Drug absorption and distribution Flashcards
What is pharmokinetics?
The study of the change in drug and metabolite concentrations in tissues and body fluids
What is a therapeutic window?
The range of concentrations that allow the drugs to reach their site of action below a toxic concentration
What is the therapeutic ratio?
Maximum non-toxic dose
Over
Minimum therapeutic dose
What is TD50?
The toxic dose of a drug for 50% of the population
What is ED50?
The minimum effective dose for 50% of the population
What is the relationship between therapeutic ration and drug safety?
The higher the therapeutic ratio, the safer the drug
What are the four parts to pharmokinetics?
Absorption
Distribution
Metabolism
Excretion
What is absorption?
Movement of the drug from point of administration to plasma
What is distribution?
From plasma to tissues and organs
What is metabolism?
Metabolism of drugs by enzymes in the body
What is excretion?
Excretion of drug or metabolite by the body
Why is ADME important?
Drug development Understanding toxicity Establishing route of administration Establishing drug dose Understanding possible drug interactions
What is the definition of bioavailability?
Fraction of unchanged drug that reaches systemic circulation
What is the bioavailability of IV drugs?
100%
What is absorption dependent on?
Route of administration
Chemical nature of the compound
Formulation
Blood flow to site of delivery
What is formulation?
Tablet or liquid form etc
What is the fastest route of administration?
Intravenous
What is the slowest form of administration?
Orally
Rectally
What are the six possible routes of administration?
Intravenously Sublingually Orally Rectally Intramuscular Subcutaneous
What is a risk involved with intravenous drug administration?
Infection
What is a side effect of intramuscular or subcutaneous drug administration?
Invasive and painful
Can cause local reactions
What is a consequence of sublingual administration?
Only a small amount can be absorbed
What must be considered when a drug is absorbed in the GI tract?
Its interactions with food
The rate of transit in the gut
pH sensitivity when passing through the stomach
What can cross the cell membrane?
Very impermeable to charged molecules
Lipophilic molecules can cross the membrane
Particulates can cross by pinocytosis
Where are weak acid and weak base drugs best absorbed?
In their uncharged states
In more alkaline conditions, more alkali drugs are absorbed
It is the same for acids
Where do drugs tend to accumulate?
Where they are ionised as they then can’t cross any membranes
What is first pass metabolism?
Enteral drugs (oral or rectal) have to pass the liver The metabolism of the drugs before they reach systemic circulation is known as first pass metabolism
What is enterohepatic circulation?
Some drugs entering the gut are absorbed, enter the portal circulation, pass from liver to bile then back to the GI tract
What drugs do not distribute?
Large drugs or those that bind to plasma proteins
Define drug distribution
How drugs equilibrate within the body after entering the systemic circulation
Where may drugs distribute?
Not at all Extracellular space Total body water Accumulate in cells Distribute to fat
What is the volume of distribution?
The volume of fluid required to contain the total amount of drug in the body at the same concentration as that present in the plasma
How do you calculate volume of distribution?
Vd = D / Cp
D = amount of drug Cp = plasma concentration
What is the effect of binding to circulation proteins on drug action?
e.g. albumin Decreases initial free concentration Slows distribution Slows clearance Prolongs duration of action
What drugs bind to albumin?
Salicylates (eg aspirin)
Warfarin
