Opioids Flashcards
Classification of opioids
Natural
Semi-synthetic
Synthetic
Natural opioids
Alkaloids derived from the opium poppy (morphine, codeine)
Semi-synthetic opioids
Chemically derived from opiates (diamorphine, hydrocodone)
Synthetic opioids
not chemically derived from opiates (fentanyl, pethidine, tramadol)
Opioids receptors
μ receptors (MOPr)
κ receptors (KOPr)
δ receptors (DOPr)
Opioids receptors bind to what type of proteins ?
Gi or Go
Gi protein function
Inhibits adenylate cyclase > reduces activity of protein kinase A
Go protein function
Galpha subunit binds to Ca2+channels > less Calcium enters cell L
Gbetagamma subunit binds to K+ channels > more K+ leaves cell
Most important opioids receptors
MOPr (gamma)
Endogenous opioids
Peptide hormones/ neurotransmitters generally released in response to pain and stress; induce analgesia
β-endorphins
produced in and released from pituitary gland; also elevates mood. Mostly acts via μ receptors
Enkephalins
released throughout brain; involved in regulation of nociception and elevates mood. Acts via μ / δ receptors.
Dynorphins
induces analgesia and but also dysphoria (anxiety, depressive symptoms) via κ receptors
Key sites of action for opioids
Peripheral
Spinal
Supra-spinal
Main site of action for opioids
Spinal
MOA of opioids
Pre-synaptic and post-synaptic suppression
Opioids are most potent at
spinal level= inhibition of presynaptic vesicle release and postsynaptic excitability in dorsal horn
Side effects of opioids on CNS
Drowsiness
Unconsciousness (overdose)
Decreased cognitive function
No clinical e edit
Side effects of opioids on Chemoreceport Trigger zone (CTZ)
Nausea
Vomiting
Side effects of opioids on Limbic system
Euphoria
Anxiolytics
Potential for abuse
Opioids receptors in enteric nervous system effect in the GI tract
Decreases gastric motility Increased water reabsorption Decreased acid secretion
Why can opioids be sued as a treatment for diarrhoea?
Decreases gastric motility Increased water reabsorption Decreased acid secretion
Side effects of opioids of GI tract
Constipation for other therapeutic uses
Effect of opioids on immune
Mast cell degranulation > Pruritis
Effect of opioids on vascular use
Histamine release > vasodilation> risk of hypotension
Effect of opioids on heart
SNS suppression > PNS enhancement (via CNS) :
Miosis
bradycardia
Cardioprotection after MI
Effect of opioids on respiratory system
Reduced sensitivity to hypoxia (via CNS medulla) > respiratory depression
Benefits of opioids on respiratory system
Treats breathlessness, cough, acute pulmonary oedema
Clinical use of opioids
Analgesia
Antidiarrhoeals
Antitussives
Opioids side effects
Drowsiness Constipation Dizziness & confusion Pruritus (some) Nausea & vomiting Euphoria Dependance & withdrawal Overdose (unconsciousness, Opioid drugs death by respiratory depression)
What is tolerance?
decreased sensitivity to drug with chronic use: increased dose required for similar effect
What cause drug tolerance in opioids
desensitisation and endocytosis of opioid receptors
Opioids withdrawal symptoms
Restlessness, anxiety, insomnia (early)
Diarrhoea, nausea, abdominal cramps, tachycardia,
high blood pressure (late, often intense)
Codeine is converted into morphine via
Hepatic metabolism
Morphine
Strong analgesic used in moderate-severe pain.
Also used in myocardial infarction, acute pulmonary oedema and dyspnoea
How is morphine administered?
Oral or injection
Infusion pumps
Analgesics often measured by “equianalgesic” comparison to which opioid?
Morphine
Codeine
Weak opioid analgesic & cough suppressant
____ of codeine is converted to morphine in first pass metabolism.
20%
In approximately 10% of population codeine is not effective, why?
Limited CYP2D6
Co-codamol
Codeine + paracetamol
Most common opioid taken
Codeine
Diamorphine (heroin)
Strong opioid analgesic severe pain Also used after myocardial infarction
Properties of diamorphine
Highly lipophilic – rapidly crosses BBB Vastly increases euphoric experience Major drug of abuse
Diamorphine as administered only via
Injection - due to first pass metabolism to morphine with oral administration
Pethidine
Weak opioid
Synthetic, minimal histamine release, ~30% effective as morphine. Fast acting & short half-life. Anticholinergic metabolite (norpethidine).
Fentanyl
Strong opioid
Synthetic, does not cause pruritis. Lipophilic (transdermal, intrathecal injection). Very strong opioid,
~50-100x morphine.
Loperamide
- Pethidine analogue (discovered 1976)
- Non-analgesic: high affinity substrate for P- glycoprotein transporter in BBB
- Effective on myenteric plexus; decreased GI motility
- Enterohepatic circulation – minimal metabolism
- Treats diarrhoea, travel sickness, IBS
Naloxone
Short acting Opioid antagonist
Respiratory recovery in newborn infants
Precipitates withdrawal in addicts
Normally by injection; oral relief of opioid constipation
Naltrexone
Long-acting opioid antagonist
Opioid addiction recovery (subcutaneous implant) Alcohol addiction recovery
Pruritus in chronic liver disease
Methylnatrexone
Opioid antagonistic
Peripheral only – relieve opioid-induced constipation and nausea
Neuropathic Pain
Pain due to nerve disorder - diabetes, damage
How is neuropathic pain treated
With antidepressants (e.g. amitryptiline) or anticonvulsants (e.g. pregabalin, carbamazepine)
Tramadol
serotonin-noradrenaline reuptake inhibitor ~25% morphine equianalgesia
Used for mod-severe pain
Tramadol is more effective to treat
Neuropathic pain
Side effects of Tramadol
Less respiratory depression, but convulsion risk Hallucination risk
Tapentadol
Similar to tramadol but only inhibits NA reuptake. ~40% morphine equianalgesia.
