Lecture 24: analgesic drugs 1 Flashcards
Opoids/Opiates analgesics cause?
Analgesia and a state of imparied consciousness
3 types of pain after injury?
- Nociceptive Pain
- Inflammatory Pain
- Neuropathic Pain
1 and 2 areeasily treated with opiates but 3 is not as easy
Routes of administration?
- oral
- parenteral
- trans-mucosal
- transdermal
Opiate vs Opioid?
Opiate is a narcotic analgesic dervied from opium poppy (natural)
Opioids are synthetic narcotics that mimic the natural poppy plant
What are opioid receptors?
They are essentially pre-synaptic, belonging to the G-protein coupled family of receptors.
Activate Gi proteins inhibits adenylate cyclase enz causing decreased Ca channel permeability decreasing response.
also increases K+ conductance hyperpolarising synaptic neuron decreasing response
Synthesis of Opioid receptors?
Synthesised in the cell body (DRG) and transported towards the central terminal i the dorsal horn and towards the periphery. Peripheral receptors become active within hours or local tissue damage. This happens around the same time that immunocompetent cells that posess opioid receptors and have the ability to synthesize opioid peptides.
Opioids, agonists and antagonists?
Agonists - Activation of ALL receptor subclasses, though with different affinities (eg. Morphine, Fentanyl, Pethidine)
Antagonists - devoid of activity in ALL recpetor classes, just attach themselves. (Eg. Naloxone, Naltrexone) -can reverse overdose and/or the analgesic effects
Agonist-Antagonist - Agonist on one type and antagonist on others (eg. Nalorphine, pentazocine)
Partial Agonist - Activity on one or more but not all receptor types (eg. Bup-re-norphine)
Uses of Opioids?
Sedation and treatment of severe and moderate pain
Relatively ineffective for neuropathic pain
NB: marked individual variations in amount required - will need to titrate up until pain is gone but not too much to give respiratory depression.
Adverse effects of Opioids?
Precautions?
- Resp depression
- Drowsiness
- Constipation
- Itching
- N and V
- Vagally mediated bradycardia
- Hypotension via vasodilation
Precautions: Sleep apnea, COPD, elderly
Natural Opiates?
Semi-synthetic opioids?
Fully Synthetic opioids?
Endogenous opioid peptides?
1 - Morphine and codeine
2 - Bup-re-norphine, Oxycodone, Di-acetyl codeine (heroin)
3 - Fentanyl, pethidine, Methadone, tramadol
4 - Endorphins, endomorphins, Enkephalins, Dynorphins
Considerations when using Opioids?
Most effective and comfortable route
Round the clock for sever to moderate pain
Consider inter-patient variability
Use of adjuvents for enhancing opioid analgesia and reducing side effects - NSAIDS or antiemetics
Considerations regarding abuse?
It is the euphoric effect that leads to abuse
- physical dependence - withdrawal
- psychological/emotional dependence - leads to physical
- drug tolerance - use opioid rotation
- opioid addiction - compulsive use despite harm
Management of opioid withdrawal? slow method?
Replace with Methadone or Bup-re-norphine that have less chance of addiction
Clonidine blocking noradrenaline decr. tachycardia and high BP
Promethazine for N + V
Diazepam for muscle cramps
Anti diarrheal for diarrhoea
Management of opioid withdrawal? fast?
Under GA th patient is not subject to withdrawal discomfort
High dose of naltrexone to remove drug from recpetors and then oral dosing afterwards to continue to reduce the risk of relapse.
Morphine features?
- Powerful analgesic and sedation
- Cough supression
- Miosis (pin point pupil)
- Altered mood (euphoria and tranquility)
- Half life of approx 3h
- low lipid solubility = slow onset long duration
- metabolised in the Liver and excreted in the urine
Side effects of morphine?
- Resp depression
- N + V
- constipation
- addiction
- Biliary colic (constricts sphincter of oddi)
- Bradycardia and hypotension
Pethidine features?
- Synthetic analgesic
- Dry mouth, tachycardia but less biliary spasm
- give in tablet (bioavail. = 50%) or injection
- High lipid solubility = fast action
- same SE as the other opioids.
Fentanyl features?
- High lipid solubility = fast onset
- Strong Mu receptor agonist
- analgesic and anaesthetic
- SE similar to opioids
- IV, IM or transderman patches (for slow onset long acting)
Iontophoresis?
A method of transdermal PCA (patient controlled analgesia) administration of ionizable drugs in which the electrically charged components are propelled through the skin by an external electric field.
Methadone features? Uses?
- Well absorbed from all routes of administration
- Rapid onset (30-60min)
- No significant cognitive impariment and no euphoria
- Safe in renal failure as it can be secreted by other methods.
- For chronic and neuropathic pain as well as opioid withdrawal and detox
Tramadol features?
- Synthetic codeine analog
- good oral bioavailability
- inhibits noradrenaline and serotonin uptake - (both stimulate inhibitory inter-neuron)
- SE: N+V, dizziness, sedation, constipation, Seritonin syndrome if given with SSRI (antidepressants), reduces threshold of epilepsy.
Codiene features?
- treats mild to moderate pain
- supress cough and an anti diarrhoeal
- Is metabolised to morphine by cytochrome P450
Nitrous Oxide features?
- Powerful analgesic
- ENTONOX - 50% N2O in oxygen good for in the field pain relief
- N + V
- non addictive
- Euphoric effect
