Analgesic Drugs Flashcards
Define analgesic drugs:
Drugs that relieve pain by modifying transmission pathways without blocking nerve impulse conduction, reducing consciousness or markedly altering sensory function.
What are the 2 major classes of analgesic drugs
simple analgesics and opioid analgesics
What are the 2 differences between efferent and afferent neurones?
Afferent neurons cary sensory information from receptors to CNS whereas efferent neurons carry motor info from the brain to the Peripheral NS
Afferent cell bodies are located outside of the spinal cord whereas efferent cell bodies are located in the ventral horn of the spinal cord.
What is the name for paracetamol in america?
Acetaminophen
What type of analgesic is paracetamol?
An aniline analgesic
What is the mechanism of action of paracetamol
It is a weak cox-inhibitor with its analgesic effects mediated in the CNS.
What is the pharmacokinetics of paracetamol? (4)
- Is rapidly absorbed through the GI tract, peak plasma conc reached after 1-2 hours.
- It extensively undergoes phase 2 metabolism in the liver to form sulphate and glucuronide conjugates which are secreted in the urine.
- A minor fraction of the drug is converted to highly reactive alkylating metabolite which is inactivated by reduced glutathione and excreted as cysteine and mercapturic acid conjugates.
- Plasma half life in healthy subjects around 2 hours.
What are the clinical effects, indications, contraindications and cautions for paracetamol?
Clinical effects: pain relief and fever reduction
Clinical indications: mild to moderate pain and pyrexia
Contraindications: None
Cautions: low body mass, liver disease and those at risk of liver disease.
what are the common formulations of paracetamol? (4)
- 500mg tablets or capsules
- 24mg/mL oral suspension.
- IV
- Suppositories
What is the dose of paracetamol and in what circumstances should you reduce this dose?
- 500mg-1g PO ever 4-6/24
- Max daily dose= 4g/day
- dose reductions for <50kg, liver disease, children
What compound formulations does paracetamol come in? (2)
- Co-codamol 30/500 tablets (w/ 30mg codeine)
- Co-dydramol 30/500 tablets (w/ 30g dihydrocodeine
What adverse drugs reactions can paracetamol have?
- relatively few
- Rare hypersensitivity reactions like thrombocytopenia, leukopenia and skin reactions
- Hepatotoxicity from overdose.
What important drug interactions does paracetamol have? (2)
- warfarin - increases anticoagulation effect
- enzyme-inducing anti-epileptic drugs like carbamazepine increases hepatotoxicity risk
Step by step metabolism of paracetamol at therapeutic dose: (2 steps)
- Predominantly metabolised by phase 2 reactions in liver to sulphate or glucuronide conjugates that are excreted in urine.
- Small amount metabolised by phase 1 reaction in cytochrome P450 system to a toxic intermediate NAPQI oxidising radical which is detoxified by reduction with glutathione
Step by step metabolism of overdose of paracetamol:
- capacity of phase 2 conjugating enzyme pathway is overwhelmed
- Large proportion undergoes phase 1 cytochrome P450 metabolism
- Toxic NAPQI radical accumulates as liver stores of glutathione depleted causing rapid hepatocellular necrosis.
What circumstances may increase rate of NAPQI radial production making hepatotoxicity more likely?
- Co-administration of enzyme inducing drugs
- Circumstances that also deplete glutathione e.g. malnutrition, alcohol dependancy
What is the treatment for paracetamol overdose?
If recognised at early stage it can be prevented by administering supplementary reducing equivalents in the form of N-acetylcysteine (NAC)
What is the difference between opiates and opioids?
Opiates refer to the natural opioids whereas opioids refers to all natural and synthetic opioids
What are opioids?
Molecules capable of being agonists at endogenous opioid receptors.
What are the 3 main subtypes of opioid receptor?
G-protein coupled receptors Mu, kappa and delta.
3 examples of endogenous opioid peptides:
B-endorphin, enkephalin, dynorphins.
7 examples of strong opiates:
Morphine, diamorphine, oxycodone, fentanyl, pethidine, methadone, tramadol
POMMDFT
2 examples of weak opioids:
Codeine and dihydrocodeine.
How do opioids work on Mu-opioid receptors? (4 steps)
- Mu-opioid receptors are coupled to adenylate cyclase, opioid binding to receptor causes inhibition.
- Reduced availability of cAMP
- Less cAMP causes inhibition of Ca2+ entry, in turn inhibiting release of nociceptive neurotransmitters like substance P, GABA, dopamine, Ach, and NA.
- Reduced cAMP facilitates entry of K+ through inwardly rectifying channels, hyperpolarize cell membranes.
