Four main processes that drugs use
ADME: Absorption, Distribution, Metabolism, Elimination
Passive absorption (AKA simple): -Types (x2) -what are they determined by?
-filtration through pores or channels is determined by osmotic/hydrostatic pressure differential -diffusion through cell membranes determined by concentration gradient and is MOST COMMONLY utilized by drugs *passive processes dont require energy and cant proceed against gradients
what generic endings indicate a weak base drug
chloride, hydrochloride, sulfate, acetate
what generic endings indicate a weak acid
passive absorption also depends on what coefficient/status?
lipid-to-water partition coefficient and ionization status
States a drug can be in when inside the body
ionized (charged/polar) and unionized add to 100%
ionized compounds: -lipid solubility -water solubility
lower lipid solubility and higher water solubility. dont pass through lipid bilayers easily
unionized compounds -lipid and water solubility
higher lipid solubility, lower water solubility
ionization status depends on what 2 factors
pKa of medication (propensity of a compound to donate [acids] or accept [bases] a proton) pH of membrane-gradient/milieu
there is a 50/50 ratio of ionized:unionized
What happens to highly ionized drugs in the gi tract/ renal tubules?
Highly ionized drugs do not readily get absorbed in GI tract OR re-absorbed from the renal tubules back into the systemic circulation. Therefore, drugs are ELIMINATRED
what happens to highly unionized drugs in the gi tract, renal tubules?
they do get readily absorbed in the gi tract or reabsorbed from the renal tubules back into the systemic circulation. NOT ELIMINATED
Active absorption: -energy needs? -gradients? -saturation kinetics?
energy requiring, saturable, movement against gradients both electrochemical and concentration
active absorption: -facilitated diffusion
does not require energy, does not proceed against gradients.
what elements are important during the Distribution phase?
active/passive transporting, ionization status, lipid-to-water partition coefficient, and PROTEIN BINDING
states of drugs in the blood stream
bound and unbound
unbound: -what value represents the unbound fraction -small value vs large value -value is opposite what?
alpha represents the unbound fraction small alpha (.1;10%) vs large alpha (.8;80%) -alpha is OPPOSITE OF % protein bound
drugs that have low protein binding are less effected by what? example
drug-drug interactions that are protein competitive. codeine (alpha of 93)
drugs that have high protein binding are more effected by what? example?
drug-drug interactions that are protein competitive ex. warfarin-97% protein bound, alpha of 3
impact of inducers/inhibitors cyt450 on prodrugs in terms of onset of action
-inducers are going to make the onset sooner, active prodrug in presence of inducer will have shorter duration of action (more enzyme activity) -inhibitors do opposite
First order kinetics -rate of elimination is proportional to what? -amount of drug removed per unit of time varies how? -percentage of the total amount of change in the Cp remains?
-rate of elimination is proportional to Cp, OR -amount of drug removed per unit of time will vary proportionately with Cp -the percentage (fraction) of the total amount of change in the Cp remains constant over time
Zero order kinetics -rate of elimination? pwhat stays the same over time? -is percentage of total amount Cp constant?
-saturable -rate of elimination is not proportional to Cp,OR -amount of drug removed per unit of time stays the same over time. -the percentage of the total amount of change in the Cp is not constant over time
what is cmax
maximum drug concentration
therapeutic range is between what two values?
MTC (maximum therapeutic Conc.) and MEC (minimum effective conc.)
duration of action
from when MEC is first reached till where it is reached again as Cp declines
Bioavailability -what abbreviation -represents what? -describes what about the absorption? -what is it considered for IV route?
-F -Represents Fraction (F) of a dose that enters circulation -describes extent of absorption, not the rate -always considered 100% (F=1) for IV route
Salt Factor: -sign -define
-S -think of it as an equivalency factor derived from potency, and represents percentage of a dose that equals the primary serum-assessed drug
3 items determining amount of drug absorbed
Dose, F, S
Volume of distribution -symbol -represents what? -is it a physiological number? -what does it numerically represent (bigger vs smaller value)
Vd, represents implied volume of compartment necessary to account for total amount of drug in body and drug-concentration in plasma. - not a physiological value -numerically represents extent of drug distribution... bigger value represents a larger body distribution "metaphorically the amount of water you would need to give you the drug concentration based on the dose you gave"
how is the Vd reported?
L/Kg so multiply by body weight to eliminate Kg
Ideal Body Weight female vs male
Female 45kg+((2.3kg x (height (in)-60 (in)) Male 50kg+((2.3kg x (height inches-60 inches))
Adjusted dosing body weight used when? how to calculate?
for ABW>40% higher than IBW Adj body weight=(0.4 x (ABW-IBW)) + IBW
Clearance: units, what does it represent
L/hr represents the volume of blood per unit of time. must get rid of the Kg first by multiplying by the patient's weight
Tau: units? what does it represent? -continuous infusion what do you use?
elimination term units=hr represents dosing interval q8h, tau would be 8. if its q.d. then tau is 24 hours *continuous infustion administration q1h tau would be 1 hour.*
Elimination Rate Constant: -units? -represents?
Kel units X^-hours represents a rate of drug eliminates described as a percentage (fraction) of drug removed per unit of time
Half-life: -units? -represents?
t1/2 units=hr -represents time required for 50% of drug to be eliminated
Steady State: -units -represents? what=what? -related to?
-Cpss units =w/v #'s -represents an equilibrium between drug administration and body clearance where rate in=rate out -related to dose, Cl, Kel, and t1/2
Amount of drug absorbed equation -units
Amount=(S)(F)(Dose) units are weight
Changing Dosage Forms equation -units
Dose of alternative formulation=amount of drug absorbed from current form divided by (S)(F) of new dosage form -weight is units
how many half lives to steady state
Concentration in plasma equation
Loading dose equation
Supplemental loading dose equation
Maintenance Dose equation
Elimination rate constant equation
Elimination rate constant 2
Half Life equation
Creatinine Clearance equation
-male vs female