Absorption and Distribution Flashcards
What is absorption?
A mass transfer process of unchanged molecules from the site of absorption into the bloodstream.
Where is the site of absorption usually?
Usually the same as the site of administration but not always the case.
Name some of the factors which may impact the drug reaching the plasma.
-Physiochemical properties of drug (molecular size, shape, how likely it is to ionise in certain environments, its lipophilicity, etc.)
-Dosage form
What is the bioavailability of IV drugs?
100%
In which type of medication do we not want any absorption?
Topical medication
What is the intention of topical medication?
Drug not to make it into the systemic circulation, i.e. for it not to be absorbed.
Why is topical medication useful?
By applying medication directly to the affected part, and ensuring that it isn’t systemically absorbed means that we can avoid “off-target” adverse effects by reducing overall exposure beyond the site of action.
Give an example of a topical medicine.
Creams, eye drops, etc but also local anaesthetics,
How do local anaesthetics bring about their
effect?
Pain signals rely on fast-acting voltage-gated sodium channels
How can local anaesthetics be administrated?
Creams, numbing gels, injections
Why do you not want local anaesthetics to be absorbed?
-If you take the drug away from the site of action, you terminate its effect.
-Fast-acting voltage-gated sodium channels are not confined to the peripheral pain-transmitting nerves.
What are the effects of too much anaesthetic in the CNS?
Agitation, tinnitus, visual disturbance… seizures
->this is because paradoxically excitatory due to blockade of cortical inhibitory pathways
What are the effects of too much anaesthetic in the heart and CVS?
Complex, but eventually bradycardia, hypotension and cardiac arrest (difficult to salvage)
Suggest some steps that will minimise the chances of local anaesthetic getting into the circulation.
-Avoid injecting into circulation.
-Avoid injecting into highly vascular tissues.
-Co-administer the drug w adrenaline as will cause vasocontriction and reduce the chances of the drug being absorbed.
Name two forms of administration you might choose when you want the drug to be absorbed systemically.
-Enteral administration
-Parental administration
->for your info-
enteral=oral; sublingual; rectal
parental=SC, IM ,pulmonary, nasal, IV
What administrative group is the most desirable?
Why?
Oral
->cheapest, no equipment required, easiest, non-invasive
What can solubility be affected by?
Gut contents
Where are most drugs absorbed?
Small intestine as has larger surface area than stomach
What is first class metabolsim?
Any metabolism that happens before the drug gets into the systemic circulation.
What is phase 1 metabolism?
Phase I metabolism involves the additional of a functional group.
What is phase 2 metabolism?
Phase 2 metabolism involves the addition of a conjugation.
What is the first barrier for drugs administrated orally?
Involves surviving those pre-systemic chemical and biological changes.
What is the main barrier to absorption?
Endothelium
Define paracellular movement.
Drugs moving between cells.
Define transcellular movement.
Drugs moving across the cells themselves.
How do the majority of drugs get into the cell?
By dissolving in the lipid membrane and diffusing across.
What prediction can Fick’s First Law allow us to make?
Predict how effively
What prediction can Fick’s First Law allow us to make?
Predict how effectively the drug will be absorbed.
What is the driving force for Fick’s First Law?
Driving force is the drug concentration
Name one function of pericytes.
Regulating gene expression in endothelial cells.
Name the two main drugs involved in drug binding,
Albumin
Alpha-1 acid glycoprotein.
What is the lipid solubility of general anaesthetics
Highly lipid soluable.
What types of drug are more likely to need transport mechanims?
Drugs that are less lipophilic and more polar.
What is the real volume of distribution?
Physiological and is based on the total water in the body in which the drug could be dissolved.
What is the apparent volume of distribution?
Theory
Proportionality constant between the total amount of drug in the body and the amount in the plasma at any one time
What do drugs w high volume of distribution tend to do?
Tend to leave the plasma (more distribution)
What do drugs w low volume of distribution tend to do?
Tend to remain in the plasma (less distribution)
What drives the therapeutic effect?
Plasma conc.
How does the level of distribution impact half life?
Drugs with a high volume of distribution tend to have a longer half life.
What is the volume of distribution used to calculate?
Loading dose
Gives pros and cons of oral administration.
P- cheaper, easier, no equipment
C-more factors which will affect absorbtion
Gives pros and cons of IV.
P-speed
C-100% bioavailability means rapidly perfused compartments get rapid exposure; needs to be aqueous solution; acceptability
Gives pros and cons of IM.
P-usually safer than IV; rapid absorption of aqueous drugs
C- Painful; clots, abscesses etc; dependence on blood flow
Gives pros and cons of SC.
P- Similar to IM, but less painful etc
C- Irritation; impact on local tissue
How can dosage form be manipulated to impact absorption?
By altering liberation of the drug from it’s dosage form.
What are the only parts of the kinetic process that are under our control?
Liberation and absorption.
