Final - Pharmacokinetics Flashcards
Time to steady state
3-5 half lives
Bioavailability of IV drugs
100%
Context Sensitive Half Time
50% decrement time
Time reqd to reach 50% of concentration after infusion stopped
Time delay between change in plasma concentration and drug effect
Hysteresis
Volume of distribution
Vd=dose/concentration
Who has larger Vd: 100kg male or 70kg female?
Larger person = larger Vd
In critically ill, AAG leads to _____ fraction unbound drug, _____ Vd
Decreased
Decreased
In critically ill, Albumin levels lead to ______ fraction unbound drug, _____ Vd
Increased
Increased
Highly albumin bound Drugs
Propofol
Morphine
Propranolol
Verapamil
Medium albumin bound Rx
Aspirin
Carvedilol
Omeprazole
Midazolam
Low Albumin bound Rx
Carbamazepine Ceftriaxone Dexamethasone Diazepam Itraconazole Phenytoin Valproic Acid Warfarin Diltiazem
Which drug form causes a clinical effect?
Unbound, free drugs
AAG bound Rx - High
Lidocaine
Fentanyl
Propranolol
Verapamil
AAG bound Rx - Medium
Midazolam
AAG bound Rx - Low
Carbamazepine
Diltiazem
After large IVF administration, how will Vd effect hypophilic + lipophilic Rxs?
Hydrophilic —>increased Vd (dec serum concentration)
Lipophilic —> no change
Hepatic Clearance
CLh=E x Qh
Hepatic clearance = Hepatic blood flow x extraction ratio
Hepatic blood flow increases d/t
Increased CO
Hyperdynamic phase of sepsis
Hepatic blood flow decreases d/t
Hypovolemic/Hemorrhagic/Cardiogenic shock Hypodynamic phase of sepsis MI/Acute HF exacerbation Increased Intrathoracic pressure Spinal anesthesia
Which phase of biotransformation is most often outside liver/no CYP involvement?
Hydrolysis - Remifent, Succs, esmolol, ester local anesthetics
CYP inducer = _____ serum concentrations
Decreased
CYP inhibitor = ______ serum concentrations
Increased
Pt is hypothermic, how will intrinsic clearance change?
Decreased metabolism thru CYP —> enzyme activity decreases
Increased serum concentrations
Renal injury will effect intrinsic clearance how?
Decreased metabolism via CYP - increased concentration
Goal of Phase I biotransformation
Make Rx more polar/water soluble (hydrophilic) —> allow elimination via phase II
Hepatic extraction ratio
Fraction of Rx removed during 1 pass thru liver
Range: 0-1
Hepatic extraction ratio: 0
Liver does not metabolize drug
Hepatic Extraction Ratio: 1
Hepatic metabolism entirely dependent on blood flow
Hepatic Extraction Ratio: High
> 0.7
Propofol, Bupivacaine, Diltiazem, Fentanyl, Ketamine, Lidocaine, Meperidine, Metoprolol, Morphine, Naloxone, Nifedipine, Propranolol, Sufentanil
Hepatic Extraction Ratio: Intermediate
0.3-0.7
Alfentanil, methohexital, midazolam, Vecuronium
Metabolism dependent on hepatic blood flow, intrinsic clearance, fraction unbound drug
Hepatic Extraction Ratio: Low
<0.3
Diazepam, Lorazepam, methadone, phenytoin, rocuronium, theophylline, thiopental
Clearance is independent of hepatic blood flow; varies with changes in hepatic enzyme activity
CYP inducers
St. John’s wart Rifampin Phenytoin Carbamazepine Phenobarbital *increase metabolism
CYP inhibitors
Amino, cimetidine, clarithromycin, diltiazem, erythromycin, grapefruit juice, fluconazole, isoniazid, ritonavir, verapamil
*decrease metabolism
Drugs that undergo significant renal clearance in anesthesia
Aminoglycosides, carbapenems, cephalosporins, PCNs, quinolones
pancuronium/rocuronium/Suggamadex
Neostigmine, Pyridostigmine
Atenolol, nadolol, procainamide, digoxin
Drugs excreted via pulmonary system
Volatile anesthetics
Generally speaking - fungals cleared thru
Liver
Generally speaking - antbx cleared thru
Kidney
Potency
Amount of drug needed to cause an effect
Large range between MED/MTD
Large therapeutic window
Argatroban and Bivalirudin are dosed on what pharmacodynamic parameter
aPTT
LMWH is dosed on what lab value
Anti-Xa
