Immunology Block: Pharmacology 2 - Drug Disposition

Front 1

what's drug disposition?

Back 1

what happens to a drug after it's given to the patient. it's specifically divided into absorption, distribution, metabolism, and excretion.

Front 2

what does absorption mean? what does metabolism generally do?

Back 2

putting the drug in the vascular compartment.

metabolism generally makes a drug less lipophilic and more hydrophilic, facilitating excretion.

Front 3

ionized vs. unionized - which are more likely to get transported across the GI mucosa and equilibrate?

Back 3

unionized cross far better.

Front 4

what's MEC?

Back 4

minimal effective concentration - it's a plasma concentration of a drug that's required for minimal activity.

note that the concentration of a drug at its receptor site determines its duration and intensity.

Front 5

do high blood levels of a drug guarantee high action?

Back 5

no - if the drugs are all protein bound, not much is going to happen.

Front 6

what are some biological mechanisms of absorption?

Back 6

filtration through pores

diffusion across a membrane.

pinocytosis.

and active transport using energy.

Front 7

what drug factors and what biological factors influcence drug diffusion?

Back 7

biological properties: thickness of membrane, surface area of membrane, blood flow to the area.

drug properties: more lipophilic = more absorption. more neutral = more absorption. also, the size of the drug matters.

Front 8

at what molecular weight do we talk about filtration through plasma membrane pores?

Back 8

less than 55.

Front 9

what's p-glycoprotein? what things affect it?

Back 9

PGP is a major way that drug absorption is resisted.

PGP is excreted from the GI tract, the kidney, liver, blood brain barrier.

Cimetadine, grapefruit juice - these inhibit PGP, meaning drugs are more readily absorbed when taking these.

rifampin, st. john's wort = inducers of PGP (more likely to excrete drug).

Front 10

what things undergo pinocytosis?

Back 10

large molecules, anticancer drugs, and vitamin b12.

Front 11

what makes a drug more lipid soluble?

Back 11

replacing an oxygen with a single SULFUR. note that sulfate makes you less lipid soluble.

alkyl or aryl groups = more lipid soluble

halogens too.

Front 12

what's ion trapping?

Back 12

the idea that an uncharged molecule crosses into a cell, gets ionized, and is trapped there. this is good for absorption.

weak acids are readily absorbed in the stomach due to the low pH of the environment, which tends to protenate the acid (HA) and keep it neutral.

once in the cell, with its higher pH, the hydrogen tends to be lost and it forms an ion.

when it comes to weak bases, they're BH+ already. In the stomach, it stays protenated and doesn't get absorbed.

in the intestines, with a pH of between 7 and 8, the hydrogen can come off a bit and it neutralizes, goes into the cell.



So: weak acids, great abosorption in stomach, less but good in the small intestine.

weak acids - almost no absorption in stomach, some absorption in the small intestine.

Front 13

what models can describe the rate of drug absorption?

Back 13

zero order kinetics - this is rare. it means that the rate is independent of the concentration of drug - alcohol is this way.

first order kinetics - more common. means that absorption of the drug goes down constantly, in proportion to the remaining amount of drug still to be absorbed.

Front 14

what's distribution?

Back 14

movement from the circulation (into which it was absorbed) into the tissues where it's going to work.

maybe it goes where it should, maybe it goes where it shouldn't and react with weird things.

only a small % of the drug is near its receptors - the rest of it around the body is what'd dictating its intensity and duration.

Front 15

what's the most important binder of drugs in the blood?

Back 15

albumen! albumen makes up >50% of the plasma proteins and interacts especially well with small drugs.

Front 16

what can happen if you give someone two drugs that both bind to the same sites on albumen or other plasma proteins? what are some specific sites?

Back 16

because the number of receptors is limited, this can cause a dramatic increase in the amount of free drug in the plasma available for action - which can cause adverse effects (overdose?)

type 1 site is for warfarin. bad news if you use valproic acid and sulfas.

type 2 site is about diezapam. bad nws if you're using aspirin too.

Front 17

what can rapidly enter the brain?

Back 17

things that are fat soluble - like morphine and barbituates.

Front 18

what's redistribution and what drugs should i immediately think of?

Back 18

lead and thiopental.

lead gets distributed into the RBC's for awhile, then into the bone long-term.

thiopental - VERY LIPID SOLUBLE - it'll initially localize (like in seconds) into the brain, kidney, liver, kinda everywhere. but then it redistributes slowly to the muscles and fat.

so, when you give the drug, people pass out instantly, then wake up in 15 minutes when the drug ends up in their fat/muscles.

then if you give the drug again, they'll pass out for weeks.

Front 19

what are the main ways we excrete things?

Back 19

in the bile (from the liver).

also, from the kidney.

excretion can also happen from random glands, the genital secretions, expired air, saliva, etc. Kidney is most important.

Front 20

talk about kidney excretion: also, talk about the excretion/reabsorption of electrolytes:

Back 20

kidney is all about filtration, reabsorption, and secretion.

bowman's capsule allows things smaller than 55 KD out of the blood (most drugs are like this).

if the drugs are lipid soluble, they'll get reabsorbed in the distal tubules.

electrolyte style drugs can be dramatically affected by urine pH, which can be adjusted.

if you lower pH (more acidic), you're going to excrete weak bases. you're going to reabsorb weak acids.

think that the urine doesn't like to have things in it that are like it (osmosis) - if it's acidic, it doesn't want weak acids. if it's basic, it doesn't want weak bases.

So, if you raise the pH, it won't dissolve the bases, and weak bases will be retained.

Front 21

what else can happen in the kidney?

Back 21

renal secretion - mechanisms for both acids and bases, and it happens in the proximal tubule.

note that penicillin is one of these.

Front 22

talk about biliary secretion - contrast IV from oral drugs.

Back 22

IV drugs get do the liver through the hepatic artery, while orally absorbed drugs get there through the hepatic vein.

water soluble things more likely to get put into the bile.

note that some drugs, when exit bile into the intestine, are then excreted in waste. most, however, are immediately reabosrbed and continue the cycle.

Front 23

what about milk?

Back 23

its pH is pretty low, so it likes dissolving basic drugs like THC, cocaine, and morphine. meaning that these accumulate and kill baby.