CNS Flashcards
Choline esters
direct cholinomimetics
ACh, methacoline, bethacol, carbachol
Poor PO
Hydrophilic, not to CNS
Hyolised GIT
Alkaloid cholinomimetics
direct
pilocarpine, muscarine, nicotine
Good PO, lipophilic, go to CNS
renally excreted
Bethanachol
choline ester direct cholinomimetic
for paralytic ileus and urinary retetntion
Edrophonium
Alcohol inderict cholinomimetic
tensilon test for MG
Physostigmine
carbamate indirect cholinomimetic
short T1/2
Crosses BBB
tx atropine OD / cholinergic agitation
Tx cholinergic poisoning
pralidoxime
atropine
supportive
Tertiary antimuscarinics
atropine, tropicamide, pirenzipine, scopolamine
lipid soluble, cross BBB
Quaternary antimuscarinics
glycopyrolate, ipratropium, benztropine
don’t cross BBB
Benztropine
quaternary antimuscarininc
doesn’t cross BBB
use in parkinsons
Used in dystonic reactions
Glycopyrolate
quaternary antimuscarininc
doesn’t cross BBB
used for excess secretions
Poorly absorbed - F 0.05
Cycloplegics and duration
antimuscarinincs, paralysis ciliary muscle
tropicaimide - 15-60m
cyclopentolate - 3-6h
atropine 5-6d
Tx bladder spasm, incontinence
oxybutinin - M3 antagonist
solifenacin - more M3 selective
Trospium - less CN effects
Contra indications to atropine
BPH precaution
Glaucoma, MG, GI obstruction, paralytic ileus
Alpha 1 agonist
phenylephrine
Alpha 2 agonist
Clonidine
Beta 1 agonist
isoprenaline (1=2), dobutamine
Beta 2 agonist
isoprenaline (1=2), dobutamine
Phentolamine
reversible alpha 1+2 antagonist
tx pheochromocytoma, skin ischaemia secondary to adrenaline
given IV
phenoxybenzamine PO longer half life (irreversible)
Alpha 1 selective antagonists
Tx BPH and HTN
prazosin (T1/2 3h) doxazosin an terazosin (T1/2 12)
F0,6, VD0.6, 98% PB
Tamsulosin alpha 1a more prostate specific
Beta blocker OD
dec BP and HR, dec BSL
propranolol - Seizure, prolonged QRS and PR
sotalol - inc QTc
Tx glucagon, atropine and isoprenaline
Beta 1+2 + alpha 1 blockers
labetolol, carvedilol
B1+2 blockers
Timolol
Propranolol
Nadolol - long T1/2 15h
Selective B1 blockers
Atenolol - less well absorbed, renally excreted)
Metoprolol
Esmolol
Glaucoma inc outflow
cholinomimetics - pilocarpine
prostaglandins - latanoprost
non selective alpha agonists - epinephrin
Glaucoma dec aqueous humor
alpha 2 agonists - brimonidine
Beta blockers - timolol
Diuretics - acetazolamide
AH is BAD
Mechanism local anaesthetic
bind intracellular part voltage gated sodium channel in open and active state, inhibits depolarisation
Uncharged crosses membrane, charged active at receptor
In rested state difficult to activate (harder than in inactive state)
sympathetic affected first, then small myelinated fibres
Factors effecting local anaesthetic response
inc by inc K
dec by in Ca
Dec by acid
Inc by inc blood flow
Ester vs amide local anaesthetic
esters e.g. tetracaine procaine rapidly eliminated inplasma by pseudocholinesteraases
amides e.g. lignocaine metabolised in liver longer T1/2
Camparison half life lical anaesthetic
Prilocaine 1.5 - 50%pb vd261
Lidocaine 1.6
Bupicocaine 3.5 - 95%pb
Ropivocaine 4.2 vd47
SE Locals
Prilocaine - methaemoglobinaemia
Lidocaine - seizures
Bupivocaine - arrhythmias
SE suxemethonium
increased intra abdo pressure
Increased IO pressure
Increased Icp
excess salvation
muscle pain
bradycardia
Increased K+
Malignant hyperthermia
Atracurium
isoqunolone non depolarising muscle relaxant
metabolised spontaneously/ by plasma esterases so good in hepatic and renal failure
metabolites can cause seizures
Causes histamine release
! seizures
Half lives muscle relaxants
short - 5m sux and mivacurium
mid - 20-40m vec, roc, atracurium
long - >40m panc, tubacurarine
Pancuronium
steroid non depolarising muscle relaxant
long half life >40
Highly protein bound
Renally excreted (other steroid hepatically)
Increased CO an HR (sympathomimetic)
Emergency drugs given down ETT
Naloxone
Atropine
Vasopressin
Epinephrine
Lidocaine
Mechanism volatile anaesthetics
increase threshold for firing via K+ channels therefore reduce neuronal activity
Volatile MAC
Most to least
NOS
des
sevo
iso
en
halothane
methoxy
n.b. metabolism other way round i.e. methoxy most metabolised
AEs volatiles
hepatic - halothane
renal - methoxy + en + sevo
megaloblastic anaemia - NOS
inc ICP
inc HR - des + iso
Des best for heart problems
Typical antipsychotics
D2 antagonists
Phenothiazines - chlorpromazine, fluphenazine (more potent)
Thioxanthines
AUTONOMIC SEs
Butyrophenones - haloperidol
EPSEs
Atypical antipsychotics
5HT2 antagonists
greater effect on negative symptoms
Thioridazine
typical antipscyhotic
most fatal in OD, inc QTc
Drug increasing lithium conc
Thiazides
AceI + ATII
NSAIDs
Metronidazole
Hyponatraemia
Dehydration
Drugs decreasing lithium conc
Acetazolamide
Osmotic diuretics
Theophyline
Caffeine
Buspirone
Non sedating anxiolytic
partial 5HT and A1 agonist
D2 antagonist
Mechanism benzos and barbs
both bind near GABAa receptor opening chloride channels causing inc GABAnergic inhition
Benzo frequency
Barbiturates length
barbs also inhib glutamate
Flumazenil
reversal benzos
binds alpha 1 subunit GABAa
reverses except resp
interacts TCAs
Benzo with no active metabolites
lorazepam
Drug increasing level/ duration anaesthetic muscle relaxants
gentamicin
Metabolism benzos
hepatic oxidation via p450 then conjugation to glucoronides
Ethanol metabolism
via alcohol dehydrogenase and MEOS to acetylaldehyde
via aldehyde dehydrogenase to acetate
Fomepezil
alcohol dehydrogenase inhibitor
Aldehyde dehydrogenase inhibitors
Disulfarim
Metronidazol
Trimethoprim
Drugs tx ETOH abuse
naltrexone - opioid receptor antagonist
acamprosate - NMDA antag, GABA ag
disulfarim - aldehyde dehydrogenase inhibitor
Methanol poisoning
metabolised by alcohol dehydrogenase to formaldehyde and formic acid
dec VA, seizures, brady
treat with ETOH and fomepezol
Ethelyne glycol poisoning
via alcohol dehydrogenase to glycoaldehyde -> glycolic acid -. oxalic acid
calcium oxalate in kidneys - renal tubular necrosis, hypocalcaemia
high anion gap acidosis
formic acid - toxic to retina
Tx ETOH, fomepezol, bicarb, dialysis
MAOIs in parkinsons
Mainly MAOb but some a action a high dose
Rasagaline selegeline
adjuvant to levodopa
CI with SSRIs an TCAs risk seratonin syndrome
COMTi
Entacapone
decreases levodopa breakdown peripherally
does not enter CNS
prolongs levodopa action
increases tox levodopa
tolcapone - hepatotoxic
Benztropine
Muscarininc antagonist in basal ganglia
reduces tremor and rigidity in parkinsons
Antiemetic in parkinsons
domperidone - doesn’t cross BBB
Ergot derivatives
ergotamine
agonist 5HT3 and A1
causes vaso constriction
!! risk MI, gangrene, ischaemic bowel from prolonged vasopspasm
Tryptan mechanism
5HT1 agonist
- cranial artery vasoconstriction
- inhibit nerotransmission
- inibitis neuro inflam peptides
Thioridazine
Typical antipsychotic
Increases QTc
Most potent
Na valproate PK
A: po/iv
D: small vD 0.15,T1/2 9-18h, 90%PB
Examples TCAs
imipramine, amitryptaline
Example MAOi
mocelbamide, phenelzine, selegeline
Barbiturate excretion
in urine completely metabolised, except phenobarbitone - 30% unchanged
Chlorpromazine SE
postural hypotension, impotence and failure to ejaculate
Cholestasis
Antiepileptic causing hyponatraemia
carbemazepine
Half life atropine
2h
cycloplegic effects 6-7days
Beta blocker low vD
atenolol - not lipid soluble
otherwise mainly high vD
Contraindication phenobarbital
porphyria
T1/2 midazolam, diazepam
M: 2-4h (tmax 15-20m)
D:20-80h
(tmax 1-2h)
Weak bases, absorbed in SI
Amantadine
increases dopamine synthesis and release
antiviral
Not metabolised
Dopamine agonists
bromocriptine (ergot), pramiprexole, ropinarole
Carbidopa
inhibits AAD (peripheral metabolism ldopa)
reduces dose ldopa by up to 75%, increases amount crosses BBB
Levodopa interactions and CI
MAOi - hypertensive crisis
B6 - inc peripheral decarboxylation
CI - psychosis, angle closure glaucoma, PUD, melanoma
Benzos short half life
zolpidem and triazolam
Local anaesthetic pK
8-9
cations when injected
Works on open na channels
Treatment absence seizures
ethosuximide
sodium valproate
clonazepam
Duration withdrawal benzodiazepines
2 weeks plus
