Pharm revision 2 Flashcards
two common features of GAs
loss of consciousness
suppression of reflex responses
Inhalation
NO
Diethyl ether
halothane
enflurane
IV GA
propofol
etomidate
GABAa units important in anaesthetics
Beta 3 = supression of reflex in IV
alpha 5 = amnesia in IV
alpha 1 = suppression of reflex inhalational
what other targets do inhalational GAs have
block NMDA type glutamate
neural nicotinic ACh receptors
TREK background leak potassium channels
2 parts of LA
aromatic and basic amine side chain
general characteristics of LA’s
do not influence resting membrane potential
selectively block small diameter and non-myelinated
weak bases
spinal vs epidural anaesthesia
spinal - sub arachnoid space
epidural = epidural space
lidocaine CNS effects
stimulation
restlessness
confusion
tremor
M1/M3 receptors are
Gq IP3 DAG linked
M2 receptors are
Gi cAMP linked
nAchR muscle vs ganglion
alpha alpha beta delta gamma
alpha x 2 beta x 3
pilocarpine and glaucoma
constriction of pupil leads to drainage via canals of schlemm
how do muscarinic agonists affect vasculature
vasc endothelial cells to make NO via M3
induces smooth muscle relaxation
what type of drug are bethanecol and pilocarpine
choline esters
alkaloids
pilocarpine and bethanecol side effects
blurred vision sweating GI pain hypotension resp distress bradycardia
cholinesterase inhibitors dosage effects
low dose = muscarinic inc
moderate = inc at all autonomic ganglia also
high = depolarising block at autonomic and NMJs
CNS effects of non polar anticholinesterases and eg
physostigmine
excitation but then unconsciousness, resp depression death
how to treat anticholinesterase poisioning when does it happen
organophosphate
atropine iv
pralidoxime iv
dual action of ganglion blocking drug and problem
ion channel and receptor blocker
use dependent
when is trimetaphan used
hypotension during surgery bc just blocks receptor
cns effects of atropine and hyoscine
mild restless and agitation
cns depression or paradoxical excitation
tropicamide moa and use
machr antag
mydriasis retina examination
machr antag and parkinsons
block M4 leads to dec inhibition of dopamine neurones
machr antag and asthma
ipratropium blocks bronchoconstriction
cant get into systemic bc ionised
side effects of first gen antipsychotics
EPS
chlorpromazine has anticholinergic more
clozapine
5ht2a antag resistant and negative neutropenia agrnaulocytosis myocarditis
quetiapine
H1 antag
less eps
aripiprazole
partial agonist d2 5ht1a
less side effects but no more efficacious
depression symptoms
misery low self esteem loss of motivation anhedonia slowing of thought and action loss of libido loss of appetite
unipolar depression reactive vs endogenous
stressful life event non familial
unrelated to external stress
familial
TCAs MOA
neuronal monoamine re-uptake inhibitors
also affect on alpha 2 , muscarinic, histamin, serotonin
antidepressants delayed effects
beta
5ht2a
TCA PK
highly PPB
hepatic metabolism into active metabolites
TCA unwanted
atropine like postural hypotension sedation due to h1 Acute toxicity = excitement delirum, coma resp depression CVS dysrhythmias and VF
TCA interactions
aspirin, phenytoin, warfarin
Hepatic = neuroleptics and oral contracepetives due to competition
potentiation of CNS
antihypertensive
MAOi eg
phenelzine
MAOi unwanted
atropine like but less than tca postural hypo sedation and seizures weight gain hepatotoxicity
MAOi interactions
tyramine
TCA = hypertensive
pethidine = hyperpyrexia, restlessness, coma, hypotension
Moclobemide
reversible MAO-A inhib with less drug interactions
SSRI interaction
TCA hepatic enzymes
interact with MAOis
SSRI unwanted
nausea diarrhoea insomnia loss of libido
Vanlafaxine
dose dependent reuptake inhib more ofr 5ht
2nd line for severe
SNRI
mirtazapine
alpha 2 antagonist
inc serotonin and na release
SSRI intolerant patients
thiopentone
barbiturate inducing anaesthetic
problems with barbiturates
low safety enzyme inducers potentiate cns depressants dependence tolerance
3rd bdz
oxazepam
which short acting bdz can become long
oxazepam
unwanted effects of bdz
sedation confusion amnesia ataxia potentiate cns depressants less tolerance dependence free plasma conc inc
zopiclone
short acting
acts at bdz receptors
minimal hangover but dependency problem
what else can you give for anxiety
antidepressant ssri
antipsychotic quietiapine
propranalol
buspirone = 5ht1a agonist with fewer side effects
type 1 and type 2 receptors
ionotropic
metabotropic
type 2 receptor structure
1 subunit 7 transmembrane domains
type 1 receptor structure
4/5 subunits with transmembrane alpha helices
drug enzyme interactions
false transmitter
pro drug
enzyme inhibitor
receptor reserve
not all receptors need to be stimulated to generate max response = sensitivity
3 exceptions to target site rule
antacids
GAs reduce synaptic trasnmisison with interaction
osmotic purgatives
2 eg of drugs that act on transport system
TCAs
cardiac glycosidess
4 things that affect drug distribution
regional blood flow
extracellular binding
capillary permeability
localisation in tissue
half life equation for first order kinetics
volume of distribution x log2 clearance
4 ways cross lipid membrane
diffusion
aqueous pores
carrier molecules
pinocytosis
reduction reactions where and why
GI tract
low oxygen bc reductases are bacterial enzymes
n-oxidation
oxidation of nitrogen
dative covalent
amino oxide
what does n-demethylation do
remove pharmacological activity
Enzyme for n-oxidation
flavine containing mono oxygenase
what molecule causes fish odour syndrome
trimethylamine
p450 active site
porphyrin ring and ferric fe3+
methylation effect on polarity
dec polarity
where are p450 and FCMO
ER
where is alcohol dehydrogenase
cytoplasm
two types of reduction enzymes
esterases
amidases
why is glutathion conjugation important
conjugated with electrophiles so they can be excreted
important so they do not cause DNA and protein damage
glucoridination conj agent
UDPGA
PAPS =
3 phosphoadenosine 5 phosphosulphate
properties of sulphation
v polar and water soluble
intermediate for methylation
s-adenosyl methionine
what is glutathione
glycine
glutamine
cysteine
oxidation cycle p450
nadph gives electron to make fe2+ from fe3+
oxygen binds and takes electron so you have unstable oxygen and fe3+
nadph another electron to make more unstable oxygen
drug becomes OH, oxygen + protons -> water
N-demthylation
oxidation of methyl group in a nitrogen
makes formaldehyde HCHP
o- demythylation
oxidative attack of p450 on methyl group attached to oxygen to make formaledehyfe HCHO
adrenaline clinical uses
asthma emergencies acute bronchospasm cardiogenic shock spinal anaesthesia local anaphylaxis
adrenaline unwanted actions
tachy arrhythmias cold extremeites htn pulmonary oedema cerebral haemmorhage
phenylepinephrine pk
resistant to comt
SS in glaucoma
alpha 2 dec humour formation
alpha 1 = vasoconstrcition
beta blockers = less b1 bicarb production needed to make aqueous humour
isoprenaline
beta agonist resistant to MAO and uptake 1 cardiogenic shock acute HF MI
salbutamol pk
resistant to mao and comt
salbutamol other use
threatened premature labour
beta agonist side effects
reflex tachy
tremor
blood sugar dysregulation
beta blocker uses
arrhythmias
hypertension
angina
glaucoma
methyldopa
alpha methyl NA which competes with NA
not broken down
alpha 2 agonist
angina types
stable = pain on exertion unstable = pain with less and less exertion variable = occurs at rest caused by coronary
ethosuximide
t-type calcium antagonists
reduces activity in thalamic neurones
absence
levetiracetam
SV2a preventing glutamate release
myoclonic
topoiramate
NMDA and Kainate
partial
diazepam
inc gaba inhibtion
status epilepticus
sodium valproate
inhibits gaba transaminase
inc gaba mediated inhibition
what gives opioids their analgesia effects
tertiary nitrogen
why is codeine a prodrug
no hydroxyl group at position 3 so cant bind
opioids PK
weak base
absorbed in small intestine
ionised in blood
morphine metabolism
morphine 6 glucuronide is a agonist too
less side effects
codeine metabolism
2d6 slow but makes in into morphine
3a4 fast and deactivates
what do opioids do centrally
hyperpolarisation
dec calcium in
dec AC
where does nrpg affect
nrm
where do opioids act in pain pathway
NRPG
PAG
Dorsal horn
how do opioids have anti tussive
inc serotonin which depresses inspiratory neurones
inhibit cholinergic contraction of smooth muscle
opioids and respiratory depression
prebotzinger complex
chemoreceptors
opioids and nv
activate ctz
opioid tolerance due to
tissue tolerance and receptor internalization
opioid antagonists
naloxone
why does opioids cause hypotension
histamine release
Pathophys parkinsons
lewy bodies in cell bodies
neurites in acons
abnormally phosphorylated neurofilaments ubiquitin and alpha synuclein
another dopa decarboxylase inhib
benserazide
comt inhibitors
entacapone
tolcapone
Dopamine receptor agonists for parkinsons
ergot = bromocriptine and pergolide
cardiac fibrosis
non-ergot = ropinirol = extended release and aptch
MAOb inhibi = selegiline reduces dosage l dopa required
parkinsons ANS
olfactory
orthostatic hypotension
constipation
parkinsons neuropsych
slee
memory
depression
irritabiility
inflammation hypothesis
microglia inc release of inflammatory mediators and cytotoxic proteins
inc phagocytosis
dec neuroprotective
3 anticholinesterases for alzheimers
donepezil = reversible
rivastigmine = pseudoreversible ache bche
transdermal patch
galantamine = reversible but also alpha 7 nachr
nmda blockers
memantine use dependente
