Pharmacology - Foundation Flashcards
Pharmacokinetics
It is how the drug gets to its site of action. Considerations: What form should the drug be in? Where do you put it? How much is needed? How often does it need to be taken?
What are the four factors that need to be considered when making a drug?
Administration, absorption, distribution and elimination
What is administration?
How the drug is given to the patient?
It can be given orally, subcutaneous, intravenous, rectal, etc…
What are the factors that may influence the choice of route of administration?
Patient convenience: If it is more convenient for the patient then they are more willing to take it regularly or for the course of their treatment (patient compliance).
Cost: Drugs that are cheaper are more readily accessible to more patients. Need to take into consideration the cost of preparation for how the drug is administered (e.g. need for sterility for injectable drug).
Bioavailability: When the drug is administered, it can be metabolised by a number of different pathways that will affect much of the drug makes it to the site of action. Intravenous drugs may require less of the drug as it is not metabolised through first-pass metabolism in the liver compared to oral drugs.
Local vs systemic: Some drugs will act on various site around the body compared to others. Route of administration may reduce the side effect of the drug to other sites of the body that are not needed. Can reduce concentration of drug if administration is local compared to systemic
Types of route of administration
Oral: tablets/capsule/suspension (liquid form)
Skin: nicotine patches/ external creams/ ointment
Lungs: gaseous general anaesthetic
Nose: cocaine
Rectum antibiotics
Injectable: Subcutaneous (under the skin, e.g. insulin - protein would be broken down by enzymes if given orally), intramuscular (into muscle, e.g. penicillin G - stomach acid would break it down), Intravenous (diazepam - for status epilepticus, doesn’t require absorption)
Rapid IV administration
Fastest route, avoids absorption, drug distributes rapidly and reaches equilibrium state the fastest, drug behaves as if in a single compartment, most drugs eliminated at a rate that is proportional to the concentration of the drug in the plasma (fastest elimination rate - first order kinetics)
Drug distribution
Driven by circulation (therefore would not work if person is dead). It is rarely uniform but occurs rapidly.
Steps
1. Drug is diluted by the blood.
2. Drug moves into the extracellular fluid (only drugs that are able to escape the vasculature - small/organic/not protein bound)
3. Binds to cells/taken up into cells (requires specific binding, usually lipid soluble)
Factors that influence drug distribution
Molecular size of the drug: smaller makes it easier for drug to move out of vasculature
Ability to bind to plasma protein: will freely move into extracellular fluid if not bound
Lipid solubility: easier to cross cell membranes (too much —> taken up into lipids and be sequestrated into lipids)
What is the volume of distribution?
“Volume of body water in which a drug appears to be dissolved in after it has distributed throughout the body” —> this give the apparent volume, not real volume
V(d) = X/C, where X is the amount in body and C is the concentration in plasma
What are the factors determining the volume of distribution?
Amount of drug that binds to plasma protein: greater concentration appears in plasma, the smaller the volume of distribution is
Drug elimination
Term used to describe the rate at which the drug disappears from the blood.
Elimination can occur by: excretion (primarily by kidneys - physical expulsion of the drug from the bloodstream) and metabolism (primarily by the liver - chemical change)
Usually drug is eliminated by a combination of both
Process of excretion by the kidneys
Three steps involve:
1. Glomerular filtration: drug move into the Bowman’s capsule due to leaky vessels (removed from blood stream) - passive filtration that is limited by glomerular filtration rate. Only occurs for drugs not bound by plasma proteins
- Tubular secretion: active process where drug is taken out of blood by active carrier (can remove protein bound drugs but this process can be competitively inhibited - probenecid)
- Tubular reabsorption: passive movement of drugs re-entering the bloodstream by diffusing across the cell membrane of the tubule and peritubular capillary (process is pH dependent - can be manipulated, e.g. aspirin overdose)
How do drugs cross cell membranes?
Most drugs move across the membrane via simple diffusion, driven by a concentration gradient. However this only applies to drugs that are soluble in lipids (lipid solubility of a drug).
Lipid solubility can be manipulated by pH. Most drugs are usually a weak acid/base so that when they are placed in a solution, drug become ionised. When uncharged, drug is more lipid soluble - able to move across membranes more easily. When charged, lipid solubility is reduced.
Example: acidic drugs get taken into cells in low pH (more acidic solutions) while basic drugs get into cells more at higher pH (more basic solutions)
Drug metabolism
Drug metabolism is the biotransformation of a drug. This involves a chemical change to a drug which normally includes enzyme-catalysed reactions. Process usually occurs in most tissues but mainly in the liver. Process try to increase water solubility of the drug to facilitate in its excretion
Phase I metabolism
Involves adding a chemical functional group onto the drug (e.g. hydroxyl, carboxyl)
Cytochrome p450 is responsible for many phase I drug metabolism reaction. It belongs to a superfamily of enzymes. It’s action can be inhibited or enhanced by drugs - leads to drug-drug interaction
