Chapter 4 - Pharmacokinetics

Question 1

Hepatic enzyme activity is generally reduced in what populations?

Answer 1

Infants and elderly

Question 2

Individuals with cirrhosis of the liver will require — dosage due to less metabolic activity in the liver?

Answer 2

Less

Question 3

First Pass Metabolism explained

Answer 3

After drugs are orally administered, they have to bypass the liver where they lose a certain percentage of their effect.

Question 4

First Pass Metabolism - traced

Answer 4

1. Oral drug administration
2. Drugs absorbed from the small intestine into the hepatic portal vein
3. Drug enters portal circulation and travels to liver
4. On first pass through the liver, the drug is metabolized to a less active form
5. Drug metabolites (in their less active form) leave the liver for distribution to the tissues

Question 5

Metabolism AKA

Answer 5

Bio transformation

Question 6

Bioavailability - defined

Answer 6

The proportion of the drug that is active and available when it reaches systemic circulation

Question 7

Grapefruit juice will effect bioavailability by…

Answer 7

Destroying cytochrome P-450

Question 8

Factors that affect liver Metabolism…

Answer 8

Age-infants and elderly have less active liver enzymes

Cirrhosis

Genomics

Question 9

When a drug is metabolized by the liver, it increases — solubility

Answer 9

Water

Question 10

Certain drugs increase metabolic activity of the liver, thereby increasing the rate of their own metabolism. What is this called?

Answer 10

Enzyme induction

Question 11

Pro-drug

Answer 11

A drug is inactive until it has metabolized into its active form; first pass may increase these drugs activity

Example: codeine bio transforms into morphine

Question 12

Hepatic microsomal enzyme system (P-450)

Answer 12

Complex in the liver with the primary job of inactivating drugs and accelerate their excretion

Question 13

Conjugates -

Answer 13

Make drugs more water soluble and ready for excretion by the kidneys

Question 14

The chemical conversion of a drug so it can be easily removed by the body is referred to…

Answer 14

Metabolism

Question 15

High First Pass Metabolism

Answer 15

Refers to drugs that are a subject to being fully metabolized in one pass

Example: verapamil oral dose 125mg versus IV 5mg (note: if the patient has liver disease however, and is prescribed the 125mg, all of the dose may go to the bloodstream)

Question 16

Blood Brain Barrier

Answer 16

Makes brain tumors hard to treat as many drugs cannot permeate

Question 17

Fetal Placental Barrier

Answer 17

Important protection from harmful substances. However, alcohol, caffeine and cocaine can cross!

Question 18

How the body deals with the medication on a physiological level is called…

Answer 18

Pharmacokinetics

Question 19

Passive Transport AKA Diffusion

Answer 19

High concentration to low concentration

Small, ionized, lipid soluble

Small water soluble agents (urea, alcohol and water) can enter through pores of the plasma membrane

Question 20

Active Transport

Answer 20

Chemicals move against concentration gradients

Large, ionized, water soluble molecules that have difficulty passing lipid bi-layer

Question 21

Co-Transport

Answer 21

The movement of 2 or more chemicals together across the plasma membrane

Question 22

Receptors

Answer 22

When drugs bind to a receptor protein, this will typically activate a second messenger system which produces the biochemical response

Question 23

Most common receptors are…

Answer 23

Transmembrane receptors linked to G proteins which activate second messenger systems.

Receptors include: beta adrenoreceptors, alpha adrenoreceptors

Question 24

Absorption

Answer 24

Movement from the site of administration across membranes and into circulating fluids.

Absorption determines the time it takes for a drug to produce an effect.

Question 25

Factors that affect absorption:

Answer 25

Drug formulation, route of administration, size of the drug molecule (large molecule must wait for active Transport), surface area of absorptive site, digestive motility (diarrhea the drug will not absorb as well), blood flow (deltoid vs gluteus), lipid solubility of drug (lipid soluble drugs pass the plasma membranes easier), pH environment (non-ionized is readily absorbed)

Question 26

Distribution

Answer 26

The physiologic movement of drugs from the circulation to the tissues

Question 27

Factors that affect distribution…

Answer 27

Membrane permeability (lipid solubility)

Tissue affinity (adipose tissue, bone marrow)?

Volume of distribution

Protein binding drug - drug-protein complexes become too large to cords capillary membranes; Albumin; Coumadin is 99% bound

Question 28

Drug/Food Interactions

Answer 28

Senna acts as a laxative which will affect absorption

St. John’s Wart can decrease effects of Coumadin

Calcium will bind to tetracycline and inhibit absorption

Grapefruit can cause the body to absorb too much or not enough of a drug

Question 29

Minimum effective concentration

Answer 29

Amount of drug needed to produce a therapeutic effect

Question 30

Toxic concentration

Answer 30

Level of drug that will result in serious adverse effects

Question 31

Therapeutic range

Answer 31

Plasma drug concentration between the minimum affective concentration and toxic concentration

Question 32

Plasma half life

Answer 32

Length of time needed to decrease drug plasma concentration by 1/2

Question 33

Filtered at the glomerulus

Answer 33

Free drugs, water soluble agents, electrolytes, and small molecules

Question 34

Proteins, blood cells, and drug protein complexes are not filtered because of their large size

Answer 34

Secretion

Question 35

Non renal routes of excretion

Answer 35

Biliary, pulmonary, salivary, mammary, skin, gastrointestinal, genital

Question 36

The greater the half life…

Answer 36

The greater the time it takes to excrete

Question 37

Loading dose

Answer 37

A higher amount of drug often given only once or twice to prime the blood stream with a sufficient level of drug