Chapter 3- Drug Interactions Flashcards
Pharmacodynamics
The effect or change that the drug has on the body
Additive effect toxicity
Drugs that have similar end effects through different mechanisms/receptors can cause additive effects.
Risk with concurrent use of benzodiazepines and opioids
Due to the heightened fatality risk when opioids and benzodiazepines are taken together, the FDA placed a boxed warning to all drugs in both classes.
Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
Aspirin + warfarin interaction
Warfarin causes anticoagulation through inhibition of vitamin K dependent clotting factors. Aspirin blocks the effects of platelets. They both cause increased bleeding and this effect is greater when taken together.
Antagonist
Blocks the agonist from binding to its receptor.
Naloxone as an antagonist
Naloxone is a mu-receptor antagonist; it saturates the mu receptors and blocks the opioid from binding. Naloxone is used to reverse respiratory depression, but will also reverse the analgesic effect.
Synergism
Present when two drugs taken in combination have a greater effect than obtained by simply adding the two individual drugs together.
Oxcodone + Acetaminophen synergy
The mechanisms of analgesia between oxycodone and acetaminophen are different and do not overlap. When taking the drugs together the effect is greater than the individual drugs
Pharmacokinetics
The effect the body has on the drug (ADME)
Chelation
Occurs when a drug binds to polyvalent cations (ex, Mg++, Ca++, Fe++) in another compound
Example of chelation
antacids or iron supplements
Chelation of quinolone antibiotics
Occurs when quinolones bind to calcium-containing drugs and dairy products. When taken together, the antibiotic will not dissolve, will not be absorbed, and the infection may not be adequately treated.
Examples of drugs with polyvalent cations or other binding properties
Antacids, multivitamins, sucralfate, bile acid resins, aluminum, calcium, iron, magnesium, zinc, phosphate binders
Polyvalent cations should be separated from what drugs?
Quinolones, tetracyclines, levothyroxine. oral bisphosphonates
The majority of PK drug reactions occur during
metabolism in the liver
Ritonavir and darunavir interaction
Ritonavir inhibits the metabolism of darunavir, which “boosts” darunavir levels and increases its efficacy in treating HIV.
Clarithromycin + warfarin interaction
Clarithromycin inhibits warfarin metabolism, increasing the INR and risk of bleeding.
Warfarin would need to be decreased.
Rifampin + warfarin interactions
Rifampin induces warfarin metabolism, decreasing the INR and increasing the risk for blood clots.
Warfarin would need to be increased.
Primary route of drug excretion
Renal
Probenacid + penicillin interaction
Probenacid blocks the renal excretion of penicillin. Giving probenacid with penicillin can be beneficial when high penicillin levels are needed to cross the BBB and provide effective treatment of neurosyphilis.
Sodium bicarbonate + aspirin interaction
Salicylate overdose results in toxicity.
IV sodium bicarb alkalinizes the urine, causing salicylate to become ionized. Ionized compounds are more hydrophilic and will stay in the urine, causing less to be reabsorbed in the renal tubules. Compounds that stay in the urine will be renally excreted.
What is the purpose of CYP450 enzymes?
catalyze Phase I reactions that either produce essential compounds or uncover or insert a polar group on a compound to facilitate renal excretion.
Prodrugs
Taken in an inactive form and are converted by CYP450 into the active form.
Why are prodrugs used?
To extend the dosing interval and to prevent drug abuse