Pharmacokinetics & DI Flashcards
Pharmacokinetics is?
What the body does to the drug.
Absorption, distribution, metabolism and excretion
Pharmacodynamics is?
What the drug does to the body.
Relationship between drug concentration at site of action and both therapeutic and adverse effects.
Zero order kinetics
Constant amount of frug (mg) removed per unit of time regardless of how much drug is in the body
First order kinetics
- Most drugs
- Constant PERCENT of drug removed per unit of time
Michaelis-mente Kinetics
- Saturable kinetics
- Starts as 1st order and as concentration increases above Km (concentration at which rate of metabolism is half max) rate of metabolism becomes mixed (first and zero), at even higher doses it becomes zero order
Example: phenytoin, theophylline, voriconazole
-Phenytoin has saturable kinetics even at therapeutic drug concentrations. Do small dose increase by 30-50mg if concentration >7mg/L (RR10-20 mcg/ml). In other words steady state concentration becomes very high causing toxicity.
Sms of phenytoin toxicity: slurred speech, fatigue,
Half life and steady state
T1/2= 0.693/ke
Ke= Cl/Vd
Cl= (FxDose)/AUC
Vd=dosegiven/concentration
-Elimination half life: time for drug concentration to decrease by 50%. Depends on drug concentration in first order kinetics.
Steady state: rate if drug intake =rate of elimination. -Takes 5 half lives in first order kinetics with no loading dose
-5 lives to eliminate more than 95% of drug
Warfarin metabolism?
Interacts with which inducers/inhibitors and what is the effect on INR?
CYP2C9
Strong inducer: Rifampin, dose of warfarin will have to be increased 100-300% time
String inhibitor: amiodarone, decrease warfarin dose by 30to 50%
How long does it take to see full effect of this interaction?
Codeine/tramadol is a prodrug off morphine and is activated by which enzyme?
CYP2D6
- Not inducible enzyme
- Ultra rapid metabolized (UM) results in increase morphine»>more analgesia and risk of respiratory depression
- Inhibition (fluoxetine,paroxetine) results in decrease codeine conversion to morphine»>less analgesia
Grouping of DI:
Usual Inducers?
Usual inhibitors?
Cyp3A4 Inducers:
- anticonvulsants (carbs, Oxa, eslicarb, phenytoin, phenobarbital)
- rifampin, rifabutin, rifapentine
- smoking
- primidone
- simeorevir
- St. John’s wort
CYP 3A4 Inhibitors:
- azole antifungals
- amiodarone and dronaderone
- diltiazem, verapamil
- quinidine
- Microlides( not azithromycin)
- PI IHV drugs and ritonavir
- grapefruit juice
- Cimetidine, cyclosporine, cobicistat
Substrates of CYP3A4?
Anticoagulants: apixaban, riva, R warfarin)
Statins: atorva, sinva,lova) use Rosu
Glucuronidation DI:
UGT1A1 enzyme drug interaction example?
Raltegravir concentration would decrease if strong inducer rifampin used.
How to fix? Increasing dose of Ral to 800mg BID?
Amiodarone DI
Digoxin and warfarin doses need to be decreased (30 to 50%) when amiodarone started
Cyp3A4
Digoxin interacts with what Disease state?
Decline in renal function and HYPOkalemia (regardless of digoxin game level)
Amiodarone
Grape fruit juice interacts with?
Inhibit 3A4
>1.2L/day Intake
Avoid with: Silva,lova,nifedipine,tacrolimus
Ticagrelor increased bleeding risk
Other cyp3A4 substrates
Opioid analgesics DIs
-Fentanyl, hydrocodone, oxy, methadone
Are Cyp3A4 substrates
Interaction with inhibitors of enzyme will lead to resp depression
Removal of inducer would cause increased drug levels it dose is not adjusted
Avoid with inhibitors:
Oxy has BBW
Methadone has a warning
Warfarin drug interactions that increase bleeding risk
NSAIDs,SSRIs, SNRIs, ginkgo (no efectbon INR), fish oils, vitam E, willow bark
5Gs that can increase bleeding risk: Ginkgo Garlic Ginger Glucosamine Ginseng
Drug interactions that cause hyperkalemia risk
Aldosterone blockers
- Avoid use if baseline k is >5
- Avoid use with concurrent NSAIDs
Additive accumulation: ACEs/ARBs, aliskerin, amiloride,trianterene, salt substitutes, drospirenone OC,
Other: tacrolimus and cyclosporine, canaglifozin, bactrim, pentamidine
Tx of chronic hyperkalemia:
- hold or reduce RAAS drugs
- Petiromer (valtessa) PO
- sodium zirconium cyclosilicate (lokelma) fastest response
- k binders may allow to keep dose of RAAS agents needed for indication (e.g heart failure) at recommenced dose.
- Avoid periods of fasting to prevent insulin response. -avoid NSAIDs
- use diuretics with RAAs agents helps
Max dose of simvastatin when taking amiodarone
20 mg
What anticonvulsants do not inhibit it induce cyp?
Leve
Lamo
Gana
Pregaba
What anticonvulsants are not a substrate or cyp450?
Leve Lamo Gaba Pregaba Oxacarb Eslicarb Topi Rufinamide
Anticonvulsant inducers will decrease dose of what 3A4 substrates?
Amiodarone, dronaderone Antiretrovirals: PI, NNRTIs Clozapine COC Cyclosporine Digoxin DOACs: riva,apixa, edox,
What 2C9 and or/2C19 inhibitors will increase PHY concentration?
Amiodarone Cenobamate Fluconazole Fluoxetine Omeprazole
What anticonvulsants are sting Cyp inhibitors?
Valproate
Cannabinoid
What anticonvulsants are strong inducers?
PHY-zero order kinetics
PHB
CBZ-autoinducer
Mod inducers:
Oxa
Eslicarb (>1200mg)
Topi (>200mg)
Cenobamate: both inducer and inhibitor
Lamotrogine DI- hepatic megabolims glucuronic acid conjugation
Levels decrease by: PHenytoin Phenobarbital Carba Estrogen
Increased with:
Valproate
COC oral concentration decreased by?
COC affect concentration of which anticonvulsant?
1- Strong inducers: Clobazam Eslicarb Oxcarb Perampanel Rufinamide Topi Cenobamate
Use: IUD, implant, Depo provera
2- Lamotrigine levels decreased by 40-60% by estrogen component of COC.
