Care Viii Pharmacology Lectures 1-3 2008

Front 1

drug movement into, within, and out of the body

Back 1

Pharmacokinetics (definition)

Front 2

Pharmacokinetics (includes)

Back 2

1. absorption
2. distribution
3. elimination
-excretion
-metabolism

Front 3

drug actions and their mechanisms

Back 3

Pharmacodynamics

Front 4

transfer of drug from site of administration to systemic circulation

Back 4

Absorption

Front 5

transfer of drug from systemic circulation to tissues

Back 5

Distribution

Front 6

removal of drug from body

Back 6

Elimination

Front 7

Excretion

Back 7

renal and/or hepatobiliary

Front 8

Metabolism

Back 8

mainly by the liver

Front 9

Mechanisms of drug transport

Back 9

1. passive diffusion
2. filtration
3. carrier-mediated transport
4. receptor-mediated
endocytosis

Front 10

primary means by which drugs cross membranes

Back 10

Passive diffusion

Front 11

the ratio of the concentration of the drug in two immisible phases: a nonpolar liquid (representing membrane) and an aqueous buffer (representing the plasma)

Back 11

lipid-water partition coefficient (Kp)(definition)

Front 12

lipid-water partition coefficient (Kp) (formula)

Back 12

Kp = [drug] in lipid phase/
[drug] in aqueous phase

Front 13

The higher the Kp, the more ________ (lipid/water) soluble, the _______ (faster/slower) the rate of transfer across biological membranes.

Back 13

1. lipid
2. faster

Front 14

Two main catagories of passive diffusion of electrolytes

Back 14

1. weak acids
2. weak bases

Front 15

Weak acids

Back 15

HA = H+ + A-
examples:
R-COOH
R-OH
R-SH

Front 16

Weak bases

Back 16

BH+ = B + H+
example:
R-NH2

Front 17

the pH at which half of the molecules are in the ionized form and one half are in the unionized form

Back 17

pKa (definition)

Front 18

Only the __________ (unionized/ionized) forms of the drug or the _________ (uncharged/charged) drug can pass through or across the membrane (or is tranferred) by passive diffusion.

Back 18

1. unionized
2. uncharged

Front 19

What are the predominate forms when pH < pKa?

Back 19

HA and BH+

Front 20

What are the predominate forms when pH > pKa?

Back 20

A- and B

Front 21

What is the relationship between HA and A- and BH+ and B when pH = pKa?

Back 21

HA = A and BH+ = B

Front 22

passage of molecules through pores of porous structures (as in the renal glomerulus and capillary endothelium cells)

Back 22

Filtration (definition)

Front 23

drug combines with a transport protein in the membrane and the complex can move across the membrane

Back 23

Carrier-mediated transport
(definition)

Front 24

Carrier-mediated transport
(types)

Back 24

1. active transport
2. facilitated diffusion

Front 25

1. carrier or receptor
mediated
2. selectivity (not for all
drugs)
3. energy-dependent -ATP
hydrolysis
4. one-way process (drug
accumulation)
5. It can be saturated
6. It can be inhibited

Back 25

Active transport

Front 26

1. carrier or receptor
mediated
2. selectivity
3. does not require ATP
4. bi-directional (no drug
accumulation)
5. It can be saturated

Back 26

Faciliated diffusion

Front 27

the binding of some peptide hormones, growth factors, antibodies, and other substances to their receptors on the cell surface can trigger a process of endocytosis that brings both the receptor and the ligand into the cell

Back 27

Receptor-mediated endocytosis

Front 28

Receptor-mediated endocytosis is _______(more/less) selective compared with carrier-mediated transport.

Back 28

more

Front 29

What are the major routes of drug administration?

Back 29

1. Enteral
2. Parenteral

Front 30

through the GI tract

Back 30

Enteral administration (definition)

Front 31

Enteral administration
(examples)

Back 31

1. oral
2. sublingual
3. rectal

Front 32

outside the GI tract
(for poorly or not stable drugs)

Back 32

Parenteral administration
(definition)

Front 33

Parenteral administration
(examples)

Back 33

1. intravenous (IV)
2. intramuscular (IM)
3. subcutaneous (SC)

Front 34

Enteral administration
(advantages)

Back 34

1. safe
2. convenient
3. economical

Front 35

Enteral administration
(disadvanges)

Back 35

1. limited absorption
2. emesis (as a result of
gastric irritation)
3. some drugs can be
destroyed by the digestive
enzymes and low gastric pH
in GI tract
4. irregularities in
absorption in the presence
of food or other drugs
5. requires patient
cooperation
6. may be metabolized by
first-pass effect

Front 36

First pass effect
(explanation)

Back 36

drugs administered orally are first exposed to the liver and may be extensively metabolized before reaching the rest of the body

Front 37

Parenteral administration
(advantages)

Back 37

1. better regulated and more
predictable absorption
2. can more accurately select
effective dose
3. avoids first pass effect

Front 38

Parenteral administration
(disadvantages)

Back 38

1. risk of infection
2. pain associated with
injection
3. difficulties in self
medication

Front 39

transfer of drug from site of administration to systemic circulation

Back 39

Drug absorption
(definition)

Front 40

Sites of absorption through the GI tract

Back 40

1. mouth
2. stomach
3. small intestine
4. large intestine

Front 41

Which site of absoption is
this?
1. Small amount of surface
area but good blood flow -
best for potent drugs
2. transfer by passive
diffusion - good for
lipid soluble drugs
3. can bypass first pass
effect

Back 41

Mouth

Front 42

Drugs that are _______ (weak acids/weak bases) will be absorbed better than (weak bases/weak acids) in the stomach.

Back 42

1. weak acids
2. weak bases

Front 43

Accumulation of weak base drugs in the stomach

Back 43

Ion trapping
(definition)

Front 44

Which site of absorption is
this?
1. moderate surface area
2. good blood supply
3. drugs absorbed here will
experience the first pass
effect
4. transfer is by passive
diffusion
5. low pH (1-2)
6. ion trapping

Back 44

Stomach

Front 45

Which site of absorption is
this?
1. the primary site for most
drugs
2. large surface area -
folds, villi, microvilli
3. pH = 5-8
4. passive diffusion
5. absorption can also take place by active transport, facilitated diffusion, endocytosis, and filtration

Back 45

Small intestine

Front 46

The primary site of absorption in the GI tract.

Back 46

Small intestine

Front 47

Which site of absorption is
this?
-Not important for drug absorption, if the drug is absorbed effectively in the small intestine

Back 47

Large intestine

Front 48

Factors that modify absorption in the GI tract

Back 48

1. surface area of absorption
2. route of administration
3. gastric emptying (food)
4. intestinal motility

Front 49

Factors that modify absorption
in the GI tract: Surface area of absorption

Back 49

larger = better
(small intestine)

Front 50

Factors that modify absorption
in the GI tract: Route of administration

Back 50

GI tract - first pass effect

Front 51

Factors that modify absorption
in the GI tract: Gastric emptying

Back 51

-Small intestine
-for all drugs - acidic, basic, or neutral substances
-high fat foods - delays gastric emptying - slow absorption

Front 52

Anything that _______ (delays/accelerates) gastric emptying will decrease drug absorption.

Back 52

delays

Front 53

Anything that _______ (delays/accelerates) gastric emptying will increase drug absorption.

Back 53

accelerates

Front 54

Anything that delays gastric emptying will _______ (decrease/increase) drug absorption.

Back 54

decrease

Front 55

Anything that accelerates gastric emptying will _______ (decrease/increase) drug absorption.

Back 55

increase

Front 56

Factors that modify absorption
in the GI tract: intestinal motility

Back 56

-depends on whether the drug is completely absorbed under normal condition

Front 57

Intestinal motility:
If completely absorbed early upon entry into the small intestine, increasing intestinal motility _______ (will/will not)significantly affect absorption.

Back 57

Will not

Front 58

Intestinal motility:
If not completely absorbed before entry into the small intestine, increasing intestinal motility will _______ (slow down/facilitate) drug absorption.

Back 58

slow down

Front 59

Intestinal motility:
If not completely absorbed before entry into the small intestine, decreasing intestinal motility will _______ (slow down/facilitate) drug absorption.

Back 59

facilitate

Front 60

Intestinal motility:
If not completely absorbed before entry into the small intestine, __________(increasing/decreasing) intestinal motility will slow down drug absorption.

Back 60

increasing

Front 61

Fraction of administered drug that reaches the systemic circulation

Back 61

Bioavailability

Front 62

Bioavailability is ________ (reduced/increased) by first pass effect.

Back 62

reduced

Front 63

True or false.
Bioavailability is altered by changes in gastrointestinal motility.

Back 63

true

Front 64

True or false.
Bioavailability can be reduced by other substances present in the GI tract.

Back 64

true

Front 65

movement from circulation to other body compartments

Back 65

drug distribution

Front 66

Factors affecting distribution

Back 66

1. regional blood flow
2. capillary permeability
3. rate of transfer from
interstital fluid into
tissues
4. binding to plasma proteins

Front 67

Perfusion rate

Back 67

blood flow to tissue mass ratio

Front 68

The heart, kidney, liver, lung and brain all have ______ (higher/moderate/lower) perfusion rates.

Back 68

higher

Front 69

Muscles and skin have ______ (higher/moderate/lower) perfusion rates.

Back 69

moderate

Front 70

Adipose tissue has a ______ (high/moderate/low) perfusion rate.

Back 70

low

Front 71

The liver has ______(larger/smaller) fenestrae than the brain.

Back 71

larger

Front 72

True or false.
The liver has greater filtration potential than the brain.

Back 72

true

Front 73

The brain has _______ (larger/smaller) fenestrae than the liver.

Back 73

smaller

Front 74

True or false.
The brain has a lower capillary permeability.

Back 74

true

Front 75

The liver has _____ junctions,
and the brain has _____ junctions.

Back 75

1. slit junction - liver
2. tight junction - brain
(blood-brain barrier)

Front 76

What is the most common and quickest means of transfer from interstitial fluid into the tissues?

Back 76

Passive diffusion

Front 77

True or false.
Binding to plasma proteins is reversible.

Back 77

true

Front 78

What are the consequences of drugs binding to plasma proteins?

Back 78

1. cannot go to its receptor
at the site of action
2. cannot be distributed to
body tissue
3. cannot be metabolized by
enzymes
4. cannot be excreted from
the body

Front 79

True or false.
Bound drugs are pharmacologically inactive.

Back 79

true

Front 80

True or false.
Drug binding to plasma proteins will delay the onset of drug action.

Back 80

true

Front 81

Drug binding to plasma proteins will ________ (decrease/increase) the intensity of drug action?

Back 81

decrease

Front 82

True or false.
Drug binding to plasma proteins may prolong drug action. (Creating a reservoir of non-metabolized drug in the body).

Back 82

true

Front 83

What are the three main types of plasma proteins?

Back 83

1. albumin
2. lipoproteins
3. alpha1-acid glycoprotein

Front 84

This is the primary serum protein responsible for drug binding. It also has the strongest affinity for weak acid.

Back 84

albumin

Front 85

Albumin has the strongest affinity for ___________ (weak acid/weak base).

Back 85

weak acid

Front 86

These bind lipid soluble drugs. The binding capacity is dependent on their lipid content.

Back 86

Lipoproteins

Front 87

This plasma protein is inducible by acute injury, trauma, and stress.

Back 87

alpha1-acid glycoprotein

Front 88

The _____ (more/less) plasma proteins, the less free drug available.

Back 88

more

Front 89

Drugs are removed from the body or drugs are transferred from the internal environment to the external environment.

Back 89

drug excretion

Front 90

What are the sites for drug excretion?

Back 90

1. kidney - urine
2. liver - bile
3. skin
4. lung
5. milk

Front 91

What are the types of renal excretion?

Back 91

1. glomerular filtration
2. active secretion
3. passive reabsorption

Front 92

Which type of renal excretion is this?
-two active transport systems
-relatively non-specific
-unidirection - accumulation
and excretion

Back 92

active secretion

Front 93

Unionized, lipid soluble drugs(substances) are __________ (reabsorbed/excreted).

Back 93

reabsorbed

Front 94

Ionized, lipid insoluble drugs
(substances) are __________
(reabsorbed/excreted).

Back 94

excreted

Front 95

True or false.
More ionization = more secretion

Back 95

true

Front 96

Which site of excretion is described?
-gases and volatile liquids
-simple diffusion from the blood into the airway

Back 96

lung (pulmonary excretion)

Front 97

What are the characteristics of drug metabolism?

Back 97

1. chemical change in a drug
2. forms more water soluble
metabolites
3. usually terminates drug
action

Front 98

The ______ is the dominant organ in drug metabolism.

Back 98

liver

Front 99

What are the two types of reactions in drug metabolism? What are their phases?

Back 99

-non-synthetic rxns - phase I
-synthetic rxns - phase II

Front 100

What are the types of non-synthetic reactions?

Back 100

1. oxidation reactions
2. reduction
3. hydrolysis

Front 101

Oxidation reactions are mostly by...

Back 101

cytochrome P450

Front 102

What are the two active transport systems in active secretions?

Back 102

1. organic acids
2. organic bases

Front 103

constant percentage of drug eliminated per unit time

Back 103

first order elimination

Front 104

time to reduce plasma levels by one half

Back 104

plasma half-life

Front 105

constant amount of drug eliminiated per unit time

Back 105

capacity limited (zero order) elimination

Front 106

dose below which there is no response

Back 106

threshold

Front 107

half of possible maximum response

Back 107

mid-range

Front 108

dose to produce 1/2 of the possible maximum response: (ED50)

Back 108

potency

Front 109

maximum response

Back 109

ceiling

Front 110

how well the drug binds

Back 110

affinity

Front 111

the ability to produce a response

Back 111

intrinsic activity

Front 112

Agonists _____ (have/don't have) intrinsic activity.

Back 112

have

Front 113

Antagonists _______ (have/don't have) intrinsic activity.

Back 113

don't have

Front 114

drugs that interact with a receptor to produce a response

Back 114

agonists

Front 115

drugs that can produce the full response (Intrinsic ability = 1)

Back 115

full agonists

Front 116

drugs that produce a response less than that of full agonists (intrinsic activity > 0 and < 1)

Back 116

partial agonists

Front 117

-have affinity
-have no intrinsic activity
-block the binding by an agonist to its receptor
-blockade can be overcome
-reduce potency of agonist

Back 117

competitive antagonists