Drug Interactions Flashcards by Sarah Assaf

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.

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Why is it difficult to obtain an accurate estimate of the incidence of drug interactions?

1) Unawareness
2) Under reporting

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Which patients suffer from much greater rejection rates of transplants?

Epileptic patients (due to drug interactions)

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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

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Drug interactions can be:

1) Useful
2) No consequence
3) Harmful

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How can drug interactions be useful?

1) Increased therapeutic effect
2) Minimize adverse effects
3) Block acutely an adverse effect (antidote)

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Imipenem deactivation can be countered with which drug?

Cilastatin

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Isoniazid neuropathy can be prevented by:

Pyridoxine (B6)

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What are some severe adverse drug interactions?

1) Unwanted pregnancy
2) Stroke
3) GI or cerebral hemorrhage
4) Cardiac arrhythmias
5) Blood dyscrasias

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Which 2 drugs can cause blood dyscrasias?

Allopurinol and azathioprine

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What are the mechanisms of drug interactions?

1) Chemical
2) Pharmacodynamic
3) Pharmacokinetic

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Chemical drug interactions happen by:

Mixing drugs together outside of the body

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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

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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

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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

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Warfarin mode of action?

Inhibits the coagulation cascade

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Aspirin mode of action?

Inhibits platelet function

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Aspirin may predispose to ___ by direct irritation and by inhibition of PGE2 biosynthesis in the gastric mucosa.

Gastric bleeding

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Give an example of interruption of physiological control loops.

β-blocking drugs with insulin mask insulin-induced hypoglycemia symptoms

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Combined diuretics can cause:

1) Excessive intravascular fluid depletion
2) Electrolyte loss
3) “Pre-renal” renal failure

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Thiazide and loop diuretics commonly cause:

Hypokalemia = digoxin toxicity (because of increased binding of digoxin to plasma membrane Na+/K+ -ATPase)

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β2-Agonists (salbutamol) may reduce:

The plasma potassium concentration

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Potassium-sparing diuretics with potassium supplements and/or ACEi may cause:

Hyperkalemia

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___ is one of the most common
causes of fatal adverse drug reactions.

Hyperkalemia

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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

Drug Interactions Flashcards

(126 cards)