Analgesia Flashcards
(30 cards)
List the major classes of analgesic drug
NO PLAN • N- non-steroidal anti-inflammatory drugs (NSAIDs) • O- opioids • P- paracetamol • L- local anaesthetics • A- α2 agonists • N- NMDA antagonists
What are NSAIDs?
non-steroidal anti-inflammatory drugs
Definition:
• In literal terms ANY drug that has anti-inflammatory properties that is not a steroid..
• NSAID in the medical world is refined to mean any drug that exerts its anti-inflammatory effect through the inhibition of cyclooxygenase (COX)
The majority of NSAIDS used in practise are COX 2 selective = have more of an effect on COX 2
What is cyclooxygenase?
The enzymes that produce prostaglandins are called cyclooxygenase (COX). There are two types of COX enzymes, COX-1 and COX-2. Both enzymes produce prostaglandins that promote inflammation, pain, and fever
Mechanism of action of NSAIDS
The main mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins
When do we use analgesics?
For management of acute pain – pain that begins suddenly, usually sharp in quality,
Main affect NSAIDS
o Analgesia, Anti-inflammatory, Anti-pyrexia
How to admin NSAIDS
are acids therefore water soluble: administered IV, IM, SC, orally, and some are in topical preparations for dermal application
Side effect NSAIDS
o Affect renal auto regulation of blood flow in some species
o GI ulceration (horse hindgut, dogs and cats gastric or duodenal)
o Affect blood clotting: pro or anti
o Liver metabolism – can cause problems if previous liver damage, build up and toxicity
o Closure of ductus arteriosus
o Photosensitisation
o Hypersensitivity
Opioid
main analgesic effects occur in the dorsal horn (substantia gelatinosa) of the spinal cord
• prevent the release of excitatory neurotransmitters (substance P, glutamate) from nociceptor nerve endings, and/or reduce the responsiveness of connecting neurones to those signals
Also you find opioid receptors in places with inflammation = opioids will have a greater effect by reducing some excitatiry input into the spinal chord
Opiod admin
Main effects
IV, IM, SC, TM
o Analgesia
o Sedation/ narcosis - administered alongside phenothiazine (ACP) or butyrophenone (fluanisone) = neuroleptanalgesia
Side effects of opioids
Although list is long, relatively milk vs benefits:
o Bradycardia
more likely seen with full mu agonists and large dose, and also if already under GA Morphine (horses), methadone
o Respiratory depression
more likely seen with full mu agonists and large dose and also if already under GA, Morphine (horses), methadone
o Reduced GI motility
o ‘excitement’ – locomotor excitement (e.g. walk forward, headpressing)
Horse and cats more likely
Avoid admin things like butorphanol to horse want to sedate or show as encourages it to move forward
o Vomiting – particularly with morphine in SA but obvs not in horses!
o Addiction in people why opioids often subject to controls
o Dysphoria – extreme excitement unhappy way – admin too much
o Euphoria - extreme excitement happy way – admin too much
o Panting e,g. methadone in dogs particularly, not too worried
list opioid receptors
mu (µ), kappa (κ), and delta (δ)
(Forget about delta)
- Mu agonism = analgesia and narcosis
- Main analgesia
- Little sedation - Kappa agonism = sedation and analgesia
- Some analgesia, mostly in gut
- Provides sedation
Name full mu agonists (main drugs for analegsia in opioid class
- Morphine (horse), Methadone (SA), pethidine, fentanyl
- pethidine should NOT be administered IV as this causes histamine release
- Morphine and methadone are main full mu drugs get in veterinary species 3-6 hrs analgesia
- Some sedation, not as good as butotphanol
Name partial Mu agonist
o Partial mu agonist – not as great 2nd messenger so analgesia not as great as full. Good for intermediate pain. Lasts longer than other opioids 6-8 hrs analgesia
o used in companion animals the UK, very useful in cats
Name and talk about a mixed opioid agonist
• Butorphanol – great addition to sedation
o Mixed agonist (mainly agonistic at kappa and Mu antagonist)
o used in companion animals the UK
o Kappa agonist so useful for enhancing sedation but nothing painful
o Main opiod sedative, less analgesia
How can we admin opioids?
o IV o IM o SC o PO o Topical o Transmucosal o Extradural (epidural) or spinal o Synovial o BUT bioavailability of oral admin is generally poor so pretty much everything other than oral.
Paracetamol
- Still do not know precise mechanism of action
- serotonergic and cannabinoid pain pathways in the CNS BUT very weak COX effects
- NOT an NSAID => does not have COX inhibition side effects e.g. GI ulceration, renal blood flow, patent ductus arteriosus
- Can use it alongside NSAIDs
- Licensed in dogs and pigs
Route of admin para
• Routes of administration:
o excellent bioavailability after oral use in all species tested in (horses and dogs), IV injectable off licensed (human) formulation available useful in small animals – 1ml/kg
main effect para
• Main effects: Analgesia, Anti pyrexia
o Although little evidence on how good of an analgesic it is
o Used lot though
o Really good antipyrexic – think due to COX 3 in hypothalamus, pituitary
• Side effects:
o Hepatotoxicity: requires hepatic metabolism so care in animals with impaired hepatic function (monitor liver enzymes e.g. osteoarthritic patients if on paracetamol)
o Hypotension IV formulation if injected too rapidly
Admin over 20 mins
o TOXIC IN CATS (destroys rbc’s - DO NOT USE! NEVEREERERER
Local anaesthetics
2 types: Amides and Esters
- The only TRUE analgesic as they actually STOP input. All others reduce pain
MOA Local anaesthetics
o Administer outside nerve fibre
o Crosses cell membrane into centre axon
o In centre changed to a form that acts on receptor
o Effect on action
o Works by:
Blocking Na channels in cell membrane of neurones, stop action potentials
Stopping AP, stop transmission of neuronal inputs into spinal chord, along SC and into brain. TRUE analgesic
Local anaesthetics amides
• Anti arrhythmic (class Ia) – sodium channel blockers blocked in any excitatory cells (including in heart)
• Lidocaine (SA), mepivacaine (horses), bupivacaine (SA)
o AMIDES
o last longer, liver metabolism required to break down
o small animals and horses
o Lidocaine thought to have anti-inflammatory and Pro kinetic effect
Local anaesthetics esters
• Procaine (farm animals) o ESTERS o breakdown quickly in tissues by tissue esterases so have short duration of action o best used topically o short acting
What are local anaesthetics influenced by?
o Vasodilation E.g. lidocaine. The greater the degree of vasodilation the shorter the duration of action as drug ‘washed’ away. The degree of vasodilation also affects potency (as drug does not hang around for long) o Tissue distribution - The ability of the drug to spread through the tissue to the site of action i.e. the nerve, or tissue affects the speed of onset i.e. better distribution = faster onset but may also get shorter duration o pKa (degree of ionisation): unionised form is the active form and crosses cell membranes more easily. High pKa = more ionised drug => slower onset of action o Lipid solubility - high lipid solubility means cross cell membranes easily= fast onset action o Protein binding - highly protein bound l.a.’s last longer as ‘protected’ from metabolism by liver e.g. bupivacaine has higher protein binging then lidocaine so lasts longer
