Lecture 1 General Principles of Pharmacology

Question 1

List the routes of drug administration

Answer 1

Enteral (by the GI tract): Oral, Sublingual, Buccal, and Rectal
Parenteral (injections): Intravenous (IV), Intramuscular (IM), and Subcutaneous (SC)

Other: Inhalation, Transdermal patches, Topical (eye drops, ear drops, skin creams/etc.)

Question 2

First pass effect

Answer 2

initial metabolism of the drug in the liver before the drug reaches systemic circulation.
This reduces the amount of active drug that can reach the bloodstream.

The first pass effect affects the oral route of administration the most because drugs go straight from the stomach/intestines to the liver via the portal vein.

Other routes can be partially affected by it such as inhalation or rectal.

Question 3

Which routes undergo first pass effect?

Answer 3

Oral, rectal and inhalation (partial first pass effect)

Question 4

Which route allows 100% bioavailability of the drug?

Answer 4

Intravenous (IV) – immediate onset of action, works most rapidly in emergencies

Question 5

Pharmacokinetics vs pharmacodynamics

Answer 5

how the drug passes through the body (ADME) vs how the drug interacts with the body (at its targeted receptor)
ADME = Absorption, Distribution, Metabolism, Excretion

Metabolism: how the body chemically modifies the drug into metabolites (active or inactive molecules); occurs primarily in the liver when talking about systemic drugs
Excretion: kidney is the most common, but can also occur in bile/defecation, sweat, breast milk, tears, saliva, lungs

Question 6

List the factors that allow drugs to move most easily through cell membranes to get into the bloodstream

Answer 6

Size (smaller more easily pass) 
Ionization (non-ionized/non-polar more easily pass)
Lipophilicity (lipophilic, hydrophobic, lipid soluble more easily pass)
Concentration gradient (higher dose/concentration allows easier/faster rate of diffusion) 
Surface area (increased surface area, easier to pass)

Note: ionized forms are polar/hydrophilic/water soluble, so they do NOT pass through cell membranes (lipid membranes do NOT let molecules through that are large or charged).

Question 7

What mechanism do most drugs move through membranes (passive diffusion, active transport, facilitated diffusion, or endocytosis/bulk flow – uses ATP)?

Answer 7

Passive diffusion

Question 8

Explain why most systemic drugs are weak organic acids and weak organic bases

Answer 8

chemically, this allows the drug to exist in two different forms: ionizedd and non-ionized forms, with the amount of each form depending on the pH of the environment they are in.

ex. a drug that is a weak acid will have a higher ratio of non-ionized form in an acidic environment to pass the stomach membranes
ex. a drug that is a weak base will have a higher ratio of non-ionized form in a basic environment to pass the intestine membranes.

Question 9

Endogenous, Exogenous, Bioavailability, Prodrug

Answer 9

Endogenous–substances made outside of the body; exogenous–substances made outside the body
Bioavailability–amount of administered dose of a drug that reaches the systemic bloodstream
Prodrug–inactive compound that can be converted to an active form by enzymes

Question 10

What is the calculation representing the drug’s propensity to remain in the bloodstream (plasma) or to redistribute to extravascular compartments?

Answer 10

Volume of Distribution

Question 11

What does a low and high Vd (volume of distribution) suggest?

Answer 11

Low indicates the drug is staying in the bloodstream

High indicates the drug is distributed to other extravascular compartments in the body

Question 12

Which order of kinetics is dependent on drug concentration? Note: a higher drug concentration will result in a higher elimination rate.

This first order elimination kinetics is also the most common in drugs.

Answer 12

First Order Elimination Kinetics

Question 13

Which order of kinetics is not dependent on drug concentration–resulting in a constant elimination rate?

Answer 13

Zero-Order Kinetics

ex. Alcohol

Question 14

A measure of the body’s efficiency in eliminating the drug from systemic circulation–takes into account Vd and t 1/2 (half-life)

Answer 14

Clearance

Question 15

List the organs with a high blood flow

Answer 15

GI tract, kidneys, liver, lungs, brain, and eye

Question 16

Define the Blood-Brain-Barrier (BBB)

Answer 16

contains capillary endothelial cells with tight junctions which are surrounded by astrocytes, creating an extra semi-permeable barrier that protects the brain from foreign/toxic substances. This makes the BBB less permeable to drugs than most other parts unless they are very fat soluble.

Question 17

List 5 tissues/places where some drugs can accumulate in the body

Answer 17

Muscles, fat, teeth, bones, and blood

Question 18

What is the main goal of metabolism? In what organ does metabolism of systemic drugs primarily take place?

Answer 18

The main goal of metabolism is to make the drug hydrophilic for filtration/excretion in the kidneys.

The liver.

Question 19

Pharmacodynamics: Define Agonist, Full Agonist, Partial Agonist, Antagonist

Answer 19

Agonist – drug that binds and activates a receptor
Full Agonist – drug that binds and activates a receptor that produces a maximal response
Partial Agonist – drug that binds and activates a receptor lower than the maximal response, no matter how much of the drug is given
Antagonist – drug that binds to a receptor but doesn’t activate it. The antagonist drug blocks/inhibits/prevents the binding and actions of agonists.

Question 20

Describes the tendency for a drug to bind to a receptor, or how tightly a drug binds to the receptor.
Note: BOTH agonists and antagonists have this toward a receptor

Answer 20

Affinity

Question 21

A measure of the amount (concentration/dose) of a drug that is required to achieve a desired effect.

The less drug that is needed to produce an effect, the more _____the drug.

Answer 21

Potency ; potent

Question 22

Effective Dose 50 (ED 50)
Toxic Dose (TD 50)
Lethal Dose (LD 50)

Answer 22

the dose of a drug that produces 50% of its maximum response

the dose of a drug at which 50% of the population experiences a toxic effect

the dose of a drug that is expected to produceg 50% mortality in a population

Question 23

The margin of safety between the dose which can provide the maximum therapeutic effect and when unwanted adverse effects begin. The wider the range, the safer the drug is to administer. The narrower the range, the more dangerous the drug.

Answer 23

Therapeutic Index

Question 24

Therapeutic Index Formula

Answer 24

TD / ED

Question 25

Does an agonist have both affinity and efficacy? What about an antagonist?

Answer 25

Yes;

An antagonist ONLY has affinity, but NOT efficacy because an antagonist doesn’t activate a receptor.

Question 26

Describes the maximum response (effect) of a drug when it binds to a receptor

Answer 26

Efficacy