Absorption and distribution Flashcards
Define absorption?
Process of mass transfer from site of administration to
bloodstream
What is IV taken in?
- IV: Introduced directly to bloodstream
- No absorption, but (all of it) does get into the bloodstream
What counts as topical administration?
- Topical = “of a place”
- Skin, mucous membranes, ears, eyes
it is not intended to reach the systemic circulation (ie not
absorbed)
Why would we not want to reach systemic circulation?
can reduce off target adverse affects
How do local anaesthetics work?
block the fast acting voltage gated sodium channels in membrane of nerve cells
Why don’t we want local anaesthetic drugs to be absorbed?
if take drug away from site of action- terminate its effect
fast acting voltage gated sodium channels are not confined to the peripheral pain - critical to normal function of other excitable tissues - such as CNS and the heart
What happens if local anaesthetic absorbed too much in CNS?
paradoxically excitatory due to blockade of cortical inhibitory
pathways (agitation, tinnitus, visual disturbance… seizures)
What happens if local anaethetic absorbed too much into heart and cvs?
complex, but eventually bradycardia, hypotension and
cardiac arrest (difficult to salvage)
How do we ensure local anaesthetic is safely used?
dosing
patient specific factors
don’t inject into circulation
avoid to highly vascular tissues (co-administer with adrenaline)
What route for absorption should be used when systemic absorption is desired?
Enteral ((oral; sublingual; rectal)
Parenteral (SC; IM; pulmonary? Nasal?)… IV
What are the factors affecting oral absorption?
- Solubility: can be affected by gut contents
(eg tetracyclines) - Gastric emptying time
- pH change throughout gut
- Gut flora
- First pass metabolism (liver and gut
mucosa) - (Also lung): Phase I (less than liver) and II
metabolism (as much as the liver) - Illness
What are the barriers for drug administered orally?
surviving pre systemic and biological changes
endothelium - to make to blood
What ways can drugs move when endothelium involved?
paracellular- between the endothelial cells
transcellular- across cells
How are most drugs absorbed?
- Drugs resembling physiological
compounds – carrier-mediated - Vast majority: Lipid soluble
- Diffusion- Fick’s law
What are the key features of ficks first law?
- Diffusion is rate limiting step
- Diffusion coefficient
- (Size etc)
- Partition coefficient- lipophility
- Thickness of membrane
- Total membrane area
- Driving force is the drug
concentration - ‘Sink’ condition
What is happening in sink condition?
the rate at which the substance is used or removed is directly proportional to how much of the substance is still present.
Give features of facilitated transport?
Facilitated diffusion
* Channel proteins: molecules of
appropriate size and charge
* Carrier proteins
* Facilitated diffusion of large
molecules
* Active transporters
What is problem with drugs absorbed via facilitated transport?
Michaelis menten kinetic (zero order) - eventually increasing dose doesn’t increase rate of absorption
How is endothelial cell integrity supported in brain?
pericytes- regulating gene expression in endothelial cells and expression of carrier mediated transport systems controlled
What are the very protected tissues?
brain, testis, ovary and placenta
What are the main proteins involved in drug binding?
albumin and alpha 1 acid glycoprotein
What are dosing strategies aimed for?
getting plasma concentration of free drug high enough to bring about a therapeutic effect - problem with protein binding drugs `
