M&R Session 9 Flashcards
What four things does the pharmaceutical process consider?
Formulation
Compliance
Site of administration
Bioavailability of drug
What question does the pharmaceutical process consider?
Is drug getting into patient?
What is the advantage of using a specific site of administration?
Concentrates drug at site of action
Decreases systemic absorption
Decreases off-target effects
What is the bioavailability of a drug?
The proportion that makes it to the circulation unchanged
What does the bioavailability of a drug depend on?
1st pass effect
Gut absorption
Pharmaceutical factors
How is bioavailability calculated?
(AUC oral)/(AUC injected) x 100
What question does the pharmacokinetic process consider?
Is drug getting to site of action?
What is the therapeutic ratio?
max. tolerated dose/min. effective dose
= LD50/ED50
What is LD50?
Toxic dose in 50% of the population
Give an example of a drug with a small therapeutic index.
Warfarin
Give an example of a drug with a large therapeutic index.
Penicillin
What does a small therapeutic index indicate?
A large overdose is needed before adverse effects occur
What is the disadvantage of a fast release prep?
May be above [toxic] for a short amount of time
What is the disadvantage of a slow release prep?
May not remain in the therapeutic window for long
What question does the pharmacodynamic process consider?
Is drug producing desired effect?
What question does the therapeutic process consider?
Is this translated to a therapeutic effect?
What is first pass metabolism?
When drugs administered orally undergo oxidation and conjugation in the liver before reaching systemic circulation
What alternative administration routes can be used to avoid first pass metabolism?
Parenteral (IV, IM, SC)
Rectal
Sublingual
What is the volume of distribution?
Theoretical volume into which drug is distributed if this occurred instantaneously
Why do hydrophobic drugs appear to have a huge volume of distribution?
Absorbed by fat so don’t enter bloodstream
What property of a drug does the volume of distribution indicate?
Hydrophobicity
What determines the action of a drug at its receptor and its elimination?
Protein binding
What are protein binding interactions?
2nd hydrophobic drug binds displacing 1st and causing it to reach toxic levels
When are protein binding drug interactions important?
When object drug is:
>90% bound to albumin
Has a small volume of distribution
Has a low therapeutic ratio
Give two examples of object drugs and their precipitant drugs.
Warfarin - sulphonamides, aspirin, phenytoin
Tolbutamide - sulphonamides, aspirin
How low is the dose of Class I (object) drug used to keep [free drug] low?
A dose lower than the number of albumin binding sites
What doses are Class II (precipitant) drugs used at?
Doses higher than the number of binding sites so object drug is displaced
Why are drug binding interactions transient?
Elimination rate rises as it is dependent on free drug levels which have risen
How quickly is a new steady state restored in brung binding interactions?
Within a few days
What is first order kinetics?
Rate of elimination is proportional to drug level
What is special about the half life of a drug that follows first order kinetics?
It is defined
How does first order kinetics appear on a linear scale?
Exponential decrease
How does first order kinetics appear on a log scale?
Linear
At what drug doses are first order kinetics seen?
Low
How is the therapeutic response from a dose increase of a first order kinetic drug described?
Predictable
What is zero order kinetics?
Rate of elimination is a constant
Why is the rate of elimination constant in zero order kinetics?
The reaction is saturated
Are first or zero order kinetic drugs more long lived?
Zero order
How do zero order kinetics appear on a linear scale?
Straight line
At what drug doses are zero order kinetics seen?
High
What happens to the therapeutic response as the elimination mechanism is saturated?
Suddenly escalates
How many half lives does it take to reach a new steady state in repeated drug administration?
5
Does the number of half lives needed to reach a steady state in repeated drug administration depend on dose of frequency of administration?
Nope
If the half life of a drug is long and a rapid effect is desired, what kind of dose is used?
Loading dose
What often determines a loading dose?
Volume of distribution
What is used to top up a loading dose?
Maintenance doses
Give two examples of drugs which utilise loading doses.
Digoxin - AF
Heparin - anticoagulation
By what two methods can drug elimination take place?
Metabolism
Excretion
Briefly describe the process of drug metabolism.
Enters through portal/systemic circulation –> phase I –> oxidation +/- hydrolysis –> phase II –> conjugation products
What enzymes are used in the liver to metabolise drugs?
Mixed function oxidases consisting of cytochrome P450 reductase
What property of cytochrome P450 allows it to act on a range of drugs?
Low substrate specificity
What kind of drugs does P450 reductase have an affinity for?
Lipid soluble
What alters P450 levels?
Diet/drug interaction can induce or inhibit
When in P450 susceptible to drug interactions?
Low therapeutic ratio
Drug at minimum effective concentration
Zero order metabolism
Give three examples of P450 inducers.
Phenoarbitone
Rifampicin
Cigarette smoke
What determines if a drug is ionised or not when excreted by the kidney?
pH of filtrate
Which moiety of drug is lipid soluble and can easily cross membrane for excretion?
Non-ionised
Which fraction of the drug is filtered?
Free fraction
Can drugs be actively secreted by the tubules?
Yes
Give an example of a drug which can be secreted by tubules and its location of secretion.
Penicillin by PCT
Which drugs are seen most rapidly in the urine?
Ionised, lipid-insoluble
What does passive reabsorption depend on?
pH
What effect does acid and alkaline urine have on the absorption of weak acid drugs?
Acid urine = increased absorption
Alkaline urine = decreased absorption
What effect does acid and alkaline urine have in the absorption of weak bases?
Acid urine = decreased absorption
Alkaline urine = increased absorption
How is aspirin poisoning treated?
Weak acid so forced alkaline diuresis to decrease absorption
How should the maintenance dose of a drug with a longer half life due to kidney excretion be altered?
Decreased
How does half life relate to time taken to reach steady state?
Longer half life = longer time to reach steady state
In prescription in renal disease, what two things can be altered?
Loading dose
Protein binding
How is protein binding altered when prescribing in renal disease?
Application of a co-molecule
