Lecture 1 - Physiologic Disposition

Question 1

Biotransformation is

Answer 1

Rx metabolism

Question 2

Examples of physiologic dysfunction causing drug disposition

Answer 2

renal/liver, gastric motility (absorption)

Question 3

Pharmacokinetics =

Answer 3

effect of BODY on drug (ADME)

Question 4

Pharmacodynamics =

Answer 4

effect of DRUG on body

Question 5

Central compartment connected to :

Answer 5

Therapeutic site of action
Tissue reservoir
Unwanted site of action
Kidney
Liver

Question 6

In absorption/distribution, lipoid membranes b/w :

Answer 6

Rx origin “&” IM
Rx origin “&” GI
Central comp “&” peripheral comp
Central comp “&” excretion/reabsorption

Question 7

Barriers to Central Compartment (Blood)

Answer 7

LIPID MEMBRANES

metabolic inactivation / chemical interactions

Question 8

active transport forms

Answer 8

facilitated diffusion, drug transporters

Question 9

passive transport forms

Answer 9

paracellular transport, diffusion, filtration, bulk transport, carrier-facilitated

Question 10

Molecular size effect on Drug absorption

Answer 10

smaller the Rx = faster crossing membrane/absorption (pores and water channels)

Question 11

Diffusion depends on

Answer 11

• -LIPID SOLUBILITY

- -Area/Thickness/Concentration Gradient

Question 12

Diffusion : partition coefficient w/ absorption?

Answer 12

Big partition coefficient = faster reabsorption (more lipid soluble)

Question 13

Ionized/Un-ionized goes across membrane by SIMPLE DIFFUSION?

Answer 13

ONLY UN-IONIZED molecule simple diffuses across membrane

Question 14

Weak acid in Acidic pH becomes

Answer 14

less ionized

Question 15

Weak base in Basic pH becomes

Answer 15

less ionized

Question 16

pKa is

Answer 16

pH for 50/50 ionized/un-ionized

Question 17

at steady state, weak bases go

Answer 17

from basic to acidic side

(un-ionized form crosses)

Question 18

at steady state, weak acids go

Answer 18

from acidic to basic side

(un-ionized form crosses)

Question 19

If pH is the same on both sides,

Answer 19

Rx total amount SAME on both sides

Question 20

difference in pH causing ion movement towards opposite =

Answer 20

ion trapping, pH partitioning

Question 21

IV pros

Answer 21

Rapid onset
Accurate level control
Direct

Question 22

IV negs

Answer 22

Non-removable
High [ ] injections
Fluid overload

Question 23

IM pros

Answer 23

better than SubQ (fast, less irritation, faster absorption w/ vasoconstrictor)

Question 24

SubQ negs

Answer 24

pain, irritation/infxn, local necrosis

small volume only

Question 25

Inhalation pros

Answer 25

surface area perfusion local + systemic Need Equipment

Question 26

Inhalation negs

Answer 26

Allergic Rxns | Route for party drugs "&" work toxins

Question 27

how to enhance topical absorption

Answer 27

oily suspension, hydrated skin

Question 28

which more permeable, dermis or epidermis

Answer 28

dermis (burns, denuded, abraded)

Question 29

topical negs

Answer 29

allergic rxns

Question 30

3 enteral routes

Answer 30

sublingual, rectal, oral

Question 31

Which don't have first pass effect?

Answer 31

IV, Sublingual/buccal, IM,

Question 32

Sublingual drain into

Answer 32

superior vena cava

Question 33

Rectal used for

Answer 33

unconscious patients, childrens, stomach irritation

Question 34

Rectal - how much Rx will lose in first pass to liver

Answer 34

1/2

Question 35

Rectal negs

Answer 35

absorption incomplete/ irregular

Question 36

Oral pros

Answer 36

cheap, safe

Question 37

Which have sustained release?

Answer 37

oral, topical, IM/SubQ

Question 38

Oral negs

Answer 38

irritate GI Much Rx lost Irregular absorption OD

Question 39

Major site for Rx absorption

Answer 39

Small Intestine | **surface area, transit time

Question 40

Absorption rate w/ stomach emptying rate

Answer 40

faster stomach emptying = faster absorption | water

Question 41

Drug distribution - major factors

Answer 41

BLOOD FLOW | protein binding

Question 42

Drug distribution path

Answer 42

blood --> muscle --> fat

Question 43

what stops Rx from passing through Cap Fenestrations into extracellular space?

Answer 43

binding to albumin

Question 44

BBB walls

Answer 44

tight junctions lined w/ perivascular glial cells ONLY very lipid soluble pass (same in testes)

Question 45

_______ goes in BREAST MILK

Answer 45

basic | breast milk pH (6.8)

Question 46

Metabolism affect on Rx solubility...

Answer 46

INCREASES Rx solubility

Question 47

Metabolism in liver, ALSO...

Answer 47

lung, kidney, intestine, placenta, ...

Question 48

xenobiotic

Answer 48

chem in environment

Question 49

Phase I / Functionalization Rxn

Answer 49

Redox, Hydrolyses

Question 50

Phase II / Synthetic Rxn

Answer 50

Conjugation

Question 51

Microsomal

Answer 51

CYP450 (from ER enzymes)

Question 52

CYP450 has ___ functional isozymes in humans

Answer 52

50

Question 53

Enzymes involved in metab of 50% Rx

Answer 53

CYP 3A4 / 3A5

Question 54

CYP 450 cycle

Answer 54

NADPH gives (e-), Rx is reduced, then oxidized, then OH added, to make MORE SOLUBLE

Question 55

CYP 450 Rxn type

Answer 55

Phase I

Question 56

common CYP P450s

Answer 56

CYP3A CYP 2E1 CYP 2D6 CYP 2C

Question 57

Pro-drug - if INHIBIT cyp (metab) =

Answer 57

less efficacy

Question 58

Non- prodrug - if INHIBIT cyp (metab) =

Answer 58

toxicity, too much Rx

Question 59

ex. first pass toxification

Answer 59

acetaminophen

Question 60

Phase II rxn types

Answer 60

``` CONJUGATIONS: **transferases Glucuronidation Sulfation Glutathione Methyl/Acetyl ```

Question 61

Phase II rxns require

Answer 61

cofactors

Question 62

Glucuronidation/Sulfation-conjugated Rx (metab) removed by

Answer 62

KIDNEY active transporters

Question 63

Glutathione conjugation (metab) used for

Answer 63

detoxification

Question 64

Drug/Drug interaction sources

Answer 64

METABOLISM inhibit/induct | TRANSPORTER inhibit/induct

Question 65

CYP450 inhibition by

Answer 65

``` competitive inhibition (reversible) Direct inhibition (irreversible) ```

Question 66

Phase II enzyme inhibition by

Answer 66

depletion of cofactors | ex. nutrition - no glucuronidation

Question 67

P450 induction by

Answer 67

repeated exposure = up enzyme production / down enzyme degradation (CYP2E1 - alcoholics)

Question 68

Drug transporter inhibition from

Answer 68

competitive inhibition b/w substrate and Rx

Question 69

Types of drug transporters

Answer 69

Influx : OATP | Efflux: P-gp (MDR1/ABCB1)

Question 70

diseases that affect Rx metabolism

Answer 70

hepatic/renal | cardiac, thyroid, inflammatory mediator

Question 71

excretion includes

Answer 71

LUNGS, hair, sweat, breast milk

Question 72

Renal excretion limited by

Answer 72

protein binding, large size

Question 73

who can't secrete organic ion Rxs from proximal tubule transporters?

Answer 73

Newborns (1st few weeks)

Question 74

Bioavailable has already passed

Answer 74

liver

Question 75

enterohepatic cycling

Answer 75

cleave glucurinide, reabsorbed in sm. intestine (ileum)

Question 76

Area under the curve - Non-prodrug w/ INDUCTION of enzyme

Answer 76

less Rx in plasma (less area)

Question 77

Area under the curve - Non-prodrug w/ INHIBITION of enzyme

Answer 77

more Rx in plasma (more area)

Question 78

Pro drug - UP/INDUCE Cyp450 -->

Answer 78

more Rx in plasma