Pharmacology Flashcards
How do NSAIDs reduce pain
Act at the site of injury
They block the synthesis of prostaglandins which decreases nociceptor sensitisation in inflammation
Also decrease recruitment of leukocytes that cause inflammation
How do local anaesthetics work
They supress nerve conduction by blocking sodium channels
How do opioids work to reduce pain
Suppressing synaptic transmission of nociceptive signals
Block the first step in the dorsal horn of spinal cord
Can also work higher in CNS to activate inhibitory controls - in the PAG or the nucleus raphe magnus
How do tricyclics work to reduce pain
The decrease the reuptake of key substances such as adrenalin and 5HT
How do antiepileptics work to decrease pain
They target ion channel that become upregulated in nerve damage
Decreases release of NT from nociceptive neurons - less firing
Describe the ladder of analgesics
Paracetamol or NSAID at bottom - mild pain
Weak opioids such as co-codamol for moderate
Strong opioids - morphine for severe pain
What is the difference between opioids and opiates
Opiates are substances that are extracted from opium
Opioids refers to any agent that acts on opioid receptors
Describe supraspinal anti-nociception
The way the brain regulates pain
Regions involved in pain perception send signals to brainstem nuclei which can then send fibres to the spinal cord to modify the pain signals
Which brain regions are involved in pain and emotion perception
Cortex
Amygdala
Thalamus
Hypothalamus
What is the significance of the periaqueductal grey matter
Excitation of this area provides profound analgesia
Can be activated by endogenous opioids or morphine (and related drugs)
Once active it suppresses nociceptive transmission at the spinal cord
What type of receptors are opioid receptors
G-protein coupled
What are the major adverse effects of opioids
Addictive potential Respiratory depression - worse when asleep Postural hypotension Nausea and vomiting Confusion, dysphoria, hallucinations Dizziness Myoclonus Hyperalgesia if excessive use
What type of pain are opioids not good at treating
Neuropathic
How is morphine metabolised
Metabolised in the liver
Glucuronidation reaction produces an inactive product (M3G) and an active analgesic (M6G)
Excreted by the kidney
How can morphine be delivered
IV - acute setting
IM, SC or orally in general wards
Which administration route for morphine is best for chronic pain
Oral
Immediate as oramorph
or Sustained release
How long do sustained release morphines last
12-24hrs
High dose in tablet which is released slowly
Describe the use of diamorphine
More lipophilic than morphine
Crosses the BBB rapidly when given IV
Only used for severe post-op pain
Heroin is in this class
How is codeine used
For mild/moderate pain as it is a weaker opioid
Given orally
Has anti-diarrhoeal action
How is codeine metabolised
In the liver
Converted to small amounts of morphine which gives the analgesia
Some people have variations in the enzymes that do this so codeine wont work as well
What are the 2 main synthetic forms of codeine which are more potent
Oxycodone
Hydrocodone
Describe the use of fentanyl
Extremely potent - 100x more than morphine
Given IV in some surgeries to act as analgesic in anaesthesia
Can be given as transdermal patch in chronic pain states
Describe the use of pethidine
Used in acute pain, particularly labour
Rapid action when given IV, IM or SC
Short action so not good for chronic pain
What drugs can not be used alongside pethidine
MAO inhibitors - anti-depressant and Parkinson drug
Will cause excitement, convulsions and hyperthermia
Describe the use of buprenorphine
Partial agonist of opioid receptors
Used in chronic pain with syringe drivers
Slow onset but long duration
Describe the use of tramadol
Significant analgesic action by potentiating descending pathways
Given orally
DONT give to epileptics
Describe the use of methadone
Weaker agonist
Given orally
Long duration of action
Used for chronic cancer pain or heroin withdrawal
How is naloxone used
It is a competitive agonist for opioid receptors
Used to reverse opioid toxicity
Given IV, IM or SC
Need to monitor dose and patient as toxicity can recur in longer acting preparations
When may a newborn baby need naloxone
If they have respiratory depression due to opioid toxicity from mother taking pethidine as a painkiller in labour
What is the risk with naloxone administration
Sudden withdrawal can make people agitated and violent
Particularly in addicts
What drugs are antagonist of opioids
Naloxone
Naltrexone - oral and long half life
Alvimopan
What actions do NSAIDs have
Analgesia
Antipyretic
Anti-inflammatory
Give examples of NSAIDs
aspirin
ibuprofen
naproxen
diclofenac
How do NSAIDs work (in general)
Inhibit synthesis of prostaglandins by inhibiting COX-1 and 2 enzymes
Where are the COX enzymes active
COX-1 is active continuedly
COX-2 is induced at the site of inflammation by cytokines
Most therapy of NSAIDs is due to COX2 inhibition
What are the adverse effects of NSAIDs
GI damage - as COX1 produces a protective prostaglandin
COX2 specific are prothrombotic so use is limited
Which drugs are useful for neuropathic pain
Gabapentin and pregabalin - anti-epileptics
Amitriptyline - tricyclics
Carbamazepine
When is gabapentin used
Migraine prophylaxis
When is pregabalin used
Painful diabetic neuropathy
How does carbamazepine work to reduce pain
Blocks voltage activated Na channels which become upregulated in damaged nerve cells
When is carbamazepine used
First line to control pain intensity and frequency in trigeminal neuralgia
