Analgesia Flashcards
1
Q
why are opioids less commonly used for chronic pain management?
A
due to poor oral bioavailability
2
Q
which class of analgesia is not often used for chronic pain management?
A
opioids
3
Q
why are opioids a good choice as a perioperative drug?
A
They give good sedation and analgesia
4
Q
What effect can opioids have at high doses?
A
excitation
5
Q
what effect do opioids have on the heart?
A
bradycardia
6
Q
what effect do opioids have on respiratory drive?
A
cause respiratory depression
7
Q
what effects do opioids have on the GI system?
A
nausea and vomiting (premed), decreased GI motility
8
Q
what effects do opioids have on the urinary system?
A
various urinary effects - bladder less sensitive to urge to urinate
9
Q
which class of analgesic can have antitussive effects?
A
opioids
10
Q
what effect do opioids have on inotropy?
A
minimal effect
11
Q
what effects do opioids have on the eyes?
A
effects on the pupil - miosis in dogs (and most mammals), mydriasis in cats
12
Q
what are the pharmacological effects of opioids in mammals?
A
analgesia
sedation
excitation
bradycardia
respiratory depression
nausea and vomiting, decreased GI motility
various urinary effects
antitussive
effects on pupil (miosis/mydriasis)
13
Q
what type of system is the opioid system?
A
endogenous
14
Q
what are the 3 families of naturally occurring opioid peptides (neurotransmitters)?
A
beta-endorphin
leucine and methionine - enkephalins
dynorphins
15
Q
where are the opioid receptors mainly found?
A
in the brain and spinal cord
16
Q
what are the 4 types of opioid receptor?
A
mu
kappa
delta
NOP (nociceptin opioid peptide) receptor
17
Q
what are the subtypes of the delta opioid receptor?
A
delta 1 and 2
18
Q
where are the delta opioid receptors found?
A
brain
peripheral sensory neurones
19
Q
what is the function of the delta opioid receptors?
A
analgesia
antidepressant effects
convulsant effects
physical dependence
may modulate mu opioid receptor-mediated respiratory depression
20
Q
what are the subtypes of the kappa opioid receptor?
A
k1, k2, k3
21
Q
where are the kappa opioid receptors located?
A
brain
spinal cord
peripheral sensory neurones
22
Q
what is the function of the kappa opioid receptors?
A
analgesia and sedation
anticonvulsant effects
depression
neuroprotection
dissociative/hallucinogenic effects
dysphoria
diuresis
miosis
stress
23
Q
what are the subtypes of the mu opioid receptor?
A
mu 1, mu2, mu3
24
Q
where are the mu opioid receptors located?
A
brain
spinal cord
peripheral sensory neurones
intestinal tract
25
what are the functions of the mu1 opioid receptors?
analgesia
physical dependence
26
what are the functions of the mu2 opioid receptors?
respiratory depression
miosis
euphoria
reduced GI motility
physical dependence
27
what are the functions of the mu3 opioid receptors?
possible vasodilation
28
where do opioid drugs act?
at the opioid receptors
29
what common opioid drugs are full agonists?
methadone and fentanyl
30
what common opioid is a partial agonist?
buprenophine
31
what common opioid is a mixed agonist-antagonist?
butorphanol
32
what is the antagonist for opioids?
naloxone
33
which opioids are associated with analgesia?
mu agonists
34
which opioids provide the most effective analgesia?
full mu agonists
35
why are full agonists effective analgesic agents?
they bind to and activate a receptor with the maximum response that an agonist can elicit at that receptor
36
why are partial agonists less effective than full agonists?
they bind to and activate a receptor but only have partial efficacy, even if they bind to all receptors
37
what is potency?
the amount of drug required to see a given effect
38
what is efficacy?
the relative ability of a drug-receptor complex to produce a maximum functional response
39
which is more potent out of methadone and buprenorphine?
buprenorphine
40
which is has better efficacy, methadone or buprenoprhine?
methadone
41
by which routes can opioids be administered?
IV
orally
subcut
IM
oral transmucosal (buccal)
42
why is pethidine not administered IV?
can induce allergic reactions
43
what route of opioid administration is less efficacious in cats?
subcut buprenorphine
44
why do opioids have poor oral bioavailability?
very significant first pass metabolism
45
what are the advantages of administering opioids IV?
rapid onset of action
reliable uptake
painless - drug volume unimportant
46
what are the disadvantages of administering opioids IV?
need IV access
47
what is the advantage of administering opioids IM?
reliable uptake
48
what is the disadvantage of administering opioids IM?
painful, particularly if administering large volumes
49
what is the advantage of administering opioids SC?
easy to perform
50
what is the disadvantage of administering opioids SC?
unreliable uptake
51
what is the advantage of administering opioids OTM?
easy to perform
52
what is the disadvantage of administering opioids OTM?
only certain opioids (cats and buprenorphine)
53
what is the advantage of administering opioids transdermally?
good for chronic use
54
what is the disadvantage of administering opioids transdermally?
no licensed products
55
what is the advantage of administering opioids epidural/spinal?
very effective analgesia for the right cases (mostly intraoperative)
56
what is the disadvantage of administering opioids eipdural/spinal?
no licensed opioids for this
technically difficult
57
what does the onset of action of a drug depend on?
route of administration
58
what is the peak effect of a drug?
the time it takes for a drug to reach the maximum concentration after administration of a drug that needs to be absorbed
59
which opioids are ultra-short-acting?
fentanyl (mins)
unlicensed - alfentanil, sufentanil, remifentanil
60
which opioids are short-acting (2hrs)
butorphanol
pethidine
61
which opioids are medium-acting (2-4hrs)
methadone and morphine
62
which opioids are longer-acting (6hrs)
buprenorphine
63
what has the main effect on duration of action of an opioid?
dose given
64
what are the 4 most common misconceptions surrounding opioid administration to animals?
opioids cause mania in cats
opioids cannot be re-dosed within their expected 'duration of action'
respiratory depression can occur
opioids cannot be combined with other classes of analgesic drug
65
why is 'opioids cause mania in cats' a misconception?
only occurs at really high doses and generally in pain-free cats e.g. overdosing at pre-med
66
why is 'opioids always cause respiratory depression' a misconception?
it is a significant issue in humans but with vet patients it is mostly an issue with patients who are anaesthetised where there is airway control and we can ventilate if necessary
67
which other drug cannot be given with opioids?
tramadol (and other opioids)
68
which opioid is a partial mu agonist?
buprenorphine
69
which opioid is a kappa agonist?
butorphanol
70
what do side effects of opioids mostly relate to?
potency - those with greatest analgesic efficacy have the greatest likelihood of side effects
71
when are side effects of opioids less likely to be seen?
when the animal is in pain
72
how do opioids cause bradycardia and how can this be treated?
vagally mediated
can be treated with anticholinergics (atropine, glycopyrrolate)
73
what can occur with low IV doses of anticholinergics to treat bradycardia?
might promote a worsening of the bradycardia
74
what can occur with high IV doses of anticholinergics to treat bradycardia?
tachycardia
75
how should you manage accumulation of opioids in the body?
decrease frequency of dosing
76
why can management of gut stasis with opioid use be tricky?
pain causes reduced gut motility but so do opioids
77
list the common opioid drugs in order of analgesic efficacy (least to most)
butorphanol
buprenorphine
pethidine
methadone and morphine
fentanyl
78
when might morphine be a better choice clinically than methadone?
if a CRI is needed
79
what are the effects of fentanyl?
dose-dependent respiratory depression
bradycardia
useful for CRI as very short-acting
80
what are the advantages of methadone compared to some other opioids?
equi-or more efficacious analgesia and reduced nausea/vomiting compared to morphine
minimal CVS and respiratory side effects
81
why is pethidine rarely used in practice?
short acting - limits post-operative use
large volume - painful IM
histamine release if given IV
methadone is just better lol
82
why is buprenorphine painful on injection and not palatable to cats?
multi-dose preparation has preservative
83
which schedule 3 opioid should be kept in a locked cupboard?
buprenorphine
84
does butorphanol have good analgesic efficacy?
no - if any it is short lived, likely to require higher doses than given clinically
85
does butorphanol give good sedation?
yes
86
why is butorphanol attractive to practitioners?
not subject to controlled drugs regulations
87
what must be considered when using naloxone?
analgesic effect of opioid will also be reversed - need to provide alternative
88
what is the advantage of using intra-operative local analgesia?
spares inhalational agent in CVS unstable patients
89
what dosing interval should be used for methadone if being administered repeatedly over several days?
12-18 hours to prevent accumulation
90
which opioids are used for CRI?
morphine, fentanyl if morphine inadequate
91
how do local anaesthetics work (broadly)?
by preventing an action potential in the nerve, preventing nerve conduction
92
what causes an action potential?
voltage-dependent opening of Na+ and K+ channels in the cell membrane
93
what does the Na/K pump do?
pump ions against their concentration gradient to maintain an electrical gradient
94
how is the membrane depolarised?
rate of Na+ entry exceeds K+ exit
95
how is the action potential generated
depolarisation sets off a Na+ positive feedback whereby more voltage=gated Na+ channels open and the membrane becomes more depolarised - if a threshold is reached, an AP is generated
96
how does the membrane repolarise?
when Na+ channels become inactivated and a special set of K+ channels open and K+ leaves the axon
97
where are voltage operated Na+ channels present?
in all excitable tissues
98
what do local anaesthetics do to the sodium channels?
block them, therefore blocking nerve conduction
99
what effect are local anaesthetics said to have?
membrane stabilising effect
100
what are the main types of nerves in the body?
motor, sensory and autonomic
101
what are the different types of sensory nerves?
proprioceptors, mechanoreceptors and nociceptors
102
what are the types of autonomic nerves?
preganglionic B
postganglionic C
103
why are larger diameter axons more resistant to LA block?
they are more heavily myelinated
104
which axons are more resistant to LA block?
larger diameter axons - more heavily myelinated
105
which axons are more susceptible to LA block?
c fibres (unmyelinated)
Aδ fibres (thinly myelinated)
106
why is there a nociceptive block before proprioceptive/mechanoreceptive/motor blockade?
C fibres and Aδ (nociceptive) fibres are preferentially blocked
107
which types of linkage can a LA have in structure?
ester or amide
108
what is the basic structure of a LA drug?
an aromatic group (lipophilic) with a basic side chain/tertiary amine (hydrophilic)
with an ester OR amide linkage
109
why is the side chain important in LAs?
only the uncharged form can penetrate lipid membranes and enter the nerve cell
110
what is the pKa of LAs?
weak bases (pKa 8-9)
111
how does the pKa affect onset of action of LAs?
the higher the pKa, the slower the onset of action
112
why are LAs less effective in inflamed tissue?
a greater proportion of the drug will be ionised and therefore less drug can penetrate the nerve membrane to bind to the sodium channel
113
list lidocaine, bupivicaine, procaine and ropivacaine in order of toxicity (least to most)
procaine
lidocaine
bupivacaine
ropivacaine
114
what is the relationship between LA toxicity and potency?
toxicity increases as potency increases
115
what affects the duration of action of LAs?
ease of penetration and amount of drug reaching sodium channels (lipid solubility)
strength of binding to the sodium channels
speed of removal (dependent on tissue perfusion)
metabolism of LA (ester vs amide)
116
what is the easy way to remember ester vs amide?
ester - no i in the name before the -caine
amide - i in the name before the -caine
117
how stable are ester linkages?
relatively unstable
118
how are ester linkages broken down?
rapidly broken down by pseudocholinesterase - hydrolysis of the ester link
119
which LA linkage is more stable?
amide linkage
120
how are LAs with amide linkage metabolised?
subject to biotransformation with conjugation in the liver
121
do ester or amide linkages have a longer half life?
amide linkages
122
what is formed as a product of ester hydrolysis?
PABA
123
what can production of PABA result in?
allergic reactions
124
how is PABA formed?
as a product of ester hydrolysis
125
does the CSF contain esterases?
no
126
what breaks down the amide link?
cytochrome P450 enzymes
127
what can affect breakdown of amides?
hepatic disease can prolong or inhibit metabolism
128
which drugs can increase breakdown of amides?
barbiturates - induce enzymes
129
which drugs can inhibit breakdown of amides?
drugs which inhibit P450 enzymes e.g. midazolam
130
why are local anaesthetics often made into a salt solution?
they are poorly water soluble
131
why can LAs sometimes sting on injection?
often are made into a hydrochloride salt solution which lowers the pH
132
which formulations can lidocaine come in?
sterile solutions for parenteral use
aerosols for nasal/airway use
topical patches
133
what is baricity?
the weight of one substance compared with the weight of an equal volume of another substance
134
why do LAs for epidural have high baricity?
to avoid spread high into the epidural space
135
what is added to epidural LAs to make them heavier?
glucose
136
what is the baricity comparator substance for spinal anaesthesia?
cerebrospinal fluid
137
why is adrenaline commonly added to LAs?
vasoconstrictor - reduces speed of systemic absorption and therefor prolongs duration of action
138
how does adrenaline prolong effects of LAs?
reduces the speed of systemic absorption
139
what are the benefits of adding adrenaline to LAs?
prolongs duration of action
reduced risk of toxicity
reduces bleeding at the injection site
140
what state must a drug be in to be systemically active?
unbound and unionised
141
what is the relationship between plasma protein binding, concentration and pH?
percentage binding decreases as concentration rises or pH falls
142
what is the significance of plasma protein binding with LAs and patients with liver failure?
reduced plasma proteins in patients with liver failure
143
which species is lidocaine licensed for?
dogs, cats, horses
144
what is the onset of action of lidocaine?
2-5 minutes
145
what is the duration of action of lidocaine?
20-40 minutes
146
which has a lower cardiotoxicity, lidocaine or bupivacaine?
lidocaine
147
which species is bupivacaine licensed for?
none - has to be used under cascade, owner needs to provide consent to use it
148
what is the duration of action of bupivacaine?
6 hours
149
which has a longer onset of action, lidocaine or bupivacaine?
bupivacaine
150
what is contained in EMLA?
mixture of lidocaine and prilocaine in a cream
151
how can maximum absorption of EMLA be achieved?
cover with an occlusive dressing
152
how long does it take to see the full effects of EMLA?
30-45 mins
153
what is EMLA commonly used for?
IV catheterisation
154
is EMLA licensed in veterinary species?
no
155
what are the main types of toxicity caused by local anaesthetics?
neurotoxicity
CVS toxicity
156
157
can local anaesthetics be re-dosed?
no
158
why should local anaesthetics always be drawn up into the smallest possible syringe?
essential to give accurate dose, especially in smaller patients
159
what type of toxicity is seen at lower concentrations of local anaesthetic?
CNS toxicity
160
what is seen in CNS toxicity with regards to local anaesthetic use?
generalised CNS depression that is proportional to the (unbound) drug -
minor behavioural changes
muscle twitching and tremors
tonic-clonic convulsions
CNS depression/respiratory depression and death
161
how can we treat CNS toxicity due to LAs?
symptomatic treatment - BDZs to control seizures, O2 suppplementation, intubation and controlled ventilation if required
162
what CVS signs are seen with LA toxicity?
hypotensions and dysrhythmias
163
how does LA toxicity cause hypotension?
depression of myocardial contractility
direct relaxation of vascular smooth muscle
loss of vasomotor sympathetic tone
164
which common LA typically causes dysrhythmias?
bupivacaine
165
how are dysrhythmias caused by LA toxicity?
lipophilicity means rapid entry to sodium channels during systole
drug remains bound to the sodium channel during diastole
presents as re-entrant arrhythmias
166
how can CVS toxicity as a result of LA use be treated?
symptomatically
anticholinergic for bradycardias
fluid therapy with inotropic support if needed
consider intralipid IV ('mop up' thr LA)
167
how can LA toxicity be prevented?
don't exceed 'safe' max dose
if greater volume needed, dilute with saline
use appropriately sized syringes for accuracy
use appropriate size needles to minimise tissue trauma
aspirate before injection to confirm not in blood vessel
168
which LA blocks can RVNs carry out?
any that don't enter a body cavity
169
which LA blocks can RVNs not carry out?
epidural/pleural catheter
170
what is epidural anaesthesia?
injection of anaesthetic drug into the epidural space
171
what is spinal anaesthesia?
injection of an anaesthetic drug into the sac of CSF surrounding the spinal cord and nerves
172
in which animals is epidural anaesthesia more difficult to perform?
in obese and pregnant patients
any other patients where anatomical landmarks are affected
173
how can epidural injection be made easier to perform accurately?
use of U/S or x-ray
174
what are some of the contraindications for epidural injection?
skin infection at puncture site
sepsis
coagulation impairments
175
can anaesthetics used for epidurals have preservatives in?
no - must be sterile and preservative-free
176
what else might be added to an epidural injection?
opioids
medetomidine
ketamine
177
what are the possible side effects of an epidural block?
hypotension
hypothermia
urinary retention
infections
slowed hair regrowth
178
what is the difference between local and regional anaesthesia?
size of affected area
local - small discrete area e.g. infiltration
regional - blocks a larger area
there is cross-over
179
what are some examples of loco-regional anaesthesia?
blocks - ophthalmic, dental, limb nerve blocks
intravenous regional anaesthesia
intra-articular
wound soaker catheters
180
which topical LAs are licensed?
only the laryngeal spray for feline intubation
181
where can infiltration be carried out?
anywhere on the body provided there is enough tissue to infiltrate
182
is infiltration local or regional anaesthesia?
local
183
give some examples of infiltration
testicular for castration
ovarian ligament
around a skin tumour to be excised
incisional line block
ring block of distal limb/tail
intraperitoneal
184
how is infiltration usually carried out?
injected in a V shape or reverse pyramid into the area of interest
185
can RVNs perform infiltration blocks?
not any that require entry into a body cavity (but could act as the VS's hands under direction)
186
what are the pros of initiating NSAID therapy for chronic pain (e.g. OA) in dogs?
quick onset of action - non-pharmacological methods take long time
extensive evidence base to support analgesic efficacy, effective doses and re-dosing interval
licensed in dogs and cats for short and long-term treatment
187
why is it important to manage chronic pain in patients?
chronic pain is maladaptive and of no benefit to the animal
the feeling of pain comprises the sensory discriminative aspect being processed by the brain and then interpreted with both physical and emotional components
pain is a significant welfare issue
188
what is nociceptive pain?
pain originating from tissues which are not part of the nervous system
189
what is neuropathic pain?
pain originating from tissues in the nervous system
190
what is released when nerves are damaged?
cholecystokinin
191
what does cholecystokinin do?
antagonises opioid-mediated analgesia
192
why are opioids less effective in patients with neuropathic pain?
cholecystokinin is released by nerve damage, which antagonises opioid mediated analgesia
193
which type of analgesics are less effective against neuropathic pain?
opioids
194
how do most NSAIDS work?
by inhibiting prostaglandin production from arachidonic acid by inhibiting the COX enzyme
195
where do most NSAIDs work?
in the periphery
196
where can NSAIDs work in the CNS?
in the dorsal horn by inhibiting COX (precise mechanism of action unknown)
197
what do the adverse effects associated with NSAID administration relate to?
the protective functions that prostaglandins have in the body
bow easily the NSAID can leave the circulation and cross into the tissues
198
what are the 2 types of prostaglandins?
consititutive - 'housekeeping'
inducible - those induced by inflammation
199
what leads to the side effects of NSAIDs?
blocking of the protective functions provided by the constitutive prostaglandins
200
which COX isoenzyme produces which type of prostaglandin?
COX-1 isoenzyme - constitutive
COX-2 isoenzyme - inducible
201
why are the newer NSAIDs advantageous in terms of patient safety?
they are more COX-2 specific and have less effect on the constitutive (protective) prostaglandins
202
what do all the veterinary NSAIDs with a peri-operative license have in common?
they all show COX-2 selectivity
203
how can renal side effects of NSAIDs be reduced?
prescribing those with a degree of COX-2 selectivity
204
what GI functions do prostaglandins have?
maintenance of mucosal blood flow
bicarbonate and mucous secretion
epithelialisation
205
what GI side effects can NSAID use lead to?
GI ulceration and bleeding
206
what do prostaglandins regulate in the renal system?
GFR
renin release
sodium excretion
207
why should we be wary of giving NSAIDs under anaesthesia?
blockade of the vasodilatory PGs may cause a decreased GFR at times of low circulating blood volume (e.g. hypotension, hypovolaemia) - can induce kidney failure
208
what renal side effects can NSAIDs lead to?
water retention and oedema
hypertension
may impair GFR in patients with renal disease of hypotension
may cause renal ischaemia in patients with hypotension
209
what are the hepatic side effects of NSAID use?
NSAID therapy will usually induce liver enzymes in normal dogs - link to hepatopathy?
210
what are the CNS side effects of NSAID use?
may see idiosyncratic dullness and lethargy in cats
211
what is important to consider in terms of haemostasis and NSAIDs?
older NSAIDs that are unspecific for COX can affect clotting
212
do newer NSAIDs affect blood clotting?
they will prolong markers of blood clotting if given for long courses (30-90 days) but these are not linked to clinical signs of bleeding
213
how can we reduce the risk of side effects with chronic NSAID use?
do not exceed licensed dose
do not give 2 NSAIDs concurrently
do not give with corticosteroids
do not give to hypotensive/dehydrated patients
warn owners about risks of NSAIDs
214
when is GI ulceration more likely with NSAID use?
if the animal has pre-existing GI ulceration, liver disease and/or is geriatric
215
why do we not commonly combine NSAIDs with gastroprotectants?
there is limited evidence to support combining with gastroprotectants/antacids/H2 antagonists
216
why should we not administer NSAIDs to patients with hypotension?
prostaglandins are essential in maintaining renal blood flow and GFR during hypotension
217
what signs should we tell owners to look for when administering NSAIDs?
vomiting/diarrhoea
signs of blood in the faeces
dullness
anorexia
218
which parameters should be monitored in animals on NSAID therapy (gold standard)?
clinical examination and history
haematology and biochemistry
urinalysis
blood pressure
219
when should patients be re-checked after starting NSAID therapy?
re-check regarding side effects 1-2 weeks after starting treatment (side effects most likely to occur in first 2 weeks)
220
how often should high-risk patients on NSAIDs be monitored?
NSAIDs should be avoided in high-risk patients
221
how often should medium-risk patients on NSAIDs be monitored?
rechecked monthly +/- blood work/blood pressure/urinalysis
222
which patients are medium-risk for side effects due to NSAID use?
those with concurrent disease in a target organ)
223
how often should low-risk patients on NSAIDs be monitored?
should be re-checked every 3-6 months
224
what are some other treatment options if NSAIDs are not efficacious alone/poorly tolerated?
NSAID cycling - swap drugs (only one licensed in cats at present)
introduction of analgesic adjunctive therapies e.g. gabapentin
non-pharmacological therapies e.g. diet, weight management, physiotherapy, acupuncture
225
