Pharmacokinetics + Pharmacodynamics Flashcards
List the phases of drug absorption (4)
- Absorption
- Clinical effect
- Metabolism
- Excretion
Define enteral drug administration
Administered via the gut
Define parental drug administration
Not administered via the gut
List forms of drug administration (5)
- Oral
- Intravenous
- Injected through a vein straight into bloodstream - Intramuscular
- Injected through a muscle - Subcutaneous
- Injected under skin to fatty tissue - Inhalation
- Absorbed through lungs
What form of parenteral drug administration works slowly?
Subcutaneous- has to pass through more
Advantages of oral administration
Socially acceptable
Disadvantages of oral administration (4)
- Slow onset
- Variable absorption
- Gastric acid may destroy drug
- 1st pass metabolism
List some other factors affecting oral drug absorption (5)
- Lipid solubility and ionisation
- Drug formulation
- Gastrointestinal motility
- Interactions with other substances in the gut
- GI tract disease
Define 1st pass metabolism
When drug conc is greatly reduced before it reaches the systemic circulation
- Because the liver metabolises the drug
Where does all blood from the GI tract drain to?
Hepatic portal vein
What veins in the GI tract do not drain to the hepatic portal vein?
Sublingual and rectal veins
What does the HPV drain to
Liver
What happens when the liver inactivates the drug?
More needed by oral route to get desired effect (e.g. glyceryl trinitrate)
What happens when the liver activates the drug?
Makes an active form of an inactive drug
Less needed by oral route
(e.g.Valaciclovir —> Aciclovir )
Disadvantages of non oral drug administration (3)
- Allergic reactions most severe
- Access difficulties/self medication
- Drug cost higher
What are the advantages of non oral drug administration?
Predictable plasma levels
No first pass metabolism
1st pass metabolisism is important when considering drug dosage
What can abnormal liver function cause? (3)
- Extremes of life
- Liver disease
- Drug interactions changing drug metabolism
Why is there a difference in severity with relation to oral and non-oral drug administration?
ORAL
- Allergic reaction not as dangerous as there could be 30 minutes before the drug has an effect
NON ORAL
- Allergic reaction more severe as the drug goes straight to the blood so there is less time to act
Define the term bioavailability
Proportion of an ingested drug that is available for clinical effect
What factors modify the bioavailability?
- Dosage form
- Destruction in the gut
- Poor absorption
- 1st pass metabolism
When would you want the bioavailability of a drug to be as low as 0%?
If you want to keep the drug working in the gut and not have it go into the bloodstream
Define drug distribution
How much of the body is the drug diluted in?
Where in the body are drugs diluted in?
Vascular
Tissues
CNS
How does lipid binding affect the volume of distribution?
Creates a slow release from accumulation
What happens if a drug bound to a plasma protein is inactive?
Can act as a reservoir
How can plasma proteins act as a reservoir for drugs?
If the drug is used up, the plasma protein releases more so allows the reaction to act for much longer
Give examples of drugs that can interact by competitive binding.
Warfarin + Aspirin
Define drug metabolism
Preparing the drug from elimination from the body
Give examples of phase 1 reactions of drug metabolism (3)
- Oxidation
- Reduction
- Hydrolysis
What is the effect of phase 1 metabolism?
Conversion to metabolites of lesser, equal or greater activity- changes its shape
Give examples of phase 2 reactions of drug metabolism (4)
- Conjugation
- Sulphation
- Methylation
- Acetylation
What is the effect of phase 2 metabolism?
Conversion to inactive metabolites- add to larger molecule that the body naturally eliminates
List examples of drug excretion (5)
- Renal - urine
- Liver - bile
- Lungs - exhale gas
- Sweat
- Saliva
List disorders of excretion (2)
- Renal disease
2. Liver disease
How does chronic renal failure (from renal disease) affect drug administration?
Drug doses must be reduced
How does liver failure (from liver disease) affect drug administration?
Drug doses must be reduced
Do drugs distribute themselves evenly around the body?
No- normally go to places where blood flow is higher and eventually even out
What is planning drug use based on?
The idea of body compartments
How does the drug behave in a single compartment model?
Drug behaves as if it is evenly distributed throughout the body
How does the drug behave in a two compartment model?
Drug behaves as if it is in equilibrium with different tissues in the body
Define pharmacokinetics
Study of how an organism affects the drug
How is pharmacokinetics studied? (2)
- Drug clearance
2. Repeated drug dosing
What features are involved in drug clearance? (3)
- Plasma half life (time for 1/2 drug to be removed)
- 1st order kinetics
- 0 order kinetics
What form of diffusion does drug elimination/absorption occur through?
Passive diffusion
How is drug removal related to the drug concentration in first order kinetics? (2)
- Drug removal is proportional to the drug concentration
- Logarithmic graph of elimination is a straight line
What can drug elimination be saturated by?
High drug concentrations
What happens during zero order kinetics in relation to drug elimination?
Constant amount of drug is eliminated per unit time
What happens during a paracetamol overdose? (3)
- Can cause irreversible liver damage which can affect blood clotting
- It is metabolised by zero order kinetics
- It is toxic to the liver but not many other places
What could too frequent a dosing schedule of drugs result in?
Plasma levels that may be toxic
What does the dosing schedule of drugs depend on?
The drugs therapeutic index
What could too infrequent a dosing schedule of drugs result in?
Sub-therapeutic plasma levels and no clinical effect
How can drugs affect each other?
One drug may increase or decrease the metabolism of another
What form of drug absorption is the least reliable?
Oral route
