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Pharm Test 1 > Lecture 1 - Physiologic Disposition > Flashcards

Lecture 1 - Physiologic Disposition Flashcards

1
Q

Biotransformation is

A

Rx metabolism

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2
Q

Examples of physiologic dysfunction causing drug disposition

A

renal/liver, gastric motility (absorption)

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3
Q

Pharmacokinetics =

A

effect of BODY on drug (ADME)

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4
Q

Pharmacodynamics =

A

effect of DRUG on body

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5
Q

Central compartment connected to :

A 
Therapeutic site of action
Tissue reservoir
Unwanted site of action
Kidney
Liver
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6
Q

In absorption/distribution, lipoid membranes b/w :

A

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

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7
Q

Barriers to Central Compartment (Blood)

A

LIPID MEMBRANES

metabolic inactivation / chemical interactions

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8
Q

active transport forms

A

facilitated diffusion, drug transporters

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9
Q

passive transport forms

A

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

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10
Q

Molecular size effect on Drug absorption

A

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

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11
Q

Diffusion depends on

A
  • -LIPID SOLUBILITY

- -Area/Thickness/Concentration Gradient

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12
Q

Diffusion : partition coefficient w/ absorption?

A

Big partition coefficient = faster reabsorption (more lipid soluble)

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13
Q

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

A

ONLY UN-IONIZED molecule simple diffuses across membrane

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14
Q

Weak acid in Acidic pH becomes

A

less ionized

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15
Q

Weak base in Basic pH becomes

A

less ionized

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16
Q

pKa is

A

pH for 50/50 ionized/un-ionized

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17
Q

at steady state, weak bases go

A

from basic to acidic side

(un-ionized form crosses)

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18
Q

at steady state, weak acids go

A

from acidic to basic side

(un-ionized form crosses)

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19
Q

If pH is the same on both sides,

A

Rx total amount SAME on both sides

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20
Q

difference in pH causing ion movement towards opposite =

A

ion trapping, pH partitioning

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21
Q

IV pros

A

Rapid onset
Accurate level control
Direct

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22
Q

IV negs

A

Non-removable
High [ ] injections
Fluid overload

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23
Q

IM pros

A

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

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24
Q

SubQ negs

A

pain, irritation/infxn, local necrosis

small volume only

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25
Q

Inhalation pros

A

surface area
perfusion
local + systemic
Need Equipment

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26
Q

Inhalation negs

A

Allergic Rxns

Route for party drugs “&” work toxins

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27
Q

how to enhance topical absorption

A

oily suspension, hydrated skin

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28
Q

which more permeable, dermis or epidermis

A

dermis (burns, denuded, abraded)

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29
Q

topical negs

A

allergic rxns

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30
Q

3 enteral routes

A

sublingual, rectal, oral

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31
Q

Which don’t have first pass effect?

A

IV, Sublingual/buccal, IM,

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32
Q

Sublingual drain into

A

superior vena cava

33
Q

Rectal used for

A

unconscious patients, childrens, stomach irritation

34
Q

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

A

1/2

35
Q

Rectal negs

A

absorption incomplete/ irregular

36
Q

Oral pros

A

cheap, safe

37
Q

Which have sustained release?

A

oral, topical, IM/SubQ

38
Q

Oral negs

A

irritate GI
Much Rx lost
Irregular absorption
OD

39
Q

Major site for Rx absorption

A

Small Intestine

**surface area, transit time

40
Q

Absorption rate w/ stomach emptying rate

A

faster stomach emptying = faster absorption

water

41
Q

Drug distribution - major factors

A

BLOOD FLOW

protein binding

42
Q

Drug distribution path

A

blood –> muscle –> fat

43
Q

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

A

binding to albumin

44
Q

BBB walls

A

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

45
Q

_______ goes in BREAST MILK

A

basic

breast milk pH (6.8)

46
Q

Metabolism affect on Rx solubility…

A

INCREASES Rx solubility

47
Q

Metabolism in liver, ALSO…

A

lung, kidney, intestine, placenta, …

48
Q

xenobiotic

A

chem in environment

49
Q

Phase I / Functionalization Rxn

A

Redox, Hydrolyses

50
Q

Phase II / Synthetic Rxn

A

Conjugation

51
Q

Microsomal

A

CYP450 (from ER enzymes)

52
Q

CYP450 has ___ functional isozymes in humans

A

50

53
Q

Enzymes involved in metab of 50% Rx

A

CYP 3A4 / 3A5

54
Q

CYP 450 cycle

A

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

55
Q

CYP 450 Rxn type

A

Phase I

56
Q

common CYP P450s

A

CYP3A
CYP 2E1
CYP 2D6
CYP 2C

57
Q

Pro-drug - if INHIBIT cyp (metab) =

A

less efficacy

58
Q

Non- prodrug - if INHIBIT cyp (metab) =

A

toxicity, too much Rx

59
Q

ex. first pass toxification

A

acetaminophen

60
Q

Phase II rxn types

A 
CONJUGATIONS:
**transferases
Glucuronidation
Sulfation
Glutathione
Methyl/Acetyl
61
Q

Phase II rxns require

A

cofactors

62
Q

Glucuronidation/Sulfation-conjugated Rx (metab) removed by

A

KIDNEY active transporters

63
Q

Glutathione conjugation (metab) used for

A

detoxification

64
Q

Drug/Drug interaction sources

A

METABOLISM inhibit/induct

TRANSPORTER inhibit/induct

65
Q

CYP450 inhibition by

A 
competitive inhibition (reversible)
Direct inhibition (irreversible)
66
Q

Phase II enzyme inhibition by

A

depletion of cofactors

ex. nutrition - no glucuronidation

67
Q

P450 induction by

A

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

68
Q

Drug transporter inhibition from

A

competitive inhibition b/w substrate and Rx

69
Q

Types of drug transporters

A

Influx : OATP

Efflux: P-gp (MDR1/ABCB1)

70
Q

diseases that affect Rx metabolism

A

hepatic/renal

cardiac, thyroid, inflammatory mediator

71
Q

excretion includes

A

LUNGS, hair, sweat, breast milk

72
Q

Renal excretion limited by

A

protein binding, large size

73
Q

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

A

Newborns (1st few weeks)

74
Q

Bioavailable has already passed

A

liver

75
Q

enterohepatic cycling

A

cleave glucurinide, reabsorbed in sm. intestine (ileum)

76
Q

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

A

less Rx in plasma (less area)

77
Q

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

A

more Rx in plasma (more area)

78
Q

Pro drug - UP/INDUCE Cyp450 –>

A

more Rx in plasma

Pharm Test 1 (6 decks)

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