Pharmacokinetics and Pharmacodynamics Flashcards
Define Pharmacokinetics
What the body does to the drug
Define Pharmacodynamics
What the drug does to the body
Which is the only type of drug that can elicit an effect on the body?
Only free drug can elicit a pharmaceutical response
What is bioavailability?
The fraction of an orally administered drug that reaches the systemic circulation as intact drug (F)
What is the bioavailability of an IV drug?
100%
How do you calculate bioavailability?
Bioavailability = AUC oral x100%
AUC IV
What factors affect bioavailability?
-
Absoprtion
- Formulation
- Age
- Food (chelation, gastric emptying)
- Vomiting/ Malabsorption (Crohn’s)
- First pass metabolism
Identify on the curve, absorption, distribution and elimination
What are modified release preparations?
Standard preparations have to be administered several times a day
Modified release are taken less often and are absorbed over a longer period
- Plasma concentration determination shifts more towards the rate of absorption
What factors affect the distribution of therapeutic agents?
- Blood flow (to target organ) , capillary structure
- Lipophilicity and hydrophilicity
- Protein binding
What are the different types of proteins that drugs can bind to
- Albumin- acidic drugs
- Globulins - hormones
- Lipoproteins - basic drugs
- Glycoproteins - basic drugs
Explain the one compartment model of distribution
Drug only distributed in one compartment, no equilibrium established
Explain the 2 compartment model of distribution
Slower distribution across the different compartments of the body
Equilibrium established between the different body compartments
Elimination can start to happen before an equilibrium in body tissues is established
How can drug-protein binding affect distribution if a second drug is administered?
When is this clinically important?
Bound drug can be displaced from a binding site → now free drug that can elicit a response
Clinically important if:
- highly protein bound
- narrow therapeutic index
- low Vd
What is volume of distribution? (Vd)
The apparant volume of drug in the body releative to its concentration in plasma
Low Vd= mainly in plasma
High Vd= well distributed throughout body compartments
How do you calculate Vd?
Vd= Dose/ [Drug] plasma
How do you calculate a dose based on Vd?
Vd x [Drug] plasma = dose
What are the 2 phases of metabolism?
Phase 1: CYP450s → oxidation reaction → forms lipophilic metabolites
Phase 2: Conjugation reaction → excretion by kidney to urine or gall bladder in bile
What are the main isoenzymes of CYPs? How are these induced/inhibited
CYP1A - induced by smoking
CYP2C - many inhibitors
CYP2D - metabolises many drugs
CYP2E - Alcohol metabolism
CYP3A - ~50% therapeutics
What are pro-drugs?
Drugs that are adminstered inactively, and are activated by CYP450 enzyme metabolism
e. g. perindopril → dopamine
e. g. codeine → morphine
What factors can affect the activity of CYP450s?
- age
- hepatic disease
- blood flow
- alcohol
- cigarette smoking
Which CYP does grapefruit inhibit?
CYP3A4
Effects statin metabolism - CYP3A4 inhibited so statin levels remain high
What are the routes of drug elimination from the body?
- Primarily via the kidneys
- Other routes:
- Fluids- sweat, tears, genital secretions, saliva, breast milk
- Solids- faeces, hair
- Gases- volatile compounds
By which routes are low molecular weight and high molecular weight metabolites respectively excreted?
Low molecular weight polar metabolites- by the kidneys
High molecular weight metabolites- by hepatic route
