opiids and narcotic analgesics Flashcards
Which size/shape of axons have slower signal propogation?
Larger diameter
Unmyelinated
What underpins the gate control theory of pain in the dorsal horn?
Other sensory information (in greater amounts/ covering larger areas) such as touch and muscle joints) overrides pain due to modulation via inhibitory GABA pathways
N.B. The trigeminal pathway is still gated but in a different way
Which 7 types of drugs are used for analgesia?
- Local anaesthetics
- General anaesthetics
- NMDA (glutamate) receptor antagonists
- Voltage-gated calcium channel blockers (selective = into spinal cord) &
- Anti epileptics (blocks overactive Ca channels)
- NSAIDs - especially for low grade pain
- Cannabinoid CB1 receptor agonists (animals)
What are NSAIDs used to treat? What is its method of action?
Inflammatory pain
Used to cleave cyclooxygenase (produces prostaglandins = pain, fever and inflammation)
What is an opiate?
Natural substance produced by opium poppy = binds and activates opioid receptors
What is an opioid?
Any drug (synthetic or natural) that binds and activated opioid receptors
What is a narcotic analgesic (narcotics)?
Any drug with the potential for abuse (traditionally opioids only) e.g. Cocaine
What are the 4 well defined classical opioid receptors?What are their classic names? (and their new names?)
μ (MOPr)
δ (DOPr)
κ (KOPr)
Opiod receptor like 1 ORL1 = (NOPr)
-> N.B. not relavent in analgesia
What type of receptors are opiod receptors?
GPCR
What is the principal transduction mechanism for Opioid receptors?
Gi/o= inhibits Ca= activates K= activates cAMP -> PKA = other mechanism (not the main pathway for analgesia)
What are the 3 consequences of opioid receptor activation?
- Inhibit transmitter release
- Inhibit neuronal firing
- Disinhibition (removes inhibitory influence = excitation!)
What is the opioid structure similar to?
Tyrosine
What is the terminal Amino acid for most opioid peptides?
Tyrosine
Name two μ opioid receptor agonists:
- DAMGO
- Morphine (partial)
Name two μ opioid receptor antagonists:
- CTOP
- Naloxone (all types of receptors but strongest with μ)
Name a δ opioid receptor agonist:
DPDPE
Name two δ opioid receptor antagonists:
- Naltrindole
- Naloxone
Name a κ opioid receptor agonist:
Enadoline
Name two κ opioid receptor antagonists:
- nor-binaltrophimine
- naloxone
Give an example of a drug that show mixed activity
Pentazocine (μ antagonist & κ agonist)
What are the 4 behavioural effects of μ opioid receptor agonists:
- Analgesia
- Euphoria
- Respiratory depression
- Constipation
What are the 4 behavioural effects of κ opioid receptor agonists:
Analgesia
Dysphoria/Hallucinations
No respiratory depression
Diuresis
What are the 2 behavioural effects of δ opioid receptor agonists:
Analgesia
Antidepressant/proconvulsant
What are the 5 desirable effects of opioids?
- Analgesia
- Euphoria
- Constipation
- Sedation (premed for surgery)
- Cough suppression
What is the other effect of opioids?
Pupil constriction
What are the 8 undesirable effects of opioids?
- Respiratory depression
- Euphoria
- Constipation
- Sedation
- Nausea and vomitting
- Tolerance (need to increase dose over time)
- Psychological dependence
- Physical dependence
Which two neurotransmitters are found in the 1st synapse for pain to the CNS (A delta/c fibres)?
- Substance P
- Glutamate
Which membranes in the synapse are μ opioid receptors located?
On both the pre and post synaptic membrane
What is the effect of opioids on presynaptic μ opioid receptors?
Reduces transmitter release
What is the effect of opioids on postsynaptic μ opioid receptors?
Hyperpolarisation (activating potassium channels) = decreased size of action potential
What happens in disinhibition?
A decrease in GABA release (by decreasing Ca) = hyper polarisation of inhibitory interneurone = less inhibition and increased activity in projection neurones
In which pathways can disinhibition occur?
Descending inhibitory pathways
What causes Euphoria in Opioid users?
Disinhibition in ventral tegmental area (VTA) = enhanced dopamine release in nucleus accumbens
What are the 3 main problems with opioids?
- side effects
- Breakthrough pain (with chronic use)
- Neuropathic pain (doesn’t treat all kinds of pain)
Why are drug combinations used?
To reduce side effects
Possibly due to synergy (binding to other drug used)
Which two drugs is co-codamol a mixture of?
Codeine
Paracetamol
Which two drugs is co-codaprin a mixture of?
Codeine
Aspirin
Which two drugs is co-proxamol a mixture of?
Dextroproxyphene
Paracetamol
N.B. this is not used as much now
Which two analgesic drugs are recommended for mild pain in the WHO pain ladder?
Non opioid drugs (ibuprofen & paracetamol)
Which analgesic drug is recommended for moderate pain in the WHO pain ladder?
Mild opioid e.g. codeine
Which analgesic drug is recommended for severe pain in the WHO pain ladder?
Opioid e.g. morphine
Which type of pain can be unresponsive to opioids?
Neuropathic pain
Which drugs are used as an alternative to opioids in neuropathic pain?
Antidepressants e.g. amitriptyline
Antiepileptics e.g. gabapentin & Carbamazepine
How does the anti epileptic drug gabapentine produce an analgesic effect?
Modulates Na and Ca Channels
Which 6 inflammatory mediators are released following tissue damage?
- Histamine
- Bradykinin
- 5-HT
- Prostaglandin
- ATP
- Acidosis (H)
What are collaterals?
Neurones that feedback to the area of tissue damage
Which chemicals are released by collaterals?
- Substance P
- CGRP (Calcitonin gene related peptide)
What effect does substance P have in the area of tissue damage?
- Histamine release from mast cells (= pain and inflammation)
- Vasodilation
What effect does CGRP have in the area of tissue damage?
Vasodilation
Which types of nerve fibres produce the sensation of pain?
Nociceptive fibres
Where do nociceptive fibres first synapse in the spinal cord?
The dorsal horn
