Pharmacokinetics Flashcards
Define Pharmacokinetics
What the body does to a drug.
It has four properties which are:
Absorption= transfer of drug from the site of administration to the bloodstream
Distribution
Metabolism
Elimination
Define Pharmacodynamics
This what the drug does to the body
What are the routes of drug administration
Enteral=oral, sublingual, transbuccal, intraduodenal
Parental= intravenously, Subcutaneous, intramuscular, oral inhalation, nasal inhalation ,
Define Absorption
Describe the mechanism of absorption of drugs from the GI tract
drug into the blood plasma, during this stage the drug crosses the cell membranes
Passive diffusion= Drug moves toward the concentration gradient, from a high concentration to a lower concentration. This is namely lipid soluble drugs.
Facilitated Diffusion=Drug enters the cell via drug transporters from an area of an high concentration to a low concentration. this process does not require ATP
Active transport= Carrier proteins are used to transfer bigger molecules such as sugar, ions, aminoacids, pyrimidines. This process works against the concentration gradients and uses ATP
Endocytosis/Pinoytosis= involves engulfment of a drug molecule by the cell membrane and transport into the cell by pinching off the drug to form vesicle. B12 is an example of this. This is for larger molecules
Exocytosis= The cell secretes the vesicle out of the cell. For larger molecules
Define Distribution
Drug leaves the blood stream and enters the extracellular fluids and then the tissues
Define Elimination
Inactivation +Excretion of the drug from the body
Describe first-pass metabolism
This is when the drug is administered orally and passes through the liver, when some of the drug is metabolised first before reaching the rest of the body . This does not happen with IV medications.
List the factors influencing absorption
1 Chemical structure 2 water/lipid-soluble 3 pH of drug 4 route of administration 5 type of medication 6 Blood flow to the absorption site 7 The surface area of the absorption site 8 Contact time at the absorption site 9 Bioavailability
Define Bioavailability
The amount of administered drug which enters the systemic circulation
Why is it important to understand the drug Bioavailability
This is to calculate the drug dosage for intravenous routes
Calculation= Oral intake/ Iv intake * 100
List the factors affecting bioavailability
1 First-pass hepatic metabolism
2 Chemical instability
3 Solubility of the drug
4 Nature of the drug formulation
Factors influencing distribution
1 Blood flow to the tissues, is due to the unequal distribution of the cardiac output. Such organs with high blood flow are the brain, kidneys and liver.
2 Capillary permeability, in the brain, the capillaries of the blood-brain barrier, are closely fused together, this mean drugs cannot pass through. This is different compared to organs such as the liver and spleen where there is a higher capillary permeability.
3 Binding of plasma proteins and tissue proteins i.e Albumin this is reversible, however, slows down the process of drug distribution.
4 Hydrophobicity
Define biotransformation/ metabolism
This is the process of detoxifying
breaking down the drug to become more polar so it can be removed from the system
List the reactions of Phase 1 reaction
Describe the process of phase 1 drug metabolism
Oxidation, Reduction and hydrolysis reaction
These reactions are important as it converts hydrophobic compounds into more water-soluble (polar ) by adding a hydroxyl group O-H or amine group NH2 so that it can be excreted.
Hepatic cytochrome P450 system is very important in oxidation reaction
Oxidation reaction is the most common reaction
Which organ primarily takes part in Phase 1 drug metabolism
Liver
Other organs include the kidneys, lungs, glands
Describe phase 2 reaction
This is called a conjugation reaction, as the drug from phase 1 are still too lipophilic thus cannot pass through the kidneys, so reactions with endogenous substrate is needed.
Glucuronic acid, sulfuric acid , amino acids, methyl and acetyl
[Note: Drugs already possessing an –OH, –NH2, or –COOH group may enter Phase II directly and become conjugated without prior Phase I metabolism.] The highly polar drug conjugates may then be excreted by the kidney or in bile.
Define excretion
This is the process by which the drug leaves the body
List the different ways in which drugs are excreted
Urine bile breast milk saliva sweat glands air
Outline the process of drug elimination
Which organ primarily involves the elimination of drugs
The kidneys are the main organ which eliminates drugs. The drug has to be ionised and polar so that the drug will remain in the kidneys and not reabsorbed in the distal tubules.
The drug enters the glomerular filtration passes through the proximal tubules ….
Define half-life
This is the amount of time for the drug to reach half of its concentration
Define clearance
The volume of plasma that is removed from the drug per a minute
calculated - drug metabolising and drug eliminated organs
Define volume of distribution
theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.[
Define Stead y-state concentration
This is the plasma concentration of a multiple dosed or continuously infused drug when the drug will accumulate until-the amount administered per unit time is equal to the amount eliminated per unit time.
