Pharmacology of Pain Flashcards
What is the primary mechanism of action of Paracetamol?
unclear
- activation of descending serotonergic pathways via 5HT3 receptor activation
- inhibits reuptake of endogenous endocannabinoid receptors
- mild inhibition of COX
What is the drug target of paracetamol?
unclear
- 5HT3 receptors/cannabinoid reuptake proteins/COX
What are the main side effects of paracetamol?
signs of poisoning: - nausea - vomiting - right subcostal pain (hepatic necrosis) OVERDOSE - liver damage - renal damage
How would you describe the properties of paracetamol?
- analgesic
- anti-pyretic
What are some examples of weak opioids?
- codeine
- tramadol
What are some examples of strong opioids?
- morphine
- fentanyl (heroin)
What are is the primary mechanism of opioids?
- depressant effect on cellular activity
- activation of opioid receptors leads to decreased perception or increased tolerance of pain
- anti-tussive effect due to decreased activation of afferent nerves relaying cough stimulus from the airways to the brain
What are is the drug target of opioids?
opioid receptors
What are the main side effects of opioids?
mild:
- nausea
- vomiting
(increased activity in chemoreceptor trigger zone)
- constipation
(opioid receptor in the GIT can reduce gut motility)
What are the signs of a opioid overdose?
respiratory depression
caused by both direct and indirect inhibition of respiratory control centre
What the primary mechanism of Co-amoxiclav?
Amoxi-
- binds to bacterial penicillin binding proteins.
- prevents transpeptidation (the crosslinking process for bacterial cell wall synthesis)
-Clav
- beta lactamase inhibitor
(bacterial enzyme that degrades beta lactam antibiotics and therefore confers resistance.
What is the drug target of Co-Amxoclav?
Amoxicillin:
penicillin binding proteins
Clavulanate:
beta lactamase
What does projectile vomiting suggest?
norovirus
What are the main side effects of Co-Amoxiclav?
generally well tolerated
- nausea
- diarrhoea
What is the recommended management of gastroenteritis?
- oral rehydration
- analgesis
What bacteria does Amoxicillin act on?
semisynthetic broad spectrum ABx, against gram positive and negative microorganisms
what needs to be given when administering home management plans?
safety netting, if not improved in xxx, go to hospital
How do hypersensitivities to penicillin present?
- rash
- can lead to anaphylactic reactions
*What is the primary mechanism of Lactulose?
- non-absorbable disaccharide
- reaches the large bowel unchanged
- water retention via osmosis and an easier to pass stool
- can be metabolised by colonic bacteria
- the colonic metabolism of sugars has an additional laxative effect.
Describe a pain pathway?
- sensory neurone
- synapses with a spinothalamic neurone in the spine (to the hypothalamus)
- return of an inhibitory response (modulation), to prevent pain stimulus relay
- inhibitory effect dependent on the size of the pain/extent of the trauma
What is the drug target of lactulose?
no drug target
What are the main side effects of Lactulose?
- abdominal pain
- diarrhoea
- flatulence
- nausea
How long does it take for Lactulose to have a clinical effect?
- works in 8-12 hours
- may take up to 2 days to improve constipation
When is lactulose prescribed?
prescribed prior to commencement of opioid therapy to improve symptoms associated with constipation
What is released from inflammatory tissue?
- peroxides
Why is paracetamol not an anti-inflammatory?
- inhibits the action of peroxidase activity
What is the impact of cannabis on pain?
enhances anandomides, causing an increased inhibitory effect from the hypothalamus
How do NSAIDS/paracetamol cause a central analgesic effect?
paracetamol - arachadonic acid buildup
- preventing the metabolism anandomide is broken down into arachodonic acid (similar to negative feedback)
What is the management plan for acute appendicitis?
- analgesia
- NBM, IV fluids (crystalloids)
- IV ABx
What is the effect of morphine on a cellular level?
- binds to the opioid receptor (G-protein coupled)
- inhibition of ATP to cAMP conversion, causing reduced cellular activity
- reduced calcium influx, less exocytosis (less neurotransmitter release)
- increased K+ efflux, hyperpolarising the cell
- the neurone is hyperpolarised and therefore cannot depolarise
Where do opioids act on the pain pathway?
- loss of peripheral opioid receptors around the sensory nerves
- spinal cord, decreased action of the spinothalamic innervation due to depressive effect
- neurone modulation (inhibitory effect on pain),, GABA inhibition is inhibited by the opioids. Therefore the descending pathway is now active, by removing the inhibitory factor (GABA)
what happens on to the pain pathway when not in pain?
inhibition of the modulation of the descending inhibitory perception of pain by GABA
What are the properties of effective drugs that are able to permeate the blood brain barrier?
- lipid based
- able to actually bind to the receptor when reached
What is the optimal oil-water partition coefficient to pass the blood brain barrier?
1.5-2.7
What is opioid receptor binding dependent on?
- hydroxyl group at position 3
- tertiary nitrogen
What happens in the conversion of a phase 1 to a phase 2 metabolite?
active metabolite with a side chain to reduce reactivity to ease clearance
What is a phase 1 metabolite?
highly reactive metabolite
What is a phase 2 metabolite?
reactive metabolite + side chain to provide stability
What happens to codeine and heroin in order to act on the brain?
once in the brain, converted into the morphine
What is thought to be the most effective opioid?
heroin (due to lipid solubility)
What is used to treat an opioid overdose?
naloxone (IV or nasal spray)
What are the properties of agonists?
- affinity
- efficacy
What are the properties of antagonists?
only affinity
What are the structural differences between morphine (agonist) and naloxone (antagonist)
- tertiary H (short side chain allows for efficacy)
- side chain >2 carbons means that there is no efficacy
What can codeine be metabolised into?
inactive: norcodeine
active: morphine
How long does it take for naloxone to come into effect?
instantaneous
How does opioid overdose cause respiratory depression?
- cardio-respiratory control centre
- multiple opioid receptor
- opioids bind to the opioid receptors causing a depressive effect
- only seems to happen at high doses due to resistance
What causes pupil constriction in opioid overdose?
- opioids cause pupil constriction directly
- diagnostic
What is responsible for the metabolism of codeine into morphine?
cytochrome P450 enzymes in the liver
- CYP3A4, fast codeine to norcodeine
- CYP2A6, slow codeine to morphine
What is the effect of taking codeine orally (why is it considered weak)
due to the difference in the metabolism into the different metabolites
- codeine to norcodeine (90%) cause fast
- codeine to morphine (10%) cause slow
How do you calculate the dosage of codeine for opioid pain management?
- total codeine/day
- conversion factor for morphine to codeine
- morphine/conversion factor = codeine/day
