Lecture 4 - Pharmacokinetics Flashcards
What are the 6 steps in the journey of a drug through the body?
Administration Absorption Distribution Metabolism Excretion Voiding
What does the acronym ADME define?
The 4 steps in the body the drug goes through Absorption Distribution Metabolism Excretion
What are the two different types of administration regarding the proportion of the body affected?
Systemic and Local
What do the terms systemic and local administration mean and what is the difference?
Systemic administration - the entire organism is exposed to the drug after administration
Local administration - drug exposure is restricted to one area of the organism
What do the terms “enteral” and “parenteral” mean in terms of administration?
Enteral - administration is via the GI tract
Parenteral - administration is via anywhere but the GI tract
What are the 7 different routes of drug administration?
Moving down the body: Inhalation Ingestion Intramuscular Dermal Subcutaneous Intravenous Intraperitoneal
What is the general aim of any form of administration of drug?
To get the drug into the bloodstream
What are the general paths of ingested and inhaled drugs into the bloodstream?
Ingestion - Drug enters GI tract, gets absorbed and taken to the liver, travels to the liver via hepatic portal system and then enters systemic circulation.
Inhalation - Lungs are well perfused, drug enters lungs then diffuses across pleural membrane into circulation.
What are the two ways drug molecules move around the body?
Bulk flow transfer - moves in bulk in the bloodstream to the tissues
Diffusion transfer - moves molecule by molecule over short distances
What are the two environments drugs have to traverse?
Lipid
Aqueous
What are barriers and compartments defined as in the body regarding environments?
Lipid environments = barriers
Aqueous environments = compartments
What are the drugs’ methods of crossing barriers inside the body?
Diffusing through lipid (if they are lipid-soluble)
Diffusing through aqueous pores in the lipid (if they are polar)
Carrier molecules
Pinocytosis (engulfing of the molecule and taking it in by the cell, not quite the same as endocytosis)
What are the preferable environments of polar and non-polar drugs?
Polar = aqueous environments Non-polar = lipid environments
What type of equilibrium do most drugs exist in and why is this?
Dynamic equilibrium, they exist in the body as both their polar (acid/base form) and their non-polar (neutralised) forms
What environmental features affect the ratio of polar (ionised) and non-polar (non-ionised)?
The pH of the environment
The pKa of the molecules
Is aspirin ionised or non-ionised in the stomach and why?
Non-ionised
Aspirin is an acidic molecule and has a pKa of 3.4. The stomach has a very low pH, around 1, which is much lower than the pKa of 3.4 thus the majority of aspirin molecules are non-ionised.
Is aspirin ionised or non-ionised in the small intestine and why?
Ionised
The pH is basic, 7+ in the small intestine and is higher than the pKa of 3.4.
Where is aspirin better absorbed and why?
Aspirin is much better absorbed in the stomach as a much greater proportion of the molecules exist in an unionised state, due to the low pH, allowing it to easily cross lipid membranes and enter the cells. Aspirin is absorbed in the small intestine but it is very slow due to a higher proportion of its molecules existing in an ionised state, due to the high pH, making it difficult for it to cross lipid membranes.
Why is both soluble and enteric-coated aspirin used?
Soluble aspirin is absorbed much more quickly since the majority of it is absorbed in the stomach very quickly due to its unionised form majority. e.g. treating headache fast
Enteric-coated aspirin is used to treat longer-term conditions as its coating survives the stomach acid environment and the aspirin is then slowly absorbed over a long period of time in the small intestine. e.g. treating arthritis
What is the concept of “ion trapping” and why is it useful?
When the drug enters the blood, it exists as both ionised and unionised molecules. The unionised molecules get “mopped up” or bound to proteins in the blood in a protein-drug complex while ionised molecules continue free. This means the drug is effectively “trapped” since it can only enter its target cells when in the free unionised form. This is useful in prolonging a drug’s half-life such as aspirin.
What are the four factors influencing drug distribution?
Regional blood flow
Extracellular binding (plasma-protein binding)
Capillary permeability
Localisation
Why does regional blood flow affect drug distribution?
Tissues with high perfusion rates are going to absorb drugs faster. Tissues may increase in perfusion when their activity increases e.g. skeletal muscle during exercise
Why does extracellular binding (such as to plasma proteins) affect drug distribution?
The body only absorbs free molecules so if the molecule is bound then it cannot be absorbed. The greater the degree of binding, the longer the half-life as it will take longer to absorb all the drug into the cells
Why does capillary permeability affect drug distribution?
The greater the capillary permeability, the better the drug is absorbed. Small water-filled gaps between endothelial cells lining the vessel allow ionised drug molecules (such as aspirin in blood) to pass through. Distribution can also depend heavily on the capillary architecture (fenestrated, continuous, discontinuous)
