CNS drugs Flashcards
what is the difference between MAO enzymes A and B?
A found in brain, liver, placenta, GIT and pulmonary endothelium. breaks down 5HT3, NA and dopamine and melatonin
B - found in brain, NOT found in infants. breaks down tyramine, phenylethylramine and dopamine.
give example of MAOI selective for MAO-A?
moclobemide
pirlindole
what are the effects of benzos?
CNS:
- sedation, reduced REM sleep
- anxiolysis
- hypnosis
- anti epileptic
- anterograde amnesia
muscle relaxation through affects in dorsal horn
CVS and resp
reduced SVR
reduced TV (slight increase in RR)
how do benzos work?
bind BDZ1 and BDZ2 receptors which then associate and modulate GABA A to increase opening and conductance of ion channel - increase chloride and hyperpolarisation
does midazolam have any active metabolites?
yes - oxazepam
what are the metabolites of diazepam?
nordiazepam, temazepam , oxazepam
which of the benzos has the longest eliimination half life?
diazepam - 36 hours
what type of molecule is flumazenil?
imadazobenzodiazepine
what is the elimination half life of flumazenil?
50 mins
significance of this is that may need to repeat dose or give as IV infusion
when is flumazenil contraindicated?
long QTc/ QRS prolongation
dont give in mixed overdose e.g. TCA - may precipitate seizures
which sympathetic ganglia are not adjacent to spinal cord (exceptions)?
coeliac and hypogastric
which sympathetic fibres leave spinal cord?
preganglionic - travel in white communicates (myelinated)
then after ganglion = grey communicates
what ANS branch does stellate ganglia contain?
sympathetic
what fibres of the sympathetic nervous system does the sphlanchnic nerve contain?
preganglionic
how many divisions of ANS?
sympathetic
parasympathetic
(enteric NS - thought to be the 3rd branch)
what is the NT carried by each synapse in autonomic NS?
between pre and post ganglionic - ACh and nACh - in both symp and parasym
sympathetic post ganglionic - NA and adrenoceptors
parasympathetic post ganglionic -ACH and mACHR
exception - sympathetic sweat glands - ACh
where is the alpha 2 receptor predominantly located?
pre-synaptic
what is the main source of a2 receptors?
circulating catecholamines
what does NA do to B2 and A1 receptors on smooth muscle?
a1 - vasoconstriction to all smooth muscle except that of GIT
B2 - vasodilation of skeletal, bronchial and uterine smooth muscle
what enzyme is deficient in phenylketonuria?
Phenylalanine hydroxylase
which receptor are adrenaline and NA mosly different?
Adrenaline and noradrenaline differ mainly in their effects at β2 adrenoceptors, to which noradrenaline has a much lower affinity.
what is the half life of adrenaline?
1 to 3 mins
what is the effect of ANS on the bladder?
sympathetic - relaxes
parasympathetic - contracts
what is the effect of ANS on the erection and ejaculation?
sympathetic - ejaculation
parasymp - erection
point and shoot
what receptors are present in ganglion of parasymp fibres?
mostly nicotinic
but can also get muscarinic - exicitatory
what is a NANC NT?
non adrenergic non cholinergic neurotransmitter.
what does anti-cholinergics do to eye pressure?
dilate pupil, reduce drainage, increase eye pressures.
how does ipratropium work?
muscarinic antagonist
bronchodilation
Gq
what is clonidine?
a2 agonist
this reduces NA release - hypotension
also analgesic
where does doxazocin act?
a1 blocker
reduces SVR
what do CaCB do to CVS system?
reduce contractility and CO
reduce HR - reduce conduction through AVN
reduce SVR
how do phosphodiesterase inhibitors reduce SVR?
cAMP –> PKA –> phosphorylates MLCK –> inhibits muscle contraction.
phosphodiesterase breaks down cAMP
hence inhibiton will inhibit muscle relaxation
give examples of 2 PDE (phosphodiesterase) inhibitors that act on CVS
milrinone
Levosimendan (ca sensitiser too)
what is the effect of PGE inhibitors on cardiac function?
improved ionotropy but not immediate
they enhance effects of other ionotropes e.g. adrenaline
what is ranolazine?
inhibitor of late inward Na current
used in angina
can spinal be done with anti-platelet therapy?
monotherapy with aspirin - yes no contraindication
ticagrelor - stop 5 days before
how long is dual anti-platelet therapy after PCI?
6 to 12 months
then aspirin alone
which angina meds should/ shouldnt be continued during surgery?
statins, aspirin , b blockers , anti htn (except ACE) - continue
ramipril - stop
ticagrelor / clop - stop
which ion channel do CaCB effect?
L type
which vessels do nitrates dilate?
veins predominately
what do CaCB do to neuromuscular block?
prolong
which commonly used drug can ranolazine interact with ?
ondansetron - both cause long QT
what is the mechanism of action of phentolamine?
alpha antagonist
which vessels do CaCB mostly affect?
arterial vasodilation
what does phenytoin do to cyp450?
inducer
decreases levels - carbemazepine, COCP, warfarin, clopidogrel, steroids, PPI
which AED is a P-glycoprotein (P-gp) inhibitors? what does this mean?
phenytoin
normally this pump eliminates drugs. hence inhibition increases conc of drugs / absorption.
e.g pf dabigatran
which anti-epileptics are least likely to be associated with anti-epileptic hypersensitivity syndrome?
levetiracetam
gabapentin
pregabalin
valproate / topimarate
what is anti-epileptic hypersensitivity syndrome?
rare, potentially fatal
This syndrome typically includes symptoms such as fever, rash, and systemic involvement (e.g., hepatitis, nephritis, and hematologic abnormalities). AEDs most commonly associated with AHS include carbamazepine, phenytoin, phenobarbital, and lamotrigine.
when is ICP monitoring in epilepsy advised?
In the 4th stage (aka Refractory Status, 30-90 mins)
what is the mechanism of action of …
topiramate, vigabatrin, phenytoin, tiagabine and pregabalin?
topiramate - glutamate blocker
vigabatrin - Gaba transaminase inhibitor
phenytoin - Na channel blocker
tiagabine - GABA reuptake inhibitor
pregabalin - Inhibition of alpha 2-delta (α2–δ) subunit of voltage-gated calcium channels (VGCC)
which drugs inhibit MAO A and B?
MAO-I A= moclobemide - reversible
MAO-I B = selegeline and rasagiline - irreversible
Isocarboxazid is a non-selective MAOI that binds irreversibly to MOA-A and MOA-B.
which antimicrobial agent has MAOI activity?
Linezolid inhibits the action of MAO-A and can interact with MAOI to cause serotonin syndrome.
which antipsychotic causes agranulocytosis?
clozapine
what type of anti-psychotics are chlorpromazine and flupentixol?
Chlorpromazine is a typical antipsychotic of the phenothiazine class.
Flupentixol is a typical antipsychotic of the thioxanthene class.
