Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
65 Cards in this Set
- Front
- Back
|
Serotonin
|
- serotonin is neurotransmitter synthesised in the serotenergic neuron in CNC, enterochromaffin cells of GIT and platelets
- main breakdown product is 5HIAA, excreted in urine (test for this with carcinoid syndrome) |
|
|
serotonin syndrome
|
- syndrome due to drug induced changes in sensitivities of serotonin receptors in CNS
- risk factors: use of 2 or more serotergic drugs eg tramadol, SSRI, TCA, MAOI, ST Johns Wort, methylene blue (therapeutic use, overdose or drug interaction) |
|
|
serotonin syndrome clinical manifestation
|
1/ neurological: clonus, hyper-reflexia, tremor, rigidity, shivering (incoordination, ataxia)
2/ mental: confusion, elevated mood, coma (hyperactivity, agitation, restlessness) 3/ autonomic: fever/hyperthermia, sweating (tachycardia, tachyopnoea, hypo/hypertension) Major and minor criteria DDX: NMS, sepsis, MH onset typically within 24/24 of starting drug |
|
|
Serotonin syndrome treatment
|
- cease all serotenergic drugs
- supportive therapy, typically gets better in 24/24 - may need HDU monitoring in severe cases - anxiolysis with benzo - B blockers for control of autonomic symptoms - cooling for hyperthermia - cyproheptadine (antihistamine with antiserotinergic effects) - rarely chlorpromazine |
|
|
PCA safety
|
institution factors:
- PCA accreditation with annual review - PCA protocol - inservice on PCA use - prescription only by pain service - daily review by pain service - ceased by pain service with clear plan on oral analgesia and weaning Equipment - standardised equipment with prefilled bags and syringes with clear labelling - lockable PCA pumps that can only be accessed by use of key or code - PCA pumps can be interrogated for hourly and daily use - anti-reflux and siphon valves - IV maintenance fluid to prevent delivery of large bolus - naloxone on ward -mandatory use of O2 whilst on PCA patient: - tailored dose for patient - only prescribed to those with cognitive and physical ability to use - no other opioids to be given unless approved by APS nursing - hourly observations, incl RR, sedation scores and SpO2 - mandatory 2 accredited person check when initiating or changing program - ability to contact APS for review and metcall |
|
|
PCA limitations
|
- NESB background
- patient must have cognitive and physical ability to push button eg paediatrics, dementia, arthritis - cant be pushed by anyone else than patient - increased nursing requirement with 1/24 obs - must acquire equipment - only commenced and managed by APS - better at maintaining rather than establishing analgesia - PCA masking other pathology eg compartment syndrome |
|
|
Ficks Law of diffusion
|
= SA x conc difference x (solubility/square root MW)/ thickness
|
|
|
Buprenorphine
|
- partial mu agonist and kappa antagonist
- has ceiling effect for respiratory depression and sedation, but not analgesia - anti-hyperalgesia properties due to kappa antagonism - 30x potency of IV morphine when given transdermally - PK absorption given by ficks law of diffusion if transdermal (also can be given s/l or IV), slow onset and offset distribution: highly protein bound, steady state by 3/7 metabolism: 70% excreted unchanged in faeces (safe in renal failure), remainder metabolised by liver with extreme weak analgesic properties elimination: 1/7 for S/L, 12/24 for patch |
|
|
Peri-op management buprenorphine
|
- continue patch if seen pre-op (could increase by 25% or cease 3/7 pre-op and commence agonist but more labour intensive and difficult to manage, need pain specialist advice)
- use gabapentin to reduce opioid requirement - intra-op multimodal strategy (WHO analgesia, regional, ketamine, use 1/3-1/6 of total daily dose as breakthrough bolus dose - post-op hand over to nursing staff about patch, clear analgesia plan, referral to APS if pain issues |
|
|
codeine
|
- same structure as morphine, but methyl group added to 3 hydroxyl group -> increases lipid solubility but reduced activity
- comes as tablets or syrup, and in combination with other drugs - dose is 0.5-1mg/kg - 1/10th potency as morphine - PK A - 60-70% bioavailability, little 1st pass metabolism D - high lipid solubility M - ~10% metabolised to morphine (also C-6-G, norcodeine, hydrocodone) E - in urine, t1/2 3/24, dose reduce in renal failure |
|
|
codeine pharmacogenetics
|
- codeine metabolised by CYT2D6 to morphine
- 2D6 demonstrates genetic polymorphism (poor, intermediate, normal and ultrarapid metabolisers) - poor metabolisers get little/no analgesia (~9% of UK popn, 30% HK popn) - 5% are ultrarapid metabolisers, leading to sig increase in morphine levels (death in breastfed neonate from ultrarapid mother) - CYT2d6 can be influenced by other drugs |
|
|
predictive factors for chronic pain
|
patient factors
- psych vulnerability (anxiety, depression, catastrophising) - female - younger adults - workers compensation - genetic predisposition surgical - moderate/severe pain for >1/12 - repeat surgery radiotherapy and neurotoxic chemo - surgical approach and nerve damage (amputation, thoracotomy, mastectomy, inguinal hernia, CAGs, LUSCS) anaesthetic: - duration of post-op pain - post-op pain severity |
|
|
interventions to decrease chronic pain
|
general
- good surgical technique - multimodal analgesis to minimise postop pain severity specific (reduce pain at 6/12) - regional (epidural for thoractomy, for colonic resection + ketamine infn, prior to limb amputation to reduce phantom limb pain) - spinal for LUSCS - wound infiltration - paravertebral for mastectomy pharm - ketamine reduces phantom limb pain - gabapentin for mastectomy non-pharm - pre-op counselling |
|
|
chronic pain
|
- chronic pain present for >2/12 or beyond expected duration of normal tissue healing
|
|
|
pain
|
unpleasant sensory or emotional experience due to actual or potential tissue damage, or described in terms of such damage
|
|
|
peripheral sensitisation
|
- nociception via Adelta and C nerve fibres
- altered peripheral nociception peripheral sensitisation via release of inflammatory mediators from damaged cells eg 5HT, cytokines, prostaglandin which activate primary nociceptors and enhance transmission leading to hyperalgesia - once peripheral sensitisation has occured then low intensity mechanical stimuli which would not normally be perceived as painful are now perceived as painful |
|
|
central sensitisation
|
- NMDA receptor activation
- activation of primary afferent nociceptive fibres leads to release of glutamate which activates AMPA receptor and removes Mg plug from NMDA receptos - activation and prolongation of subsequent afferent nociceptive transmission = wind up - wind up occurs due to repeated stimulus causing an increase in response from dorsal horn neurons and leads to an increase in receptor size in DRG, decrease in threshold and increase in magnitude and duration of response - CNS microglial cell activation occurs from excitatory neurotransmitters producing COX2 which increases sensitivity of 2nd order neurons, leading to neuroplasticity via gene transplation - central thalamic and cortical modulation |
|
|
tolerance
|
predictable decrease in physiological effect of drug with time, with increasing drug requirement to achieve the same effect
|
|
|
physical dependence
|
-physiological to the constant presence of the drug
- abrupt withdrawal will lead to withdrawal symptoms |
|
|
addiction
|
- aberrant maladaptive drug seeking and taking behavious eg cravings, compulsive drug use and loss of control over use
- not predictable cf tolerance |
|
|
pseudoaddiction
|
- behaviour which seems inappropriately drug seeking but due to under treatment of pain
|
|
|
opioid induced hyperalgesia
|
- sensitisation of pro-nociceptive pathways leading to pain hypersensitivity
- important to differentiate from tolerance (both result from opioid use, both result in poor analgesia, but treatment different, with tolerance increase dose with OIH decrease dose) risk factors - remifentanil use (only short duration required, magnitude of effect in direct relation to dose given, abolished by co-administration of ketamine) - chronic opioid use protective factors - low dose - NMDA receptors - opioid rotation - paracetamol, NSAIDS - Mg - clonidine - N20 |
|
|
methadone
|
- synthetic opioid
- available as PO, PR or IV preparation - cheap - needs to be prescribed by pain specialist or GP with licence to prescribe PK A - good bioavailability M - no active metabolites, safe in renal failure. Possibility of interaction of drugs with CYTP450 system E - long t1/2 and variable (1st order and zero order kinetics), hard to titrate quickly due to long t1/2, increased risk of accumulation PD - mu opioid agonist, also NMDA antagonist and monoamine (5HT and NA) reuptake inhibitor - less euphoria less addictive potential - less likely to cause constipation - long Qt - equivalent dosing is hard, need pain specialist involvement |
|
|
opioid conversion
|
morphine PO: morphine s/c or IV = 3:1
morphine PO: oxycodone PO = 3:2 moprhine PO: hydromorphone PO = 4:1 morphine IV: hydromorphone IV = 5:1 oxycodone PO: oxycodone IV = 2:1 morphine IV: fentanyl IV = 50:1 eg 10mg morphine = 200mcg fentanyl fentanyl 25mcg patch = morphine 100mg PO/day buprenorphine patch 10mcg/hr = morphine PO 20mg/day IV 100: epidural 10: intrathecal 1 |
|
|
intrathecal morphine
|
- involves addition of preservative free morphine into subarachnoid space
- acts at laminae 1-2 of dorsal horn Pros: - spinal usually technically easy cf epidural - prolonged analgesia (dose related, >12/24 up to 18-22/24) - opioid sparing effect in 1st 24/24 - no motor block - earlier oral intake - earlier mobilisation, decreasing DVT risk Cons - need preservative free solution - risk of complications from spinal eg PDPH, nerve damage, failure, bleeding, infection - risk of drug error with dilution - respiratory depression, peak up to 7/24 but can occur up to 24/24 - N and V 40% - pruiritis 40% - need supplemental analgesia after worn off - urinary retention - risk of reactivation of herpes zoster - lacks titratability - needs 1/24 observations - need hospital and nursing familiarity |
|
|
gabapentin MOA
|
- anti-convulsant which binds to voltage gated Ca channels and decreases neurotransmitter release and neuronal excitability
|
|
|
gabapentin and acute pain
|
- single periop dose
- not a dose dependent effect/optimal dose is lacking pros - level 1 evidence for improved analgesia at rest and with movement - opioid sparing effect - reduced vomiting, itch and urinary retention - anxiolytic - increased early mobilisation - anti-hyperalgesia - reduced neuropathic pain in burns or traumatic nerve injury cons: - no reduction in post-amputation pain at 30/7 - additional doses dont add benefit (except in setting of neuropathic pain) - only available as PO preparation - no reduction in opioid side effects despite dose reduction - dizziness, ataxia, headache |
|
|
gabapentin and chronic pain
|
- effective for treatment of chronic pain
- proven role in diabetic neuropathy, post herpetic neuralgia, malignantpain, phantom limb pain, post spinal injury central pain - safer side effect profile cf TCA - not proven to prevent chronic pain (except mastectomy) |
|
|
N2O Advantages
|
PC
- cheap - odourless PK - low blood gas solubility means rapid onset and offset. Can use 2nd gas effect to speed inhalational induction - MAC sparing for other agents PD - CNS: analgesic - CVS: increased SNS outflow, more haemodynamic stability cf other volatiles - GU: no effect on uterine tone |
|
|
N2O disadvantages
|
PC:
- flammable unable to achieve 1 MAC at 1 atmosphere PK - diffusion hypoxia at end of case PD CNS: increase CMRO2 and CBF with increase in ICP, can increase gas filled spaces eg inner ear CVS: direct myocardial depression, increases PVR, increase homocysteine levels can increase ischaemia Resp: increase size of PTx, limits FiO2 - Haem: irreversibly inhibits methionine synthesis -> megoblastic changes in bone, teratoegnic, decreased immune fn - GIT: PONV |
|
|
ENIGMA trial
|
- anaesthesiology 2007
- multicentre RCT - compared Fi0.3/N2O and Fi0.8/air - found higher PONV, fever, wound infection, pneumonia, atelectasis - no difference in hospital stay (primary outcome) - trend towards higher AMI and mortality in N2O free group - unclear if due to N2O or higher FiO2 - ENIGMA 2 analysing Fi0.3/N2 vs Fi0.3/N2O on mortality and AMI |
|
|
NSAIDs advantages
|
- effective analgesia (nsNSAID and COX2 equal, level 1 evidence)
- part of multimodal analgesia strategy (WHO ladder) reduces opioid and opioid related side effects by 20-50% (particularly NV and sedation) - multiple preparations eg IV, IM, PO, PR, topical - cheap and readily available - COX2 not found to increase cardiac events after non-cardiac surgery |
|
|
NSAIDs disadvantages
|
- related to blockade of COX and prostaglandins
- bleeding with nsNSAIDS due to inhibition of platelet activity eg adult tonsils (not kids) - prothrombotic effects from COX2 specific due to unopposed action of thromboxane - renal impairment due to blockade of prostaglandin which acts to maintain RBF and GFR (higher risk if also on other nephrotoxins eg ACE, dehydrated, pre-existing renal impairment) - bronchospasm from prostaglandin inhibition. most common with aspirin. Only seen with nsNSAIDs, not COX2 - ?decreased bone healing (animal studies) - CV thrombotic events with COX2 |
|
|
Herbal medications
|
- no formal policy from ANZCA, ASA recommends cease 2/52 before surgery
- many herbal medications are except from licensing, so no QA - CVS: ephedra and ginseng have sympathomimetic effects - CNS: kava and valerian can prolong sedation - Haem: 4 Gs (ginger, garlic, ginseng and gingko) all have antiplatelet effects - Renal: herbal diurectics eg green tea, spearmint immune: prolonged use of echinacea can cause immunosuppression |
|
|
Naltrexone
|
-opioid agonist
- difference from naloxone is prolonged activity and increased bioavailability - used in ETOH and opioid abstinence therapy by preventing high associated with these drugs - available as tablets, also as s/c implant - has short half life but see prolonged blockade of receptors, may be daily, alternate daily or weekly dose - difficulty with pain management consult with pain specialist with elective surgery, cease 3/7 beforehand (risk of relapse) risk of opioid overdose if cease naltrexone due to increase in numbers of opioid receptors with emergency surgery, multimodal strategy, regional can use opioid but will need higher dose than usual due to competition at receptors |
|
|
ketamine pharmacology
|
- MOA: non-competitive NMDA receptor antagonist
- racemic mixture of R and S enantiomers PK - multiple routes: Po, IV, s/cut, IM, epidural, intrathecal - high lipid soubility metabolism via liver to norketamine then excreted in urine t1/2 2.5/24 PD: CVS: SNS activation increases CO and MAP, but direct myocardial depressant, increases PVR CNS: increases CBF and therefore ICP, dissociative anaesthetic, emergence delerium and hallucinations, concerns re apoptosis in children <2 Resp: increase RR and preserves laryngeal reflexes and tone GIT: NV and salivation |
|
|
ketamine use
|
1/ IV induction agent for GA
- dose is 1-2mg/kg, produced dissociative anaesthesia - rapid onset (poor endpoint) and duration 5-10mins can maintain via ketamine but risk of awareness due to difficulty in monitoring EEG - caution in those with catecholamine depletion as direct myocardial depressant effect 2/ sedation and analgesia for short painful procedures - PO or IV titrate to effect 3/ bronchodilation in severe asthma - via sympathomimetic effects - useful induction agent 4/ acute pain management - opioid sparing effect - bolus of 0.1mg/kg then 0.1-0.4mg/kg/hr - reduces central sensitisation and anti-hyperalgesic properties 5/ chronic pain - may switch off central sensitisation - effective for phantom limb pain 6/ pre-med in behaviourally difficult patient or paediatrics - rapid onset via IM route or oral route - 3mg/kg IM sedation (5-10mg/kg induction IM) - 3mg/kg PO 7/ field anaesthetic agent - can be used as sole agent - beneficial cardiorespiratory effects |
|
|
neuropathic pain
|
-pain arising as a direct consequence of a lesion or disease affecting the somatosensory system
- underdiagnosed - has no benefit cf nociceptive pain which occurs due to activation of nociceptors - can arise from damage anywhere to nervous system from peripheral nociceptors to cortical neurons |
|
|
paraesthesia
|
abnormal sensation, spontaneous or provoked
|
|
|
dysasthesia
|
unpleasant sensation, spontaneous or provoked
|
|
|
hypoesthesia and hyperesthesia
|
hypo: decreased sensitivity to stimulation
hyper: increased sensitivity to stimulation |
|
|
hypoalgesia and hyperalgesia
|
hypo: diminished pain response to normal noxious stimulus
hyper: increased pain response to normal noxious stimulus |
|
|
allodynia
|
pain from stimulus that doesnt usually cause pain
|
|
|
DN4 questionnaire
|
- 10 questions
- need score of ≥4 - is pain: burning, cold, electric shocks? - associated with: pins and needles, tingling, numbness, itching - examination: hyperesthesia to pinprick, hyperesthesia to touch, allodynia |
|
|
CRPS
|
- type 1 absence of nerve injury
- type 2 occurs after known major peripheral nerve injury - more common in hands in adults and feet of children - more common in females than males - causes include trauma (accidental, surgical, occupational) and diseases eg visceral (AMI), neurological (CVA), vascular (thrombosis) |
|
|
CRPS pathogenesis
|
- exact mechanisms unclear
- thought both central and peripheral mechanisms - central sensitisation play a key role in CRPS |
|
|
CRPS presentation
|
- triad of pain, trophic and vasomotor changes
1/ sensory/pain changes - all have hyperalgesia, 1/3 have allodynia - sensory loss is non-dermatomal (temp and proprioception are first changes) 2/ trophic changes - atrophy of skin, hair and nails - demineralisation of bone -> osteoporosis 3/ vasomotor - autonomic changes in colour and temperature (from vasodilation and constriction) - motor changes with involved limb becoming weak and co-ordination deficits |
|
|
CRPS treatment
|
- multidisciplinary approach
1/ pharmacological NSAIDS NAC gabapentin steroids calcitonin TCA NMDA antagonists sympathetic blocks (particularly in early CRPS) 2/ non-pharmacological - CBT - physio - OT - TENS - mirror therapy |
|
|
sympathetic block indications
|
1/ PVD
- acute vascular disorders eg inadvertent intra-arterial injection - chronic vascular disorders eg raynauds 2/ visceral pain - ischaemic cardiac pain - chronic pancreatitis -upper abdominal cancers 3/ neuropathic pain - acute herpes zoster - CRPS 4/ hyperhydrosis |
|
|
types of sympathetic blocks
|
1/ diagnostic
- done with LA - purpose is to see if benefit from performing therapeutic block - need to ensure purely sympathetic block 2/ therapeutic block - performed with LA and neurolytic chemicals such as phenol and ETOH - primarily used in cancer and PVD phenol destroys motor and sensory fibres but nerves can regenerate ETOH more effective at destroying nerve fibres |
|
|
stellate ganglion block
|
indications
- visceral pain from IHD or cancer - vascular insufficiency in upper limb - neuropathic pain eg phantom limb, CRPS side effects - horners syndrome (ipsilateral ptosis, anhydrosis, meiosis, enopthalmus) - ipsilateral blocked nose - inadvertent vascular injection - damage to RLN, phrenic nerve, brachial plexus - perforation of trachea or oesphagus - PTx - intrathecal injection anatomy - fused inferior cervical and first thoracic sympathetic ganglion - lies on prevertebral fascia over body of C7 |
|
|
how to perform stellate ganglion block
|
- head turned away and slightly extended
- palpate chabernac's tubercle by pushing SCM and carotid laterally - use C6 as dome of pleura to C6 - push posteriorly to push oesophagus and pleura out of the way - place needle onto CT, then walk inferiomedially to hit body of C6, withdraw 1-2mm then inject - check II for spread of LA |
|
|
coeliac ganglion block
|
- main junction of the autonomic nerves supplying the upper abdominal organs
- indications are upper abdominal cancers, chronic pancreatitis side effects - bleeding (retroperitoneal haematoma) - paralysis - hypotension - erectile dysfunction - intrathecal injection - PTx - perforation of viscus how to perform - position supine - ii guidance - aim to hit body of L1 then direct anteriorly |
|
|
phantom sensation
|
- defined as any sensory perception in the missing body part, excluding pain
- almost universal |
|
|
stump pain
|
- pain localised to the site of the amputation
- may be acute or chronic - risk increased by pre-op pain |
|
|
phantom pain
|
- noxious sensory phenomenon in the missing limb
- incidence 60-80% - typically early in onset - typically intermittent, rarely constant risk factors: - pre-op pain - degree of post-op pain - pre-op chemotherapy |
|
|
mechanisms of phantom pain
|
1/ peripheral factors
- increased risk if stump pain present - peripheral sensitisation - SNS involvement 2/ central sensitisation 3/ cerebral reorganisation with time |
|
|
treatment of phantom pain
|
Pharmacological
1/ gabapentin 2/ opioids 3/ calcitonin Effective for both stump and phantom pain 1/ tramadol 2/ TCA eg amitriptyline 3/ NMDA antagonists eg ketamine Non-pharmacological 1/ mirror 2/ sensory discrimination 3/ mental imagery of limb movement 4/ TENs |
|
|
treatment of stump pain
|
- Na channel blockers eg lignocaine
|
|
|
somatic pain
|
pain from skin and superficial structures, well localised and described as aching, sharp and throbbing
|
|
|
visceral pain
|
pain from organs, less well localised and described as deep ache or throbbing
|
|
|
incidence of opioid related side effects
|
- nausea 30%
- vomiting 20% - respiratory depression 10% - pruiritis 10% - sedation 5% |
|
|
preventative analgesia
|
- drug given with beneficial effects seen far in excess of drug duration eg gabapentin at reduced mastectomy pain at 6/12
|
|
|
pre-emptive analgesia
|
- asserts that pre-operative treatment more effective than odentical treatment after incision for surgery eg morphine 10mg at start of case vs at end
|
|
|
Opioid induced ventilatory impairment (OIVI)
|
- opioid induced central respiratory depression
- decreased consciousness - upper airway obstruction |
