Pharmacodynamics Flashcards
What is the pharmaceutical process?
Is drug getting into patient?
What is the pharmacokinetic process?
Is drug getting to site of action?
What is the pharmacodynamic process?
Is drug producing desired effect?
What is the therapeutic process?
Is this translated to a therapeutic effect?
What does rate of drug action depend on?
Rate of action depends on dissolution e.g soluble aspirin used to treat MI rather than tablet
What are some drug delivery methods?
What is Oral Bioavailability of a drug?
Proportion of drug given orally (or any other route except iv) that reaches circulation unchanged..
Measured by:
– Amount (depends on 1st pass metabolism and gut absorption)
– Rate (depends on pharmaceutical factors, gut absorption
Give an equation for working out oral bioavailabity from a graph
What is therapeutic ratio?
- Defined as LD50/ED50
- Maximum tolerated dose / minimum effective dose
What is the difference between a fast and slow release prep?
What is the difference between oral and intravenous administration?
How can first pass metabolism be avoided?
–Parenteral (iv,im,sc)
– Rectal (note drainage to both portal and systemic systems)
– Sublingual (e.g. use of glyceryl trinitrate in angina)
What is volume of distribution determined by?
– Theoretical volume into which drug is distributed if this occurred instantaneously
– Obtained by extrapolation of plasma levels to zero time
Why is free drug concentration important?
Free drug determines its action at receptor
Displacement of drugs from binding sites causes Protein Binding Drug Interactions
When are protein binding interactions important?
Protein Binding interactions are important when object drug:
– Is highly bound to albumin (>90%)
– Has a small volume of distribution
– Has a low therapeutic ratio
What is the difference between a class 1 drug and class 2 drug? (with respect to protein binding)
- Class I drug (object drug) is used at dose lower than number of albumin binding sites
- Class II drug (precipitant) drug is used at doses greater than number of binding sites, and thus displaces the Class I drug
Describe the nature of drug binding to proteins
- Binding interactions are transient
- Although free drug levels rise (i.e. greater effects at receptors), Elimination rate will also rise (since this depends on Free drug levels). Steady state is restored quickly in a few days.
Give two examples of object drugs and their precipitant drugs
- Warfarin (used for AF, TIA). Precipitant Drugs are Sulfonamides, Aspirin, Phenytoin.
- Tolbutamide (used for NIDDM). Precipitant drugs are sulfonamides, Aspirin.
Describe drug elimination
Metabolism – predominantly liver
Excretion – predominantly renal
Describe the difference between first and zero order kinetics
1st order kinetics:
Rate of elimination is proportional to drug level. Constant fraction of drug eliminated in unit time. Half life can be defined.
Zero Order kinetics:
Rate of elimination is a constant.
How are first order drug kinetics shown on a graph?
How are zero order drug kinetics shown on a graph?
Describe the relationship between dosage and kinetics
How is steady state achieved in repeated drug administration?
During repeated drug administration, a new steady state is achieved in 5 half lives. This is irrespective of dose or frequency of administration.
E.G. Digoxin Half life- 36h. If maintenance dose used, will take 5 x 36 h (180 h) to steady state.
What are loading doses?
If the half life is long and a rapid effect is desired, use a loading dose.
This is often determined by the volume of distribution.
Why is the kinetics of a drug relevant?
Describe how the liver functions to metabolise drugs
Mixed function oxidases (liver microsomal enzyme) consists of cytochrome P450 reductase
Main CYP isoenzymes 1A2, 2C9, 2C19, 2D6, 3A4
– Low substrate specificity
– Affinity for lipid soluble drugs
When are drug interactions in metabolism likely to matter clinically?
- Drugs with low therapeutic ratio
- Drug is being used at minimum effective concentration (e.g. OC pill)
- Drug metabolism follows zero order kinetics
Give some examples of drug interactions clinically
Describe the process of renal excretion of drugs
- Only the free fraction of drug is filtered
- Drugs can be actively secreted by the tubules (e.g. penicillin secreted by proximal tubule)
How is pH linked to reabsorption?
Passive reabsorption of drug is dependent on pH.
- pK of drug is pH at which half of it is ionised, half is non-ionised
- Only the non-ionised moiety is lipid soluble and crosses membranes easily
Describe the renal excretion of weak acids
Describe the renal excretion of weak bases
Describe the renal clearance of aspirin, and how it is affected by pH
What are factors to consider in prescribing for renal disease?
- If drug is excreted by kidneys, half lives of drug are longer. Lower maintenance dose of the drug.
- longer half lives also means longer time to reach a steady state (remember it takes 5 half lives to reach equilibrium).
- Loading dose can be altered.
- Protein binding can be altered
