Pharmacology Flashcards
Where can analgesics act?
Site of injury- Decrease sensitisation by decreasing prostaglandins
Block nerve conduction- Block Na channels (lidocaine)
Block synapse transmission in dorsal horn
Activate inhibitory descending path
Ion channels upregulated in nerve damage
What are the rungs of the analgesic ladder?
NSAIDs/paracetamol
Weak opioid
Strong opioid
Give some examples of NSAIDs
Aspirin
Diclofenac
Ibruprofen
Give some examples of weak opioids
Codeine
Tramadol
Give some examples of strong opioids
Morphine
Oxycodone
Whats the difference between opiates and opioids?
Opiates- Substances from or structurally similar to opium.
Opioids- Anything acting on opioid receptors
What are endogenous opioids called?
Enkephalins
How does the body naturally modulate nociception?
Descending pathways from the brainstem (Supraspinal Antinociception)
Where does the Supraspinal Antinociception system arise?
Periaqueductal grey (midbrain)
Where does the supraspinal antinociception system ultimately project to?
Spinal cord
Where does the PAG project to?
Locus ceruleus (pons) Nucleus raphe magnus (medulla)
What activates the PAG?
Opioids and electrical input
What does activation of nucleus raphe magnus do?
Release 5-HT (serotonin) and enkephalins onto dorsal horn to modulate nociception.
What chemical can activate the NRM?
Opioids (morphine)
What does activation of the locus ceruleus do?
Release NA onto dorsal horn to modulate nociception.
What kind of receptors are opioid receptors?
GCPR
What kind of GCPR are opioid receptors?
Gi/o
What does activation of GCPR do?
Inhibit presynaptic VGCC channel opening (By SU. Block vesicle release).
Open postsynaptic K+ channels to hyperpol (By SU)
Inhibit adenylate cyclase (a SU. Needed for long term effects)
What are the three main categories of opioid receptor?
Mu- Main but lots of side effects
Delta
Kappa
What are some side effects of opioids?
Addiction Resp depression Constapation N+V Orthostatic hypotension Confusion Hallucinations
Name six key opioid R agonists
Mrorphine Diamorphine Codeine Fentanyl Tramadol Methadone
How can morphine be given?
IV
Oral
IM
Subcut
What receptor does morphine preferentially act on?
Mu
Where is morphine metabolised?
Liver
What is a difference between morphine and diamorphine?
Diamorphine is more lipophilic
How does codeine compare to morphine?
Weaker
How is codeine usually given?
Orally
IN addition to analgesia what other effects does codeine have?
Anti-diarrhoeal
Antitussive
What are two variations of codeine?
Oxycodone
Hydrocodone
How does fentanyl compare to morphine?
100x more potent
When and how is fentanyl used?
IV for maintenance analgesia
Transdermal for chronic pain
Describe tramadol
Weak muR agonist.
Most effects by activating NRM
What patient group should avoid tramadol?
Epileptics
Describe methadone
Weak mu R agonist. Long half life.
Good for chronic pain and addiction
Name two important opioid receptor antagonists
Naloxone
Naltrexone
How does naloxone work?
Competitive mu antagonist
When is naloxone used?
To reverse opioid toxicity. Short HL so must monitor closely to check doesn’t wear off too quickly.
Newborn babies with opioid toxicity from birth process
Describe naltrexone
Similar to naloxone but longer HL and oral availability
Broadly how do NSAIDs work?
Decrease nociceptor sensitisation
When are NSAIDs used?
To treat mild inflammatory pain
What effects do NSAIDs have?
Analgesic
Antipyretic
Anti Inflammatory
How do NSAIDs decrease nociceptor sensitisation
By decreasing prostaglandin synthesis
Which enzymes do NSAIDs inhibit to block prostaglandin synthesis?
COX1 and 2
What do prostaglandins do?
Hyperalgesia
Allodynia
Pain
What is the difference between COX1 and 2
COX1 always active
COX2 only activated locally to damage by cytokines
Is paracetamol a NSAID and why?
No because it doesn’t have any anti-inflammatory effects
Where does paracetamol work?
Centrally
What is neuropathic pain?
Pain from damaged nerves
Does neuropathic pain respond to NSAIDs and opioids?
No
What does neuropathic pain respond to?
Gabapentin
Pregabalin
Amitriptyline
Carbamazepine
How do gabapentin and pregabalin work?
Decrease the expression of the a2d SU of VGCC which is upregulated in damaged sensory nerves
Name a condition gabapentin is used for
Migraine profolaxis
Name a condition pregabalin is used for
Diabetic neuropathy
How does amitriptyline work?
Decrease reuptake of NA
How does carbamazepine act?
Blocks VGNC subtype that is upregulated in damaged nerves.
