Mdti - Pharmacology 01

Front 1

What does phamacokinetics describe?

Pharmacodynamics?

Back 1

Pharmacokinetics: Describes what happens to a drug when given to a patient

"What the body does to the drug"

Pharmacodynamics: Describes the body's response to a given drug

"What the drug does to the body"

Front 2

What 5 processes are involved in pharmacokinetics?

Back 2

1. Administration

2. Absorption

3. Distribution

4. Metabolism

5. Excretion

Front 3

What 2 processes are invlolved in pharmacodynamics?

Back 3

1. Dose Response

2. Receptor Activation
- efficacy
- Toxicity

Front 4

What are 3 main categories of Routes of Admission?

Back 4

1. Enteral - oral, rectal, sublingual

2. Parenteral - IV, IM, SC

3. Other - Inhalation, Intranasal, Topical, Transdermal

Front 5

What are the 2 main disadvantages of oral administration?

Back 5

1. Most Complicated Path

2. Most Variable Response

- Effect of food in the stomach
- Effect of gastric pH
- First pass effect
- Biotransformation in the liver/GIT

Front 6

What is the first pass effect?

Back 6

- Effect of a drug being absorbed via the GI --> Portal system and being transformed/metabolized in the liver

Front 7

What are the advantages of Parenteral Administration (IV/IA)?

Back 7

- Bypass stomache and intestines

- No first pass effect (directly into circulation)

- Rapid Onset of Action

Front 8

What is the difference between transdermal and topical administration of drugs?

Back 8

Transdermal: placed on skin but intended for systemic circulation

Topical: Intended for the area where drug is placed

Front 9

What is absorption of a drug?

For which administration routes is absorption 100%?

For which is it <100%?

Back 9

Transfer of drug from the site of administration to the systemic circulation

For IV administration 100% of drug absorbed and bioavailable

For all other routes, absorption and bioavailabilty is variable

Front 10

What are 4 main factors that affect GI absorption?

Back 10

1. Blood supply

2. Food in Stomach (delays absorption)

3. Presence of other meds in the stomach

4. pH

Front 11

What are the 4 mechanisms through which a drug can permeate a membrane?

Back 11

1. Aqueous - water soluble drugs penetrate cell membrane through aqueous channels

2. Lipid Soluble - Diffuse through cells

3. Specific Carrier Mechanism

4. Endocytosis

Front 12

How does pH affect permeability?

Back 12

Uncharged molecules are absorbed more readily. Thus if the pH changes charge on drug, changes permeability:

HA soluble (in basic solution A- not)

B soluble (in acid solution BH+ not)

Front 13

Where are weak acid drugs usually absorbed?

Weak Base?

Back 13

Weak acid: Stomach

Weak base: Intestine

Because those are the environments in which the drugs are uncharged and therefore permeable

Front 14

Can passive diffusion of drug be saturable?

Carrier Mediated Diffusion?

Back 14

Passive Diffusion: No

Carrier Mediated: Yes

Front 15

What is bioavailability?

Back 15

The fraction of the administered drug that reaches the systemic circulation in an unchanged form

Front 16

What affects Bioavailability?

Back 16

1. Anything that affects absorption (solubility, chemical structure, carrier, etc)

2. First Pass Effect (reduces it)

Front 17

What is the distribution of a drug?

Back 17

Process by which a drug reversibly leaves the blood stream and enters the interstitium and/or the cells of tissues

Front 18

To what 3 compartments to drugs distribute?

Back 18

1. Plasma (4L)

2. Extracellular Volume (14L, Plasma + Interstitial Fluid (10))

3. Intracellular Volume (28L)

Total of 42L (Total Body Water)

Note: Also goes to tissues (Bone, adipose, fetus if preggers)

Front 19

What 4 items determines where a drug distributes?

Back 19

1. Blood flow to a given site

2. Capillary Permeability (ex: blood/brain barrier)

3. Characteristics of Drug (Permeation Principles)

4. Binding to Plasma Proteins

Front 20

What role do plasma proteins play in drug distribution?

Back 20

Many drugs bind to plasma proteins

Can be competition for binding sites between different drugs

Front 21

Are drugs bound to plasma proteins active or inactive?

Back 21

Inactive

Front 22

What is volume of Distribution?

What is its formula?

Back 22

Volume of Distribution is a hypothetical volume of fluid into which a drug is disseminated prior to elimination

Vd = Bioavailable Dose / Concentration in Plasma at t=0

Front 23

What is the purpose (use) of Volume of Distribution?

What does a Large VD mean?

Small VD?

Back 23

Gives a sense of where a drug goes in the body. Allows dosage for therapeutic effect to be determined

Large VD = drug distributed throughout the body

Small VD = drug contained within the plasma

Front 24

Where does the majority of biotransformation occur?

What is the primary purpose of biotransformation?

Back 24

In the liver

Primary purpose is to inactivate the drug by converting it into a more excretable form

Front 25

What are the phases of drug metabolism (biotransformation) and what do they do?

Back 25

Phase I: Occurs by oxidation and involves Cytochrome P-450 system

Phase II: involves coupling an endogenous substrate to a drug or its Phase I metabolite

Front 26

What is the P450 system?

Back 26

- Composed of many families of heme containing isozymes that are heavily concentrated in liver and intestines

- Part of Phase I metabolism that oxidizes drugs for excretion

Front 27

In what Cytochrome P-450 (CYP) families are most drug metabolizing enzymes?

Which CYP is responsible for the metabolism of the most drugs?

Back 27

- CYP 1, 2, 3

- CYP3A4

Front 28

What 2 factors increase the activity of CYP3A4 (and thus speed up breakdown of certain drugs)?

Back 28

Increase Activity of CYP3A4: Rifambin (TB drug), St. Johns Wort

Decrease Activity: Grapefruit Juice

Front 29

What are 2 main CYP polymorphisms that are responsible for major differences in drug metabolism?

Back 29

1. CYP2D6

2. CYP2C16

Front 30

Which type of metabolites are more easily excreted, polar or apolar?

Back 30

POLAR

Front 31

What are the 4 ways that drugs can be excreted?

Back 31

1. Renal

2. Biliary (bile salts)

3. Sweat

4. Salivia

Front 32

What 2 processes compose elimination?

Back 32

1. Metabolism

2. Excretion

Front 33

What is the clearance of a drug?

Back 33

Rate of elimination (metabolism + excretion)

Front 34

The majority of drugs display what type of clearance (rate of elimination)?

Back 34

First Order Kinetics - rate of elimination is directly proportional to the concentration of the drug

AKA: elimination is not suturable

Front 35

What is the elimination half life?

Back 35

Time required to eliminate half of the amount of drug in the body or to reduce the plasma by 50%

Front 36

How many Elimination Half Lives does it take for a drug to be reduced by 90%?

Back 36

4

Front 37

How long does it take a (continuously administered drug) to reach steady state?

Back 37

4-5 half lives

Note: the TIME required to reach stead state is independent of drug dose or rate/frequency of dosing

- But dose does affect CONCENTRATION at steady state

Front 38

What is the steady state concentration dependent upon?

Back 38

1. Dosage

2. Drug Half Life

Front 39

What is the difference between a loading dose and a maintenance dose?

Back 39

Loading dose used when it's necessary to rapidly achieve a therapeutic plasma concentration (ie: anticoagulants)

Maintenance dose is given to establish or maintain a desired steady state concentration