dose
If you give warfarin with an inducer, then stop the inducer, what will happen?
Bleeding, because the dose of warfarin has not been adjusted properly.
Drug displacement from protein binding sites results
in:
Increased free or unbound fraction temporarily
Temporary increase in free or unbound fraction is quickly decreased by:
Increased elimination or distribution (clearance).
Which drugs are highly protein-bound?
1) Phenytoin
2) Lidocaine
3) Warfarin
What enhances the elimination of alkaline drugs?
Acidifying the urine pH
What enhances the elimination of acidic drugs?
Alkalinization of the urine pH
Change of urine pH can be used to enhance drug elimination in cases of:
Poisoning (salicylates,
amphetamine, etc).
Probenecid increases plasma concentrations of penicillins by:
Delaying their renal excretion
___ increases plasma concentrations of penicillins by delaying their renal excretion.
Probenecid
Salicylates and other NSAIDs can cause life-threatening ___ toxicity by inhibiting their renal excretion
Methotrexate
NSAIDs increases serum ___ levels and thus toxicity.
Lithium
NSAIDs inhibit synthesis of:
Prostaglandins
Many diuretics reduce sodium reabsorption in ___ or ___.
Loop of Henle; distal tubule
Reduced sodium reabsorption
indirectly leads to:
Increased proximal tubular
reabsorption of monovalent cations.
If you take a diuretic that reduces sodium absorption, then take lithium salts, what happens?
The lithium salts will be resorbed in the proximal tubule and cause toxicity.
Antibiotics which eliminate gut flora quickly ___(increase/decrease) the metabolism of drug conjugates back into the parent drug = more elimination
Decrease
OCPs should not be taken with:
Broad spectrum antibiotics
___ acts as efflux pump in renal
proximal tubules, hepatocytes, intestinal mucosa, pancreas, and blood-brain-barrier.
P-glycoprotein
P-glycoprotein exports drugs into:
1) Urine
2) Bile
3) Intestinal lumen
P-glycoprotein reduces drug concentration in the:
CNS
Iron and antibiotics should NOT be taken with:
Food
Tyramine should NOT be taken with:
MAOi
Calcium channel blockers should NOT be taken with:
Grapefruit
Cruciferous vegetables (Brussel sprouts, cabbage, broccoli) are inducers of:
CYP1A2
What is Glycyrrihizin glabra?
Licorice
Licorice should not be taken with:
1) Diuretics
2) Digoxin
Glycyrrihizin glabra (Licorice) is taken for:
Peptic ulcers
Glycyrrihizin glabra (Licorice) may exacerbate:
1) Hypokalemia
2) Heart failure
3) Edema
(Sodium & water retention)
Hawthorn enhances:
Hypotensive effect
