non-opioid and opioidanalgesia Flashcards
(74 cards)
1
Q
analgesia
A
absense of pain in response to stimulation which would normally be painful
2
Q
anagesic
A
pain killers
drugs that result in analgesia
3
Q
maajor calsses of analgesics
A
opiod
non-opiod - NSAIDS, paracetomol, other
4
Q
nociceptive pain
A
adaptive, high threshold pain
early warning system
5
Q
inflammatory pain
A
adaptive, low threshold pain
tenderness and promotes repair
6
Q
proostaglandin synthesis pathway
A
essential fatty acids membrane phospholipids arachidonic acid prostaglandin H2 prostacyclin, prostaglandins, thromboxane
7
Q
what do NSAIDS do
A
block cyclo-oxygenase (COX) which is normally responsible for converting arachidonic acid into Prostaglandin H2
8
Q
GI adverse effects of NSAIDS
A
GI irritability, inflammation, bleeding
gastric/duodenal ulceration (bleeds/peforations)
9
Q
renal adverse effects of NSAIDS
A
no effect if normal renal function
fl;uid retention, oedema, hypertenson (significant in patients wth heart failure
renal dysfunction/failure (acute/chronic)
10
Q
platelet adverse effects of NSAIDs
A
increase risk of bleeding (non-selectve NSAIDs)
selective COX-2 inhibition leads to increased risk of thrombotic events
11
Q
respiratory adverse effects of NSAIDs
A
15% asthmatics get NSAID-induced asthma
12
Q
3 effects of NSAIDs
A
- anti inflammatory
- analgesics
- anti-pyretic effects (prevent or reduce fever)
13
Q
choice of NSAID depends on
A
- route of administration
- duration of treatment
- patient factors
- relative contraindications in renal failure, asthma, uncontrolled hypertension, previous GI ulceration/gastritis, inflammatory bowel disease, past stroke or TIA (except aspirin), upcoming surgery or other bleeding risk
14
Q
non selective NSAIDs
A
- salicylates - aspirin
- propionic acids - ibuprofen, naproxen
- phenylacetic acids - diclofenac, ketorolac (intramuscular)
- oxicam’s - meloxicam, piroxicam
15
Q
cox-2 selective
A
coxibs - celecoxib, parecoxib (IV), rofecoxib (withdrawn)
16
Q
advantages of COX-2 selective inhibitors
A
coxibs lower GI adverse events reduced risk of intraoperative bleeding do not cause bronchospasm in NSAID sensitive asthmatics reduced risk of renal adverse effects
17
Q
issues with selective cox-2 inhibitors
A
- rofecoxib was withdrawn from market in 2004 due to increased thromboembolic events
18
Q
when are NSAIDS and coxibs useful
A
- useful as non opiod analgesics
- useful in inflammatory condtions
19
Q
when are NSAIDs and coxibs less useful
A
- elderly
- risk of GI ulcers
- patients with CV risk factors
- patients with renal risk factors
- for prolonged use
20
Q
aspirin is used for
A
analgesc effects
anti-inflammatory effects
21
Q
analgesic aspirin dose
A
analgesic dose 300-900mg up to three times per day
22
Q
anti platelet effects of aspirin
A
prevention of acute myocardial infarction and stroke
23
Q
mechanism of acton of aspirin
A
at low dose it selectively inhibts cyclooxegenase
stops platelet activation - irreversible inhibition of platelt dependant thromboxane A2 formation - inhibits vasoconstricton and platelet aggregation
24
Q
commonest toxicity of aspirin
A
G side effects simlar to NSAIDs
bleeding - rsk of subdural haemorrhage
long term hgh dose can cause hepatic or renal impairment
25
reyes syndrome
occurs at therapeutic dose of asirin
uncommon, affects mainly children
hepatic failure, encephalopathy, cerebral oedema
mortality is up to 40%
aspirin not recommended for children <12 years
26
aspirin in overdose
1-2% mortality
affects metabolic state - uncouples oxidative phosphorylation
respiratory alkalosis - direct stimulation of respiratory centre
metabolic acidosis - premorbid state
renal papillary necrosis
27
paracetamol
acetaminophen
analgesic effect
antipyretic effect
no antiinflammatory effects
28
paracetamol method of action
only theories
29
paracetamol is a recommended first line anagesic for
osteoarthritis
musculoskeletal pain in elderly
patients with renal disease
treatment of cancer pain
30
paracetamol is inactive at
kidney - no renal impairment
GI tract - no peptic ulcer risk
inflammation - not an anti inflammatory
31
oral bioavailability of paracetamol
80%
32
metabolism of paracetamol
hepatic metabolism via glucuronidaton to 2 inactive compounds (excreted in urine)
normally a small amount of a highly toxic compound NAPQI (N-acetyl-p-benzoquinolone imine) is produces and rapidly inactivated by the liver
33
paracetamol metabolism in overdose or in abnormal liver function
NAPQI levels can increase and cause hepatocellular necrosis - fulminant liver failure
34
risks for paracetamol toxicity
- accidental overdose
- starvation, malnutrition, low body weight
- HIV
- alcoholism
- deliberate overdose - often unaware of danger
35
opiate
all naturally occuring substances with morphone-like proporties
36
opiod
general term that also includes synthetic substances with an affinity for opiod receptors
37
opiod receptors
abour 400 amino acids
7 transmembrane domains
inhibitory G-protein coupled receptors
3 major classes of receptors
38
opiod agonists
opiod agonists binds to receptor and cause inhibition of neurotransmitter release
- leads to hyperpolarization of nuerones (peripheral psinal cord, brain)
39
3 classes of opiod receptors
Mu, Kappa, Delta
40
Mu opiod receptor
```
analgesia
miosis - pupillary constriction
euphoria
respiratory depression
bradycardia
reduced gut motility
physical dependance
```
41
kappa opiod receptor
analgesia
sedation
depression
miosis
42
delta opiod receptor
analgesia
physical dependance
respiratory depression
43
opiod receptors in the brain
brainstem - mu
limbic system - kappa > mu
cortex - kappa > delta > mu
44
opiod receptors in the dorsal horn of the spinal cord
presynaptic (analgesia) - mu and delta
| postsynaptic - mu and kappa
45
opiod receptors in the PNS
on nociceptive fibres expressed after injury - analgesia - mu
46
morphine
naturally occuring mu receptor agonist
| oral, IV, IM, SC
47
morphine dosing
titrate to effects - minimise life threatening adverse effects eg. sedation, respiratory depression
5-10 minute onset of action
peak effect 30-60 minutes following intramuscular administration
duration of action 3-4 hours
48
morphine metabolism
metabolised in the liver to
morphine-3-gluconuride
morphine-6-gluconuride
nomorphine
metabolites are renally excreted
49
morphine-6-glucuronide
analgesic effect
| accumulates in renal failure
50
indications fro morphine use
moderate to severe acute pain
palliative care
used perioperatively - during anaesthesia and post operative analgesia
51
considerations for morphine
variable sensitivity to opiods
hepatic and renal failure
patients at risk of airway and breathing problems
52
side effects of the mu receptor
- miosis
- euphoria
- sedation
- respiratory depression
- reduced airway reflexes
- hypotension
- pruritis
- nausea and vomiting
- constipation
- urinary retention
- physical dependance
53
codeine
prodrug
inactive until metabolised in the body
often used in combination with paracetamol/ibuprofen
analgesic effect due to demethylaton to morphine
10x less potent than morphine
54
genetic variability for codeine
10% of patients lack the enzyme to convert codeine
genetic variability with CYP-2D6 enzyme
small proportion of people are rapid metabolisers there therefore have risk of adverse effects on normal doses
55
codiene bioavailability
good oral bioavalability - usualy taken orally (IM route available)
56
uses of codiene
mild to moderate acute pain
| anttussive (cough supressant)
57
side effects of codeine
nausea, vomiting, constipation
58
oxycodone
- synthetic opiod
| predominantly Mu-opiod receptor agonist
59
clinicala uses of oxycodone
moderate to severe pain relief
60
different preparations of oxycodone
immidiate release - endone, oxynorm
controlled release - OxyContin
controlled release with naloxone - Targin
61
naloxone
is an oopiod antagonist
| reduces opdiod induced constipation and is a deterant from abuse
62
adverse effects with oxycodone
similar to morphine
tolerance and dependance can occur with all preparations
increasing rates of addiction, abuse and overdose
63
tramadol
atypical central acting analgesic with relatively weak opiod effects
has effects on non-opioid pathways as well
64
mechanism of action of tramadol
- metabolised in the liver to active metabolite
opioid receptor agonist mu > kappa, delta
serotonin reuptake inhibitor
noradrenaline reuptake inhibitor
65
tramadol compared to morphine
at equi-analgesic doses, has less respiratory depression and less constipation
66
serotonergic effects of tramadol
nausea, vomting and confusion
| interaction with other serotonergic drugs - lowers seizure threshold, avoid in epilepsy
67
uses of tramadol
useful in situations to avoid opioid adverse effects
- respiratory depression, constipation, abuse, sedation, confusion
neuropathic pain
68
fentanyl
synthetic opioid
good parenteral, mucosal and transdermal option (good GI absorption but high first pass metabolism so not effective by oral route)
69
methadone
NMDA antagonist effect
good in neuropathic pain
major use is for opioid replacement in addiction (long half life over 24 hours, less sedating, less euphoria, still addictive)
70
pethidine
effective pain relief but side effects
short half life, increased risk of seizures especially in renal failure
avoid
71
opioid tolerance
```
developmetn of the need to increase the dose to achieve the same analgesic effects
all opioid agonists
usually takes 2 weeks with morphine
limits clinial use
does not imply addiction or abuse
```
72
physical dependance occurs with
abrupt discontinuation, substantial dose reduction or administration of antagonist
occurs with opiod use of longer than a week
73
opioid withdrawal symptoms
nausea, vomiting, anorexia, diarrhea, sweating, shivering, anxiety, depresion
74
analgesic ladder
mild pain - non opioid
mild to moderate pain - opioid for mild to moderate pain plus non-opioid
moderate to severe pain - opioid for moderate to severe pain plus non-opioid with/without adjuvant analgesic
