Pharmacokinetics Flashcards
What is pharmacokinetics?
The movement of drugs in and the alteration of the drug by the body
List the pharmacokinetic processes?
Absorption
Distribution
Metabolism
Elimination
List the pharmacokinetic variables?
Bioavailability
Volume of distribution
Half life
Clearance
Absorption is to?
Bioavailability
Distribution is to?
Volume of distribution.
Metabolism is to?
Half life
Excretion is to?
Clearance.
What is absorption??
Movement of drugs from site if administration to systemic circulation.
What are the factors that affect absorption?
- Biological membranes
- Lipid-water solubility
- Physical/dosage forms
- Molecular and particle sizes
- Concentration
- Degree of ionisation and pH
- Chemical nature and route of admin
- Area of absorptive surface
- Vascularity of absorbing surface.
- Gi motility
- Diseases
- Presence of other substances.
What is bioavailability?
The percentage or fraction or portion of administered dose that reaches systemic circulation in an unchanged form irrespective of the route of drug administration.
What is distribution??
The passage of drugs from systemic circulation to other tissues that initially had no drug.
What are the factors that influence distribution?
Lipid solubility.
Ionisation at Physiological pH.
Extent of binding to plasma and tissue protein.
Presence of tissue specific transporters.
Difference in regional blood flow.
What is volume of distribution?
It is the apparent volume of drug that is distributed to provide the same conc as is in the blood plasma.
What is drug metabolism?
It’s the chemical alteration of drugs in the body.
What are the sites of metabolism?
Liver
Kidney
Lungs
Plasma
Placenta
Testis
List examples of hydrophilic drugs
Streptomycin
Neostigmine
Pancuronium
What are the phases of metab?
Phase 1
Phase 2
What is phase one reaction?
Addition of a small polar group to a drug molecule
What is the most important phase 1 reaction?
Oxidation.
List the oxidation reaction enzymes?
Monoxygenases
Cytochrome p450 heme protein
Cytochrome p450 reductase
Nadph
In Cytochrome p450, the 1st number, alphabet and 2nd number represents?
1st number-family
Alphabet- sub family
2nd number- isoenzyme
About CYP3A4??
Found in the liver, intestine and kidney.
Metabolises 50% of drugs.
Most important CYP in metabolism.
About CYP2D6?
2nd most important.
Metabolises 20-25% of drugs.
About CYP2C8/9?
Metab of frequently prescribed medications. E.g antidiabetics, anticoagulants (warfin), analgesics (ibuprofen)
About CYP2C19?
Metab of omeprazole.
About CYP1A1/2?
Theophylline
What are the reduction reaction enzymes?
NADPH
CYTOCHROME-c-reductase
Nitro reductase
Keto reductase
What is hydrolysis??
It is the breakdown of drug via taking a molecule of water
Which enzymes are involved in hydrolysis??
Carboxylesterases
Hydroxylases
Amidases
Peptidases
What is cyclization?
Formation of a ring structure in a drug molecule with a straight chain
Examples of drugs metabolised by cyclization include?
Proguanil.
What is decyclization?
It is a process where the ring structure of a drug is opened up.
Examples of drugs metabolised by decyclization?
Barbiturates
Phenytoin
Examples of phase II reactions include?
Glucoronide conjugation.
Glutathione conjugation.
Methyl, acetyl and amino conjugation.
Glucoronide conjugation is characterised by?
UDP gluconosyl transferase.
Sulfate conjugation is characterised by?
Sulfotransferase.
Which drugs undergo glucoronide conjugation?
Drugs with hydroxyl or carboxyl acid groups.
Which drugs undergo sulfate conjugation?
Drugs with phenolic group.
Glutathione conjugation is catalysed by?
Glutathione - s- transferase.
It is important in paracetamol overdose.
What is first pass metabolism?
Metabolism of a drug during its passage from the site of absorption to systemic circulation.
What are the sites of first pass effect?
Intestine, liver, lungs, skin
What are are examples of drugs that have high first class metab?
Testosterone, salbutamol, hydrocortisone.
What are the types of drug metabolising enzymes?
Microsomal enzymes.
Non Microsomal enzymes.
What are microsomal enzymes?
These are enzymes produced in the smooth ER of the kidney, liver, GIT.
E.g monoxygenases, CYP450
They are involved in phase one reaction and glucuronide conjugation.
What are non microsomal enzymes?
They are produced in cytoplasm and mitochondria. E.g oxidases, amidases, esterases.
Catalyse most of phase II reactions except glucuronide rxn
Enzyme activity is increased due to the increased synthesis of CYP450.
T/F
True.
What is half life?
It’s the time taken for plasma conc of drug to be reduced to half of its original conc.
Drugs with which molecular weight are excreted in bile?
> 300
Examples of drugs excreted in the bile include?
Erythromycin, refampicin, tetracycline, vercuronium.
List the channels of excretion?
Urine
Faeces
Sweat
Exhaled air
Saliva
Breast milk
What is clearance of drug?
Theocratical vol of plasma from which the drug is completely removed in unit time.
