Test 1.13

Front 1

Biopharmaceutics:

Back 1

*Factors related to the dosage form that affect the rate and extendt of drug reaching the systemic ciculation and ultimately the site of action.

Front 2

Pharmacokinetics:

Back 2

*The use of mathematics to characterize and predict drug disposition in the body.

Front 3

Drug disposition:

Back 3

*The sum total of processes that a drug undergoes once in the body. ADME
Absorption
Distribution
Metabolism
Excretion

Front 4

Absorption:

Back 4

*The process required for drug to get from the site of administration into the plasma (SYSCIR)

Front 5

Distribution:

Back 5

*As the drug circulates in the SYSCIR, it localizes preferentially in certain tissues (the drug "distributes" to certain tissues)
**If the drug has a higher tendency to locate in tissues, it is "HIGHLY DISTRIBUTED"
**If the drug has a higher tendency to stay in the plasma, it is NOT highly distributed.

Front 6

Metabolism:

Back 6

*The process of enzymatic conversion of drugs into metabolites

Front 7

Excretion:

Back 7

*The sum total of processes that remove a drug from the body.
**Urinary excretion
**Fecal elimination
**Sweating
**Exhalation

Front 8

Zero order

Back 8

Elimination Rate: Constant, does not depend on amt/conc of drug present
**Review equations

Front 9

First Order

Back 9

Elimination Rate: varies depending on amt/conc of drug present **Review equations

Front 10

Why do pharmacokinetics?

Back 10

*Want drug to be effective with min. or no SEs:
-need a threshold amount of drug molescules present at the drugs receptor at the site of action (usually in tissues)
-Too many drug molecules at the site of action or at unintended sites in the body can lead to toxic effects or unwanted effects
**Most of the time the concentration of drug in the tissues is proportional to (or linearly related to) the concentraion of the drug in the plasma

Front 11

Why do pharmacokinetcs?

Back 11

Example: Digoxin
*treats CHF; intended site of action is in the heart.
*taken orally, dig is absorbed into the plasma and circulates throughout the body
-As it circulates, dig is distributed into tissues, including heart tissue
-therefore, as plasma concentration of dig increases, tissue concentraion of dig increases as well

Front 12

Continued:Digoxin

Back 12

*Dig has a narrow therapeutic index (narrow range of tissues concentrations for which dig is therapeutically effective w/o causing SEs)
-Dig SEs are not trivial and can be harmful
-Can't biopsy heart tissue to determine dig concentraion at site if action
-Next best thing: measure plasma concentration levels of the dig
-Because tissie concs are proportional to plasma concs, can determine plasma concs for which dig is therapeutically active w/o being toxic or causing SEs

Front 13

Continued why do pharmcokinetics??

Back 13

*Take it a step further:
--Can find therapeutci ranges by experimentation using a population sample
--Use average range to predict appropriate plasma concentraions (and this appropriate dose)
--Once dose is given, PK allos us to monitor plasma concentraions and adjust the dose accordingly
--PK allow pharmacists to tailor dosage regimens specifically for particular pts

Front 14

PK models:

Back 14

*Allow us to visualize the course of the drug in the body by representing the body as a series of compartments
*Each "compartment" represents a tissue or group of tissues that have similar blood flor and drug affinity
*Each compartment will be similar in terms of:
-Drug distribution to the compartment
-Drug conc in that comparntment; and
-Drug elimination from that compartment
*Allows us to visualize how drugs enter the compartment and how drugs are eliminated from the compartment

Front 15

One Compartment Model, IV bolus:

Back 15

*Simplest Model: One compartment with IV bolus injection of drug
-Drug is located in one compartment of the body, the "Central Compartment"!

Front 16

Central Compartment:

Back 16

*Plasma and tissue that are highly perfused=receives a high amount of blood flow to the tissue
*Drug conc equilibrates rapidly in tissues that are highly perfused
*Examples of tissues that are part of the central compartment::
***Heart, kidneys, lungs, liver

Front 17

1 compart, IV bolus:

Back 17

*Iv bolus, therefore essentially all of the drug is in the plasma at the time of injection (t=0)
*One compartment because drug is not higly distributed to tissues outside the central compartment
*That is, there would not be any significant conc of drugs in any other tissues besides heart, kidney, lungs, liver

Front 18

One compartment Model, First Order Absorption:

Back 18

*One compartment, so drug is not distribued significantly outside the central compartment
*Instead of IV bolus admin., drug must be absorbed from a site of administations
*First order absorption occurs with any formulation that reqires an absorption step: ex. po transdermal ( not CR), IM, SQ

Front 19

Two Compartment Model, IV Bolus:

Back 19

*IV bolus, therefore essentially all of the drug is in the plasma at the time of injection (t=0)
*Drug distributes from the plasma and tissues of the central compartment to other tissues
*Elimination of drug occurs ONLY from the central compartment