Absorption, Distribution (and drug delivery systems)

Question 1

List the factors that affect absorption of a drugs from the GI tract.

Answer 1

Solubility
Gastric emptying time
pH change throughout gut
Gut flora
First pass metabolism
Illness

Question 2

Discuss the medical importance of first pass metabolism.

Answer 2

First pass metabolism is important clinically because it can reduce the bioavailability of a drug - meaning that less of that drug makes it to the systemic circulation, this then means there is a need for a higher dosage.
It can also help decrease the toxicity levels by metabolising the drug before it reaches the systemic circulation.
If the first pass metabolism is impaired this can lead to:
- Increased bioavailability and toxicity
- The need to adjust the dosage - to prevent adverse effects.

Question 3

Describe first pass metabolism

Answer 3

First pass metabolism is essentially the initial metabolism that happens to a drug primarily in the liver and, to a lesser extent in the gut wall, for example, before it reaches the systemic circulation.

Question 4

Discuss the benefits of intravenous medication.

Answer 4

This kind of medication has no need for absorption, and still ALL of the drug makes it into the bloodstream.
Has an immediate onset, 100% bioavailability, no first pass metabolism, accurate dosing.

Question 5

Discuss the benefits of topical medication.

Answer 5

This kind of medication is not intended to reach the systemic circulation - so is not absorbed:
This,
Reduces “off-target” adverse effects.
Reduces exposure beyond site of action

Question 6

Describe the benefits of inhaled medication

Answer 6

Inhaled medication provides a rapid delivery.
This route allows for lower dosage as there is no first pass metabolism or contact with the systemic circulation - reducing side effects.
Non-invasive.

Question 7

Describe what is meant by bioavailability.

Answer 7

Bioavailability is the extent and rate at which the drug reaches its site of action.

Question 8

Describe the factors that effect bioavailability.

Answer 8

-First pass metabolism
-Gastric emptying
-GI pH
-Enzymatic activity
-Perfusion
-Protein binding…
Protein binding is important in bioavailability as it determines the amount of free (available) drug in the blood stream - this affects the drugs immediate pharmacological activity.
-Albumin
-Alpha1-acid glycoprotein
-Lipoproteins

Question 9

Define Cmax

Answer 9

Cmax is the maximum plasma concentration achieved of a drug after entering the circulation - indicating the peak exposure of drug in the body.

Question 10

Define Tmax.

Answer 10

This is the time taken to get to Cmax - the peak exposure of drug in the body.
This provides information about the rate of drug absorption.

Question 11

Define AUC.

Answer 11

Area under the curve.
This indicates the total exposure to the drug.

Question 12

Define zero order and first order.

Answer 12

Zero order indicates that the rate of drug ADME is constant and does not depend on concentration.
First order indicates that the rate of drug ADME is proportional to the drug concentration.

Question 13

Define T1/2

Answer 13

The half-life of a drug refers to the time it takes for the drug to decrease to half its initial concentration.
Is clinically important for dosing intervals, steady-state concentration and the time for drug clearance after stopping treatment.

Question 14

Define Vd

Answer 14

This is the volume of distribution of a drug.
Can be real (physiological) or apparent (theoretical).
Real - Based on total water content of body in which drug is dissolved.
Apparent - Proportionality constant between total amount of drug in the body and the amount of plasma at any one time.
The volume of distribution is used to determine the loading dose.
Drugs with a higher volume of distribution, tend to have a longer half-life.

Question 15

Define clearance.

Answer 15

Clearance refers to the amount of drug cleared by the body per unit of time.
It is a measure of efficacy of the body (in organs e.g. liver, lungs, kidney) in eliminating the drug.
Important clinically: Clearance helps to determine the maintenance dose required to achieve an steady therapeutic concentration.

Question 16

Describe the blood-brain barrier as a barrier to drug distribution.

Answer 16

The BBB is a semi-permeable, highly selective barrier that regulates the entry of substances into the brain from the bloodstream.
It has tight-junctions (epithelium).

Question 17

Describe the placenta as a barrier to drugs.

Answer 17

The placental barrier is a semi-permeable membrane between the maternal and foetal blood streams that facilitates which drugs - if any - are passed from the mother to the child.
It is selectively permeable - lipophilic drugs are more likely to cross than hydrophilic drugs, other characteristic of drugs can also determine their passage: molecular size and protein-binding.
The mechanisms of passage across the placental barrier include:
- Active transport
-Facilitated diffusion
-Passive diffusion.

Question 18

Describe the testis as a barrier to drugs.

Answer 18

The blood-testis barrier is a highly selective, semi-permeable barrier protects sperm cells from the effects of drugs and other threatening molecules and situations:
The BTB protects developing sperm cells from toxins, immune responses and fluctations in the blood environment.