Immunology Block: Pharmacology 4 And 5 - Pharmacokinetics I And Ii

Front 1

define loading dose, maintenance dose, volume of distribution, clearance, elimination half life.

Back 1

loading dose = first dose.

maintenance dose is the amount you have to give to keep the drug up in the level wanted.

V=dose/concentration in plasma.

half life :
t1/2 = .693/Cl

Front 2

which p450 is most susceptible to grapefruit juice?

Back 2

Cyt 3A4 - this is in the intestinal tract.

Front 3

Calculate Vd - what does it mean? in particular, tell me about ethanol, heparin, gentimycin, THC, and thiopental

Back 3

this is the volume of distribution. It's the you calculate the drug distributed into, based on blood concentration.

Vd = loading dose / blood concentration.

Ethanol's Vd = total body water, because it distirbutes evenly everywhere.

heparin's is the same as the amount of blood, as it binds to blood proteins.

thiopental has a HUGE "apparent" Vd because it distributes into the fat, making its blood concentration artifically low. Same for THC.

Gentimycin = extracellular fluid volume, as it gets out into the interstitium but doesn't cross cell membranes.

Front 4

so generally, what can you say about drugs with really high Vd or really low Vd?

Back 4

if it's really high, it probably binds to tissue components preferentially.

if it's really low, it probably stays in the plasma and that means it binds up plasma proteins.

Front 5

where are the major places of drug elimination?

Back 5

the liver for metabolism, the kidney for excretion.

Front 6

what in the kidney dramatically affects resorption?

Back 6

the pH of the urine can vary from 5 to 8, which is a huge difference. remember that basic urine is really good at dissolving weak acids.

just remember that acidic urine makes meth leave the body.

Front 7

what's Cl? talk about in relation to the kidney. What's regular GFR and what can you say about drugs whose clearance is around, above, or below GFR?

Back 7

clearance. it's measured such that you can say a certain volume of blood is completely cleared of the drug per unit time.

mL/min, etc.

GFR is normally 125 mL/min.

If the Cl is right around 125 mL/min, you can assume that the drug is freely filtered and not resorbed.

if it's lower than 125 ml/min, you can guess that it's resorbed.

if it's higher than 125/min, you can guess that it's net secreted.

Front 8

talk about liver clearance:

Back 8

two methods. Type 1 includes p450. Type 2 is conjugation.

Note that biliary secretion requires ACTIVE TRANSPORT

note that liver clearance depends on blood flow to the liver, how strongly the drug binds plasma proteins (stronger binding = less clearance), and the intrinsic ability of the hepatocytes to metabolize the drug.

note that if intrinsic ability is really high, induction/suppression of p450 makes no difference.

Front 9

how do you measure pharmicokinetics, what's on the graph's axis, and what are some typical features?

Back 9

y axis = concentration in blood, x = time.

note that if there's no clearance, you still see a sharp drop in blood concentration immediately after giving the drug - this is due to redistribution into other tissues (called redistribution clearance).

if there is clearance, it decays exponentially (remember that clearance is measured in Mg/minute - and the concentration keeps going down.

Front 10

what kind of clearance do most drugs have? what does this have to do with half life?

Back 10

first order - this means it decays exponentially.

half life is always assicated with first order clearance. not with zero order.

Front 11

what are some zero order drugs?

Back 11

ethanol, phenytoin, and salicaytes. aspirin?

Front 12

What's Css? What's maintenance dosing?

What determines Css?

Dosing rate?

Back 12

Steady state concentration. note that maintenance dosing is the amount of drug to give to keep the drug in its theraputic window.

Css is when your dosing equals your clearance - so input = output.

dosing rate = Css * Cl.

Front 13

what if you want someone to take drugs at home?

Back 13

then you have to include the bioavailability.

dosing rate / BA * interval (every 12 hours or whatever).

Front 14

getting to steady state - what factors influence this?

Back 14

only one factor - the half life!

Front 15

imagine giving a steady dose of drug and a single dose - what's special about 3.3 half lives?

Back 15

if you're infusing the drug, it'll take 3.3 half lives to get to 90% of possible plasma concentration.

if you're giving a single dose, it'll take 3.3 half lives to have only 10% of the drug left in the blood.

Front 16

describe difference between loading dose and repeated maintenance doses?

Back 16

if you give a single laoding dose, you should immediately end up in the eheraputic level. if you start off giving repeated maintence doses, you'll eventually get there, but it'll take awhile.

Front 17

what's our equation that we have to know for blood concentration?

Back 17

t1/2 = 0.693 * Vd / Cl