Drug Absorption and Distribution Flashcards
What is pharmacokinetics?
The study of the change in drug and metabolite concentrations in tissues and body fluids
(what the body does to the drug)
What is the therapeutic window of a drug?
The concentration range of a drug taken orally between the maximum non-toxic and minimum therapeutic concentration
What is the therapeutic ratio/index?
The ratio of the maximum non-toxic dose compared to the minimum therapeutic dose.
Safest drugs have the highest therapeutic ratio
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.
How can the therapeutic ratio be measured?
TD50/ED50
Explain the acronym ADME as a way of thinking about pharmacokinetics?
Absorption: movement of a drug from the point of administration to the plasma
Distribution: from plasma to tissues and organs
Metabolism: of drugs by enzymes in the body
Excretion: of drug/metabolite by the body
What is ADME important for understanding?
drug development understanding toxicity Establishing route of administration Establishing drug dose Understanding possible drug interactions
what is bioavailability?
fraction of unchanged drug that reaches systemic circulation.
(eg. intravenous drug delivery is 100% bioavailable)
How can bioavailability be decreased?
poorer absorption
first pass metabolism
what does absorption depend on?
Route of administration: intravenous is fastest
Chemical nature of compound: Lipophilicity (the higher the better), Charge (uncharged is faster), Size (smaller the better)
Formulation: A key area in pharmacy research (eg. liquid, gelatin capsule, etc)
Blood flow rate to the site of delivery
What are the different formulations of drugs and what are their relative speeds of absorption?
Liquids - absorb faster than capsules or tablets due to the greater area for exchange
Gelatin-Coating tablets - slow absorption and decreases local peak concentrations
Capsules - containing granules with differently soluble coatings allowing for controlled release
Intramuscular injection of an oily depot of lipophilic drugs - allows for the very slow release. (eg. anti-psychotic drugs in non-compliant patients)
What is the fastest and slowest route of administration?
Intravenous (IV) is the fastest
Sublingual (sI; under the tongue) is absorbed relatively quickly but not as fast as IV
Orally(po) / Rectally (pr) are slow routes of administration
what is a risk with an intravenous administration?
potential risk of infection
What is the issue of a sublingual route of administration?
Only a small amount of the drug can be absorbed and therefore it requires a very potent drug.
What is a transcutaneous route of administration of drug?
Only suitable for some drugs, where a lipophilic carrier is needed to cross the skin.
Often given in the form of a patch which when stuck on allows the drug to be absorbed.
What is Enteral absorption?
Absorption via the GI tract.
This can be either orally or rectally
What should be considered when taking an enteral drug?
Consider its interaction with food
Consider the rate of transit in the gut
For oral delivery, consider the pH sensitivity given the need to pass through the stomach
Consider the first pass metabolism
What is first pass metabolism?
Whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of drug lost during the process of absorption which is generally related to the liver and gut wall
What form of a weak base drug is charged?
For a weak base, the protonated form is charged (more alkaline) then there will be more uncharged form present and the drug will cross membranes
What form of a weak acid drug is charged?
Protonated form is uncharged, so under more acidic conditions then there will be more uncharged form present. and the drug will cross membranes
what are the general principles of pH and the effect on drug movement?
Difference in pH can determine where the drug will accumulate
Drugs tend to accumulate wherever they are ionised, as it is difficult for them to leave such compartments.
what is the enterohepatic circulation and how do drugs travel through it?
Some drugs entering the gut are absorbed, enter the portal circulation, pass from liver (with or without conjugation) to bile then back to the intestinal tract.
What is the distribution of a drug?
how drugs equilibrate within the body after entering the systemic circulation
What are some common fates of drugs to be distributed to?
no distribution
Distribution through extracellular space
Distribute through 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 work out the volume of distribution?
Vd = D / Cp
D - amount of drug
Cp - concentration of drug in plasma
What is the purpose of a drug binding to circulating proteins?
Decreases the initial free concentration
Slows distribution
Slows clearance
Prolongs duration of action
Give an example of a drug bound by albumin?
Warfarin and salicylates bind to circulating plasma proteins. When more than one of these drugs is present, there can be competition for binding, increasing the free drug concentration.