Pharmacodynamics Flashcards
why is thiopentone stored at a pH of 11
to promote its ionised form to make it lipid soluble. otherwise it would precipitate out of solution
it is an acid with pKa 7.6
what type of molecule (acid or base) is thiopentone, propofol and etomidate?
thio and propofol = weak acids
etomidate = weak base
Is fentanyl an acid or base?
weak base
what is the pKa of fentanyl and morphine, what does this mean?
both weak bases
fentanyl = 8.4
morphine = 7.9
therefore bases ionise below pH so at pH 7.4 more fentanyl will be ionised
what amine group does morphine have?
tertiary amine
what is the pka of the carbonate/bicarb buffer system?
6.4
what type of drug is meperidine ?
opioid, weak base
Aka pethidine
are NSAIDs acids or bases?
all weak acids
what is the pka of paracetamol ? is it an acid or base?
9.4
weak acid
what is the pka of remifentanil?
7.1
which is the only volatile agent NOT to exist as a stereoisomer?
sevoflurane
for levobupivacaine, ropivacaine and etomidate which isomer R or S is the clinically useful one?
bupivacaine and ropivacaine - S
Etomidate - R
how does sugamadex work pharmacodynamically?
Chelating agent - encapsulates roc
which drugs work by neutralisation
antacids
protamine
What is meant by an ionotrophic receptor
ligand gated
ion channel
NOT the same as VG ion channel
what 2 factors does drug potency depend on?
affinity and efficacy
which value represents drug affinity and potency?
kd = affinity
EC50 = potency
the lower for each , the more potent/higher affinity.
what is efficacy?
Efficacy is an inherent property of an agonist and reflects its ability to activate the receptor and produce a maximal biological response
which value from the drug response curve defines efficacy
Emax
define intrinsic activity
Intrinsic activity (IA) is the drug’s maximal efficacy as a fraction of the maximal efficacy produced by a full agonist.
what type of intracellular receptors are oestrogen and thyroxine
oestrogen - type 1 - cytoplasmic
thyroxine - type 2 - nuclear
how do intracellular receptors work?
intrinsic transcriptional activity, bind via zinc fingers
what activates thyroid receptors?
can be active with or without ligand.
ligand = T3/T4
when active it binds to thyroid response element (not transcription activating domain)
how are anticholinesterases divided?
Anticholinesterases are divided into short-, medium- and long-acting.
what test is diagnostic for myasthenia gravis?
Tensilon test
how is neostigmine hydrolysed?
same way as ACh just takes much longer
how long do long acting anticholinergics last
weeks due to covalent bonds
what is SLUDGE syndrome of cholinergic overdose characterised by?
salivation
lacrimation
urination
defacation
GI upset
emesis
where is carbonic anhydrase found?
renal tubules
pancreatic
parietal cells
RBC
ciliary epithelium of eye
where are COX1 and 2 found
COX 1 all cells
COX 2 - inflammatory cells
how are mono-oxidase enzymes classified?
They are classified as MAO-A, RIMA or MAO-B
where are mono oxidase enzymes found?
attached to mitochondria.
which family are mono-oxidase enzymes from?
flavoprotein
which MOA is found from birth?
MOA-A
how do MAO work?
remove amine
where are MAO found?
brain, liver, lung and placenta
what does MAO-A breakdown?
MAO-A breaks down MANS (melatonin, adrenaline, noradrenaline and serotonin
which drugs should MAO be avoided with?
never in combination with SSRI/SNRIs - increased levels in brain of NT –> hypertensive crisis
which other conditions can MAO be used in?
depression
prophylaxis migraines
parkinsons
which drug causes red man syndrome?
vancomycin
what law do michelias menton kinetics obey?
law of mass action
which part of the liver contains high levels of CYP450
Centrilobular hepatocytes (zone 3) contain high concentration of CYP 450 enzymes.
what is the main mechanism of CYP450 enzyme induction
increase in gene expression - takes some time to develop
how does dexamethasone affect CYP450
inducer
how doe rifampicin, paroxetine and erythromycin effect…
diltiazam, warfarin, betablockers
Rifampicin induces CYP2C9 with a risk of inadequate anticoagulation by warfarin.
Paroxetine inhibits CYP2D6, reducing the metabolism of beta-blockers.
Erythromycin inhibits CYP3A4, reducing the metabolism of diltiazem.
what type of drug reaction is sux apnoea?
Type B - Bizzare
what type of drug reaction is hypoglycaemia with aspirin?
type A
what are the different methods for defining drug reaction?
Type A and B - understandble / bizzare - i.e. reasoning
coombs - immunologicals
DOTS - timing, dose and susceptibility
what are pseudoallergic reactions?
present like allergy due to histamine release
not immune mediated
what is innate tolerance?
Innate tolerance describes a lack of sensitivity to a drug the first time it is administered
how can tolerance be classified
Acquired tolerance can be subdivided into three main categories: pharmacokinetic, pharmacodynamic and behavioural tolerance
which drugs show tachyphylaxis?
ephedrine
hydralazine
define summation, synergism and potentiation…
summation - effects are additive
synergism - combined effect is more that added affect of each alone
potentiation - one increases effect of another but doesnt have an effect itself
which herbal meds interact with NSAIDs?
garlic, ginger, ginseng, gingco, st johns
