Pharmacokinetics Flashcards
What are the main causes of alterations in absorption, distribution, metabolism, and elimination?
- age
- genetic factors
- end-organ damage
- drug interactions
What is idiosyncratic?
- occur in a small minority of patients
- sometimes with low or normal doses
- poorly understood
What is a pharmacodynamic interaction?
interaction between 2 or more drugs that leads to either…
- accentuation/synergism
- attenuation/antagonism
Do pharmacodynamic interactions directly involve absorption, distribution, metabolism, or excretion?
NO
What type of interaction changes the basic kinetic properties of absorption, distribution, metabolism, and elimination?
pharmacokinetic interactions
NOT pharmacodynamic
What is the mechanism of this drug interaction…
tetracycline ABX (tetracycline, doxycycline, minocycline) + antacids
antacid impairs absorption of ABX → ↓ ABX efficacy
What are the clinical implications of this drug interaction…
erythromycin / clarithromycin / metronidazole / ciprofloxacin / trimethaprim-sulfamethoxazole + warfarin
ABX inhibit the metabolism of warfarin → ↑ serum concentration of warfarin → ↑ risk of bleeding
What are the clinical implications of this drug interaction…
NSAID + warfarin
Additive effect on ↓ platelet aggregation → additive risk for bleeding (especially GI bleeding)
What are the clinical implications of this drug interaction…
ASA + warfarin
Additive effect on ↓ platelet aggregation → additive risk for bleeding (especially GI bleeding)
What are the clinical implications of this drug interaction…
Tramadol + antidepressants (DDI highest risk for MAO-I)
↑ risk of serotonin syndrome
What is the mechanism and clinical implications of this drug interaction…
Protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir) + BZD
protease inhibitors are CYP450 3A4 inhibitors → ↓ metabolism of benzodiazepine → ↑ benzodiazepine concentrations → ↑ risk of benzodiazepine side effects (↑ sedation depth and duration)
What is important to know about drugs affects on pregant people?
- increased cardiac output
- increased renal blood flow
- decreased albumin
What is important to know about drugs affects on people with diabetes?
- gastric stasis
- nephrotic syndrome
What are drug cautions with myasthenia gravis?
- Aminoglycosides
- Fluoroquinolones
- Tetracyclines
- Macrolides
- Magnesium
- Beta blockers
- Procainamide
- Neuromuscular blocker
What is a side effect?
unrelated to the affect of the drug
What is a toxic reaction?
exaggeration of the clinical affect of the drug
What is an allergic reaction?
immune system response to a substance, potentially causing severe symptoms
What is pharmacokinetics?
WHAT THE BODY DOES TO THE DRUG
- kinetics, body, drug
KBD
Killer baby deer
What is pharmacodynamics?
WHAT THE DRUG DOES TO THE BODY
- dynamics, drug, body
DDB
Double D’s :)
How is kinetics used in drug development?
- used to determine optimal dose
- important in the clinical setting for toxicology, therapeutic monitoring, drug interactions, dose adjustments, effect of illness, organ dysfunction
Kinetcs focuses on concentrations of drug in the…
plasma
What is Cp?
The goal is to get Cp within a therapeutic window in order to elicit appropriate response without causing _________
toxicity
What is MTC vs MEC?
- minimum toxic concentration
- minimum effective concentration
Where on this graph is a good place to be for the drug to be effective.
between MEC and Cmax
Where is a dangerous level to be on this graph
near/above MTC
What does clearance determine?
maintenance dose-rate
What does the volume of distribution (VD) determine?
the loading dose
What does half-life determine?
the time to steady state and dosing interval
The kinetic parameters for a drug are determined by using what method of insertion?
IV injection or infusion (100% bioavailability)
What is clearance?
- Volume of plasma cleared of drug per unit of time
- index of how well a drug is removed irreversibly from the circulation
What is used to determine the dose-rate (dose/unit time) required to maintain plasma concentration of a drug?
clearance
In zero order kinetics the rate of absorption/elimination _______ depend on the drug concentration
does not
What are the rate limiting processes for zero order kinetics?
- fixed number of enzymes, carrier, or active transport proteins
- saturation occurs
What drugs use zero order kinetics?
- PHENYTOIN
- WARFARIN
- HEPARIN
- ETHANOL
- ASPIRIN (HIGH DOSE)
- HALF LIFE (T ½ ) DECREASES OVER TIME
- THEOPHYLLINE
In zero order kinetics the half life _________ with decreasing concentration
decreases
In first order kinetics the decline in Cp ________ with concentration
varies
In first order kinetics the half life _________ with decreasing concentration
sames the same
In first order kinetics concentration decreases by ____% per each T 1/2
50%
To maintain a steady state (CPss), administration rate must be equal to rate of…
elimination
What is the volume of distribution (VD)?
volume into which a drug appears to be distributed with a concentration equal to that of plasma
To reach a target Cp (plasma concentration) you have to “fill up the tank” using…
VD (volume of distribution)
VD can or cannot exceed the actual body volume?
It can far exceed it
Drugs with _____ VD tend to be polar and water soluble
small
What is the definition of half-life?
- time of the drug concentration to halve
What does half-life provide an index for…
- time course of drug elimination
- time course of drug accumulation
- choice of drug interval
It takes approximately ___ half-lives for a drug to either reach steady state (CPss) or be eliminated from the body
5
What is steady state kinetics?
point at which the amount absorbed equals the amount eliminated per unit of time
What is the equation of half-life?
What is the equation for elimination rate constant?
What is the equation for volume of distribution?
What is the equation for loading dose?
What is the equation for clearance?
What is the equation for steady state concentration (IV)?
What is the equation for steady state concentration (PO)?
