PHARMACOLOGY Flashcards
During his last few months of life the patient was prescribed morphine. Describe how morphine works
- Morphine attaches to opioid receptors (Mu receptors)
- Morphine reduces membrane excitability and hence action potential firing frequency
- Opioids act on the dorsal horn as well as the peripheral terminals of nociceptive afferents neurons
- Thus preventing pain signals travelling up the spinal column
- Morphine also increases release of enkephalins and 5-HT (serotonin) onto dorsal horn neurons via stimulation of the periaqueductal grey matter (PAG) and the raphe nucleus
Describe how paracetamol helps to reduce fever
- Paracetamol is a COX enzyme inhibitor
- It is thought to be selective for COX-3
- COX enzymes stimulate the production of prostaglandins
- In fever, the temperature set point is elevated by the production of PGE2
- Bacteria/viruses act on the immune system and stimulate production of cytokines (IL-1. TNF-alpha) which stimulates PGE2 synthesis
- Paracetamol helps to prevent PGE2 synthesis which is the main compound that alters the homeostatic temperature set point in the hypothalamic neurons that regulate body temperature
- By blocking PGE2 synthesis, paracetamol brings down the temperature set point to normal
where are glucocorticoids secreted from?
- from the cortex within adrenal glands
what are the 3 main types of opioid receptors and their functions?
- Mu (for morphine): analgesia, euphoria (but also constipation, respiratory depression)
- Kappa (for ketcyclazocine): analgesic at periphery (but also dysphoria, hallucinations)
- Delta for vas Deferens: analgesic effects at spinal cord
what are the effects and side effects of morphine?
EFFECTS:
- analgesia, euphoria, sedation, pupil constriction
SIDE EFFECTS:
- nausea and vomiting (chemoreceptor trigger zone in medulla)
- constipation (from reduced motility and muscle tightening)
- respiratory depression (inhibits respiratory centres in brainstem)
- suppressed cough reflex
- tolerance with recurrent use: desensitisation of Mu receptors, dose has to be increased
- dependence: physical (restless, aggression, runny nose, shivering) and psychological (cravings may persist for months and years)
where are opioids metabolised and excreted?
- metabolised in liver
- excreted in urine
what are some considerations to take into account when prescribing morphine?
- most morphine derivatives have a short half-life so have to be given several times a day
- IV/IM morphine: choose lower dose as compared to oral
- synthetic opioid patches go on releasing the drug for days and days so check and remove if toxicity is suspected, or if change in drug/dose is needed
what should you do if patient has toxicity to opioids?
- Naloxone is most important drug (opioid receptor antagonist)
- reverses opioid actions on mu receptor
- given IV/sc in acute opioid toxicity (eg. drowsy patient with small pupils and poor respiration)
- however, can trigger acute physical withdrawal (patient can become aggressive)
what pathways do NSAIDs and aspirin block?
- cyclooxygenase (COX enzymes)
- COX 1, COX 2, COX 3
what pathways do corticosteroids block?
- they block the conversion of phospholipids to arachidonic acid
why can NSAIDs cause GI problems?
- NSAIDs block COX enzymes
- one of the multiple things produced from COX enzymes are prostaglandins
- prostaglandins provide GI mucosal protection which prevents acid from dissolving your stomach
- NSAIDs also directly erode the gastric lining
why do NSAIDs have anti-inflammatory, analgesic, and antipyretic effects?
- Anti-inflammatory: decreases lvls of prostaglandin E2 and prostacyclin
- Analgesic: decreases lvls of prostaglandins which makes nerves less sensitive to inflammatory mediators (eg. bradykinin)
- Anti-pyretic: decreases lvls of IL-1
what drugs can be given to reduce the risk of GI problems?
- Proton pump inhibitor (PPI) or H2 antagonist: to reduce gastric acid
- Misoprostol: prostaglandin analogue that increases gastric mucus to protect stomach
what pathway does methotrexate target?
- folate pathway
what drug should be taken with methotrexate, when should you not give methotrexate, and what drug should you not give methotrexate with?
- folic acid should be given (on another day) to reduce toxicity
- avoid if patient has liver problems
- do not give methotrexate and trimethoprim together
