Kinetics Flashcards
what are the main causes of the main alterations in ADME
- age
- genetic factors
- end organ damage
- drug interactions
what are the types of variability in ADME
- pharmacokinetics
- pharmacodynamic
- idiosyncratic
describe idiosyncratic variability
- 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:
-accentuation/synergism
- attenuation/antagonisn
what is an example of accentuation/synergism
calcium channel blocker and a beta blocker
what is an example of attenuation/antagonism
narcan and opiods
do pharmacodynamic interactions have to do with ADME
no
do pharmacokinetic interactions have anything to do with ADME
yes
what drugs do we need to check for interactions with/what drugs have many other drug interactions
- warfarin
- digoxin
- TCAs
- phenytoin
- carbamazepine
- lithium
- methotrexate/cyclosporine/tacrolimus
- HIV medications - protease inhibitors
- rifampin
- paxlovid
what is the result of the interaction of tetracycline and antacids
antacid impairs absorption of ABX resulting in decrease ABX efficacyw
what is the result of the interaction between erythromycin/clarithromycin/ metronidazole/ciprofloxacin/trimethaprim- sulfamethoxazole and warfarin
ABX inhibits the metabolism of warfarin resulting in increased serum concentration of warfarin and increasing the risk of bleeding
what is the result of the interaction between NSAID and warfarin
additive effect on decreased platelet aggregation resulting in additive risk for bleeding, especially GI bleeding
what is the result of the interaction between ASA and warfarin
additive effect on decreased platelet aggregation ->additive risk for bleeding, especially GI bleeding
what is the result of the interaction between tramadol and antidepressants
increased risk of serotonin syndrome
what is the result of the interaction between protease inhibitors and BZD
protease inhibitors are CYP 450 3A4 inhibitors -> decreased metabolism of benzodiazepine -> increased benzodiazepine concentrations -> increased risk of benzodiazepine side effects which are increased sedation depth and duration
what are the things to consider with pregnant patients
- increased cardiac output increases distribution of drugs
- increased renal blood flow increases elimination of drugs and decreases the duration and effects of drugs
- decreased albumin which decreases binding of drugs -> more free drug to act -> drugs have more pronounced effects
what are the considerations for patients with uncontrolled DM
- gastric stasis -> decreases rate of absorption of drugs
- nephrotic syndrome -> glomerulus gets damaged -> protein gets in kidneys -> proteinuria -> damages kidneys and generalized edema in body -> decreases rate of absorption of drugs -> decreased albumin -> more pronounced drug effect
what medications will worsen myasthenia gravis
- aminoglycosides
- fluoroquinolones
- tetracyclines
- macrolides
- magnesium
- beta blockers
- procainamide
- neuromuscular blockers
what is a side effect and give example
unrelated to clinical drug effect, predictable, dose related
- ex: an ABX causing GI upset
what is a toxic reaction and give example
- an exaggeration of the clinical effect, predictable, dose related, happens when you take too much of. adrug
- EX: taking beta blocker twice -> drop in BP and dizzy
describe an allergic reaction
immune mediated responses, happen quickly and are very dangerous
what is the positive to dental drugs
- primarily single dose or short term tx
- large margin of safety
- extensive hx of use
what is pharmacokinetics
what the body does to the drug
what is pharmacodynamics
what the drug does to the body
how do we use kinetics
- important in drug development and clinical testing, needed to determine optimal dose
how are kinetics important in the clinical setting
- toxicology
- therapeutic monitoring
- drug interactions
- dose adjustments
- effect of illness, organ dysfunction
time course of drug concentration in kinetics depends on ______
ADME
kinetics focuses on:
concentrations of drug in plasma
what can you use to calculate precise doses to achieve a precise concentration
kinetics
what is the goal of plasma concentration
get plasma concentration within a therapeutic window in order to elicit appropriate response without causing toxicity
what does clearance determine
the maintenance dose-rate
what does the volume distribution determine
the loading dose
what does the half life determine
the time to steady state and dosing interval
CL, VD, and half life are derived from a:
time/concentration curve
what is the definition of clearance
volume of plasma cleared of drug per unit of time
the clearance is the index of:
how well a drug is removed irreversibly from the circulation
the clearance determines the dose/rate required to:
maintain a CP
how do you calculate clearance of a drug - what is the formula
- creatinine clearance
- males: 140 - age / SCR
- women: 140 - age/ SCR ) x 0.85
describe zero order kinetics
- rate of absorption/elimination doesnt depend on the drug concentration
- rate limited process- fixed number of enzymes, carrier, or active transport proteins; saturation occurs
- half life decreases over time
what are the only drugs that undergo zero order kinetics
- phenytoin
- warfarin
- heparin
- ethanol
- aspirin (high dose)
- theophylline
what is the relationship on zero order kinetics
linear
half life _____ with decreasing concentration in zero order kinetics
decreases
describe first order kinetics
- the decline in plasma concentration is not constant with time, but varies with concentration
- the half life stays the same
- concentration decreases by 50% per each half life
- majority of drugs follow first order elimination
what is the relationship of first order kinetics
logarithmis
length of half life in first order kinetics is _____
constant
what does the rate constant measure and what is its variable
- KE
- KE = 0.693 / half life
what is the formula for clearance
CL = KE x VD
to maintain steady state plasma concentration administration rate must equal:
rate of elimination
how will the CP eventually reach steady state
when repeated doses of a drug are given in short enough intervals and elimination is first order
during IV infusion, drug levels:
increases exponentially in a way equivalent to the drugs half life
how many half lives is steady state achieved after
5
what does volume of distriution tell you
volume into which a drug appears to be distributed with a concentration equal to that of plasma
- tells you where the drug distributes
what is an equation for VD
F x dose /CP0
what is the bioavailability for IV drugs
1 (100%)
what does a large VD indicate
tells us it gets everywhere in the body and are more lipophilicd
drugs will small VD:
are more polar and water soluble
what does half life provide an index of
- time course of drug elimination
- time course of drug accumulation
- choice of drug interval
how many half lives does it take for drugs to be eliminated from the body
5
what is the definition of steady state kinetics
- point at which the amount absorbed equals amount eliminated per unit time
what is the formula for concentration of steady state kinetics
- CSS = KA / (VD x KE)
what is the formula for CSS in calculating oral doses
- CSS = (1.44 x DM x F x half life) / (T x VD)
what is the formula for calculating an initial load dose
D = (VD x CSS) / F
what is the formula for repeat loading dose
D = (VD)(CSS - Cmeasured) / F
what is the formula for loading dose
D = Vd x CSS
