module 2 pharmacokinetics pharmacodynamics Flashcards
what is pharmacokinteics
it is what the body does to the drug, administration, distribution, metabolism, excretion ADME
what is pharmacodynamics
what the drug does to the body, drug concentration as related to magnitude of effect
Why Study clinical PK?
individualize patient drug therapy
maximize efficacy, mnimize toxicity and adv reactions
monitor drugs with narrow therapeutic index
monitor drug PK/PD as a diagnostic tool for some underlying diseases
define Absorption and factors affecting it
Movement of the drug from the site of administration into the general circulation
Affected by factors such as: Route of Administration, pH, Blood flow to the absorption site, Total surface area available for absorption & Contact time at the absorption surface
define Bioavailability (F)
The proportion of administered drug that reaches the systemic circulation in unchanged form
define Bioequivalence
a desirable feature of a generic drug dosage form (after patency is expired for a brand drug) is that it produces the same serum concentration / time profile as its brand name counterpart.
When generic drug product meets this requirement, it is said to be Bioequivalent to the brand drug.
define distribution and the factors affecting it
The transfer of drug from the general circulation into different organs of the body
Affected by factors such as: Blood flow, Capillary permeability (Esp. BBB), Binding of drugs to plasma proteins
why is drug distribution different in elderly and pediatrics than adults?
due to difference in body composition and protein binding
define volume of distribution
Vd is a hypothetical volume that relates drug serum concentrations to the amount of drug in the body.
Vd can be very small. eg?
warfarin 5-7L
drug primarily contained in the blood
Vd can be large. eg?
digoxin 500L
drug distributes widely and is mostly bound to body tissues
give the formula for Loading Dose
LD = Vd (L) x Desired Plasma Concentration
define metabolism and the factors affecting the drug
Process of converting drugs to another form by the action of enzymes
Affected by factors such: Age, Disease, Genetics, Enzyme inducers & Enzyme inhibitors
define excretion/clearance and the factors affecting the drug
The volume of blood completely cleared of the drug per unit time. Expressed as volume per unit time (e.g. L/h or mL/min.)
Affected by factors such: Age, Disease and pH
What are the organs responsible for excretion?
Glomerular filtration matures in relation to age, adult values reached by 3 yrs of age
the half life of a drug depends on the size of the administered dose. t/f
false. does not depend on the size of the dose.
how is the dosage interval of a drug determined?
The dosage interval for a drug is determined by its half-life.
give the formula for Maintenance Dose
Maintenance Dose = Average Css x Cl
define half life elimination rate constant and give its formula
K is Fraction of drug in the body removed per unit time (hr)
k = Cl / Vd
give the formula for t1/2
t1/2 = 0.693/k
what happens at Css?
Serum drug concentrations increase until the rate of drug administration equals the rate of drug metabolism & excretion
what happens in linear kinetics?
the rate of elimination is proportional to the amount of drug present
what happens if dosage is increased in linear kinetics
there is a proportional increase in plasma drug levels
what happens in non linear pharmacokinetics
rate of elimination is constant regardless of amount of drug present
When steady-state concentrations is different than expected after dosage change, there are two typical explanations. what are they?
Saturated plasma protein binding sites e.g. Valproic acid
Autoinduction of drug metabolism:
e.g. Carbamazepine
drugs that exhibit non linear pharmacokinetics are easy to dose correctly. t/f
false. Drugs that exhibit non-linear pharmacokinetics are often very difficult to dose correctly.
what happens in Michaelis-Menten Kinetics
Follows linear kinetics until enzymes become saturated
what happens when ezymes become saturated in michaelis menten kinetics
Enzymes responsible for metabolism become saturated resulting in non-proportional increase in drug levels
the michaelis menten kinetics is known by another name. what is it?
This phenomenon is also known as “Saturable pharmacokinetics”.
give examples of drugs that follow michaelis menten kinetics
Phenytoin and salicylic acid.
how long does it take for Css to be achieved
4-5 half lives
give 4 examples of Pharmacokinetics Drug-Drug Interaction
Absorption e.g. Ketoconazole and gastric acid suppressants
Distribution e.g. drugs with difference in protein binding affinity
Metabolism: e.g. enzyme induction & enzyme inhibition
Excretion e.g. drugs competing to same excretion mechanism
why is creatinine clearance used to asses renal function in patients.
It is renally excreted entirely unchanged and offers a clinically convenient measure of the renal function
The most commonly used equation for calculation is ___________.
Crockcroft-Gault.
what is useful to identify therapeutic failures and unanticipated toxicity
pharmacogenetics
define therapeutic index. give its formula.
TI = toxic dose / effective dose
TI is a measure of a drug’s safety
A large number = a wide margin of safety
A small number = a small margin of safety
Why Measure Drug Concentrations?
To individualize therapy
To diagnose toxicity (including addiction)
To guide withdrawal of therapy
To assess adherence to therapy
To determine whether a patient is already taking a drug before starting therapy (e.g. theophylline in an unconscious patient with asthma)
In research (e.g. to monitor for drug interactions in post-marketing surveillance
Using population pharmacokinetics).
Potential for Error When Using TDM
Assuming patient is at steady-state
Assuming patient is actually taking the drug as prescribed
Assuming patient is receiving drug as prescribed
Not knowing when the drug concentration was measured in
relation to dose administration
Assuming the patient is static and that changes in condition don’t affect clearance
Not considering drug interactions
what is used to measure the drug concentration for the following drugs Aminoglycoside antibiotics Cyclosporin Digoxin and digitoxin Lithium Phenytoin Theophylline Paracetamol and salicylate (overdose)
Aminoglycoside antibiotics (plasma or serum)
Cyclosporin (whole blood)
Digoxin and digitoxin (plasma or serum)
Lithium (serum)
Phenytoin (plasma or serum)
Theophylline (plasma or serum)
Paracetamol and salicylate (overdose) (plasma or serum).
Other drugs are sometimes measured. give examples
Anticonvulsants other than phenytoin
Tricyclic antidepressants
Anti-arrhythmic drugs
Anticonvulsants other than phenytoin (e.g. carbamazepine, valproate)
Tricyclic antidepressants (especially nortriptyline)
Anti-arrhythmic drugs (e.g. amiodarone).
