Session 9 Flashcards
(14 cards)
What factors influence the pharmaceutical process (getting it into the body) of a drug?
Formulation of drug: solid or liquid (usually quicker release). A once daily dose has a higher patient compliance.
Site of administration: focal (eyes, skin, inhilation) or systemic (enteral - sublingual, oral, rectal. Parenteral - subcutaneous, intramuscular, IV)
What is oral bioavailability of a drug?
The proportion of the dose given by any method other than IV that reaches the systemic circulation in unchanged form. It can be expressed as:
- Amount - depends on first pass metabolism and gut absorption.
- Rate of availability - depends on pharmaceutical factors and rate of gut absorption
What is the therapeutic ratio?
Maximum tolerated dose/Minimum effective dose
Lethal dose to 50% of people (LD50)/Effective dose in 50% of people (ED50)
Give an example of a drug with a small therapeutic window and one with a large therapeutic window
Warfarin - small, care taken with prescriptions
Penicillin - large
What is the first pass effect and how can it be avoided?
Blood from the gut reaches the liver by the portal system, where the liver could metabolise the drug before it gets into the systemic circulation.
Avoided by parenteral, sublingual or rectal routes
What is the volume of distribution?
The theoretical volume into which a drug has distributed assuming that this occurred instantaneously. Calculated as amount given/plasma concentration at time zero.
When do protein binding interactions of drugs become important?
If the drug is highly bound to albumin (>90%)
If the drug has a small volume of distribution
If the drug has a low therapeutic index
Define an object and a precipitant drug
Object (class 1) drug is used at a dose much lower then the number of albumin binding sites Precipitant (class 2) drug is used at a dose greater than the number of binding sites. When administered simultaneously, class 1 drugs are displaced by class 2 drugs, raising the free active level of the class 1 drug and can increase the risk of toxicity.
What is first order kinetics?
When the rate of elimination is proportional to the drug level. There is a constant FRACTION of drug eliminated per unit of time - a half life can be defined.
What is zero order kinetics and how can it go wrong?
When the rate of elimination is constant (e.g. At very high concentrations when the enzymes are saturated).
It gives a therapeutic response that can suddenly escalate as elimination mechanisms saturate (e.g.alcohol).
When is a steady state reached during repeated drug administration?
In 5 half lives of that drug, irrespective of dose or frequency of administration. If half life is long and a rapid effect is desired (emergency), a loading dose is used before the maintenance dose.
What happens during phase 1 of drug metabolism in the liver?
Oxidation, reduction and hydrolysis by the cytochrome P450 system and NADPH. Enzymes are inducible and inhibitable and drug metabolism can be targeted in this way.
What happens during phase 2 of drug metabolism in the liver?
Conjugated water soluble products are formed
What urine pH is favourable for the excretion of weak acids/weak bases?
Weak acids (e.g. Aspirin) - less tubular absorption in alkaline urine because they become ionised so cannot pass through the membrane. The charged drugs stay in the tubule lumen hence increasing secretion. Weak bases (e.g. Amphetamine) - less tubular absorption in acidic urine because they become ionised so cannot pass through the membrane. Acid urine thus increases secretion.
