02. Introduction to Pharmacokinetics

Question 1

Define Pharmacodynamics

Answer 1

The effects of drugs and their mechanisms of action. “The effect of the drug on the body.”

Question 2

Define Pharmacokinetics

Answer 2

The movement of the drugs through the body. “The effect of the body on the drug.”

Question 3

Define Pharmacotherapeutics

Answer 3

The clinical (therapeutic) use of drugs. “Using drugs to treat disease.

Question 4

Define Therapeutic index

Answer 4

Ratio: “Effective dose vs. harmful dose.”

Question 5

How do drugs cross membranes? (3)

Answer 5

• Via channels and pores
• Via transport systems
• Via direct penetration of the membrane (lipid soluble drugs do this)

Question 6

ADME

• Acronym to communicate the basic tenets of _______________.
• What does it stand for?

Answer 6

Acronym to communicate the basic tenets of pharmacokinetics.

• Drug ABSORPTION
• Drug DISTRIBUTION
• Drug METABOLISM
• Drug EXCRETION

Question 7

Define drug absorption.

Answer 7

The movement of a drug from the site of administration into the blood.

Question 8

Define drug distribution.

Answer 8

Once in the blood, the movement of drugs throughout the body.

Question 9

DRUG METABOLISM

• also known as…
• define, give primary organ

Answer 9

• AKA Biotransformation.
• The enzymatic alteration of drug structure. Done by and large by the liver. For most drugs this is the first step in their excretion.

Question 10

3 routes of drug administration

Answer 10

1) Enteral (orally or g-tube)
2) Parenteral (skin, inhaler, etc)
3) IV (absorption process is skipped with this one– straight to the blood.)

Question 11

Liver excretes to _______

Kidney excretes to _______

Answer 11

Bile, urine.

Question 12

3 drug characteristics that affect pharmacokinetic movement

Answer 12

• Lipid solubility
• Ionization
• Protein binding

Question 13

LIPID SOLUBILITY

• Define
• Pharmacokinetic parameters affected (2)

Answer 13

• A measure of the ability of a drug to dissolve in water verses lipid.
• Effects…
  1) Membrane diffusion
  2) ADME (Absorption, distribution, metabolism, excretion)

Question 14

IONIZATION (Pka)

• Define
• Pharmacokinetic parameter affected

Answer 14

• When drugs are charged. Acidic drugs are ionized in basic solutions and basic drugs are ionized in acidic solutions.
• Effects RATE and LOCATION of drug absorption.

Question 15

PROTEIN BINDING

• Define
• Pharmacokinetic parameter affected (3)

Answer 15

• The extent to which a drug binds to plasma proteins

- Effects distribution, metabolism and excretion.

Question 16

Define Bioavailability

Answer 16

The fractional extent to which a dose of drug reaches the blood stream and its site of action. (Eg if you take 100mg of teh drug and it has a bioavailability of 50%, that means that only 50 mg is going to hit the bloodstream.)

Question 17

Bioavailability is usually talking about what route of administration?

Answer 17

Oral

Question 18

Bioavailability depends on (3) factors

Answer 18

1) Physiochemical properties of the drug
2) Route of administration
3) Metabolic or excretory capacity by the liver or intestines for the drug.

Question 19

What are 3 types of patients whose bioavailability you really want to pay attention to?

Answer 19

• Infants
• Elderly
• Liver compromised

Question 20

Characteristics of ORAL administration

• Drug absorption
• Advantages
• Disadvantages

Answer 20

• Absorption is variable and can depend on many factors
• Pro: Most convenient and economical, often also the most safe.
• Con: Requires patient compliance. Bioavailability can be erratic and incomplete.

Question 21

Characteristics of INTRAVENOUS administration

• Drug absorption
• Advantages
• Disadvantages

Answer 21

• Bypasses absorption. Potential immediate effects – suitable for large volumes and irritating substances.
• Valuable for emergency use, permits titration.
• Increased risk of adverse side effects.

Question 22

Titration

Answer 22

Method of drug administration where you are giving someone an individual dose based on the particular therapeutic target you want. You can really only do this with an IV drug.

Question 23

Characteristics of SUBCUTANEOUS administration

• Drug absorption
• Advantages
• Disadvantages

Answer 23

• Absorption can be prompt or slow depending on drug preparation, can be affected by changes in blood flow to tissue.
• Suitable for self-administration
• Not suitable for large volumes, possible pain or necrosis as site.

Question 24

Characteristics of INTRAMUSCULAR administration

• Drug absorption
• Advantages
• Disadvantages

Answer 24

• Absorption can be prompt or slow depending on drug preparation, can be affected by changes in blood flow to tissue.
• Suitable for self-administration
• Contraindicated with anticoagulants (because there is a potential for more bleeding)

Question 25

2 characteristics of SUBLINGUAL administration

Answer 25

- Absorbed via oral mucosa | - Bypasses the liver

Question 26

3 characteristics of TRANSDERMAL administration

Answer 26

- Absorbed through intact skin - Drugs are usually highly lipid soluble - Compromised skin integrity can greatly affect absorption

Question 27

3 characteristics of RECTAL administration

Answer 27

- 50% of drugs absorbed via the rectum will bypass the liver - Absorption can be irregular and incomplete. - Some drugs may irritate the rectal mucosa

Question 28

3 characteristics of INTRA-ARTERIAL administration

Answer 28

- Administration requires great care - Can help localize drug effects (very dilute by the time drug passes to the rest of the body) - Bypasses liver

Question 29

2 characteristics of INTRATHECAL administration

Answer 29

- Drugs administered into CSF (in spinal subarachnoid space or brain intravenous space) - Bypasses BBB

Question 30

5 characteristics of INHALED (pulmonary absorption) administration: - Absorbed through what? - Used mostly for ______ and _________ - Speed of absorption - Bypasses _______ - Provides local application for what organ?

Answer 30

- Absorbed through pulmonary epithelium and mucous membranes of the respiratory tract - Used mostly for gases and aerosolized droplets - Almost instantaneous absorption - Bypasses liver - Provides local application when lungs = target

Question 31

3 characteristics of TOPICAL application

Answer 31

- To mucous membranes - Usually for local effects - Only occasionally systemically absorbed

Question 32

Drug distribution is dependent on 4 physiological factors:

Answer 32

- Cardiac output - Regional blood flow - Capillary permeability - Tissue volume

Question 33

Drug distribution is dependent on 3 physiochemical properties:

Answer 33

- Lipid solubility - pH partitioning - Drug binding to plasma proteins and / or tissue macromolecules

Question 34

What is pH partitioning?

Answer 34

Sometimes a drug will cross the membrane in an un-iodized form, then becomes iodized in that place and cannot leave that space.

Question 35

What is sequestration, in talking about drug distribution? +example

Answer 35

When a drug enters into a certain tissue type and sort of lingers. That tissue becomes a reservoir for that drug, thus changing the distribution aspects. Example: PROSAC is relatively fat-soluble, so it has a high level of sequestration, meaning that it takes a few weeks for a patient's blood levels to climb to therapeutic levels.

Question 36

Usually, the metabolism of drugs causes inactivation. If the metabolism of a drug causes ACTIVATION, the drug is called a ______.

Answer 36

Prodrug

Question 37

For most drugs, metabolism involves ___________ reactions that generate more polar inactive metabolites that are more readily excreted from the body.

Answer 37

Biotransformation

Question 38

Enzyme systems for drug metabolism are found primarily in the (1). Other sites of metabolism include (2), (3), (4)

Answer 38

1) Liver 2) GI Tract 3) Kidneys 4) Lungs

Question 39

Superfamily of liver enzymes responsible for biotransformation of the vast majority of drugs.

Answer 39

The Cytochrome P-450 Superfamily

Question 40

Drug tolerance happens at one of two places.

Answer 40

1) The site of action | 2) The site of metabolism (ie the liver ups its game)

Question 41

Basis for drug-drug interactions (5):

Answer 41

- Drug inducers vs. drug inhibitors - Common inducers and inhibitors - Drug tolerance and cross-tolerance - Inter-individual variation in metabolic capacity for certain drugs - Metabolic activation of chemicals to toxic and carcinogenic derivatives

Question 42

What is cross-tolerance?

Answer 42

Pt builds tolerance for one drug and subsequently has tolerance for similar drugs

Question 43

Usually, _________ are eliminated in their unchanged form, and ________ are eliminated in an inactive form (after biotransformation

Answer 43

Water soluble drugs | Lipid soluble drugs

Question 44

- 3 most common drug excretion routes | - 5 other drug excretion routes

Answer 44

- Renal, biliary, fecal | - Seat, saliva, tears, breastmilk, lungs

Question 45

Considerations of the renal excretions of drugs (4):

Answer 45

- Lipid solubility - Organic anions and cations - Renal blood flow - GFR (Glomular Filtration Rate) and urinary output

Question 46

What is the fundamental tenet of clinical pharmacokinetics?

Answer 46

A relationship exists between the pharmacological effect of a drug and the accessible blood or plasma concentration of that drug.

Question 47

Four important parameters of pharmacokinetics:

Answer 47

- Bioavailability - Volume of distribution - Clearance - Elimination half-life

Question 48

With a long half life, it takes a ______ time to get a steady dose.

Answer 48

LONGER

Question 49

What is a loading dose?

Answer 49

You jack up the dose to get effects sooner, then lower it to a maintenance dose.