4225081
| Question | Answer |
| Define nociception | Detection of noxious stimuli |
| Give 4 examples of substances which cause pain signals | H+ Histamine NGF Prostaglandin |
| Where do first order neurons of the lateral spinothalamic pathway synapse? | Substantia gelatinosa |
| Where do second order neurons of the lateral spinothalamic tract decussate? | Spinal Cord |
| How to voltage gated calcium channel blockers work? | Reduce transmission from primary to secondary neuron |
| How do cannaboid CB1 receptor agonists reduce pain? | Inhibit activation of primary neuron |
| How do non-steroidal anti-inflammatory drugs reduce pain? | Prevent action of prostaglandin |
| Define Opiate | Naturally occurring agonists of opioid receptors |
| Define opioid | Any drug that acts on the opioid receptor |
| What subtype of G protein are most opioid receptor actions mediated through? | Gi/o |
| What does the 'a' subunit do when the Gi/o protein is activated? | Decreases cAMP |
| What are the two main effects of BY subunit? | i) Inhibits Ca2+ voltage gated channel, reducing influx of calcium, preventing neurotransmitter release ii) Activates voltage gated K+ channel, increased outward K+ current leads to reduced postsynaptic excitability |
| Summarise the 3 main effects of opioid receptors? | 1) Inhibit transmitter release 2) Inhibit neuronal firing 3) Disinhibition (removal of inhibitory influence causes excitation) |
| Which amino acid forms the main structural part of opioids? | Tyrosine |
| Which opioid receptors does y-endorphin bind to? | u/d |
| met-enkephalin | d/u |
| Leu-enkephalin | d/u (partial at u) |
| dynorphin | k |
| Which subtype of receptor doesn't allow exogenous receptors to bond? What is the start of the endogenous peptide that does bond? | ORL1 Phenalamine |
| Which drug is a non-selective antagonist at all opioid receptor subtypes? | Naloxone |
| Which subtype of receptor is the most important target for analgesia? | u |
| What are the four main behavioural responses to u receptor activation? | analgesia, euphoria, respiratory depression, constipation |
| What are the four main behavioural responses of k receptor activation? | Analgesia, dysphoria/hallucinations, no respiratory depression, diuresis |
| What are the three main behavioural of delta receptor activation? | Analgesia, antidepressant, proconvulsant |
| What other important side effects are caused by opioids? (4) | Addiction, tolerance, nausea/vomiting, sedation |
| What are the three main general problems with opiods? | Side effects Breakthrough pain Neuropathic pain is resistant to opioids |
| How are opioids most important pre and post synaptically? | Pre synaptically: Inhibition of VG Ca2+ channels Post-synaptically: Activation of VG K+ channels |
| Name two places in the CNS where injection of opioids reduces pain? | 1) Dorsal horn of spinal cord 2) Peri Aquaductal Grey |
| How does injecting into PAG reduces pain? | Activation of descending inhibitory pathways |
| Explain in terms of GABAergic neurons and projection neurons how opioids cause disinhibition and how this causes analgesia. | Tonically active GABAergic can be stopped from firing by opioids. Disinhibits projection neuron which was inhibited by GABAergic neuron. Second order projection neuron is then able to inhibit second order neurons in the spinal cord and prevent pain transmission. |
| How do opioids induce euphoria? | Disinhibition to Ventral Tegmental Area (VTA) Enhances dopamine release in the nucleus accumbens |
| Which receptors are mainly responsible for analgesia, addiction/withdrawal to morphine? | u |
| What are the three main uses for opioids? | Pain Relief Treatment of severe diarrhoea Cough supression |
| What are the four types of pain opioids treat? | Acute Chronic (eg cancer) During surgery Post-operative surgery |
| What is Buprenorphine | Partial agonist |
| What are the clinical uses of Buprenorphine? (high and low doses) (3) | 1)Treatment of morphine addiction at high doses 2)Treatment of moderate acute pain lower doses 3) Treatment of moderate chronic pain at even lower doses |
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