Module 11 Flashcards
Drug can interact with what?
Other drugs, food in our diet
The risk of drug interactions increases (almost _______) with what?
The number of medications a patient takes
increases almost linearly
Drug interactions are especially important in what cohort? Why?
Seniors - b/c the average 65 year old takes 7 medications
What is the most common type of drug-drug interaction?
Those affecting pharmacokinetics
When two or more drugs interact, there are 3 possible outcomes, these are?
1 - increased effects
2 - Decreased effects
3 - Generation of a new effect
Drug interactions can increase drug effects by either an increase in the _______ effect or an increase in ________ effects.
therapeutic
adverse
Describe an example of increased therapeutic effect from drug-drug interactions.
Sulbactam - inhibitor of the bacterial enzyme that inactivates ampicillin
Co-administration increases the therapeutic activity of ampicillin
Describe an example of increased adverse effects from drug-drug interactions.
Warfarin and aspirin coadministration - can lead to potentially life-threatening side effects
Give an example of a drug-drug interaction that reduces therapeutic effects.
Clopidogrel + omeprazole
Omeprazole inhibits CYP2C19 - which converts the pro-drug clopidogrel to its active metabolite - therefore anti-coagulation doesn’t occur to an appreciable amount
Give an example of a drug-drug interaction that reduces adverse effects.
Naxolone and morphine overdose
Naxolone is a competitive antagonist of morphine - prevents coma, respiratory depression or death from morphine OD
Give an example of a drug-drug interaction that generates a new effect.
Disulfiram inhibits acetaldehyde metabolism causing severe hangover-like symptoms within 10 minutes of alcohol consumption
What are the different types of drug interactions?
Direct physical interaction
Pharmacokinetic interaction
Pharmacodynamic interaction
Combined toxicity
Direct physical or chemical interaction of two or more drugs
Direct physical interaction
Interactions affecting ADME
Pharmacokinetic interactions
Interactions affecting receptor binding
Pharmacodynamic interactions
Two or more drugs exhibit toxicity to the same organ
Combined toxicity
The most common direct interaction occurs when?
When two or more IV solutions are mixed together
Often, mixing IV solutions causes a ________ to form.
IF this occurs, what should be done?
precipitate
in that case, throw it out
Drug solutions should never be mixed without consulting a _________ _______.
compatibility chart
Which drug should never be mixed with another drug?
Diazepam
Although direct drug interactions are more common when mixing medications, they may also occur following __________.
What is an example?
Administration
Sodium bicarbonate followed by calcium gluconate - form a precipitate in the blood
By far the most common type of drug interaction experienced in patients.
Pharmacokinetic interaction
What is the most common drug interaction with respect to alteration of pH?
Antacids - increase gastric pH and thus absorption of weak bases in the stomach
Antacids dramatically affect the absorption of this type of formulation.
Enteric coated drugs - can get dissolved in the stomach as the pH is increased
Describe chelation/binding drug interactions and give an example.
One drug binding another in the intestine.
Bile acid sequestrants usually bind intestinal bile and prevent their absorption in the intestine (cholestyramine) - binds to digoxin in the intestine, decreasing its absorption
Describe an example of altered blood flow from drug-drug interactions.
Epinephrine (vasoconstriction) and a local anesthetic - decreases absorption - allows it to remain at the injection site for longer
Describe how gut motility affects drug absorption and give two examples.
Laxatives increase gut motility and decrease drug absorption
Opiates decrease gut motility and increase drug absorption
If vomiting occurs within ___-___ minutes of taking one or more medications, it is likely that absorption is incomplete.
However, when can toxicity occur?
20-30
IF the drug entered the intestine before the patient vomitted, adding more drug may cause toxicity
Describe how drugs that kill intestinal bacteria affect absorption.
Intestinal bacterial mostly de-conjugate phase II drug metabolites and increase enterohepatic recycling.
Killing them off decreases plasma drug concentration
Describe how both sodium bicarbonate and ammonium chloride affect pH.
sodium bicarbonate raises pH
Ammonium chloride decreases it
(extracellular pH)
Describe a way in which sodium bicarbonate is used as a drug-drug interaction to alter pH.
Sodium bicarbonate raises pH extracellularly, and draws out aspirin into the ECF (used in OD cases)
Describe how protein binding drug-drug interactions work.
The drug with the higher affinity knocks off the lower affinity drug, increasing the free concentration of the displaced drug
One of the most important and common types of drug metabolism.
Altered drug metabolism
Most drug-drug interactions affecting metabolism occur where?
the liver or intestine
Increased synthesis of CYP enzymes
induction
Induction is a ______ process, therefore it may take __-___ days following exposure to the enzyme inducer before induction occurs
delayed
2-10 days
Once the inducer is stopped, it takes _-__ days before the CYP enzyme levels return to normal.
7-10
For each of the following, describe their inductive effects. Cigaretee/marijuana smoke Rifampin Phenobarbital BBQ'd food Alcohol
1 joint = same inductive effect as 5-10 cigs
Rifampin - induces CYP3A4
Phenobarbital induces many CYPs
BBQ’d food - induces CYP1A2
Alcohol induces CYP2E1 (cirrhosis decreases it however)
Typcially, enzyme inhibition results in _______ plasma concentration of the parent drug.
increased
Describe what enzyme is inhibited by the following. Antibiotics/anti-fungals HIV protease inhibitors SSRIs Fluvoxamine Grapefruit juice
antibiotics/anti-fungals - CYP3A4 HIV protease inhibitors - CYP2C19 SSRIs - CYP2D6 Fluvoxamine - CYP1A2 Grapefruit juice - CYP3A4
How does altered blood flow affect excretion?
Decreased renal blood flow means decreased filtration and thus excretion
Give examples of drugs affecting blood flow and excretion.
NSAIDs cause renal vasoconstrictions
Beta blockers decrease Cardiac output
Describe an example of altering pH in drug excretion.
In amphetamine overdoses (weak base), the pH of the renal filtrate is acidified by ammonium chloride
Provide an example of drug-drug interactions affecting tubular secretion, and how it works.
Probenecid - a drug used to treat gout - blocks the transporters responsible for moving penicillin from the blood, into the tubule lumen
Thus, penicillin excretion decreases, and plasma concentration rises
What are the two main types of pharmacodynamic drug interactions?
Interactions that occur at the same receptor
Interactions that occur at separate sites
usually, drug interactions that occur at the same receptor are the result of an ________ blocking the action of an _______.
antagonist
agonist
Describe an example of an interaction occuring at the same receptor used to treat drug overdose.
Naxolone - competitive antagonist - binds to receptors that morphine binds to
Describe drug interactions that occur at separate sites.
Morphine and diazepam both are CNS depressants. Although they function on different receptors (opioid receptor and benzodiazepine receptor, respectively), the combination of their effects is enhanced CNS depression
Give two examples of drugs that interact for combined toxicity.
Acetominophen and alcohol - both hepatotoxic
Isoniazid and rifampin - both used to treat TB and are hepatotoxic (both are usually necessary unfortunately)
What foods must patients taking MOA inhibitors avoid?
Foods containing thyramine - aged cheese, yeast, red wine, sauerkraut, cured meat and soy sauce
Why must patients avoid tyramine containing foods when taking MOA inhibitors?
MAO inhibitors inhibit the breakdown of tyramine
Tyramine causes increased NE release from peripheral nerve terminals and can cause potentially fatal HTN.
What are symptoms of a HTN crisis caused by high tyramine levels?
Tachycardia, severe HTN, headache, nausea, and vomiting
