Analgesia

Introduction to pain study day

Paracetamol
 Active metabolite of phenacetin

 Weak COX inhibitor peripherally

 Central effects important
 ? Via COX3
 ? Via endogenous cannabinoid antagonism

 Well absorbed orally

 20 – 50 % protein bound
 Liver metabolism
Paracetamol ACETAMINOPHEN
 Indications
-mild to moderate pain; pyrexia with discomfort.

 Contra-indications
-hepatocellular failure; liver disease; intravenous infusion in preterm neonates
-Overdosage with paracetamol is particularly dangerous as it may cause
hepatic damage which is sometimes not apparent for 4 to 6 day

 Cautions
-alcohol dependence; hepatic impairment; chronic malnutrition; dehydration;
G6PD deficiency; maximum daily infusion dose 3 g in patients with
hepatocellular insufficiency, chronic alcoholism, chronic malnutrition, or
dehydration; before administering, check when paracetamol preparation
last administered and cumulative paracetamol dose over previous 24 hours.

Preparations-Oral (tablet/Syrup), PR, IV

NSAIDS
 Analgesic
 Anti-inflammatory
 Antipyretic
 Antithrombotic

Via prostaglandin production inhibition

 Diclofenac (Voltaren)
 Ibruprofen
 Tenoxicam
 Naproxen
 Paricoxib- (selective inhibitor of cyclo-oxygenase-2=Cox 2)
 Etoricoxib
NSAIDS
 Indications
 pain and inflammation in rheumatic disease and other musculoskeletal
disorders; acute musculoskeletal pain; painful and inflammatory
gynaecological conditions; post-operative pain; migraine; severe painful
inflammatory infections of the ear, nose, or throat

 Contra-indications
 hypersensitivity to aspirin or any other NSAID
 asthma, severe heart failure
 active gastro-intestinal ulceration or bleeding;
 history of recurrent gastro-intestinal ulceration or haemorrhage (2 or
more distinct episodes)
 and in patients with a history of gastro-intestinal bleeding or perforation
related to previous NSAID therapy (see also NSAIDs and gastro-
intestinal events)
NSAIDS Cautions
 Elderly
 Allergic disorders
 Coagulation defects
 Connective-tissue disorders
 Patients at risk of peptic ulceration or gastro-intestinal
bleeding (see also contra-indications)
 Inflammatory bowel disease
 Cardiac impairment
 Uncontrolled hypertension; heart failure; ischaemic heart
disease; peripheral artery disease
 Cerebrovascular disease
 Renal impairment
Tramadol

 Synthetic analogue of codeine

 Good oral absorption
 Weak opioid activity
 Blocks noradrenaline reuptake
 Blocks serotonin reuptake
 Metabolised to active compounds
Tramadol-Side effects

 Nausea
 Drowsiness
 Sweating
 Postural hypotension
 Urinary retention
 Dry mouth
 Minor delay in colonic transit
 Seizures /serotonin syndrome
Tramadol

 Synthetic analogue of codeine

 Good oral absorption
 Weak opioid activity
 Blocks noradrenaline reuptake
 Blocks serotonin reuptake-Caution with
SSRI’s, Epilepsy
 Metabolised to active compounds
TRAMADOL - SIDE EFFECTS
 Nausea
 Drowsiness
 Sweating
 Postural hypotension
 Urinary retention
 Dry mouth
 Minor delay in colonic transit
 Seizures /serotonin syndrome
Pharmocological opioid effects
 Analgesia
 Euphoria
 Respiratory depression
 Nausea and vomiting
 GI tract
 Urinary retention
 Pupillary constriction
 Anti-tussive
 Pruritis
 Hypotension and bradycardia
 Immunosuppression
Morphine

 Readily absorbed orally

 Low bioavailability (25%)
 Active metabolite M6G
 Renal excretion
 Multiple routes of administration-IV,
IM,SC, IT, Orally
Fentanyl

 Very lipid soluble

 Short action
 Liver metabolism
 Less histamine release
 Transdermal preparation/IV/Nasal
Oxycodone

 Oxynorm (quick release) &

Oxycontin/Oxydone (controlled release,
Bi-phasic)
 89% bioavailability
 Metabolised to noroxycodone &
oxymorphone (weakly active)
 Safer in renal failure
 Possible value in neuropathic pain
Codeine Phosphate

 Naturally occurring in opium

 Well absorbed but limited bioavailability
 Good CNS penetration
 Metabolised to morphine for action
 Phenotypic variation in metabolism
 Much more constipating
Pethidine

 Fully synthetic
 Well absorbed orally
 Moderate bioavailability
 Multiple receptor effects
 Antispasmodic (theoretically)
 Potentially toxic metabolite
 Euphoria +++
Methadone

• Synthetic racemic mixture

• Longacting, slow oral absorption
• Half life 15-40 hours
•  and NMDA receptor activity
• Liver metabolism
• Various routes of administration
• Blunted euphoric effect
Naloxone-Opioid antagonist
 Naloxone is a pure narcotic antagonist

 It prevents or reverses the effects of opioids, including

respiratory depression, sedation and hypotension.

 Following parenteral administration naloxone is rapidly distributed

in the body. It is metabolised in the liver, primarily by glucuronide
conjugation and excreted in the urine

 Rapid onset, within 2 min.

 Short half life.
Opiophobia

 Patients
 “I don’t want to become an addict”
 “Am I dying?”

 Health professionals
 Inappropriate perception of side effects
KETAMINE
Main action at NMDA receptor (antagonist)
 Anaesthesia
 Pain relief
 profound analgesia
 attenuates morphine tolerance (but not side
effects)
 prevents wind up and sensitisation
KETAMINE - SIDE EFFECTS

 Psychological - hallucinations, dreams

 Increased CNS metabolism, blood flow
and ICP
 Sympathomimetic effects
 Increases uterine tone
ADJUVANT DRUGS
 Antidepressants
 Tricyclic
 Others
 Antiepileptics
 Gabapentin
 Phenytoin, clonazepam, valproate, carbamazepine
 Membrane stabilisers
 Lignocaine
 Mexiletine
 Flecainide
 Others
 Clonidine
 Baclofen
 Calcitonin
 Entonox
 Capsaicin
TRICYCLICS

 Amitriptyline, Nortripyline, Dothiepin

 Multiple receptor effects but esp NA/5HT
reuptake blockade
 Dry mouth, constipation, blurred vision, urinary
retention, tachycardia, postural hypotension,
heart block, sedation, weight gain
GABAPENTIN

 Structural analogue of GABA

 Gabapentin specific binding site
 Variable bioavailability
 Renally excreted unchanged
 Titrated from low dose to reduce side effects
 Unsubsidised (unless special authority)
 Pregabalin
GABAPENTIN - SIDE EFFECTS

 Somnolence (15%)
 Dizziness (10%)
 Fatigue (6%)
 Headache (5%)
 Nausea (3%)
 Ataxia (2.5%)
 Weight gain (1.6%)
 Blurred vision (2%)
CLONIDINE
 Presynaptic antiadrenergic activity
 Good oral absorption but best transdermal /
epidural
 Uses
 Neuropathic pain
 Sympathetically mediated pain
 Reduces opioid requirements in long term therapy
 Helps opioid withdrawal
 Side effect - sedation, dry mouth, postural
hypotension, weakness, fatigue, impotence,
agitation, insomnia
CALCITONIN

 Endogenous hormone
 Parenteral administration
 Analgesic action unknown
 Side effects - nausea, flushing, pruritis,
allergy
 Evidence for phantom limb pain
RENAL FAILURE

 Morphine - active M6G

 Pethidine - toxic norpethidine
 Tramadol - M1 metabolite
 Amitriptyline - active metabolites
 Gabapentin - unchanged in urine
 Baclofen - unchanged in urine
Non-pharmacological
management
 Heat
 Acupuncture
 Physiotherapist (tens)
 Relaxation therapies
 Hypnosis
 Alternative remedies
Entonox

2 Premixed Gas: 50% Nitrous Oxide

50% Oxygen
 Weak Anaesthetic but good analgesic
 Onset Action: Approx 1-2 Minutes
 Duration Action: < 5 Minutes
 Compatible with all other drugs
 Rapid elimination from the blood via the
lungs

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ADMINSTRATION

 Given no sooner than 2

Hrs following a full meal
to reduce risk of
aspiration

 Check prescription with

cylinder

 Cylinder should be at
least ¼ full at beginning
of procedure

 Only the patient must

hold the
mask/mouthpiece
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 Commence at least 2
CLEANING EQUIPMENT

 Single use mouthpieces, facemasks &

filters and tubing are disposable
 Disposable Mask/mouthpiece/tubing can be
used repeatedly by Pt but filter to be
disposed of after each treatment

12/18/2019 1:36 AM
SUMMARY
• Altered level of
Use of Entonox consciousness or head
injury with impaired
GCS
The patient requires Any
• Hydrocephalus or
Analgesia Contraindications? raised ICP eg shunt
dysfunction
• Pneumothorax
• Bowel Obstruction
Long term only Short term or ‘fill in’ No
• Air Embolism
analgesia - Entonox
• Severe obstructive
• Show the patient how to use the airways disease
equipment.
• Is the patient • Severe bone
• Before use check there is more than
1/4 tank of entonox or a full spare willing and able to marrow suppression or
cylinder. Yes use the system? similar haematological
disorder
• Do you have a clean mask/mouth • Is it prescribed?
piece and filter? • Myringoplasty
• Facial Injuries
• Pregnancy 1st
• Maintain contact and observe trimester
Begin therapyat least the patient throughout.
1-2 min prior to • Vomiting
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procedure • Record in notes duration,
effectiveness, side effects