Lecture 5

Question 1

Key Concept

Answer 1

Active drugs must reach the drug target at sufficient concentrations and for sufficient duration to achieve desired biologic effect.

Question 2

Steps Drug must take to be Absorbed (2)

Answer 2

1. Absorption - movement into the bloodstream or lymphatic system
2. Distribution - movement from blood to tissue
   Exceptions: drugs intended for only local effects or injected directly into blood

Bioavailability, distribution, and absorption are all linked

Question 3

Absorption Key Points (4)

Answer 3

1. Drug must move from site of administration to site of action
2. There are membrane barrier drug must pass to reach action site
3. Drug properties dictate movement through membranes
4. Specialized transport properties also dictate drug movements

Question 4

Bioavailability

Answer 4

Definition: fractional extent to which a dose of drug reaches its site of action or biological fluid (usually blood) from which drug has access to its action site

• Function of anatomical site from which absorption takes place
• Anatomical, physiological, and pathological factors also influence bioavailability
• Therefore, routes of administration have a direct effect on bioavailability

Question 5

Routes of Admin + % in Systemic Circulation

Answer 5

IV - 100%
Transdermal - 80-100%
Subcutaneous - 75-100%
IM - 75-100%
Oral, rectal, and inhalation = highly variable

Oral is highly dependent on first pass metabolism

ROUTES INFLUENCE HOW QUICKLY A DRUG REACHES ITS TARGET AND IF IT IS DISTRIBUTED BROADLY OR LOCALLY

Question 6

First Pass Metabolism

Answer 6

• Drugs that enter GI go through portal vein and the liver before reaching systemic circulation
• This can significantly reduce drug’s bioavailability
• Portal vein also takes nutrients to liver, reason why drugs must go through this first pass as well

Question 7

Enteral

Answer 7

• Intestine administration
• Placement of drug directly into ANY part of GI
• Includes oral, sublingual, and rectal

Question 8

Parenteral

Answer 8

• Non-intestine administration

- Includes injection (IV, IM, SQ), topical, and inhalation

Question 9

Main factors affecting absorption & distribution are… (2)

Answer 9

1. Amount of blood flow
2. Rate of blood flow

SA also an important determinant of uptake

Question 10

Parenteral Pros (3)

Answer 10

1. Necessary for certain drugs (Ex: TNF-alphas)
2. Bioavailability typically is more rapid, extensive, and predictable (effective dose can be delivered more accurately)
3. May be necessary if oral isn’t an option for patient

Question 11

Parenteral Cons (3)

Answer 11

1. Greater infection rate, especially when done over extended periods of time
2. May be painful
3. May be difficult to self inject if it is needed

Question 12

Enteral Site of Administrations

Answer 12

Differ by the following factors:

• Saliva (mouth)
• pH (stomach)
• Mucus (stomach and intestine)
• Enzymes
• Microbes (intestine)

Question 13

GI Absorption Factors

Answer 13

-Most occurs in the small intestine, rate depends on ionization and lipid solubility
Factors: site of GI tract (pH), GI motility, blood flow, particle size and formulation, GI enzymes, gut flora and other gut content

Question 14

Bioavailability

Answer 14

The fractional extent to which a dose of drug reaches its site of action or a biological fluid from which the drug has access to its site of action.

Question 15

First Pass Effect

Answer 15

Decrease of bioavailability as a consequence of hepatic metabolism and excretion

Question 16

Absorption

Answer 16

Movement of a drug from its site of administration into the central compartment (typically bloodstream, see Figure slide 4)

Question 17

Distribution

Answer 17

Movement from the blood into the tissue and interstitial spaces.

Question 18

Enteral

Answer 18

Drug administration into any part of the GI tract

Question 19

Parenteral

Answer 19

Administration other than the GI tract

Question 20

Enteric

Answer 20

Being or possessing a coating designed to pass through the stomach unaltered and to disintegrate in the intestines