Lecture 11 Flashcards
Drug interactions (46 cards)
1
Q
How does the risk of drug interaction increase with the number of medications a patient takes?
A
linearly
2
Q
What is the most common type of rug-drug interaction?
A
those affecting pharmacokinetics
3
Q
What are the 3 possible outcomes of drug interactions?
A
- increased drug effects
- decreased effects
- generation of a new effect
4
Q
What kind of increased effects can we get?
A
- increase therapeutic effects
- increased adverse effects
5
Q
Example of increased therapeutic effects
A
- ampicillin (antibiotic) rapidly inactivated by bacterial enzymes (poor therapeutic response)
-Sulbactam inhibits bacterial enzymes that inactivate ampicillin
ampicillin + sulbactam = increased therapeutic activity of ampicillin
6
Q
Example of increase adverse effects
A
- warfarin (anticoagulant) used to thin blood
- aspirin (analgesic) also things blood
warfarin + aspirin = bleeding (potentially life threatening)
7
Q
What kind of decreased effects can we get?
A
- reduced therapeutic effect
- reduced adverse effect
8
Q
Example of reduced therapeutic effects
A
- Clopidogrel (anticoagulant) requires metabolic activation by CYP2C19
- omeprazole (treats stomach ulcers) inhibits CYP2C19
Clopidogrel + omeprazole = active metabolite of clopidogrel not formed, insufficient anticoagulation occurs
9
Q
Example of reduced adverse effects
A
- morphine (analgesic) treats pain
- overdose can produce coma, respiratory depression or death
- naloxone (competitive antagonist) can reverse effects
10
Q
Example of a generation of a new effect
A
- Disulfiram helps treat chronic alcoholism
- alcohol normally metabolized to acetylaldehyde (makes you feel hungover) then acetic acid
- disulfiram inhibits metabolism of acetylaldehyde which increases hangover like symptoms within as little as 10 minutes of drinking
11
Q
What are the 4 different types of drug interactions
A
- direct physical interaction
- pharmacokinetic interaction (most common)
- pharmacodynamic interaction
- combined toxicity
12
Q
Direct physical drug interactions
A
- occurs when two or more IV solutions are mixed together, which often = precipitate forming
- if this occurs IT SHOULD NOT BE ADMINISTERED
- solutions should never be mixed without consulting a compatibility chart
13
Q
Example of a direct physical drug interaction before administration
A
- diazepam (a benzodiazepine) should never be mixed with another drug
14
Q
Example of a direct physical drug interaction after administration
A
- sodium bicarbonate + calcium gluconate can form a precipitate in the blood
15
Q
In what way do drug interactions affect absorption?
A
- altered pH
- chelation/binding
- altered blood flow
- gut motility
- vomiting
- drugs that kill intestinal bacteria
16
Q
How can pH and absorption be altered by drug interactions?
A
- drugs that effect gastric or intestinal pH can alter drug absorption
- most common = antacids (increase gastric pH = increase the absorption of drugs that are weak bases and decreases absorption of drugs that are weak acids)
17
Q
How can antacids effect absorption of enteric coated drugs?
A
- enteric coated drugs designed to pass through the acidic stomach without dissolution until they reach alkaline intestine
- antacids = increased stomach pH and promotes premature dissolution of enteric coated drugs
18
Q
What are the consequences of premature dissolution of enteric coated drugs?
A
- drug toxicity
- drug destruction
19
Q
How is chelation/binding and absorption affected by drug interactions?
A
- some drugs bind with each other in the intestine which causes the formation of insoluble complexes that cant be absorbed
20
Q
Example of chelation/binding issues with drug interactions
A
- bile acid sequestrants bind intestinal bile acids and prevent their absorption from the intestine and excreted in the feces
- cholestryramine (BAS) binds to digoxin and decreases its absorption
21
Q
How is blood flow and absorption altered through drug interactions?
A
- drugs that decrease blood flow decrease the absorption of drugs
22
Q
Example of blood flow alteration through drug interactions
A
- local anesthetic alone may diffuse into blood away from injection site
- epinephrine causes vasoconstriction
- local anesthetic + epinephrine = decreases absorption of anesthetic due to vasoconstriction = anesthetic staying at injection site where it is required to precent pain
23
Q
How can gut motility and absrption be altered by drug interactions?
A
- drugs can either increase or decrease gut motility
- laxatives = increase gut motility = decreased drug absorption
- opiate drugs (ex morphine) decrease gut motility = increase drug absoprtion
24
Q
How can vomiting and absorption be altered by drug interactions?
A
- drugs that = vomiting will decrease absorption of other drugs if taken within 20-30 min before vomiting
- can be dangerous bc if it was absorbed & another dose was administered it could result in toxicity
25
How can drug interactions affect intestinal bacteria and absorption?
- intestinal bacteria deconjugate phase II drug metabolites as part of enterohepatic recycling
- antibiotics that kill intestinal bacteria can cause decreased deconjugation and decreased absorption during enterohepatic recycling = decreased plasma drug concentration
- ex. oral contraceptives can be affected
26
In what way do drug interactions affect distribution?
- altering pH
| - protein binding
27
How can distribution be affected by altered pH from drug interactions?
- drugs that change extracellular pH influence the ionization of other drugs which is a major determinant of drug distribution
- changing the extracellular pH can draw a drug from inside the cell to outside by changing its ionization
- ex. sodium bicarbonate increases e.c. pH while ammonium chloride decreases it
28
Example of changing pH altering drug distribution
- during aspirin overdose, increasing extracellular pH with sodium bicarbonate will draw aspirin (weak acid) outside of the cell where it will become ionized and trapped
29
How can distribution be affected from protein binding from drug interactions?
- two drugs bound to sae site on plasma protein = competition for binding
- lower affinity drug will become free =increased therapeutic effect, toxicity, and/or excretion
30
In what way do drug interactions affect metabolism?
- CYP induction (increase metabolism)
- CYP inhibition (decrease metabolism)
- occur in intestine/liver
31
How long can it take for exposure to an enzyme inducer to lead to CYP induction?
2-10 days, 7-10 days for CYP enzymes levels to recover after exposure stops
32
What are some examples of CYP enzyme inducers?
- cigarette/marijuana smoke
- rifampin - induces CYP3A4
- phenobarbital - induces many CYPS
- BBQd food - induces CYP1A2
- alcohol - induces CYP2E1
- st johns wort - induces CYP3A4
33
What does CYP inhibition lead to?
= usually decreased metabolism so increased plasma concentration
34
What are some examples of CYP inhibitors?
- many antibiotics and anti-fungals inhibit CYP3A4
- HIV protease inhibitors = inhibits CYP 3A4
- omeprazole inhibits CYP2C19
- SSRIs inhibit CYP2D6
- fluvoxamine inhibits CYP1A2
- grapefruit juice inhibits CYP3A4
35
In what way do drug interactions affect excretion?
- altered blood flow
- altered pH
- tubular secretion
36
How can altered blood flow from drug interactions affect excretion?
- drugs that decrease renal blood flow = decreased glomerular filtration = decreased renal excretion = increased plasma drug concentrations
37
Examples of drugs that decrease blood flow and affect excretion
- non-steroidal anti-inflammatory drugs (NSAIDS) cause renal vasoconstriction = decrease renal blood flow
- beta blockers = decreased cardiac output = decreased renal blood flow
38
How can altered pH from drug interactions affect excretion?
- drugs that change the pH of the renal tubular filtrate can alter drug excretion due to pH partitioning and ion trapping
- can be helpful in overdoses
39
Example of an overdose in which an altered pH comes in handy
- overdose on amphetamine ( a weak base), filtrate can be acidified with ammonium chloride causing the amphetamine to be ionized and trapped in renal tubules (prevents reabsorption) and we get increased excretion
40
How can tubular secretion from drug interactions affect excretion?
- is mediated by transporters at the proximal tubule
- if one drug blocks a transporter, may block another drug from being excreted into the tubule lumen = decreased renal excretion & increased plasma concentration
41
Example of tubular secretion affecting exretion
- penicillin + probenecid = probenecid inhibits the transporter responsible for moving penicillin from the blood into tubule lumen = renal penicillin excretion decreases and plasma concentration increases
42
What are the two main types of pharmacodynamic drug interactions?
1. interactions that occur at the same receptor
| 2. interactions that occur at separate sites
43
Pharmacodynamic interactions that occur at the same receptor
- usually result of antagonist blocking the action of an agonist which causes decreased therapeutic action
- can also decrease toxicity in overdose situations
- ex. morphine + naloxone
44
Pharmacodynamic interactions that occur at separate sites
- can produce a drug interaction if they produce the same physiological response
ex. morphine and diazepam = CNS suppressors although they bind to different receptors
- when taken together = enhanced CNS depression
45
Examples of combined toxicity
- acetaminophen + alcohol = both hepatotoxic and increase amount of liver damage when taken together
- isoniazid + rifampin = treat tuberculosis and both hepatotoxic (but in this situation both required for treatment)
46
Food -Drug interactions examples
- monoamine oxidase (MAO) inhibitors + tyramine containing foods (i.e aged cheese, yeast, red wine, sauerkraut, cured meat, soy sauce) = decreased breakdown of tyramine & increased release of norepinephrine from peripheral nerve terminals leading to hypertensive crisis (i.e tachycardia, severe hypertension, headache, nausea, and vomiting)
