1.13 Analgesia Flashcards
What are the NSAIDs we need to know?
ibuprofen, aspirin , paracetamol (starting page 6)
How is aspiring taken?
oral
What occurs to aspirin after ingestion?
rapidly hydrolyzed to esterases salicylate
What is the half life of aspirin?
4-15hrs (Dose dependent)
What are the unwanted effects of aspirin
Low doses; GI irritation, hypersensitivity
Salicylism (high doses); tinnitus, vertigo, decreased
hearing
Reye’s syndrome; rare childhood disorder
Interactions; warfarin
How does aspirin have analgesic effect?
decreased prostanoid synthesis
leads to less sensitisation of
nociceptors to effects of mediators
e.g. 5-HT, kinins etc
How does aspirin have antipyretic effect?
centre in hypothalamus regulates body temperature • in fever temp raised due to synthesis of PGE2 due to pyrogens • aspirin decreases PGE2 synthesis
How does ibuprofen have analgesic effect?
• decreased prostanoid synthesis
leads to less sensitisation of
nociceptors to effects of mediators
e.g. 5-HT, kinins etc
WHat are the routes of administraiton of paracetamol?
oral, rectal and IV
How does aspirin have antipyretic effect?
• centre in hypothalamus regulates body temperature • in fever temp raised due to synthesis of PGE2 due to pyrogens • aspirin decreases PGE2 synthesis
What are the unwanted effects of paracetamol?
how common
uncommon, allergic skin reactions, hepatotoxicity with chronic use or overdose
What are the 3 types of opoid receptor?
2) where are they found?
3) which is responsible for most the therapuetic effects of opoid analgesics? (agonist or antagoinst)
4) What type of receptor are they? What enzyme they effect (activate or inhibit)?
1) 2) u, delta (peripheral pain) and k (spinal pain)
3) u (agonist)
4) G-protein linked, inhibit adenylate cyclase
What are the 3 types of opoid receptor?
2) where are they found?
3) which is responsible for most the therapuetic effects of opoid analgesics? (agonist or antagoinst)
4) What type of receptor are they? What enzyme they effect (activate or inhibit)?
1) 2) u, delta (peripheral pain) and k (spinal pain)
3) u (agonist)
4) G-protein linked, inhibit adenylate cyclase
Name 3 opoid neurotransmitters
enkephalins
endorphins
dynorphins
Name 2 morphine anatlogues that are opoids:
2) Name 2 synthetic derivatives that are opoids:
Morphine analogues diamorphine (heroin) codeine Synthetic derivatives pethidine Dextropropoxyphene
What are the 2 therapeutic effects of opioid analgesics?
analgesia and euphoria sedation
Opioid Analgesics
1) route of administraiton
2) describe absorbtion from __a___
3) does it undergoe 1st pass metabolism?
ADME
oral, rectal, i.v., i.m.
erratic absorption from gut
extensive first pass metabolism
What type of opioid is given for severe pain?
2) given for mile pain?
3) 2 can also be given for…
1) mophine and pethidine
2) codeine, dextropropxyphene and dihydrocodeine
3) cough suppresive and antidiarrhoeal
dihydrocodeine dose may be limited if patient experiences..
ADR or consitpation and nausea
dextropropoxyphene is used in combination with which other drugs?
2) it is a mild or strong analgesic?
1) aspirin and paracetamol
2) mild
When is morphine used?
2) side effect?
terminal care, pain relief
2) constipation
pethidine
1) can it be prescribed by dentists?
2) strong or weak analgesiac
3) onset rapid or slow
4) duration long or short
5) more or less lipid soluble than morphine
6) more or less constipation side effect than morphine
1) yes
2) strong
3) rapid
4) short
5) 6) less
1) how long does it take patient to become tolerant to analgesics?
2) does sensitivity ever return?
3) will they experience dependence on (name)
a) abrupt withdrawel after acute treatment
b) abrupt withdrawel after chronic treatment
1) 12-24 hrs
2) yes on withdrawel
3) yes
a) abstinence syndrome
b) n/a name
1) how long does it take patient to become tolerant to analgesics?
2) does sensitivity ever return?
3) will they experience dependence on (name)
a) abrupt withdrawel after acute treatment
b) abrupt withdrawel after chronic treatment
1) 12-24 hrs
2) yes on withdrawel
3) yes
a) abstinence syndrome
b) n/a name
pain vs nociception
pain emotion and chemical, nociception is the detection of noxious stimuli
explain the ascending pathway following nociception
- fibres ( Abeta (mechanoception) or A delta fibres (mechano and noci) or C fibres (deep pain, shallow itching)
- synapse in superficial lamina of dorsal horn spinal chord
- decussate
- to brainstem, midbrain, thalamus then:
a) cingulate cortex
b) somatorsensory cortex
c) limbic system
Describe descending pathway of limbic system:
- PAG (periaquaductal grey matter)
- RVM (rsotral ventromedial medulla)
- superficial lamina of dorsal horn of spinal chord
which fibres synpase in the superficial lamina of dorsal horn of spinal chord in: 1. 2. 3. 4. 5. 6. 7.
- A delta
- C fibres
- A delta
- A beta
- A delta
- n/a
- n/a
which fibres synpase in the superficial lamina of dorsal horn of spinal chord in: 1. 2. 3. 4. 5. 6. 7.
- A delta
- C fibres
- A delta
- A beta
- A delta
- n/a
- n/a
What enzyme do NSAIDs act on?
2) which subset of enzyme causes side effects why?
3) which subset of enzyme causes therapeutic effects why?
1) COX
2) COX 1 , expressed in most tissues
3) COX2, expressed in activated inflammatory cells
What is the function of COX enzyme?
convert AA (from damadged phospholipid) to various intermediates (PGG2, PGH2) : prostacylin (PHI2) , prostoglandins ( PGE2 or PGF2) , tromboxanes (TXA2)
excitaiton of neuron causes formaiton of what?
2) what inhibits this?
3) what produces these inhibitors?
4) What drug promotes this pathway?
1) NO
2) 5-HT, NA
3) descending inhibitory pathways,
4) opiates
What do enkephalins and GABA inhibit?
excitation of transmission neuron in nociception
what inhibits excitation of transmission neuron in nociception?
1,enkephalins and GABA
- Opiates (directly)
- 5-HT and NA (opiate indirect via descending
What activates C fibres?
mediators released by noxious stimuli: BK, 5-HT and PGs)
What is capsaicins responsible?
pain with chilli
What is role of eicosanoids
enhance pain producing effects of other agents (doesn’t stimulate nociceptive nerve endings)
What does C-fibre activation cause the release of?
neuropeptide release (SP and CGRP)
What 3 things occur in inflammation?
- nerve growth factor
- mediator release (BK, 5-HT, PGs)
- Neuropeptide releases (Substance P, calcitonin gene-related peptide)
What 3 things do NSAIDs inhibit
inflammation via inhibiting
- nerve growth factor
- mediator release (BK, 5-HT, PGs)
- Neuropeptide releases (Substance P, calcitonin gene-related peptide)
What stimulates activation of transmission neuron
- NGF production
- neuropeptide release (substance P, CGRP)
- C fibre activity
What stimulates activation of transmission neuron
- NGF production
- neuropeptide release (substance P, CGRP)
- C fibre activity
Following phospholipid cell membrane damadge what 4 things are produced?
- leukotrienes
- Prostaglandins PGE/F2
- Thromboxanes TXA2
- Prostacyclin PGI2
In the prostaglandin pathway what is first reaction?
2) enzyme
- Arachidonic acid
- Phospholipase A2
(and
related enzymes)
What can Arachidonic acid
2. give enzyme:
a) 1. leukotrienes 2. lipoxygenase
b) 1. Various intermediates
PGG2
/ PGH2
2.COX
