Pharmacokinetics and drug metabolism Flashcards
Outline the journey of a drug through the body
Absorption
Distribution
Metabolism
Excretion
(removal)
Examples of routes of administration (6/7)
Dermal, Intramuscular, Subcutaneous, Intraperitoneal, Inhalation, Ingestion (Intravenous)
Define systemic
The entire organism
Define local
Restricted to one area
Define enteral
Gastro-intestinal administration
Define Parenteral
Outside the gastro-intestinal tract
What are the 2 ways drugs enter the systemic circulation?
Bulk flow transfer = in the blood
DIffusional transfer = molecule by molecule over a short distance
Examples of aqueous compartments
blood, lymph, extracellular fluid, intracellular fluid
Example of lipid barriers
cell membranes (epithelium/endothelium)
Outline area of bulk flow, diffusion and barriers (absorption)
What substances can penetrate a lipid membrane and why?
Non-polar substance, they can dissolve in non-polar substances and won’t interact with the membrane
True or False?
Most drugs are either strong acids or weak bases
False
They are weak acids or weak bases
What does the ratio of polar and non-polar forms of a drug depend on
The pH
(ionised = polar, non-ionised = non-polar)
What factors influence drug distribution? (4)
>Regional blood flow
>Extracellular binding (plasma protein binding)
>Capillary permeability (tissue alterations - renal, hepatic, brain/CNS, placental)
>Localisation in tissues
What do highly metabolically active tissues display?
Denser capillary networks
(Increase blood flow, increase removal of waste products and delivery of O2)
Outline the effect of plasma protein binding on drug distribution
Acidic drugs = 50-80% bound to plasma proteins
If there is a high binding percentage, less is freely transported in the blood, therefore, there’ll be less of the drug available to have an effect
Where are the 2 main areas of drug excretion?
Kidneys = responsible for the elimination of most drugs
Liver = some drugs are concentrated in the bile (large molecular weight conjugates)
What is transported at the glomerulus, proximal tubule and the proximal/distal tubules
Glomerulus = drug-protein complexes are not filtered
Proximal = active secretion of acids and bases
Proximal/distal = lipid-soluble drugs
Outline how drugs are excreted from the kidneys
Why might intravenous sodium bicarbonate increase aspirin excretion?
IV sodium bicarbonate = increae urine pH = ionse aspirin = less lipid soluble = less reabsorption from tubules = INCREASE excretion
Other than the liver and kidneys, what are other routes of excretion
Lungs, Skin, GI secretion, saliva, sweat, milk, genital secretions
What is enterohepatic cycling and what is the result of this?
The drug is excreted into the gut (through bile) then reabsorbed and taken to the liver where its excreted again
This can lead to drug persistence (the drug has a continued effect)
Define BIOAVAILABILITY
The proportion of the administered drug that is available within the body to exert its pharmacological effect
Links to absorption
Define APPARENT VOLUME OF DISTRIBUTION
The volume in which the drug appears to be distributed, an indicator of distribution patterns
Links to distribution
Define BIOLOGICAL HALF-LIFE
Time taken for the concentration of the drug in the blood/plasma to fall to half of its original value
Links to metabolism and excertion
Define CLEARANCE
Blood (plasma) clearance is the volume of blood cleared of a drug in a unit of time.
Related to the volume of distribution and the rate at which the drug is eliminated from the system
Links to excretion
Which drugs will be least likely to penetrate the lipid membranes?
Ionised drug, non-ionised, protein-bound drug, lipophilic drug, a hydrophilic drug
Ionised drug
Protein-bound drug
Hydrophilic drug
Which drugs will most likely be able to penetrate a lipid membrane?
Drug elimination kinetics:
What is C0?
concentration at time zero, this can’t be measured so it needs to be extrapolated
Drug elimination kinetics:
What is Vd?
Volume of distribution (Dose/C0)
This is the volume in which the drug is distributed and indicates the pattern of distribution
Drug elimination kinetics:
What is t0.5?
The half-life of the substance
Drug elimination kinetics:
What is Kel?
The elimination rate constant (slope of the line)
What is the order of the majority of drugs?
First order
What is first-order kinetics?
Calculate clearance of a first-order drug
The amount of drug decreases at a proportional rate to the concentration of the drug remaining in the body
Clearance = Vd x Kel
(Kel = Log2/t0.5)
What is zero-order kinetics?
Calculate clearance of a zero-order drug
The amount of the drug decreases at a rate that is independent of the concentration of the drug within the body
Clearance = time x Kel
(Kel = ðC/ ðt)
What does zero-order kinetic suggest?
Implies that there is a saturable (usually enzymatic) metabolic process
