Analgesics

Question 1

What is an analgesic?

Answer 1

A drug used to relieve pain

Question 2

What is an adjuvant?

Answer 2

A drug which enhances the effectiveness/potency of another drug

Question 3

What are the different stages of the pain ladder?

Answer 3

NON-OPIOIDS: for mild-moderate pain
- Paracetamol (1st choice), low-dose aspirin

NON-OPIOID ADJUVANTS: also for mild-moderate pain.
- NSAIDs e.g. ibuprofen, diclofenac, naproxen, high-dose aspirin

WEAK OPIOIDS: for mild-moderate pain.
- Weak opioids e.g. codeine, dihydrocodiene, tramadol.
- + non- opioid adjuvant

STRONG OPIODS: for moderate-severe pain.
- Strong opioids e.g. morphine, diamorphine, fentanyl
- + non-opioid adjuvant

Question 4

What are the different type of pains? MOA & what type of drugs would you use for it?

Answer 4

1. Nonciceptive
   - MOA- Tissue-associated pathology. Direct activation of nociceptors (pain receptors)
   - e.g. Pain to stretched skin
   - Drugs= Aspirin, paracetamol
2. Neurpathic
   - MOA- Nervous system-associated pathology. Direct injury of peripheral or central nerves
   - e.g. Tumour infiltration. Damage by chemotherapy.
   - Drugs= Are generally managed w/ tricyclic antidepressant
   or with certainanti-epileptic drugs
3. MSK pain
   - back pain, psychogenic pain e.g. fibromyalgia.

Question 5

Why are NSAIDs & opioids used in combination?

Answer 5

They produce analgesia by different mechanisms
- So if the effects are additive, less of each drug can be given but the same degree of analgesia produced.

Reduces intensity of unwanted side-effects produced by each drug.

Question 6

Non-opioids: indications of use, MOA, contraindications, route of administration

Answer 6

Paracetamol & low dose aspirin (aspirin has same MOA as NSAID)

Indications of use:
- Acute MSK pain
- Pyrexia
- Less irritant to the stomach, so now generally preferred to aspirin, esp. in elderly
- Cold, Flu, fever/extremely high temperature
- muscle pain
- headache, earache, toothache

MOA:
- Mechanism is poorly defined.
- Possible inhibition of COX-3.
- has analgesic & antipyretic properties
- no useful anti-inflammatory properties.
- Prevents PGE2 synthesis- in fever, temp set point is elevated by production of PGE2
- PGE2 production is stimulated by cytokines- TNF, interleukin- which are produced by action of bacteria/viruses on immune system
- blocking PGE2 brings down temp

Contraindications- avoid use in these situations:
- Overdosage can cause hepatic damage.
- Side effects are rare.
- Interact w/ anti-coags e.g. warfarin.
- Liver diseases/problems
severely malnourished
- kidney diseases
- allergy.

Route of administration:
- Mouth- 4g daily
- IV- short-term treatment of moderate pain, only for urgent need to treat pain or hyperthermia.
- rectum

Question 7

Non-opioids adjuvants: indications of use, MOA, contraindications, route of administration

Answer 7

NSAID

Indications:
- Reduce pain, stiffness & inflammation of chronic conditions affecting bone, muscles & joints (OA, RA etc.)
- Used in acute pain incl. MSK pain, but paracetamol now often preferred
- Treat pain from secondary bone tumours
Response to drug varies between individuals & does not change progression of disease
- Menstrual pain

MOA:
- Block COX-1 & -2 which
- prevents arachidonic acid from converting to prostaglandin
- Inhibits Prostaglandin production - Reduces pain & inflammation
- Blocking COX-2 results in anti-inflammatory effect
- inhibit cox 1 & 2 > prevents conversion of arachidonic acid to prostaglandins (which cause pain) > reduces pain > anti-inflammatory, anti-analgesic, anti-pyretic

Contraindications:
- Selective COX-2 inhibitors preferable to patients w/ patients at high risk of GI side effects (aka peptic ulcers), opposed to non-selective COX inhibitors
- PPI (proton pump inhibitor) also often prescribed alongside.
- Increased risk of CVD
- Use w/ caution in elderly, pregnant, breast feeding & coagulation defects.
- Chronic Kidney disease
- cirrhoisis
- heart failure
- GI tract related illness
- blood clotting disorders.

Route of administration:
- Oral (useful in MSK diseases)
- topical creams & gels (useful in OA)

Question 8

Weak opioids: indications of use, MOA, contraindications, route of administration

Answer 8

E.g. codeine, tramdol

indications of use:
- Reduces pain by acting on CNS & GI tract
- Treats acute pain (e.g. post-op moderate pain)
- used in palliative care
- used in management of non-malignant chronic pain (pain lasting 3-6 months)
- Acute respiratory depression

MOA:
- Same drug action as strong opioids however, weak opioids have a weaker affinity for mu opioid receptor which they bind to
- Lower likelihood of dependency then strong opioids.

Contraindications:
- Head injury (opioids interfere w/ pupillary responses vital for neuro-assessment),
- Acute Respiratory depression
- Comatose patients
- Side-effects: Addiction. Constipation. Nausea. Vomiting. Compromise immune system - decreases proliferation of macrophages

Route of administration:
- For codeine: mouth, IM injection.

Question 9

Strong opioids: indications of use, MOA, contraindications, route of administration

Answer 9

E.g. morphine, fentanyl

Indications:
- Severe acute & chronic pain
- End of life care pain which isn’t relieved by previous 2 analgesics

MOA:
- Binds to mu & kappa opioid receptors in the CNS (dorsal horn)
- Causes inhibition of ascending pain pathways due the hyperpolarisation of neurons & reduced neurotransmitter release.

Contraindications:
- Drug addiction monitoring for long-term use.
- raised intracranial pressure
- risk of paralytic ileus
- Same as weak opioids

Route of administration:
- For morphine: subcutaneous injection, IM injection, oral/rectum
- Fentanyl - intravenous, epidermal, transdermal, patch.
- Diamorphine - (half dose of morphine) orally & intravenous.