Learning Drug Interactions Flashcards
Pharmacodynamics definition
Effect drug has on the body
Drugs that have similar end effects through different mechanisms/receptors can cause _____ effects
additive
Benzodiazepines and opioids risk
BBW
Sedation, respiratory depression, coma, death
Reserve for use in patients for whom alternative treatment is inadequate
Limit dose and duration to minimum required
What is synergism?
When the effect from two drugs taken in combination is greater than the effect from adding the two individual effects together
Pharmacokinetic definition
effect the body has on a drug
4 parts of pharmacokinetics
Absorption
Distribution
Metabolism
Excretion
Drugs with polyvalent cations or other binding properties should be separated from what medications?
quinolones, tetracyclines, levothyroxine, oral bisphosphonates
Where are CYP enzymes primarily located?
In the liver
Common prodrugs
Capecitabine Copidogrel Codeine Colistimethane Cortisone Enalapril Famciclovir Fosphenytoin Isavuconazonium sulfate Levodopa Lisdexamfetamine Prednisone Primidone Tramadol Valacyclovir Valganciclovir
Codeine safety consideration with CYP enzymes
Ultra-rapid metabolizers of CYP2D6 - can lead to toxicity - do not use in these patients
Poor analgesia with poor metabolizers of CYP2D6
Clopidogrel safety considerations with CYP enzymes
Do not use with CYP2C19 inhibitors (omeprazole and esomeprazole) - block conversion to active form
Major CYP inhibitors
G-PACMAN G - grapefruit P - protease inhibitors A - azole antifungals C - cyclosporine, cimetidine, cibicistat M - macroides (clari and ery, but not azithromycin) A - Amiodarone N - non-DHP CCBs (diltizem and verapamil)
Major CYP inducers
CROSS PP C - Carbamazepine R - Rifampin, rifabutin, rifapentine O - Oxcarbazepine S - Smoking S - St. John's Wort P - Phenytoin P - Phenobarbital
How long for CYP inhibitor effect to go away once stopped? Inducer effect?
Inhibitor effect goes away quickly once d/c
Inducer effect goes away 2-4 weeks once d/c
How do P-gp pumps work?
Transport drugs and their metabolites out of the body by pumping them into the gut
What effect do P-gp inhibitors have?
Increase absorption of P-gp substrates (less drug is pumped into the gut) and the substrate drug level will increase
P-gp substrates
Anticoagulants (apixaban, rivaroxaban)
CV drugs (digoxin, diltiazem, verapamil)
Immunosuppressants (cyclosporine, tacrolimus)
HCV drugs (ombitasvir, paritaprevir, dasabuvir)
Others (colchicine, saxagliptin)
P-gp inducers
Carbamazepine Phenobarbital Phenytoin Rifampin St. John's wort
P-gp inhibitors
Anti-infectives (clarithromycin, itra and posaconazole)
CV drugs (amiodarone, diltiazem, verapamil, carvedilol)
HIV drugs (cobicistat, ritonavir)
HCV drugs (ledipasvir, paritaprevir)
Others (cyclosporine, ticagrelor)
Amiodarone and Warfarin interaction risk and action that should be taken by pharmacist
Risk: amiodarone inhibits CYP2C9 which metabolizes warfarin - increased INR and bleeding risk
If adding amiodarone after warfarin, decrease warfarin by 30-50%
Amiodarone and digoxin interaction risk and action that should be taken by pharmacist
Amiodarone inhibits P-gp; digoxin is P-gp substrate
Decreased dig excretion, increases ADRs/toxicity
Additive bradycardia, arrhythmia and fatality when taken together
Decrease dig dose 50% when adding amiodarone
Digoxin and loop diuretic interaction risk
Loops decrease K, Mg, Ca, and Na
Risk of dig toxicity increases with low K and Mg and high Ca
Drugs that decrease HR interaction risk
Additive effects with medications including amiodarone, digoxin, beta-blockers, clonidine, dexmedetomidine, etc.
Statin and strop CYP3A4 inhibitors (G-PAKMAN) interaction risk and action that should be taken by pharmacist
Increase levels of CYP substrates: lovastatin, simvastatin, atorvastatin, increased myopathy risk, rhabdo, and ARF
Simva and lova are contraindicated - recommend pitava, prava, or rosuva b/c not metabolized by CYP
Warfarin and CYP2C9 inhibitors and inducers interaction risk
Increase levels of warfarin with 2C9 inhibitors
Decrease levels of warfarin with 2C9 inducers
CYP3A4 inhibitors and CYP3A4 substrates interaction risk and action that should be taken by pharmacist
Decrease CYP3A4 substrate metabolism causing increased drug concentration and increased ADR/toxicity
Do not use CYP3A4 inhibitor with opioid metabolized by 3A4 (fentanyl, hydrocodone, oxycodone, methadone)
