Pharmacology of Pain Flashcards by Fara A

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

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What is the drug target of paracetamol?

unclear

- 5HT3 receptors/cannabinoid reuptake proteins/COX

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What are the main side effects of paracetamol?

signs of poisoning:
- nausea
- vomiting
- right subcostal pain (hepatic necrosis)
OVERDOSE
- liver damage 
- renal damage

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How would you describe the properties of paracetamol?

analgesic

- anti-pyretic

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What are some examples of weak opioids?

codeine

- tramadol

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What are some examples of strong opioids?

morphine

- fentanyl (heroin)

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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

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What are is the drug target of opioids?

opioid receptors

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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)

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What are the signs of a opioid overdose?

respiratory depression

caused by both direct and indirect inhibition of respiratory control centre

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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.

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What is the drug target of Co-Amxoclav?

Amoxicillin:
penicillin binding proteins
Clavulanate:
beta lactamase

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What does projectile vomiting suggest?

norovirus

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What are the main side effects of Co-Amoxiclav?

generally well tolerated

nausea
diarrhoea

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What is the recommended management of gastroenteritis?

oral rehydration

- analgesis

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What bacteria does Amoxicillin act on?

semisynthetic broad spectrum ABx, against gram positive and negative microorganisms

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what needs to be given when administering home management plans?

safety netting, if not improved in xxx, go to hospital

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How do hypersensitivities to penicillin present?

rash

- can lead to anaphylactic reactions

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*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.

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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

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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