Pharmacokinetics I

Question 1

Xenobiotic

Answer 1

Anything that enters the body

Question 2

Drug

Answer 2

Brings about change in biological function through its chemical actions

Question 3

Prodrug

Answer 3

Inactive form of a drug, converted to an active form in the body

Question 4

Pharmacodynamics

Answer 4

Action of drug ON the body

Question 5

Drug disposition

Answer 5

Qualitative; how the body handles the drug

How it’s absorbed, distributed, metabolized, eliminated

Question 6

Pharmacokinetics

Answer 6

Quantitative description of drug disposition

Question 7

First pass metabolism occurs where?

Answer 7

Liver

Question 8

“A” in ADME

Answer 8

Absorption: transport drugs from site of admin to circulation

Question 9

“D” in ADME

Answer 9

Distribution: delivery of drug via blood to tissues, drug must have adequate concentration at site of action to produce effect

Question 10

“M” in ADME

Answer 10

Metabolism: parental compound converts to metabolite, compound made more amendable for excretion, occurs in liver, typically inactive metabolites but pharmacologically active

Question 11

“E” in ADME

Answer 11

Excretion: via kidney or intestine

Question 12

Most critical step for bioavailability?

Answer 12

Absorption

Question 13

Factors that determine absorption

Answer 13

1) property of the drug (size, acid/base, lipophilic/hydrophobic)
2) vehicle/formulation
3) route of admin and conditions at route of admin

Question 14

Route of admin most critically effects…

Answer 14

Rate of drug absorption

Question 15

What does route of drug admin influence?

Answer 15

Extent and speed drug is absorbed
1st pass metabolism or not
Efficacy and therapeutic effect

Question 16

Drug Route Administration - Enteral/Enteric

Answer 16

Oral - per os, PO
Buccal/sublingual - BU/SL
Rectal - REC

Question 17

Oral Route of Admin characteristics & issues

Answer 17

Enteral
Most common
Safest
Large SA
Intestine is site of absorption

Issues: slow & subject to liver first-pass metabolism

Question 18

Buccal/Sublingual Route Admin: characteristics

Answer 18

Enteral
Small area, HIGH vascularization
Rapid absorption to VENOUS blood
Bypass liver first pass liver metabolism

Question 19

Route of admin: rectal

Answer 19

Enteral
Performed if oral is precluded
Suppository, foam, or liquid form
Drug placement isn’t well controlled
Absorbed 50% hepatic portal vein (proximal- first pass metabolism) and 50% to venous blood (distal- bypasses first pass metabolism)

Question 20

Drug Amin Routes - parenteral

Answer 20

!! Bypass first pass metabolism !!
Subcutaneous (SC)
Intramuscular (IM)
Intravenous (IV)
Intrathecal (IT)
Inhalation
Intranasal

Question 21

Subcutaneous Injection

Answer 21

Poor blood flow
Sustained, slow release
Small volumes of drugs

Question 22

Intramuscular Injection

Answer 22

High blood flow = prompt absorption

Large volumes, prolonged release

Question 23

Intravenous Injection

Answer 23

Instant delivery - 100% absorption

Prone to adverse effects

Question 24

Intrathecal Injection

Answer 24

Subarachnoid space of spine
Bypasses BBB
Rapid effect on meninges or cerebrospinal axis
Used for spinal anesthesia

Question 25

Inhalation

Answer 25

Action on bronchioles, rapid access to circulation High vascularization Inhalation anesthetics, asthma inhalants

Question 26

Intranasal

Answer 26

Parenteral Acts on nasal mucosa Future drugs via vaccines

Question 27

Topical Drug Admin

Answer 27

Ophthalmic drops | Dermal

Question 28

Ophthalmic drops

Answer 28

Instillation into eye for local effect

Question 29

Dermal

Answer 29

Topical Local acting Systemic absorption - oily vehicles, transdermal patches, Iontophoretic and phonophoretic delivery

Question 30

Transdermal Iontophoretic Delivery

Answer 30

Delivery of ionic molecules into tissues by electric current | (-) charged drug driven into skin from cathode to anode

Question 31

Route of Drug Admin (quickest to slowest)

Answer 31

``` IV Inhalation SL IM SC REC PO Transdermal ```

Question 32

Bioavailability

Answer 32

Fraction (F) of the dose of unchanged drug that reaches systemic circulation by any route - IV dose drugs have 100% bioavailability - other admin route <100%

Question 33

Bioavailability depends on:

Answer 33

Chemical form of drug Rate of absorption Contact time with absorbing surface Enzymes and efflux transporters

Question 34

Drug Movement Across Biological Membranes

Answer 34

A - enter circulation D - traverse within the body, critical concentration needed at site of action M - drug moves into liver E - drug/metabolites must be eliminated

Question 35

Mechanisms by which drugs are transported after admin

Answer 35

Passive Transfer - bulk flow/filtration, passive diffusion | Carrier-Mediated Transport - facilitated diffusion, active transport, receptor-mediated endocytosis

Question 36

Bulk Flow/Filtration

Answer 36

Passage of compounds through intercellular pores Drug flows through intercellular clefts or fenestra

Question 37

Filtration/Bulk Flow Drug Size

Answer 37

MW < 300-500 daltons

Question 38

Filtration/Bulk Flow Drug Types

Answer 38

Ionic, lipophilic, hydrophilic, etc.

Question 39

Examples of Bulk Flow/Filtration

Answer 39

Peripheral capillaries | Glomerular filtration in kidney

Question 40

Passive Diffusion

Answer 40

Passage of drugs by dissolving into and diffusing across lipid membranes through intercellular cleft MOST IMPORTANT TRANSPORT PROCESS, most common route of transport for enteral route

Question 41

Properties of molecules that cross by passive diffusion

Answer 41

1) uncharged, non-ionized 2) lipid soluble (lipophilic, hydrophobic) - non-polar groups increase solubility (CH2, CH3, aromatic rings) - polar groups decrease lipid solubility (OH, COOH, NH, sulfates, ionized groups) 3) correlation of absorption and lipophilicity

Question 42

Lipophilicity

Answer 42

Measured by distribution in an immiscible mix of organic-aqueous solvent

Question 43

Passive Diffusion of Non/ionic Drugs

Answer 43

Small MW organic acids or bases that exist as ionized and non-ionized forms (non-ionized can diffuse, ionized cannot) Classified as acids or bases based on the uncharged (neutral) form of drug

Question 44

Charged & Uncharged Forms of Acidic Drugs

Answer 44

Acidic drug is neutral molecule which can reversible dissociate into an anion (conj. base) to yield a proton donor

Question 45

Charged and Uncharged Forms of Basic Drugs

Answer 45

Basic drug is a neutral molecule which can form a cation (conj. acid) by combining with a proton (proton acceptor)