Pharmacology: analgesics - opioids Flashcards
3 types of pain?
Nociceptive pain, neuropathic pain, neuroplastic pain
Describe the three types of pain - nociceptive, neuropathic, neuroplastic
Nociceptive pain
- Noxious stimuli can lead to the release of which chemicals?
- These chemical bind to sensory fibres (C fibres), and travel to the brain
- Role of higher centres in regulating pain?
- Descending inhibitory pathways can modulate pain signals
7 examples of analgesics?
Opioids
Paracetamol
NSAIDs
Antiepileptics
Anti depressants
Cannabinoids
Capsaicin
How might antidepressants treat pain?
Opioids, paracetamol and NSAIDs are good at treating what type of pain?
Wherease antidepressants and antiepileptics are good at treathing which type of pain?
Impact serotonin
Nociceptive pain
Neuropathic pain
OPIOIDS
MOA
- They act on ______ receptors in the ______ and ______ _____.
- They are agonists/antagonists for these receptors
- What are the three types of opioid receptors?
- Activation of which of these receptors produce the strongest analgesic effect?
Opioid receptors in the brain and spinal cord
Agonists
μ (mu), δ (delta), and κ (kappa)
mu
OPIOIDS
MOA
Mu opioid receptor
- What kind of receptor is it?
- Impacts of activating it (presynaptic and postsynaptic?)
- Overall impacts of this?
GPCR
Presynaptic: reduces cAMP, PKA activity, calcium ion influx/availability, NT release.
Postsynaptic: enhances potassium efflux to hyperpolarise the postsynaptic membrane
Reduced nociceptive signalling
OPIOIDS
MOA
Mu receptor
- Activation of mu receptors produces the strongest analgesic effect, however, it’s more likely to result in which 2 ADRs?
Respiratory depression
Physical dependence
OPIOIDS
MOA
- In addition to reducing the excitation and transmission of neurons, what is the other mechanism through which opioids work?
Activates descending inhibitory pathways (mainly via serotonin)
OPIOIDS
Indications?
Moderate-severe (acute) pain
Cough suppressant
Anti-diarrhoeal
OPIOIDS
Are they meant for acute or chronic pain? Why?
Acute - evidence shows they’re effective in treating acute pain
Not chronic - evidence doesn’t show superiority to placebo; and have ADRs
What are the traditional opioids?
What are the synthetic opioids?
Traditional
- Morphine
- Heroine
- Codeine
Synthetic
- Oxycodone
- Fentanyl
- Tramadol
- Methadone
- Buprenorphine
- Tapentadol
Morphine
- 2 formulations?
Oral (fast and slow release)
Injection (more reliable bioavailability)
Heroin (diamorphine)
- Describe its chemical structure, and how does it lead to its function?
2x morphine molecules
Makes it lipid soluble –> crosses the BBB more easily –> quicker euphoria
Codeine
- Relationship to morphine?
The pro drug of morphine
Hepatic metabolism converts 10% of codeine to morphine (hence, codeine is 10x less potent than morphine)
Oxycodone
- Is it very popular?
- Does it have a shorter or longer half life than morphine?
- Does it have both slow and quick release formulations?
Yes
Longer
Yes
Fentanyl
- Formulations
- Is it very potent, and is it very restricted?
Lozenges, patches, injectables
Yes
Tramadol
- Is it a typical or atypical opioid?
- Does it have a short or long half life?
Atypical
Short
Tramadol
- Why is it called a “dirty drug”?
- Hence, is it often used?
2 opioids used for opioid replacement (harm reduction?)
Methadone
Buprenorphine
Methadone
- Is it a weak or strong agonist?
- Is it short or long lasting?
Weak
Long lasting
Buprenorphine
- Is it an atypical opioid?
- Is it a partial or full agonist?
- Does it have a short or long half life?
- Formulations?
- Effect on respiratory depression?
Atypical
Partial agonist
Long half life
Oral film that sticks to the oral mucosa, patches
Has a ceiling effect on respiratory depression (can increase the dose, but resp depression doesn’t continue to increase)
Tapentadol
- Is it a typical or atypical opioid/
- MOA?
- What types of pain is it good for?
Atypical
Opioid agonist + NA reuptake inhibitor (antidepressant effects)
Nociceptive and/or neuropathic pain
CNS ADRs?
Physical dependence (especially with chronic use)
Respiratory depression
Dysphoria (often with high dose chronic use)
Sedation
Pupil constriction
GI ADRs?
Nausea and vomiting
Constipation
OPIOIDS
Clinical considerations
- Tolerance: what is the physiological basis of this?
Desensitisation and internalisation of opioid receptors –> need to increase the dose to achieve the previous level of effects
OPIOIDS
Clinical considerations
- Withdrawal: what is it? What side effects occur?
Occurs when you don’t take the drug?
Irritability, weightloss, GI, body shakes
OPIOIDS
Clinical considerations
- Dependence: what is it?
Psychological dependence - due to activation of the dopaminergic mesolimbic reward system
OPIOIDS
What is the opioid receptor antagonist?
Naloxone
OPIOIDS
Naloxone
- How can it treat opioid overdose?
Binds to opioid receptor to displace opioid agonist –> overcome respiratory depression
OPIOIDS
Naloxone
- Formulations?
Injection, nasal spray
OPIOIDS
Naloxone
- Why is the naloxone + oxycodone tablet combination used?
When swallowed whole, naloxone doesn’t work - oxycodone works on its own
When crushed and injected, naloxone antagonises oxycodone - don’t get the high.
OPIOIDS
Naloxone
- ADR?
May induce acute withdrawal symptoms
OPIOIDS
2 ways of cutting down?
Switching opioid drug
Tapering dose of current opioid
OPIOIDS
Switching between opioids
- Define: cross tolerance
- Is there cross tolerance between opioid drugs?
- Implications for dosages when switching?
Cross tolerance: take one type of drug and become tolerant to it; when you try a new type of drug, you’ll also be tolerant to it
Not 100%
Don’t give same dose - give 50-75%
