Learning Drug Interactions Flashcards by Grace Whitham

Pharmacodynamics definition

Effect drug has on the body

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Drugs that have similar end effects through different mechanisms/receptors can cause _____ effects

additive

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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

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What is synergism?

When the effect from two drugs taken in combination is greater than the effect from adding the two individual effects together

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Pharmacokinetic definition

effect the body has on a drug

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4 parts of pharmacokinetics

Absorption
Distribution
Metabolism
Excretion

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Drugs with polyvalent cations or other binding properties should be separated from what medications?

quinolones, tetracyclines, levothyroxine, oral bisphosphonates

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Where are CYP enzymes primarily located?

In the liver

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Common prodrugs

Capecitabine
Copidogrel
Codeine
Colistimethane
Cortisone
Enalapril
Famciclovir
Fosphenytoin
Isavuconazonium sulfate
Levodopa
Lisdexamfetamine
Prednisone
Primidone
Tramadol
Valacyclovir
Valganciclovir

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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

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Clopidogrel safety considerations with CYP enzymes

Do not use with CYP2C19 inhibitors (omeprazole and esomeprazole) - block conversion to active form

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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)

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Major CYP inducers

CROSS PP
C - Carbamazepine
R - Rifampin, rifabutin, rifapentine
O - Oxcarbazepine
S - Smoking
S - St. John's Wort
P - Phenytoin
P - Phenobarbital

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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

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How do P-gp pumps work?

Transport drugs and their metabolites out of the body by pumping them into the gut

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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

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P-gp substrates

Anticoagulants (apixaban, rivaroxaban)
CV drugs (digoxin, diltiazem, verapamil)
Immunosuppressants (cyclosporine, tacrolimus)
HCV drugs (ombitasvir, paritaprevir, dasabuvir)
Others (colchicine, saxagliptin)

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P-gp inducers

Carbamazepine
Phenobarbital
Phenytoin
Rifampin
St. John's wort

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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)

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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%

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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

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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

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Drugs that decrease HR interaction risk

Additive effects with medications including amiodarone, digoxin, beta-blockers, clonidine, dexmedetomidine, etc.

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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

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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)

Which medications specifically include instructions to not take with grapefruit juice?

``` Amiodarone Simvastatin Lvoastatin Nifedipine Tacrolimus ```

Valproate and lamotrigine interaction risk and action that should be taken by pharmacist

Valproate decreases lamotrigine metabolism, increasing lamotrigine levels and risk of serious skin reactions

Monoamine oxidase inhibitors (MAOi) + drugs that increase Epi, NE, and DA + drugs that increase serotonin interaction risk and action that should be taken by pharmacist

MAOi increase Epi, NE, DA, and 5-HT which can cause HTN crisis and serotonin syndrome Do not use together Use a 2 week washout period between serotonergic drugs and another antidepressnat

MAOi + tyramine risk foods/drinks interaction risk and

MAO metabolizes tyramine, if blocked, tyramine causes increase in NE with risk of HTN crisis Do not eat foods rich in tyramine

CYP2D6 inhibitors (amiodarone, fluoxetine, paroxetine, fluvoxamine) and CYP2D6 substrates interaction risk and action that should be taken by pharmacist

Decreased metabolism and increased ADRs and toxicity | Avoid using together or decrease dose of the substrate

CYP3A4, P-gp inhibitors + calcineurin inhibitors (tacrolimus, cyclosphorine) or mTOR kinase inhibirors (sirolimus, everolimus) interaction risk and action that should be taken by pharmacist

Decreased drug metabolism, increased ADRs/toxicity, including blood pressure, nephrotoxicity, metabolic syndrome and other adverse effects Avoid using together or decrease dose of CNI or mTOR kinase inhibitor

Phenytoin, phenobarbital, primidone, carbamazepine, oxcarbazapine + other drugs metabolized by CYP enzymeinteraction risk and action that should be taken by pharmacist

Increased substrate metabolism will cause decreased drug levels Monitor drug levels, consider increasing the dose of the substrate drug

Rifampin and cyp and P-gp substrates interaction risk and action that should be taken by pharmacist

Concentration of substrate drugs will greatly decrease | Monitor drug levels, increase dose of substrate drug level if necessary

CYP3A4 inducers + opioids that are substrates of CYP3A4 (fentanyl, hydrocodone, oxycodone, methadone) interaction risk and action that should be taken by pharmacist

Increased metabolism adn decreased opioid concentration | Assess pain level

CYP2D6 ultra-rapid metabolizers + prodrugs (codeine, tramadol) interaction risk and action that should be taken by pharmacist

Prodrug is converted to active drug more rapidly Increased active drug concentration which can cause toxicity/risk and possible fatality Do not use codeine or tramadol in patients <12 or in breast-feeding mother unless it is known she is not 2D6 UM

CYP3A4, P-gp inducers + Calcineurin inhibitors (CNIs) (tacrolimus, cyclosporine) or mTOR kinase inhibitors (sirolimus, everolimus) interaction risk and action that should be taken by pharmacist

Increased drug metabolism, decreased transplant drug levels and increased risk of rejection Avoid use together; monitor transplant drug level for efficacy

Smoking + some antipsychotics, antidepressants, hypnotics, anxiolytics, caffeine, theophylline, warfarin

Smokers who quit: drug concentrations will increase and cause toxicity Current smokers: decreased drug concentrations

What CYP enzyme does smoking induce?

1A2

What medications have additive serotonergic effects

``` Antidepressants (SSRIs, SNRIs, TCAs, mirtazapine, trazodone) MAOi Buspirone Dextromethorphan Dihydroergotamine Lithium Lorcaserin Opioids Metoclopramide Triptans Natural products (St. John's wort) Tegaserod ```

How long is the washout period for fluoxetine and why is it longer than other medications?

5 weeks | Longer half-life

What medications have additive bleeding risk side effect

``` Anticoagulants Antiplatelets NSAIDs SSRIs, SNRIs Natural products (Garlic, ginger, ginkgo, biloba, ginseng, and glucosamine, vitamin E, willow bark, fish oils (high doses) ```

What medications have risk of hyperkalemia?

Spironolactone, eplerenone Renin-Angiotensin-Aldosterone Drugs Amiloride, triamterene, salt substitutes (KCl), calcineurin inhibitors, canagliflozin, bactrim, and drospirenone-containing oral contraceptives

What medications have increased risk of QT prolongation

``` Antiarrhythmics (amiodarone, dofetilide, dronedarone, ibutilide, sotalol) Antibiotics/antifungals Antidepressants Antipsychotics (most) Antiemetics Donepezil, fingolimod, methadone ```

What dose of citalopram and escitalopram should not be exceeded in patients >60 years old and why

Citalopram 40mg/d Escitalopram 20mg/d Increased risk of QT prolongation and torsades

What medications have additive ototoxicity effects

``` AG Cisplatin Loop diuretics Salicylates Vancomycin ```

What medications have additive nephrotoxicity effects

``` AG, amphotericin B, polymyxins, vancomycin Cisplatin CNI Loop diuretics NSAIDs Radiographic-contrast dye ```

What medications have additive anticholinergic effects

Paroxetine, TCA, first gen antipsychotics Sedating antihistamine Atropine, belladona, dicyclomine, meclizine Benztropine, trihexyphenidyl Muscle relaxants Overactive bladder antimuscarinics

What medications have additive hypotension/orthostasis effects

PDE-5 inhibitors CYP3A4 inhibitors Nitrates Alpha-1 blockers

What medications are CYP3A4 substrates?

Analgesics (fentanyl, hydrocodone, methadone, oxycodone Anticoagulants (apixaban, rivaroxaban, R-warfarin) Immunosuppresants Statins (atorva, lova, simva) HIV drugs PDE-5 inhibitors Ethinyl estradiol

What medications are CYP3A4 inducers

``` Carbamazepine Rifampain Oxcarbamazepine Smoking St John's wort Phenobarbital Phenytoin ```

What medications are CYP3A4 inhibitors

Clarithromycin, erytromycin, azole antifungals, amiodarone, diltiazem, verapamil, cobicistat, protease inhibitors, ritonavir, cyclosporine, grapefruit juice

What medications are CYP1A2 substrates

Theophylline | R-warfarin

What medications are CYP1A2 inducers

``` Carbamazepine Phenobarbital Phenytoin Rifampin Smoking St. John's wort ```

What medications are CYP1A2 inhibitors

Ciprofloxacin | Fluvoxamine

What medications are CYP2C8 substrates

``` Amiodarone Dasabuvir Pioglitazone Repaglinide Rosiglitazone ```

What medications are CYP2C8 inducers

Phenytoin | Rifampin

What medications are CYP2C8 inhibitors

Amiodarone, atazanavir, clopidogrel, gemfibrozil, ketoconazole, bactrim, ritonavir

What medications are CYP2C9 substrates

``` S-warfarin Carvedilol Celecoxib Diazepam Diclofenc, meloxicam Glyburide, glipizide ```

What medications are CYP2C9 inducers

``` Carbamazepine PHenobarbital Phenytoin Rifampin Smoking St. John's wort ```

What medications are CYP2C9 inhibitors

Amiodarone Fluconazole Metronidazole Bactrim

What medications are CYP2C19 substrates

Clopidogrel

What medications are CYP2C19 inducer

Carbamazepine Phenobarbital Phenytoin Rifampin

What medications are CYP2C19 inhibitor

Esomeprazole | Omeprazole

What medications are CYP2D6 substrates

Codeine, meperidine, tramadol, tamoxifen

What medications are CYP2D6 inducers

None!!! | Patients can be ultra-rapid metabolizer

What medications are CYP2D6 inhibitors

Fluoxetine | Paroxetine