Analgesics

Question 1

How do we know we are in pain?

Answer 1

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.

Question 2

What are the Adelta fibres?

Answer 2

These sensory afferents detect mechanical pain, thermal under 5C and over 43C, chemical, the paid is fast- 5-30ms, myelinated 2-4

Question 3

What are C fibres?

Answer 3

Detech mechanic, thermal and chemical pain. Slow, 0.5-2ms, dull and buried pain, non-myelinated

Question 4

What are AB Fibres?

Answer 4

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.

Question 5

What activates the Nociceptors?

Answer 5

Inflammation. Histamine is released and combines with the receptors to activate pain.

Question 6

How do we tackle the inflammation?

Answer 6

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.

Question 7

Explain the NSAIDS inflammatory mediators

Answer 7

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

Question 8

What is cox 1?

Answer 8

Cox 1 is always produced and has a protective effect. I.e. Inhibits gastric acid secretion.

Question 9

What is cox 2?

Answer 9

It’s responsible for pain and inflammation

Question 10

What are the pharmacological sues for NSAIDS?

Answer 10

1- Antipyretic- temperature
2- Anslgesic- relief of pain with increase prediction of prostaglandins
3-Anti-inflammatory- reduces oedema, sensitisation of Nociceptors
4- Musculoskeletal pain

Question 11

What are the side effects if NSAIDS?

Answer 11

A- chronic treatment
B- indigestion
C- diarrhoea
D- nausea and vomiting
E- gastric bleeding and ulceration

Question 12

What does cox 1 synthesise?

Answer 12

PG12 and PGe2- important, NSAIDS inhibit these enzymes, mucous and HC03 secretion, decrease of acid secretion and increase of blood flow to the stomach.

Question 13

How can we reduce the side effects?

Answer 13

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.

Question 14

Explain the use of Aspirin

Answer 14

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

Question 15

Explain ibuprofen.

Answer 15

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

Question 16

Explain use of paracetamol

Answer 16

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

Question 17

Why combine NSAIDS with Opioid analgesic?

Answer 17

Combing either aspirin or paracetamol with a weak opiate will mean least chance of dependence

Question 18

Example of NSAIDS and Opiates

Answer 18

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

Question 19

Explain the opioid analogue

Answer 19

Opium; sleep, analgesia, euphoria

Enkephalins, endorphins and dynorphines binds to receptors. Naturally produced by the body, bind to opioid receptors.

Question 20

How is the inhibitory pathway active?

Answer 20

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.

Question 21

When is morphine used?

Answer 21

Mild to moderate pain: use codeine, dihydrocodeine or meptazinol

Moderate to sever pain: morphine, diamorphone (heroin) pethidine, tramadol

Question 22

Example of a interoperable drug

Answer 22

Fentanyl

Alfentanil

Question 23

Example of postoperative analgesic

Answer 23

Morphine

Question 24

What happens in overdoes?

Answer 24

Use Naloxane to reverse effects

Question 25

Explain the use of morphine

Answer 25

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.

Question 26

Side effects of morphine

Answer 26

Constipation 100%
Nausea vomiting 30%
Sedation 30%
Confusion, nightmares, hallucination 1%
Cough suppression
Drug dependence
Tolerance 
Respiratory depression

Question 27

What are local anaesthetis?

Answer 27

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

Question 28

How can local anaesthetics be applied?

Answer 28

Topically or mucosal surface
SC on the nerve endings
Nerve block
IV.

Inhibits the sodium channels so we don’t feel pain

Question 29

Examples of local anaesthetics

Answer 29

Lidocaine
Bupivicaine
Prilocaine
Tetracaine

Question 30

What are the advantage of pain?

Answer 30

1-warns individual that there is a problem
2-assists in localising the pain
3-May help with diagnosis