Session 11 ILOs - Pharmacodynamics

Question 1

Recognise main routes of drug administration into the body

Answer 1

Mneumonic - Oh T*ts, it is sir:

Oral
Transdermal

Intramuscular
Topical

Inhalation
Sublingual

Subcutaneous
Intravenous
Rectal

Question 2

List some factors affecting drug Absorption

Answer 2

Absorption is mainly in the Small Intestine

Physicochemical factors:

• Length of the SI
• Transit time
• Drug lipophilicity / pH

GI physiology:

• Motility
• Food pH
• Blood flow

First Pass Metabolism

• The process of drug metabolism by the liver by phase 1 and phase 2 enzymes, before the drug has even reached the systemic circulation = reduces the availability of the drug int he systemic circulation
• Gut lumen so gut or bacterial enzymes can denature some drugs
• Gut wall or liver where drugs are metabolised by 2 major enzyme groups: cytochrome P450s (phase 1) and conjugating enzymes (phase 2)

Question 3

Understand factors affecting drug Metabolism and Excretion

Answer 3

• Age
• Sex
• General Health/Dietary/Disease - especially hepatic, renal or CVS as it reduces the functional reserve
• Other drugs (can induce or inhibit CYP450s)
• Genetic variability (which affects CYP450s)

Question 4

Understand difference between Linear and Non-Linear Kinetics

Answer 4

Linear Kinetics:

• Where the rate of metabolism/excretion is proportional to plasma concentration of the drug
• Only if there are plenty of phase 1/2 enzymes or OAT/OCT transporters available

Non-linear Kinetics:

• Where the rate of metabolism/excretion is NOT proportional to plasma concentration
• Could start off as linear, however after you increase the dose enough, it becomes zero order elimination where drug metabolism is independent of drug dose due to saturated enzymes etc.
• Example is alcohol where relatively small increases in dose can lead to large increment increases in the plasma of the drug

Question 5

Explain the 3 ways in which drugs are absorbed (pass through the membrane) and give examples of which molecules move via this method

Answer 5

Passive diffusion

• Common for lipophilic drugs e.g. steroids
• Can be used by weak acids and weak bases (based on environment)

Facilitated diffusion
- Occurs via solute carrier (SLC) transport which is either through OATs or OCTs which are highly expressed in the GI tract, kidney or liver epithelia
- Used by molecules with a net charge within the pH range
(no clear examples)

Secondary active transport

• Uses a pre-existing electrochemical gradient
• E.g. Prozac/fluoxetine - co-transported with Na+ ions
• E.g. Penicillin - co-transported with H+ ions

Question 6

Define bioavailability and state what is used as a reference point

Answer 6

Bioavailability is the fraction of a defined dose which reaches a specific body compartment
IV bolus is used as a bioavailability reference at 100% bioavailability

Question 7

List some factors affecting drug Distribution

Answer 7

• Drug lipophilicity/hydrophilicity
• Capillary permeability
• Drug pKa and local pH
• Presence of OATs/OCTs
• Degree of the drug binding to plasma or other tissue proteins e.g. albumin (reduces the availability of binding at target site)

Question 8

State what the apparent volume of distribution (Vd) describes and outline a few factors which affect Vd

Answer 8

Apparent volume of distribution (Vd) is a model which groups all the main fluid compartments together as if they were one compartment

Factors affecting Vd:

• Changes in blood flow
• Renal failure
• Elderly/infant/cancer patients