26 Analgesic drugs Flashcards
26.01 OPIOID DRUGS
Opioid agonists: morphine, diamorphine (heroin), buprenorphine, codeine, oxycodone - actions
analgesia
sedation
euphoria/reduced anxiety
physical/psychological dependence
cough suppression and respiratory depression
inhibition of gut motility
26.01 OPIOID DRUGS
Opioid agonists: morphine, diamorphine (heroin), buprenorphine, codeine, oxycodone - MOA
activates µ opioid receptors in the brain and spinal cord to inhibit pain transmission and modify the central perception of pain
activation of κ receptors may exert an additional effect on pain transmission in the spinal cord
may inhibit the activation of sensory nerve endings
opioid receptors are G protein–coupled receptors, which inhibit adenylate cyclase activity, open K+ channels and inhibit the opening of Ca2+ channels in nerve endings
26.01 OPIOID DRUGS
Opioid agonists: morphine, diamorphine (heroin), buprenorphine, codeine, oxycodone - abs/distrib/elim
given orally or by SC/IM injection
glucuronic acid conjugation in the liver
half-lives: morphine 3-4h, buprenorphine 12h
the actions of diamorphine and codeine are due, at least in part, to metabolism to morphine
26.01 OPIOID DRUGS
Opioid agonists: morphine, diamorphine (heroin), buprenorphine, codeine, oxycodone - clinical use
moderate to severe chronic and postoperative pain (codeine for mild pain)
epidural anaesthesia
neuropathic pain
treatment of painful cough
diarrhoea
26.01 OPIOID DRUGS
Opioid agonists: morphine, diamorphine (heroin), buprenorphine, codeine, oxycodone - adverse effects
hypotension
constipation, nausea, vomiting, drowsiness, dizziness tolerance, dependence and withdrawal effects
larger doses - coma with respiratory depression
26.01 OPIOID DRUGS
Opioid agonists: morphine, diamorphine (heroin), buprenorphine, codeine, oxycodone - special notes
naloxone is an opioid receptor antagonist at µ, δ and κ receptors and given in opioid overdoses
can cause withdrawal symptoms in opioid addicts
26.02 OPIOID DRUGS
Synthetic analogues: pethidine, fentanyl, remifentanil, sufentanil - actions
analgesia
euphoria
physical/psychological dependence
respiratory depression
inhibition of gut motility
(antimuscarinic effects of pethidine cause tachycardia)
26.02 OPIOID DRUGS
Synthetic analogues: pethidine, fentanyl, remifentanil, sufentanil - MOA
activates µ opioid receptors in the brain and spinal cord to inhibit pain transmission
activation of κ receptors may exert an additional effect on pain transmission in the spinal cord
may inhibit the activation of sensory nerve endings
26.02 OPIOID DRUGS
Synthetic analogues: pethidine, fentanyl, remifentanil, sufentanil - abs/distrib/elim
given orally or IM
pethidine is subject to hydrolysis and P450 oxidation, half-life 3-5h
fentanyl is also available as a transdermal patch for long-term effects
remifentanil has a very short half-life (0.1h)
26.02 OPIOID DRUGS
Synthetic analogues: pethidine, fentanyl, remifentanil, sufentanil - clinical use
moderate to severe pain
pethidine does not reduce uterine contractions so favoured for labour pain
remifentanil and sufentanil are given IV for surgical analgesia
26.02 OPIOID DRUGS
Synthetic analogues: pethidine, fentanyl, remifentanil, sufentanil - adverse effects
constipation (less than morphine), nausea, vomiting, drowsiness, dizziness, tolerance, dependence and withdrawal effects
larger doses - coma with respiratory depression
26.03 OPIOID DRUGS
Long-acting µ opioid receptor agonist: methadone - actions
analgesia
euphoria
physical/psychological dependence
respiratory depression
inhibition of gut motility
26.03 OPIOID DRUGS
Long-acting µ opioid receptor agonist: methadone - MOA
activates µ opioid receptors in the brain and spinal cord to inhibit pain transmission and modify the central perception of pain
may inhibit the activation of sensory nerve endings
26.03 OPIOID DRUGS
Long-acting µ opioid receptor agonist: methadone - abs/distrib/elim
oral absorption
long duration of action
P450 metabolism in liver
half-life 15-40h
26.03 OPIOID DRUGS
Long-acting µ opioid receptor agonist: methadone - clinical use
analgesia
maintenance of opioid addicts and assistance in withdrawal program
26.03 OPIOID DRUGS
Long-acting µ opioid receptor agonist: methadone - adverse effects
constipation, nausea, vomiting, drowsiness, dizziness
tolerance, dependence and withdrawal effects
larger doses - coma with respiratory depression and possible cardiac dysrhythmia
26.04 OPIOID DRUGS
Atypical narcotic analgesic: tramadol, tapentadol - actions
analgesia
26.04 OPIOID DRUGS
Atypical narcotic analgesic: tramadol, tapentadol - MOA
weak agonist action at µ opioid receptors
main action: inhibits 5-HT and NA reuptake into nerve endings, so potentiates monoamine neurotransmission
analgesic action is inhibited by 5-HT3 receptor antagonists
26.04 OPIOID DRUGS
Atypical narcotic analgesic: tramadol, tapentadol - abs/distrib/elim
given orally
subject to hepatic demethylation and conjugation
tramadol half-life 6h
26.04 OPIOID DRUGS
Atypical narcotic analgesic: tramadol, tapentadol - clinical use
moderate/moderately severe pain
used postoperatively
neuropathic pain
26.04 OPIOID DRUGS
Atypical narcotic analgesic: tramadol, tapentadol - adverse effects
dizziness, nausea and vomiting
respiratory depression, constipation and addiction (but less than with morphine)
convulsions
26.05 DRUGS USED FOR NEUROPATHIC PAIN
Tricyclic antidepressants: amitriptyline, nortriptyline, desipramine - actions
reduction of neuropathic pain
26.05 DRUGS USED FOR NEUROPATHIC PAIN
Tricyclic antidepressants: amitriptyline, nortriptyline, desipramine - MOA
analgesic action of antidepressants is mainly due to inhibition of the opening of neuronal voltage-gated Na+ channels (Nav 1.7 subtype), rather than to inhibition of monoamine reuptake
Na+ channel block reduces pain transmission from site of nerve injury
26.05 DRUGS USED FOR NEUROPATHIC PAIN
Tricyclic antidepressants: amitriptyline, nortriptyline, desipramine - abs/distrib/elim
given orally
hepatic P450 metabolism (nortriptyline is a metabolite of amitriptyline)
amitriptyline half-life 12-24h
26.05 DRUGS USED FOR NEUROPATHIC PAIN
Tricyclic antidepressants: amitriptyline, nortriptyline, desipramine - clinical use
postherpetic neuralgia, diabetic peripheral neuropathy, neuropathic cancer pain
pain treatment typically requires lower doses than depression treatment
26.05 DRUGS USED FOR NEUROPATHIC PAIN
Tricyclic antidepressants: amitriptyline, nortriptyline, desipramine - adverse effects
sedation (antihistamine action, less with nortriptyline)
blurred vision, dry mouth, constipation, urinary retention (antimuscarinic action)
postural hypotension (α1-adrenoceptor antagonism)
overdose potentially fatal due to cardiac dysrhythmia, severe hypotension, seizure and CNS depression
26.06 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: gabapentin, pregabalin - actions
reduction of neuropathic pain
26.06 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: gabapentin, pregabalin - MOA
effectiveness in neuropathic pain is due to binding to the α2-δ-1 and α2-δ-2 subunits of voltage-activated Ca2+ channels (P/Q or N-type) to block Ca2+ entry and exocytosis of transmitter (glutamate) from pain nerve endings
26.06 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: gabapentin, pregabalin - abs/distrib/elim
given orally
excreted unchanged
gabapentin half-life 6h
26.06 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: gabapentin, pregabalin - clinical use
postherpetic and trigeminal neuralgia
pregabalin is also used for painful diabetic peripheral neuropathy
26.06 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: gabapentin, pregabalin - adverse effects
sedation, dizziness and unsteadiness
26.07 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: carbamazepine - actions
reduction of neuropathic pain
26.07 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: carbamazepine - MOA
inhibits the opening of neuronal voltage-gated Na+ channels to reduce nociceptive transmission from site of nerve injury
26.07 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: carbamazepine - abs/distrib/elim
given orally
active P450 metabolite
26.07 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: carbamazepine - clinical use
second- or third-line treatment of neuropathic pain
main uses: trigeminal neuralgia, diabetic neuropathy
26.07 DRUGS USED FOR NEUROPATHIC PAIN
Antiepileptic drugs: carbamazepine - adverse effects
drowsiness, headache, mental disorientation, motor disturbances
rare, but serious, adverse effects are liver damage, agranulocytosis and aplastic anaemia
serious dermatological reaction in genetically susceptible patients
strong inducer of cytochrome P450 enzymes, leading to many drug interactions
26.08 OTHER ANALGESIC DRUGS
NSAIDs
ibuprofen, naproxen - COX inhibitors
mild to moderate pain due to inflammatory disease, surgery, dysmenorrhoea, headache
paracetamol - resembles NSAIDs and is effective as an analgesic, but lacks anti-inflammatory activity
26.08 OTHER ANALGESIC DRUGS
Triptans
sumatriptan, zolmitriptan, eletriptan - antimigraine
triptans are agonists at 5-HT1B and 5-HT1D receptors
26.08 OTHER ANALGESIC DRUGS
Dopamine receptor agonists
ropinirole, pramipexole, rotigotine - used to treat restless leg syndrome, which can be painful
26.08 OTHER ANALGESIC DRUGS
Cannabinoids
nabilone, dronabinol - both synthetic cannabinoids
nabiximols - natural cannabinoids
strongest evidence for therapeutic benefit is for central neuropathic pain in multiple sclerosis
