PK lecture Flashcards
Definition: Steady State Concentration
- The constant serum concentrations that is achieved when rate of drug administration equals rate of drug metabolism and excretion
- Usually used to assess patient response and used to make new decisions
Definition: Liner pharmacokinetics
- Also known as first-order or non-saturable kinetcs
- Steady state concentrations increase or decrease proportionally according to dose.
Definition: Non-liner pharmacokinetcs
Steady stated concentrations change in a disproportionate fashion after dose is changed.
i.e : valproic acid, carbamazepine, phenytoin
Definition: Half-life (t1/2)
Time required for serum concentrations to decrease by 50% during elimination phase after absorption and distribution are complete.
- takes 3- 5 half-lives to reach steady-state concentrations during continuous/ routine dosing
Definition: Bioavailability
- The fraction of the administered that is delivered to the systemic circulation
Definition: Multi (two) compartment model
Classic drugs for two-compartment model
Represents the body as centrral compartment into which drugs us administered and as a peripheral compartment into which a drug distributes; used for drugs that slowly equilibriate with tissue compartment.
I.E VANCO, DIG
Definition: Context-Sensitive Half time
- Time for plasma concentration to decrease by 50% after discontinuing infusion
- Context sensitive half time increase with longer duration of infusion
- Short context sensitive half-life: remifentanil
- Variable context sensitive half-life: fentanyl
Definition: Biophase
- Body compartment in which the receptor sites reside
- Concentration of drug in biophase cannot be directly measured
- Usually inaccessible in humans
- Drug concentration in microscopic environment at receptors will not be same as in other measurable areas (e.g., blood, urine, CSF)
Definition: Absorption
What are the factors that affect absorption
Factors that affect absorption
- GI perfusion (GI absorption, transdermal/SC/IM absorption, vasopressor effect)
- Intestinal atrophy
- GI dysmotility/delayed gastric emptying
- Intestinal drug transporters (p-glycoprotein, cytochrome P450)
- Physical incompatibilities (drug/enteral nutrition binding, pH changes)
What is the effect of Hypothermia on transdermal drugs?
vasoconstriction = less absorption
Definition: Volume of Distribution
Vd = Dose ÷ Concentration
- Indicates the extent of drug distribution into tissues and areas of the body
- Physiologic determinants include actual volume of blood and size of various tissues and organs.
Larger person –> higher Vd
Smaller person –> smaller Vd
- Larger loading doses are needed to achieve a therapeutic concentration if volume of distribution is large.
Tissue perfusion
concept
-
Cardiac output is primary determinant of drug exposure speed to organs
- Brain, heart, lung, kidneys get highest relative cardiac output and reach equilibrium faster with blood
- Shock states –> decreased perfusion to muscle, skin, splanchnic organs
- Decreased delivery of hydrophilic drugs to areas of decreased perfusion
- Drugs (hydrophilic) with smaller Vd remain more in plasma water volume
Redistribution Concept
- Drug will distribute from the organ back to blood once concentration in the organ exceeds the blood. Once in the blood, the drug will redistribute to other tissues that are still uptaking drug
- Single bolus doses of highly lipophilic drug leads to rapid decrease in brain concentrations and redistribution to muscle
- Eventually, the adipose tissue will contain the majority of the lipophilic drug that has not been metabolized or eliminated [trapped in adipose tissue]
Protein Binding
Albumin and AAG in Critical illness state
- Critical illness state: –> Albumin decreases –> fraction unbound drug (Fu) increases Vd
- AAG increases –> Fu decreases –> decreased Vd
If your patient has one of the following:
What will happen to your lipophilic drugs?
what will happen with your hydrophilic drugs?
- No change in Vd for lipophilic drugs
- Increased Vd for hydrophilic drugs –> decrereased serum concentration
- – interstitial concentrations may be low due to larger interstitial space [dilution]
What is Phase I reaction
CYP450
CYP3A4 accounts for 40-45% of all CYP mediated drug metabolism
- Oxidation, hydrolysis, and reduction
CYP3A4 metabolism
- Alfentanil
- Diazepam
- Fentanyl
- Lidocaine
- Midozalam
- Warfarin
Defition: Hepatic Extraction ratio and metabolism
- Hepatic extraction ratio
- Fraction of drug removed during one pass through liver
- Ranges from 0 to 1
- 0 = Liver does not metabolize drug
- 1 = hepatic metabolism entirely dependent on blood flow
- Low (<0.3)
- Intermediate (0.3-0.7)
- High (>0.7
Hepatic extraction ratios of drugs used in anesthesia
Drugs that underfo significant renal clearance in anesthesia
Receptor Theory
What is Potency?
What is the definition of effective dose?
- *ED 50**
- -> Dose required for desired effect in 50% of population exposed to it
- ED50 –> can be used to compare various drug effects for a single drug
- Fentanyl EC50 for analgesia (2 ng/mL), ventilatory depression (4ng/mL), loss of response to laryngoscopy (15 ng/mL), changes to electroencephalogram (20 ng/mL)
Minimal effective dose (MED) –> Lowest dose level of a drug that provides a clinically significant response
Maximal tolerated dose (MTD) –> Highest possible, while still tolerable, dose that provides a clinically
significant response
Large range between MED and MTD –> large therapeutic window
