pharmacology 4 - intro 4 Flashcards
what is specificity? of a drug
ultimate slectivity. (not many drugs are like this) only act at one place!
what is selectivity? of a drug eg. clenbuterol - how does it act? dose dependant!
often a drug will produce more than one effect. this defines the capacity to preferentially produce on effect over another. eg. clenbuterol (acts on B2 receptors in dilate airways. ) but if you have too high of a dose then affects B1 too and this increases HR.
Explain therapeutic index? what is EC50? WHAT IS LD50?
if give 100 dogs a drug - how manyare getting the response that we want? max = when 100% get the effect we want them too! a high majority will also have adverse side effects.
EC50 – effective dose for a 50% therapeutic response
LD50 – lethal dose for a 50% response to adverse effects.
Therapeutic index is what? ratio of what?
ratio of the dose giving an undesirable effect over the dose giving a desired effect. - want curves on graph to be as far apart as they can be!! need a wider knowledge to determine how safe the drug is.
4 types of receptor?
1, ion channel
- GPCR
- protein kinases
- cytosolic receptor/nuclear receptor
explain an ion channel? EG?
cell surface transmembrane receptor. inotrophic.
very simple and rapid response
channel in cell membrane and agonist causes it to openand let ions into the cells. - depolarise etc. (na/ca/k) eg. ach - NICOTINIC.
explain a GPCR?
G-protein copled receptor.
7 transmembrane domains. sense a molecule outside the cell (ligand) and activate signal transduction inside the cell. - cell responses. eg. CAMP/PLC. 2nd messengers. - lead to CA influx etc.
draw out a GPCR pathway?
see notes
GPCR cascade?
PLC, PKC, DAG, IP3, SR - CA!!
Explain protein kinases?
mediate action of a variety of proteins eg. insulin. rapid response, modifies them by chemically phosphorylating them. fuctional change by enzymes. uses energy. ligand binds outside cell and causes enzyme to be activated which causes catalysis inside the cell of proteins.
cytosolic receptors?/nuclear
common with steroids. eg. oestrogen
receptor in cytosol and when ligand binds - transolcates to nucleus where it regulates transcription of genes. very slow effects.
explain receptor desensitisation? eg?
when exposed to a ligand - response may reach a peak and despite ligand still being there may start to drop off. recovery rapid once ligand removed. eg. Beta adrenoreceptors. may become phosphorylated and lose the g-protein connection which attracts b-arrestin and stops it all working?
receptor down regulation?
slower in onset and recovery. receptors become internalised and degraded in the cell.
tachyphylaxis?
rapid loss of responsiveness to a drug following initial dosing. many reasons for this.
drug dosing - what are regimens based on? what do you need to take into account?
normal healthy animals!!….may need to taylor the dose to the animal!
need to take into account pharmacokinetics and the steadty state!!
how would age effect drug doses?
Tbw higher in neonates - more fluid dilutes it so need drug takes longer to act and be removed from body, concentration presented to kidneys is reduced. higher vd!!!
how does species effect drug doses? what dosent the cat have? means?
NSAID unpredictable in certain species so cant swap it over. eg. cats cant preform glucuronidation (missing glucuraonic transferase) so cant give them paracetamol. metabolism is very different.
how does health status effect drug doses?
renal disease - longer half life?
hepatic - not metabolised
dehydration - lower vd. - eliminated more quickly
inflammation - drug acumultes here due to altered ph. ion trapped.
also disrupts membranes during inflamm so drug cant get into cells.
how does concurrent treatment effect drug doses?
may be an emzyme inducer/inhibitor? eg. phenobarbital.
renal disease and drugs - ? what else could you use?
reduced GFR. and tubular secretion. need to reduce dose rate - or use creatinine clearance
in renal disease what is elevated? so what?
urea and reatinine. this displaces drug from the albumen protein bound as it now binds. so more free drug circulating!!
equations for new doses?/intervals?
new interval = old x (patient cr/normalcr) this would be more than 1 as patient higher.
new dose = old x(normal/patient cr) - less than 1 as pateint higher.
hepatic disease and drugs?
complex. hard to change the dose/interval. also affects renal!! just avoid drugs which are handled by the liver.
blood flow
protein binding
metabolism.
what is TDM? ensure what first? give exapmles and why would you montior them!
therapeutic drug monitoring. ensure at a steady state forst. monitor drug plamsa levels at key times and know the target level.
phenobarbital - anti epilepsy enzyme inducer
digoxin - cardiac (narrow therapeutic index)
gentamycin - antibiotic - nephrotoxic.
