Pharmacology - Bone Pain

Question 1

CD

Answer 1

Controlled drug

Question 2

PO

Answer 2

Orally

Question 3

IV bolus

Answer 3

Single, small quantity given over small period of time into vein

Question 4

IV infusion

Answer 4

Larger quantity infused/ given over a longer time into vein

Question 5

SL

Answer 5

Sublingual

Question 6

Intrathecal

Answer 6

Into the spine

Question 7

Chemical structure of opioids

Answer 7

Activity comes from free hydroxyl on benzene ring, linked by w carbon atoms to a nitrogen

Question 8

How are variations of morphine made

Answer 8

Substitutions made at one of both the hydroxyls to give diamorphine and oxycodone

Question 9

Pharmacodynamics of opioids

Answer 9

Analgesia 
Euphoria 
Respiratory depression 
Cough suppression 
Pin-point pupils 
Nausea and vomiting 
Constipation 
Bronchospasm, hypotension, local itchiness

Question 10

Analgesia - opioids

Answer 10

Used for acute/ chronic pain

Not used for neuropathic pain

Question 11

Euphoria - opioids

Answer 11

Sense of wellbeing & contentment (μ receptor)
Dysphoria/ hallucinations к-receptor
Helps w/ analgesia as minimises the agitations and anxiety associated w/ pain/ trauma

Question 12

Respiratory depression - opioids

Answer 12

Medicated by μ receptor, decrease sensitivity of respiratory centre to arterial Pco2 levels and inhibition of respiratory rhythm generation
Commonest cause of death in acute opioid poisoning

Question 13

Pin-point pupils - opioids

Answer 13

μ + к receptor stimulation.

Question 14

Nausea and vomiting - opioids

Answer 14

Common SE, 40% pts, however transient SE

Question 15

Constipation - opioids

Answer 15

Increase tone and reduce gut motility = constipation

Also reduces drug absorption

Question 16

Bronchospasm - opioids

Answer 16

Histamine is released in states of allergy (e.g. hay fever)
Morphine releases histamine from mast cells
Local irritation
Bronchospasm in asthmatics = bad combo!

Question 17

Tolerance

Answer 17

Increasing dose to get same pharmalogical response; develops within a few days. This means in palliative care we have to keep swapping drugs.

Question 18

Switching between opioids

Answer 18

Opioids cannot be used interchangeably
Follow palliative care guidance in BNF
Use local/ trust guideline

Question 19

What causes withdrawal symptoms

Answer 19

Physical dependence on drug

μ receptor agonist removal

Question 20

Relieving withdrawal symptoms

Answer 20

Long acting μ receptor agonists (methadone/buprenorphine

Question 21

Why do we have CDs

Answer 21

Misuse of drugs act 1971 (manufacture/ supply/ possession)

Question 22

Class A drugs

Answer 22

Heroin
Cocaine
LSD
Methadone

Question 23

Class B drugs

Answer 23

Barbituates

Cannabis

Question 24

Class C drugs

Answer 24

Buprenorphine

Anabolic steroids

Question 25

Level 1 - WHO pain relief ladder

Answer 25

Pain persisting or increasing | Non-opioid +/- adjuvant

Question 26

Level 2 - WHO pain relief ladder

Answer 26

Opioid for mild to moderate pain +/- non-opioid +/- adjuvant

Question 27

Level 3 - WHO pain relief ladder

Answer 27

Opioid for moderate to severe pain +/- non-opioid +/- adjuvant

Question 28

Non-opioid in pain ladder

Answer 28

Paracetamol

Question 29

Adjuvants in pain ladder

Answer 29

NSAIDs e.g. ibuprofen, diclofenac

Question 30

Mild opioid

Answer 30

Codeine Dihydrocodeine Tramadol

Question 31

Mod-severe opioid

Answer 31

Morphine

Question 32

Mechanism of action of NSAIDs

Answer 32

Inhibits cyclo-oxygenase (COX) enzymes 1, 2 which convert arachidonic acid to prostaglandins and leukotrienes by the COX and 5-lipoxygenase pathways respectively

Question 33

COX-1

Answer 33

Produces prostaglandins that protect against mucosal damage and regulates platelet aggregation and renal blood flow

Question 34

COX-2

Answer 34

The prostaglandins here cause local pain + swelling. Inflammation also increases COX-2 production in the spinal cord where pain signals are processed

Question 35

Non-selective inhibitors

Answer 35

NSAIDs that act on COX-1 AND COX-2 (ibuprofen, naproxen) | Higher risk of stomach ulcers

Question 36

Selective inhibitors

Answer 36

NSAIDs that only act on COX-2 (celecoxib, etoricoxib)

Question 37

Therapeutic effects of NSAIDs

Answer 37

``` Anti-inflammatory = ↓Prostaglandin E2 and Prostacyclin Analgesic= ↓Prostaglandins Antipyretic= ↓Interleukin-1 ```

Question 38

-ve effects of NSAIDs

Answer 38

``` Stomach= acid gets through lining, unable to make protective mucosa, creates ulcer Platelet activity= less clotting, more GI bleeds ```

Question 39

Contraindications of NSAIDs

Answer 39

``` Severe heart failure or liver disease Asthma Hx peptic ulcer Hx gastrointestinal bleeding Adverse event with NSAIDs ```

Question 40

Mechanism of action of paracetamol

Answer 40

Weak COX inhibitor, so doesn’t exhibit anti-inflammatory effect Assumed to selectively inhibit COX-3 enzyme (mechanism not fully understood)

Question 41

Contraindications of paracetamol

Answer 41

Hx of allergic reaction

Question 42

Compound painkillers

Answer 42

Compound painkillers are made from a combination of 2 drugs- usually a standard painkiller and low dose of an opioid

Question 43

Examples of compound painkillers

Answer 43

``` Co-codamol= paracetamol + codeine Co-codaprin= aspirin + codeine Co-dydramol= paracetamol + dihydrocodeine ```

Question 44

Most effective antidepressants

Answer 44

TCAs and SNRIs (tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors)

Question 45

TCAs and SNRIs

Answer 45

Affect transmission of both NTs serotonin and norepinephrine --> reduces pain at a spinal and cerebral level

Question 46

What are anti-depressants effective in treating depression and chronic pain

Answer 46

The same parts of the brain are affected in people with major depressive disorders

Question 47

Contraindications of antidepressants

Answer 47

Arrhythmias Manic phase of bipolar disorder Heart block Immediate recovery period after M.I

Question 48

Types of opioid receptors

Answer 48

Mu Delta Kappa NOP All G-coupled receptors and cause hyper polarisation of neurones ---> reducing in firing of AP

Question 49

Mu opioid receptors

Answer 49

Responsible for most analgesic effects but also the worst side effects

Question 50

Delta opioid receptors

Answer 50

Analgesia but can also be proconvulsant

Question 51

Kappa opioid receptors

Answer 51

Analgesia at spinal level, may cause sedation, dysphoria + hallucinations

Question 52

NOP opioid receptors

Answer 52

Reverse effects of mu receptor agonists (supraspinal), analgesia (spinal), immobility + learning impairment

Question 53

Contraindications of opioids

Answer 53

``` Acute respiratory depression Comatose patients Head injury Raised intracranial pressure Risk of Paralytic ileus ```

Question 54

Side effects of opioids

Answer 54

Arrythmias, confusion, constipation, dizziness, drowsiness, dry mouth, euphoric mood, flushing, hallucinations, headache, hyperhidrosis, hypotension, nausea, palpitations, respiratory depression, skin reactions, urinary retention, vertigo, visual impairment, vomiting, withdrawal syndrome

Question 55

Action of opioids

Answer 55

Cross blood-brain barrier and access CNS to have central action