Clinical Pharmacology of Analgesics Flashcards
what is the definition of analgesia
strictly an absence of pain but clinically a reduction in the pain perceived
what are the classes of analgesic drugs
- opioids
- NSAIDs
- local anesthetics
- alpha 2 agonists
- ketamine
how do opioid analgesics work
activate μ, 𝛿; κ opioid receptors to reduce neuronal excitability
what are the effects and side effects of opioids (6)
- analgesia
- sedation (excitement)
- euphoria/dysphoria
- respiratory depression
- nausea (+/- vomiting)
- reduced gut motility
what are the pharmacokinetics of opioids
poor oral bioavailability
what is the receptor effector pathway of opioids
all opioid receptors are GPCR
- inhibit adenylate cyclase –> decreases cAMP
- promote opening of K+ channels
- inhibits opening of voltage gated Ca2+ channels
what are the indications of opioids (5)
- to relieve pain (acute > chronic, moderate/severe > mild)
- to provide sedation: alone or in combo with other drugs
- to reduce required dose of general anesthetic
- to treat diarrhea
- to control coughing
what are the contra-indications of opioids (2)
- exisiting hypoventilation: ex. myasthenia gravis –> except where pain is inhibiting adequate ventilation (fractured ribs)
- elavated intracranial pressure (ICP): ex. head trauma or brain tumours –> opioids increase PCO2 which leads to cerebral vasodilation & further increases ICP
what are the opioids authorized in vet med
- buprenorphine
- butorphanol
- fentanyl
- methadone
- pethidine
- tramadol
what receptor is activated by the opioid
primarily by μ
what receptor produces most of the opioid side effects
μ
resp depression, constipation etc
what is the difference between a full and partial agonist
full: more efficacious
partial produces a sub-maximal response
what is the mechanism of action of NSAIDs
inhibit production of prostaglandins & thromboxanes by cyclo-oxygenase enzymes (COX)
what are the effects of NSAIDs
- analgesia (anti-hyperalgesia)
- anti-inflammatory
what are the side effects of NSAIDs
- dyspepsia, GIT ulceration
- renal toxicity
- hepatic toxicity
- hepatic toxicity
- effects on hemostasis
what are the pharmacokinetics of NSAIDs
marked interspecies variability
what do indications of NSAIDs include (4)
- pain management: acute and chronic
- inflammatory disorders: antipyretic agents, endotoxemia
- management of pro-thrombic states: feline hypertrophic cardiomyopathy
- specific tumours: transitional cell carcinoma of the urinary bladder
what are contra indications of NSAIDs (8)
- acute or chronic renal disease
- impaired hepatic function
- GI tract disease/disorder, especially ulceration
- hemostatic disorders: von Willebrand’s disease & thrombocytopenia
- low effective circulating volume: due to cardiac failure, hypovolemia or shock
- patients concurrently treated with steroids
- breeding, pregnant or lactating animals (potentially teratogenic): PGs have role in ovulation, embryo implantation, parturition
- patients with unstable asthma: increased production of leukotrienes
what are NSAIDs authorized in vet med
phenylbutazone, meloxicam, carprofen, ketoprogen, vedaprofen, flunixin, tolfenamic acid, cimicoxib, firocoxib, mavacoxib, robenacoxib
what is the difference between COX 1 and COX 2
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
what would decrease the risk of GI toxicity of NSAIDs
increasing specificity of COX 2
what is the mechanisms of local anesthetics
block sodium channels preventing the initiation & conduction of action potentials
what are the effects and side effects of local anesthetics (4)
- analgesia (block neuronal transmission)
- antidysrhythmic action
- CNS toxicity: twitching, seizures, coma
- CVS toxicity: bradycardia, hypotension
what are the pharmacokinetics of local anesthetics
activity affected by tissue pH
ionization slows onset
becomes more ionized in low acidic conditions –> inflammatory tissues
what are the techniques utilizing local anesthetics (7)
- topical application
- infiltration
- instillation into a cavity or wound
- intravenous regional analgesia (Bier’s block)
- peripheral nerve blocks
- epidural (extradural) block
- systemic administration
what are topical applications of local anesthetics used for
desensitize mucous membranes or skin
what is infiltration of local anesthetics used for
desensitize dermal & subcutaneous tissues
what is instillation into a cavity or wound of local anesthetics used for
intra-pleural
intra-articular
wound “soaker” catheter
what is IV regional analgesia (Bier’s block) local anesthetics used for
desensitize distal limb for limb amputation
what are peripheral nerve blocks using local anesthetics used for
diagnostic and/or therapeutic
many examples
ex. dental nerve block
what are epidural (extradural) local anesthetics used for
desensitize perineum, hind limb and caudal abdomen
what is systemic admin of local anesthetics used for
useful in painful dogs
what are the contra-indications of local anesthetics
mostly relate to techniques rather than drugs
- epidural: hemostatic injections, pelvic/spinal fractures, pyoderma
- IV admin: lidocaine only and use adrenaline free preparation, care in cats –> NOT BUPIVACAINE
what are authorized local anesthetics in vet med
- lidocaine
- procaine
- mepivacaine
how do you chose an analgesic (6)
- analgesic efficacy
- adverse effects/safety
- legislation
- pharmacokinetics
- potency
- cost
what are the predictable differences in analgesia efficacy
opioids:
full agonists > partial agonists
μ receptor agonists > κ receptor agonists
NSAIDs: no consistent differences
what are the predictable differences in safety
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
why should you avoid extrapolating analgesics between species
marked species differences in safety and half life
what do you need to consider when chosing a peri-operative analgesic
choose a drug approved for use in anesthesized patients
ex. carprofen, meloxicam, robenacoxib
what do you need to consider with route of administration
- hospitilized paiteints: drugs can be injected (IV, IM, SC) –> except pethidine IV causes significant histamine release so IM only
- at home: orally-active drugs are preferred
- patient temperment: oral drugs may be preferred in aggressive patients providing the tablet can be hidden in food
