Pharmacokinetics - What you should know Flashcards
What are the 4 factors which influence the fate of a drug in the body?
Size of molecule
pH
lipid solubility
ionisation of drug
What are the 9 major routes of drug administration?
Oral; IV; IM; Subcut: Intrathecal (epidural); Inhalation (NEB); Epithetial; Subling: Rectal
What is Oral administration, giving an example?
Via the mouth and GI tract
Most drugs; Aspirin, paracetamol, ibuprofen
What is IV administration, giving an example?
Injected directly into the bloodstream:
Anaesthetic - Thiopentone
Analgesic - Morphine sulphate
Antiemetic - Ondansatron
What is IM administration, giving an example?
Injected into the muscle
Adrenaline
What is Intrathecal administration, giving an example?
Injected into the subarachnoid space of the spine
Epidural - Bupivacaine in labour
What is Inhalation administration, giving an example?
Absorbed via the lungs
Analgesic - methoxyflurane
Bronchodilators - Salbutamol
What is Epithelial administration, giving an example?
Applied to membrane such as the skin
HRT - oestrogen patches
Nicotine patches
What is Sublingual administration, giving an example?
Under the tongue, absorbed by vasculature
Vasodilators - Glyceral Trinitrate (GTN)
What is Rectal administration, giving an example?
Applied via the rectum
Suppository - anti-inflammatory drugs for IBD
Factors affecting absorption from the GI tract
Ionisation and lipid solubility of the drug pH of the GI contents Metabolism drug during absorption Surface area for absorption GI motility First pass metabolism
Outline the concept of drug distribution
After absorption, it will distribute through body and enter tissues in varying amounts.
Fluid compartments are separated by membrane barriers
Distribution is dependant on lipid solubility and pH of body fluids.
How is distribution dependant on lipid solubility and pH of body fluids?
Higly lipid-soluble drugs distribute widley throughout body (Tricyclics)
Lipid-insoluble drugs will be distributed in plasma and intistitial fluids.
Define the term ‘volume of distribution’ and how it is calculated.
The degree of distribution of a drug in the body. Vd=Q/C
Q= total amount of drug in the body (mg/kg)
C= [plasma] mg/L
What is volume of distribution used for?
To determine where the drug will be distributed
Low level (.5) will store throughout the body tissue
Very high level (> total body fluid) stored in the fat
How does protein binding affect distribution?
-Degree of binding alters distribution
highly bound drugs will stay in the circulation (warfarin)
-It is Reversible
introduction of new highly bound drug will reduce original
-Prevent metabolism
prolong retention time in body
What is the importance of drug Metabolism?
- Has chemical changes which affect drug
- Most result in loss of pharmacological activity
- May result in; Increased activity; change in activity; produce toxic metabolite
- Increases drug solublity, making it easier to excrete
- Mainly done by hepatocytes.
Describe Phase I metabolic reactions
- Molecular structure changes
- Oxidation, reduction, hydrolosis reactions
- Forms more reactive product
Describe Phase II metabolic reactions
- Conjugate formed between drug and Phase I metabolite
What are examples of Conjugates?
Glucuronic acid Sulphate Amino Acids Methyl Groups Acetyl Groups
What are the Metabolic actions of Pro-drugs?
- Inactive in initial form
- Metabolised to anactive form
- Usually Phase I reaction
Give an Example of a pro-drug
Enalapril - vasodilator
Hydrolysed into active form “enalaprilat”
What are the effects of drug-induced changes in rates of drug metabolism?
- Induce or inhibit production of enzymes in liver.
- Alters rate that drugs are metabolised
- Alter therapeutic effects
- Toxicity of metabolites enhanced
