5, 9/17 Pharmacokinetics 3

Exam 2, Lecture 29

what diuretic happens in loop of henle

loop diuretics

what diuretic happens in Proximal conducting tubule

osmotic

what diuretic happens in proximal part or distal conducting tubules

thiazidines

what diuretic happens in distal part of distal conducting tubule

osmotic, K-sparing

what diuretic happens in collecting ducts and tubules

osmotic

what are the different ways drugs can be eliminated

bile, feces, saliva, sweat, tears, milk, expired air

what influences how much of a drug is excreted by the kidney

degree of lipid solubility and extent of drug ionization

how much cardiac output does the kidney recieve

25%

what does the kidney do

regulates fluid, electrolyte, acid-base balance, and systemic blood pressure

what is the filtration unit of the kidney

glomerulus

what drugs are filtered from blood directly through glomerulus

only free fraction of drugs

when drugs need active transport to get into the kidney, where do they come from

walls of proximal tubule, bypassing the glomerulus

what happens to the free fraction of the drug that passes through the glomerulus

reabsorbed into blood

what happens to the ionized drugs that require active transport to enter kidney

pushed into distal tubule and collecting duct where ionised fraction is trapped in urine by urinary pH and reabsorption of non-ionized part by passive diffusion

what are the 3 methods of renal drug excretion

glomerular filtration

active tubular secretion and/or reabsorption

passive tubular reabsorption, flow dependent, nonionic back diffusion

what is glomerulus filtration

determined by size of the molecule, passive diffusion, protein bound drugs are not filtered

what requires active tubular secretion/reabsorption

transporter mediated drugs (penicillin)

what requires passive tubular reabsorption

simple diffusion, molecular size, and charge/lipophilicity

what does excretion by glomerular filtration depend on

extent of drug binding and glomerular filtration rate

which mechanism of renal elimination is saturable

active tubular secretion

what type of transporters are on the blood side of the proximal tubule

OATs

what type of drugs do carnivores have delayed elimination of

acidic, low pH/pKa

what type of drugs do herbivores have delayed elimination of

Basic, high pH/pKa

what is the urinary pH of carinvores

acidic

what is the urinary pH of herbivores

alkaline

what does total drug clearance depend on

renal blood flow

how is total renal excretion calculated

rate of filtration + secretion - reabsorption

what is first order kinetics/clearance

a constant fraction of a drug us eliminated per unit time, exponential graph

what is zero order kinetics/ clearance

a constant amount of a drug is eliminated per unit time, linear graph

what is a drugs half life

the time required to reduce the amount of a drug in the body by one half during elimination

what does half life help compare

the rate of elimination of drugs in various species

what type of kinetics do most drugs use at therapeutic doses

first order kinetics

which type of drugs have a half life that is dose dependent

zero order kinetics

how is half life calculate

0.693 * Vd

Clb (whole body clearance)

How is whole body clearance calculated

CL (hepatic) + CL (renal) + CL (other)

what is whole body clearance

plasma volume cleared of the drug per unit of time

What influences whole body clearance

drug metabolism, organ perfusion, organ function

what dose adjustment is given for renal patients for whole body clearance

25% reduction

what dose adjustment is given for liver patients for whole body clearance

50% dose reduction

what drugs become accumulated in milk

Basic drugs are more ionized and become trapped

what is the pH of mastitis milk

around 7.2, more basic than normal milk

what does the pH of mastitis milk favor

permeation of acidic compounds

what factors influence the plasma concentration of a drug

dose of the drug

formulation of the drug products

route of administration

extent of plasma protein binding, extravascular distribution, rate of elimination

what terms are associated with plasma concentration time curve

peak (maximum) concentration, Cmax

Peak Time, tmax

Half life, t ½
area under curve (AUC)

how is clearance calculated when using a graph

F (bioavail) * Dose

AUC

what is the therapeutic range of plasma concentration

a defined range of plasma concentration associated with desirable intensity of the therapeutic effect

what is steady state concentration, Css

when the amount of drug being absorbed is the same amount being cleared from the body when the drug is guven continuously or repeatedly

how is the steady state concentration calculated

RO (infusion rate)= Css * CLb (whole body clearance)

what does a drug depend on to reach its steady state concentration

its half life

how is steady state concentration achieved with a drug with a long half life

an initial large dose with mainteance doses

how many half lives are needed to reach steady state concentration in 97% of cases

4-5 half lives