Analgesics Flashcards
How do we know we are in pain?
We have a receptor that detects pain: Nociceptors and have a pathway to the brain to inform the person there is a painful stimulus
We have mechanical (cute yourself), thermal( hot/cold) and chemical damages (bleach) these activate the Nociceptors.
They have a high threshold and are not easily apactivated, need tissues damage.
What are the Adelta fibres?
These sensory afferents detect mechanical pain, thermal under 5C and over 43C, chemical, the paid is fast- 5-30ms, myelinated 2-4
What are C fibres?
Detech mechanic, thermal and chemical pain. Slow, 0.5-2ms, dull and buried pain, non-myelinated
What are AB Fibres?
Pressure, touch positions, fast 10-85 m/s, myelinated 6-22, gate control theory of pain I.e. Rub after it hurts, incredibly fast signal.
What activates the Nociceptors?
Inflammation. Histamine is released and combines with the receptors to activate pain.
How do we tackle the inflammation?
Block the production of inflammatory mediators.
Prostaglandins can sensitise the c fibres to bradykinin
Inhibit prostaglandin production of NSAIDS
Block production allows reduction of sensitivity and pain.
Explain the NSAIDS inflammatory mediators
Cell membrane is damaged–>phospholipase A2–> AA produced–> cox 1 and 2 released–> PGG2, PGH2–> PGD2- inhibits platelet aggregation and vasodilation–> PGF2g-bronchoconstrictor–> PGE2- vasodilator and hyperanglesic-> PG12- vasodilator, hyperanglesic, inhibits platelets aggregation–> TXA2 thrombotic vasconstrictor
What is cox 1?
Cox 1 is always produced and has a protective effect. I.e. Inhibits gastric acid secretion.
What is cox 2?
It’s responsible for pain and inflammation
What are the pharmacological sues for NSAIDS?
1- Antipyretic- temperature
2- Anslgesic- relief of pain with increase prediction of prostaglandins
3-Anti-inflammatory- reduces oedema, sensitisation of Nociceptors
4- Musculoskeletal pain
What are the side effects if NSAIDS?
A- chronic treatment B- indigestion C- diarrhoea D- nausea and vomiting E- gastric bleeding and ulceration
What does cox 1 synthesise?
PG12 and PGe2- important, NSAIDS inhibit these enzymes, mucous and HC03 secretion, decrease of acid secretion and increase of blood flow to the stomach.
How can we reduce the side effects?
Inhibit cox 1 we can reduce side effects : developed drugs that only inhibit cox 2 enzyme (celecoxib, etroricoxib)
Enteric-coatings tablets- doesn’t degrade and reaches the small intestine
Give drug with a protective agent- Misoprotol (PGE1 analogue, reduce amount of acid being produced) or omaprazole (PPI)
Pro-drugs: drugs administered in a inactive or less active form, once administered the prodrug is metabolised in the body to become active.
Explain the use of Aspirin
It is a preventative drug. Effective against mild pain and fever. It’s a non selective cox inhibitor. Some are allergic to it.
Should not be given to children under 16 can cause Reyes syndrome(toxicity in liver)
History of peptic ulcer ( will increase bleeding)
Haemophilia or other bleeding disorders
Patients taking anticoagulant drugs
Liver disease
Explain ibuprofen.
It’s a non selective cox inhibitor,
1st choice of drug, lower risk of side effects compared with aspirin
Indigestion, peptic ulcers
Naproxen is similar to ibuprofen but is more potent and longer lasting, fewer dose.
Other examples: disclofenac, mefenamic acid
Explain use of paracetamol
It is a antipyretic analgesic. Limited anti inflammatory action Mechanism of action not fully understood Use to treat children Toxic to the liver at 2-3 times the normal dose
Why combine NSAIDS with Opioid analgesic?
Combing either aspirin or paracetamol with a weak opiate will mean least chance of dependence
Example of NSAIDS and Opiates
Co-codamol: paracetamol and codeine phosphate
Co-cadaprin: aspirin and codeine phosphate
Both available OTC.
Less chance of dependence but not shown to give greater relief than non opioids
Increase number of side effects
Explain the opioid analogue
Opium; sleep, analgesia, euphoria
Enkephalins, endorphins and dynorphines binds to receptors. Naturally produced by the body, bind to opioid receptors.
How is the inhibitory pathway active?
When the enkephalins are released, it binds to the opioid receptors on the Adelta/C fibres, substance P released inhibited ( calcium influx), signal of pain not transmitted to the thalamus.
When is morphine used?
Mild to moderate pain: use codeine, dihydrocodeine or meptazinol
Moderate to sever pain: morphine, diamorphone (heroin) pethidine, tramadol
Example of a interoperable drug
Fentanyl
Alfentanil
Example of postoperative analgesic
Morphine
What happens in overdoes?
Use Naloxane to reverse effects
Explain the use of morphine
Acute and chronic pain
State of euphoria and mental detachment
Administration: slowly absorbed by mouth, sustained release, IV. IM. SC. rectal. Infusion by syringe pump.
Side effects of morphine
Constipation 100% Nausea vomiting 30% Sedation 30% Confusion, nightmares, hallucination 1% Cough suppression Drug dependence Tolerance Respiratory depression
What are local anaesthetis?
Small-diameter fibres are more sensitive (Adelta and c fibres)
Lipid insoluble drugs. Require injection into the nerve a on
Lipid soluble drugs can dissolve across the membrane
How can local anaesthetics be applied?
Topically or mucosal surface
SC on the nerve endings
Nerve block
IV.
Inhibits the sodium channels so we don’t feel pain
Examples of local anaesthetics
Lidocaine
Bupivicaine
Prilocaine
Tetracaine
What are the advantage of pain?
1-warns individual that there is a problem
2-assists in localising the pain
3-May help with diagnosis
