Pharmacology - Bone Pain Flashcards
CD
Controlled drug
PO
Orally
IV bolus
Single, small quantity given over small period of time into vein
IV infusion
Larger quantity infused/ given over a longer time into vein
SL
Sublingual
Intrathecal
Into the spine
Chemical structure of opioids
Activity comes from free hydroxyl on benzene ring, linked by w carbon atoms to a nitrogen
How are variations of morphine made
Substitutions made at one of both the hydroxyls to give diamorphine and oxycodone
Pharmacodynamics of opioids
Analgesia Euphoria Respiratory depression Cough suppression Pin-point pupils Nausea and vomiting Constipation Bronchospasm, hypotension, local itchiness
Analgesia - opioids
Used for acute/ chronic pain
Not used for neuropathic pain
Euphoria - opioids
Sense of wellbeing & contentment (μ receptor)
Dysphoria/ hallucinations к-receptor
Helps w/ analgesia as minimises the agitations and anxiety associated w/ pain/ trauma
Respiratory depression - opioids
Medicated by μ receptor, decrease sensitivity of respiratory centre to arterial Pco2 levels and inhibition of respiratory rhythm generation
Commonest cause of death in acute opioid poisoning
Pin-point pupils - opioids
μ + к receptor stimulation.
Nausea and vomiting - opioids
Common SE, 40% pts, however transient SE
Constipation - opioids
Increase tone and reduce gut motility = constipation
Also reduces drug absorption
Bronchospasm - opioids
Histamine is released in states of allergy (e.g. hay fever)
Morphine releases histamine from mast cells
Local irritation
Bronchospasm in asthmatics = bad combo!
Tolerance
Increasing dose to get same pharmalogical response; develops within a few days. This means in palliative care we have to keep swapping drugs.
Switching between opioids
Opioids cannot be used interchangeably
Follow palliative care guidance in BNF
Use local/ trust guideline
What causes withdrawal symptoms
Physical dependence on drug
μ receptor agonist removal
Relieving withdrawal symptoms
Long acting μ receptor agonists (methadone/buprenorphine
Why do we have CDs
Misuse of drugs act 1971 (manufacture/ supply/ possession)
Class A drugs
Heroin
Cocaine
LSD
Methadone
Class B drugs
Barbituates
Cannabis
Class C drugs
Buprenorphine
Anabolic steroids
Level 1 - WHO pain relief ladder
Pain persisting or increasing
Non-opioid +/- adjuvant
Level 2 - WHO pain relief ladder
Opioid for mild to moderate pain
+/- non-opioid
+/- adjuvant
Level 3 - WHO pain relief ladder
Opioid for moderate to severe pain
+/- non-opioid
+/- adjuvant
Non-opioid in pain ladder
Paracetamol
Adjuvants in pain ladder
NSAIDs e.g. ibuprofen, diclofenac
Mild opioid
Codeine
Dihydrocodeine
Tramadol
Mod-severe opioid
Morphine
Mechanism of action of NSAIDs
Inhibits cyclo-oxygenase (COX) enzymes 1, 2 which convert arachidonic acid to prostaglandins and leukotrienes by the COX and 5-lipoxygenase pathways respectively
COX-1
Produces prostaglandins that protect against mucosal damage and regulates platelet aggregation and renal blood flow
COX-2
The prostaglandins here cause local pain + swelling. Inflammation also increases COX-2 production in the spinal cord where pain signals are processed
Non-selective inhibitors
NSAIDs that act on COX-1 AND COX-2 (ibuprofen, naproxen)
Higher risk of stomach ulcers
Selective inhibitors
NSAIDs that only act on COX-2 (celecoxib, etoricoxib)
Therapeutic effects of NSAIDs
Anti-inflammatory = ↓Prostaglandin E2 and Prostacyclin Analgesic= ↓Prostaglandins Antipyretic= ↓Interleukin-1
-ve effects of NSAIDs
Stomach= acid gets through lining, unable to make protective mucosa, creates ulcer Platelet activity= less clotting, more GI bleeds
Contraindications of NSAIDs
Severe heart failure or liver disease Asthma Hx peptic ulcer Hx gastrointestinal bleeding Adverse event with NSAIDs
Mechanism of action of paracetamol
Weak COX inhibitor, so doesn’t exhibit anti-inflammatory effect
Assumed to selectively inhibit COX-3 enzyme (mechanism not fully understood)
Contraindications of paracetamol
Hx of allergic reaction
Compound painkillers
Compound painkillers are made from a combination of 2 drugs- usually a standard painkiller and low dose of an opioid
Examples of compound painkillers
Co-codamol= paracetamol + codeine Co-codaprin= aspirin + codeine Co-dydramol= paracetamol + dihydrocodeine
Most effective antidepressants
TCAs and SNRIs (tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors)
TCAs and SNRIs
Affect transmission of both NTs serotonin and norepinephrine –> reduces pain at a spinal and cerebral level
What are anti-depressants effective in treating depression and chronic pain
The same parts of the brain are affected in people with major depressive disorders
Contraindications of antidepressants
Arrhythmias
Manic phase of bipolar disorder
Heart block
Immediate recovery period after M.I
Types of opioid receptors
Mu
Delta
Kappa
NOP
All G-coupled receptors and cause hyper polarisation of neurones —> reducing in firing of AP
Mu opioid receptors
Responsible for most analgesic effects but also the worst side effects
Delta opioid receptors
Analgesia but can also be proconvulsant
Kappa opioid receptors
Analgesia at spinal level, may cause sedation, dysphoria + hallucinations
NOP opioid receptors
Reverse effects of mu receptor agonists (supraspinal), analgesia (spinal), immobility + learning impairment
Contraindications of opioids
Acute respiratory depression Comatose patients Head injury Raised intracranial pressure Risk of Paralytic ileus
Side effects of opioids
Arrythmias, confusion, constipation, dizziness, drowsiness, dry mouth, euphoric mood, flushing, hallucinations, headache, hyperhidrosis, hypotension, nausea, palpitations, respiratory depression, skin reactions, urinary retention, vertigo, visual impairment, vomiting, withdrawal syndrome
Action of opioids
Cross blood-brain barrier and access CNS to have central action
