Clinical Pharmacology of Analgesics

Question 1

what is the definition of analgesia

Answer 1

strictly an absence of pain but clinically a reduction in the pain perceived

Question 2

what are the classes of analgesic drugs

Answer 2

1. opioids
2. NSAIDs
3. local anesthetics
4. alpha 2 agonists
5. ketamine

Question 3

how do opioid analgesics work

Answer 3

activate μ, 𝛿; κ opioid receptors to reduce neuronal excitability

Question 4

what are the effects and side effects of opioids (6)

Answer 4

1. analgesia
2. sedation (excitement)
3. euphoria/dysphoria
4. respiratory depression
5. nausea (+/- vomiting)
6. reduced gut motility

Question 5

what are the pharmacokinetics of opioids

Answer 5

poor oral bioavailability

Question 6

what is the receptor effector pathway of opioids

Answer 6

all opioid receptors are GPCR

1. inhibit adenylate cyclase –> decreases cAMP
2. promote opening of K+ channels
3. inhibits opening of voltage gated Ca2+ channels

Question 7

what are the indications of opioids (5)

Answer 7

1. to relieve pain (acute > chronic, moderate/severe > mild)
2. to provide sedation: alone or in combo with other drugs
3. to reduce required dose of general anesthetic
4. to treat diarrhea
5. to control coughing

Question 8

what are the contra-indications of opioids (2)

Answer 8

1. exisiting hypoventilation: ex. myasthenia gravis –> except where pain is inhibiting adequate ventilation (fractured ribs)
2. elavated intracranial pressure (ICP): ex. head trauma or brain tumours –> opioids increase PCO2 which leads to cerebral vasodilation & further increases ICP

Question 9

what are the opioids authorized in vet med

Answer 9

1. buprenorphine
2. butorphanol
3. fentanyl
4. methadone
5. pethidine
6. tramadol

Question 10

what receptor is activated by the opioid

Answer 10

primarily by μ

Question 11

what receptor produces most of the opioid side effects

Answer 11

μ

resp depression, constipation etc

Question 12

what is the difference between a full and partial agonist

Answer 12

full: more efficacious

partial produces a sub-maximal response

Question 13

what is the mechanism of action of NSAIDs

Answer 13

inhibit production of prostaglandins & thromboxanes by cyclo-oxygenase enzymes (COX)

Question 14

what are the effects of NSAIDs

Answer 14

1. analgesia (anti-hyperalgesia)
2. anti-inflammatory

Question 15

what are the side effects of NSAIDs

Answer 15

1. dyspepsia, GIT ulceration
2. renal toxicity
3. hepatic toxicity
4. hepatic toxicity
5. effects on hemostasis

Question 16

what are the pharmacokinetics of NSAIDs

Answer 16

marked interspecies variability

Question 17

what do indications of NSAIDs include (4)

Answer 17

1. pain management: acute and chronic
2. inflammatory disorders: antipyretic agents, endotoxemia
3. management of pro-thrombic states: feline hypertrophic cardiomyopathy
4. specific tumours: transitional cell carcinoma of the urinary bladder

Question 18

what are contra indications of NSAIDs (8)

Answer 18

1. acute or chronic renal disease
2. impaired hepatic function
3. GI tract disease/disorder, especially ulceration
4. hemostatic disorders: von Willebrand’s disease & thrombocytopenia
5. low effective circulating volume: due to cardiac failure, hypovolemia or shock
6. patients concurrently treated with steroids
7. breeding, pregnant or lactating animals (potentially teratogenic): PGs have role in ovulation, embryo implantation, parturition
8. patients with unstable asthma: increased production of leukotrienes

Question 19

what are NSAIDs authorized in vet med

Answer 19

phenylbutazone, meloxicam, carprofen, ketoprogen, vedaprofen, flunixin, tolfenamic acid, cimicoxib, firocoxib, mavacoxib, robenacoxib

Question 20

what is the difference between COX 1 and COX 2

Answer 20

two isoforms of COX

COX 1: normal hemostasis, many physiological functions, maintaining GI tract mucosa

COX 2: maintaining renal blood flow, nerve function, bone metabolism, also induced in response to inflammatory stimuli

Question 21

what would decrease the risk of GI toxicity of NSAIDs

Answer 21

increasing specificity of COX 2

Question 22

what is the mechanisms of local anesthetics

Answer 22

block sodium channels preventing the initiation & conduction of action potentials

Question 23

what are the effects and side effects of local anesthetics (4)

Answer 23

1. analgesia (block neuronal transmission)
2. antidysrhythmic action
3. CNS toxicity: twitching, seizures, coma
4. CVS toxicity: bradycardia, hypotension

Question 24

what are the pharmacokinetics of local anesthetics

Answer 24

activity affected by tissue pH

ionization slows onset

becomes more ionized in low acidic conditions –> inflammatory tissues

Question 25

what are the techniques utilizing local anesthetics (7)

Answer 25

1. topical application 2. infiltration 3. instillation into a cavity or wound 4. intravenous regional analgesia (Bier's block) 5. peripheral nerve blocks 6. epidural (extradural) block 7. systemic administration

Question 26

what are topical applications of local anesthetics used for

Answer 26

desensitize mucous membranes or skin

Question 27

what is infiltration of local anesthetics used for

Answer 27

desensitize dermal & subcutaneous tissues

Question 28

what is instillation into a cavity or wound of local anesthetics used for

Answer 28

intra-pleural intra-articular wound "soaker" catheter

Question 29

what is IV regional analgesia (Bier's block) local anesthetics used for

Answer 29

desensitize distal limb for limb amputation

Question 30

what are peripheral nerve blocks using local anesthetics used for

Answer 30

diagnostic and/or therapeutic many examples ex. dental nerve block

Question 31

what are epidural (extradural) local anesthetics used for

Answer 31

desensitize perineum, hind limb and caudal abdomen

Question 32

what is systemic admin of local anesthetics used for

Answer 32

useful in painful dogs

Question 33

what are the contra-indications of local anesthetics

Answer 33

mostly relate to techniques rather than drugs 1. epidural: hemostatic injections, pelvic/spinal fractures, pyoderma 2. IV admin: lidocaine only and use adrenaline free preparation, care in cats --\> NOT BUPIVACAINE

Question 34

what are authorized local anesthetics in vet med

Answer 34

1. lidocaine 2. procaine 3. mepivacaine

Question 35

how do you chose an analgesic (6)

Answer 35

1. analgesic efficacy 2. adverse effects/safety 3. legislation 4. pharmacokinetics 5. potency 6. cost

Question 36

what are the predictable differences in analgesia efficacy

Answer 36

opioids: full agonists \> partial agonists μ receptor agonists \> κ receptor agonists NSAIDs: no consistent differences

Question 37

what are the predictable differences in safety

Answer 37

opioids: partial agonists "safer" than full agonists (ex. risk of hypoventilation is less with buprenorphine than methadone) NSAIDs: specific COX 2 inhibitors less likely to cause GIT signs than non-selective COX inhibitors

Question 38

why should you avoid extrapolating analgesics between species

Answer 38

marked species differences in safety and half life

Question 39

what do you need to consider when chosing a peri-operative analgesic

Answer 39

# choose a drug approved for use in anesthesized patients ex. carprofen, meloxicam, robenacoxib

Question 40

what do you need to consider with route of administration

Answer 40

1. hospitilized paiteints: drugs can be injected (IV, IM, SC) --\> except pethidine IV causes significant histamine release so IM only 2. at home: orally-active drugs are preferred 3. patient temperment: oral drugs may be preferred in aggressive patients providing the tablet can be hidden in food