Analgesics Flashcards
Aspirin, ibuprofen, naproxen
Indication: anti-inflamatory, analgesia, antipyretic
- inflammatory conditions
- oestoarthritis
- post operative pain
- menorrhagia
- low dose asprin for platelt aggregation (COX1)
Class: NSAIDs
Action:
- inhibit COX1 - decrease prostaglandins, prostacylcin, thromboxane synthesis
Adverse effects:
- GI - dyspepsia, nausea, ulceration, bleeding (PGE2 regulates acid secretion in parietal cells, PGI2 maintains blood flow and mucosal repair)
- renal - reversible decreased GFR and renal blood flow (PGE2/PGI2 vasodilation of afferent arteriole), increased blood pressure (PGE2 inhibits sodium absoprtion in the collecting duct)
Warnings:
- GI - IBD, elderly, prolonged use, smoking, alcohol, H.pylori, ulcers
- renal - CKD, heart failure (greater reliance on PGE2 for vasodilation)
- pregnancy - delayed labour and early closure of ductus arterosus
Interactions:
- GI - aspirin, glucocorticoid steroids, anticoagulants (PPI considered)
- renal - ACEi, ARbs, diuretics
Other:
- displace other highly protein bound drugs (sulfonylurea + hypoglycaemia, methotrexate + haeptoxicity, warfarin + increaed bleed risk)
Mneumonic:
Interactions e.g warfarin
Gastric ulceration
Renal impairment
Asthma sensitivity
Bleeding risk
celecoxib, etoricoxib
Indication: antiinflammatroy, analgesic, antipyretic
- long term osteo/rheumatoid arthritis
Class: NSAID
Action: selective COX2 inhibitors
Adverse effects:
- less gi
- renal - CKD, heart failure (greater reliance on PGE2 for vasodilation)
- increase MI risk - inhibit PGI2 - unopposed aggregatory effects
Paracetemol
Indication: analgesic and antipyretic
Action: COX2 selective inhibtion in CNS - decrease pain signals to higher centres (little anti-inflmatory action as inability to inhibit COX2 in the presence of peroxides in peripheral inflamation)
Adverse effects:
- few ADRs
- no effect on platelets
- limited effect on GI
- well abrobed from GI - inactivated by conjugation in liver
Overdose:
- at normal doses conjugation with glutathione renders NAPQI harmless
- hepatic glutathione is limited
- NAPQI highly nucleophilic - oxidises key enzymes causing necrosis and apoptosis
- asymtomatic initially, nausea + vomiting in 24hr, liver damage 3-4days
- iv acetylcysteine - glutathione thiol replacement (glutathione itself cannot get into hepatocytes)
Other:
Narrow therapeutic window - no. In 24hr (4x day)
Therapeutic index = toxicity
Morphine
Indication: opioid
- analgesic
Class: opioid agonist (strong)
Action:
- binds to MOP, DOP, KOP receptor
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and Glutamate release
- increase dopamine release
Absorption:
- PO, IV, IM, SC, PR
- FPM - 40% oral bioavilability
- patches and IV for breakthrough analgesia - 80% bioavailability IV/SC
- 2 mins IV, 15 mins IM, 20 mins oral
Distribution:
- very lipophilic - enters all tissues (including foetal)
- not protien binding so struggles to cross BBB
Adverse effects:
- respiratory depression -decreases sensitivity of MRC to CO2
- GI tract - constipation, vomiting
- sedation + confusion
- puritus
- tolerance and dependence
- histamine release - caution in asthmatics
Other:
- metabolism = morphine + glucoronic acid = M6G + M3G
- elimination = renal
- use oxycodone or fentanyl in renal impairment
- if regular opiates needed prescribe concurrent paracetemol to reduce their requirement
- avoid weak and throng opiates in combo - inhibit same receptors
Fentanyl
Indication: opioid
- analgesic
- anasethetic
Class: opioid agonist (stronger)
Action:
- binds to MOP receptor
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and Glutamate release
- increase dopamine release
Absorption:
- IV, epidural, inrathecal, nasal
- 80- 100% oral bioavilability
- 100x more potent and higher affinity than morphine
Distribution:
- very lipophilic - enters all tissues (including foetal)
- high protien binding so crosses BBB
Adverse effects:
- respiratory depression -decreases sensitivity of MRC to CO2
- GI tract - constipation, vomiting
- histamine release - caution in asthmatics
- LESS than morphine
Other:
- metabolism = hepatic via CYP3A4
- elimination = renal
Codeine
Indication: opioid
- analgesic
- cough depressant
Class: opioid agonist (moderate)
Metabolism:
- codeine to morphine via CYP2D6 (inhibited by fluoxetine)
- variable expression of CYP = variable response
- 1/10th potency of morphine
Action:
- binds to MOP receptor
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and glutamate release
- increase dopamine release
Absorption:
- PO, SC
Adverse effects:
- respiratory depression - worse in children
- GI tract - constipation
Other:
- elimination = glucoronidation and renal excrection
Buprenorphine
Indication: opioid
- analgesic
- addiction
Class: opioid partial agonist
Action:
- binds to MOP receptor - low kd (high affinity), low Emax (effiacy)
- decrease cAMP
- efflux of potassium - hyperpolarisation
- decrease substance P and Glutamate release
- increase dopamine release
- antagonist at KOP receptor
Absorption:
- transdermal, buccal, sublingual
Distribution:
- very lipophilic - enters all tissues (including foetal)
Adverse effects:
- respiratory depression -decreases sensitivity of MRC to CO2
- low bp, dizziness
- nausea
Other:
- metabolism = hepatic via CYP3A4
- elimination = biliary excretion
Naloxone
Indication: opioid
Class: competitive opioid antagonist
Action:
- greater affinity for MOP than morphine, less than buprenorphine
- acts at all opioid receptors
- inhibits normal cascade
- 0 Emax
Absorption:
- IV, IM, intranasal, PO
- FPM - v low oral availability
- rapid onset of action
Distribution:
- very lipophilic - enters all tissues (including foetal)
Adverse effects:
- short half life
- slow infusion
Other:
- metabolism = hepatic - naloxone -3 - glucuronide
- elimination = renal
