Opioids and NSAIDs: Mechanisms, Actions, and Effects
Opioids: Neuroanatomic Basis of Pain
Pain stimulus, receptors, thermoreceptors, mechano, chemo, polymodal. Nerve fibers – A, C – SNC.
Analgesia
State of inhibition or suppression of pain without loss of sensory capacity; consciousness is unaltered.
Endogenous Opioid System
- Peptides endogenous antigens: proopiomelacortina derived from the proenkephalin and the prodynorphin.
- Widely distributed in the body.
Opioid Receptors
Mu (?), kappa (k), sigma (or), and delta (A) receptor subtypes exist. Present in CNS, PNS, intestine, inflammatory cells.
Classification by Activity
- Pure agonists: morphine, codeine, etorphine, fentanyl, methadone, pethidine, tramadol
- Partial agonists: Buprenorphine
- Agonist-antagonists: nalorphine, pentazocine
- Pure antagonists: Naloxone, naltrexone
Mechanism of Action
Stimulation of specific receptors presynaptically:
- μ: Analgesia, respiratory depression, euphoria, sedation, release of PRL and GH, and dependence
- δ: Analgesia, release of GH
- ε: Analgesia, sedation, dysphoria, diuresis
Distribution
All opioids have the ability to cross the blood-brain barrier (morphine has low capacity). Morphine binds to plasma proteins, but due to high hydrophilicity, only 35% of union occurs. Others bind 96% (codeine, methadone, and heroin).
Metabolism
Enzymes degrade these drugs in the liver by conjugation with glucuronic acid. Morphine is downgraded to morphine-3-glucuronide (M-3-G) and morphine-6-glucoronide. M-6-G is more potent than morphine.
Actions
Analgesia: They inhibit the transmission of painful stimuli, acting mainly in the CNS. The analgesia achieved by opioids is largely due to union with μ receptors.
Cardiovascular Effects
Respiratory Effects of Morphine
Butorphanol, Codeine
Gastrointestinal Effects
Loperamide
Immunological Effects
Morphine
Analgesic in almost all species, causes excitement in horses. In dogs, it is also indicated as a preanesthetic, antitussive, and antidiarrheal. It is very well adsorbed by VO, causes a drowsy state and pleasure, and may be antagonized by naloxone.
Fentanyl
Metabolized in the liver by hydroxylation or dealkylation, a more powerful medicine. 100 times more potent than morphine, with a high capacity for addiction. Used in chronic pain and can be combined with tranquilizers (droperidol) to perform neuroleptoanalgesia. Can be used in canines epidurally. Injections can be administered transdermally.
Butorphanol
Used in dogs and horses, 3 to 5 times more potent than morphine. Acts on μ receptors (antagonism) and κ (agonism). Has antitussive activity, 80% protein binding in plasma. Its analgesic metabolites have.
Loperamide
Most important effects in the gastrointestinal tract.
- Allows bowel movements to be slower, acting on the circular and longitudinal muscles.
- Antidiarrheal
NSAIDs: Mechanism of Action
Inhibition of COX, which prevents the synthesis of eicosanoids from arachidonic acid.
Pharmacokinetics
Most are weak organic acids, distributed in the tissues by passive diffusion.
Actions
- Antipyretic action (decreased febrile)
- Anti-inflammatory action (prostaglandins, inhibition of nociception)
- Analgesic
- Antiplatelet (TXA2)
Salicylates: Acetylsalicylic Acid
Today, it is synthesized from phenol and little used in veterinary practice. It joins COX1 irreversibly. Potent antipyretic agent. Inhibition of platelet aggregation.