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Objectives
Clinical Pharmacology: At the end of this lecture you should be able to:

Indications, Signs and ◦ Understand the terms clinical pharmacology, indications, signs and symptoms
◦ Be familiar with reliable sources of drug information for therapeutics
Symptoms ◦ Describe the mechanism of action and clinical pharmacology of opioid
analgesics
PHAR3251 CLINICAL AND EXPERIMENTAL PHARMACOLOGY
DR TRUDIE BINDER

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Indication: A condition or problem which makes a particular

treatment advisable
What is Clinical Pharmacology?
Symptoms: Something the patient feels
or observes themselves, which they
Indications, regard as abnormal, e.g. pain, vomiting
Signs and
Signs: Physical or functional
Symptoms
abnormalities elicited by physical
examination, e.g. tenderness or
a swelling felt by palpation

History taking and physical examination

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What to consider? Reliable Sources of Information

Choosing suitable Australian Medicines
Select management medicines if a Using medicines safely Handbook (AMH)
options wisely medicine is considered and effectively
necessary
Therapeutic Guidelines (eTG)
What are the signs
and symptoms? Where do you find Individualize and
What is the good information? Monitor NPS MedicineWise
pathophysiology

Product Information (MIMS)

Are medicines
needed? Consumer Medicines
Information (CMI)

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Australian Medicines Handbook Therapeutics Guidelines (eTG)

Electronic resource at UNSW
Medicines Information
library & CIAP
eTG: https://tgldcdp-tg-org-
How to treat particular Antibiotic guidelines
au.wwwproxy1.library.unsw.e
conditions best known
du.au/etgAccess

AMH: https://amhonline-
Paper version updated amh-net-
annually au.wwwproxy1.library.unsw.e Eg e coli UTI
du.au/

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Example: Mr Les K, 76 year old pensioner

NPS MedicineWise
http://www.nps.org.au/ Current problems Current medications
❑ Eg Medicines, Analgesia, (indications)
Pethidine ⚫ Hypertension (6 years) ⚫ Zanidip 10 mg tabs
⚫ Hypercholesterolaemia ⚫ Atorvastatin 80mg tabs
⚫ Stroke – ischaemic (left) ⚫ Tegretol 200mg tabs
⚫ Atrial fibrillation ⚫ Iscover 75mg tabs
⚫ Depression ⚫ Gabapentin 300mg caps
⚫ Generalised tonic-clonic ⚫ Aurorix 300mg tabs
seizures
⚫ Tritace 10mg caps
⚫ Neuropathic pain (right
⚫ Sotalol 160mg tabs
side) ? Origin
⚫ OA knees

This is an example only: You do not need to remember these indications or medications

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Rx Indic/working? Adr.Monitor
Lercanidipine 10mg
Hypertension BP every 6 months
(Zanidip)
LFT (Liver function test);
Atorvastatin 80mg Raised cholesterol ❑ Indicationfor each medicine?
cholesterol
Carbamazepine Blood conc. when stable; FBC, ❑ Mechanism of action?
Epilepsy. Neuropathic pain?
(Tegretol) 200mg skin
❑ How would you know the medicine is
Clopidogrel (Iscover) Stroke prevention - previous
platelet function working?
75mg ischemic stroke & atrial fib
❑ What are the common adverse effects to
Pain (scale) Review Mr K’s be aware of?
Gabapentin 300mg Neuropathic pain – epilepsy
Renal Function
Medications ❑ How will the patient be informed about
these?
Moclobemide (Aurorix)
Depression Mood; Relapse ❑ Are there any interactions possible?
300mg

Ramipril 10mg (Tritace)

Hypertension
BP ❑? Stop any medications
Cardiac Failure
Sotalol 160mg
Atrial fibrillation BP, pulse
(Sotacor)

This is an example only: You do not need to remember these indications or medications

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The NO TEARS tool

Need and indication Case Study:
Open questions
Medication Tests and monitoring Opioids in pain
assessment: Evidence and guidelines management
Adverse events
NO TEARS Risk reduction or prevention
Simplification and switches
⚫ http://www.bmj.com/cgi/reprint/329/7463/434

Papaver somniferum

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Background
Opioids are drugs which relieve
Endogenous opioids are derived
from three precursor molecules:
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pain without causing
Pro-opiomelanocortin (POMC),
unconsciousness
pro-enkephalin and pro-dynorphin Inhibit adenylate Facilitate the Inhibit the opening
cyclase thereby opening of K+ of Ca2+ channels
/ /
Dynorphin, beta-endorphin and enkephalin
reducing channels causing thereby inhibiting
Receptor classes intracellular cAMP hyerpolarisation transmitter release
• Analgesia
Mu (m) • Motivation and reward
Kappa (k) • Feeding
• Locomotor activity
Delta (d) • Thermoregulation
• Stress and anxiety
Opioids: Cellular actions

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Definition of pain: Unpleasant sensory

and emotional experience associated
with actual or potential tissue damage Mechanism:
Opioid
Indications: inhibition of
The perception of noxious stimuli is
termed nociception Treatment of pain
pain
Opioids can change both the sensation
and the affective response

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Pain: Signs and Symptoms

Pain: Signs and Symptoms How do you measure pain?
Describe 3 signs and symptoms of pain?
Visual
Patient
Observation
/ analogue
History
scale

Numerical Verbal
Questionnaire
rating scale descriptions

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❑Circumstances associated with pain onset Visual Analogue Scale

❑Primary site of pain
Instruction: mark on the line below how strong your pain is.
❑Radiation of pain to other body areas
No pain worst possible pain
❑Character of pain e.g. sharp, stabbing, burning,
aching Numerical Rating Scale
❑Intensity of pain (pain scales)
Pain History Instruction: on a scale of 0-10, how strong is your pain
❑Timing of pain (when does it begin and how long No pain - 0 1 2 3 4 5 6 7 8 9 10 - worst pain possible
does it last)
❑Effect of pain on patients quality of life e.g. Verbal Descriptor scale
during activities or sleep Instruction: which word best describes your pain?
❑Medications taken for pain relief
None Mild Moderate Severe Excruciating

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Faces Rating Scale Factors that affect pain measurement

1. Pain Sensation Home environment

Patient beliefs

coping skills

cultural background
2. Reporting
concept of suffering

gender

placebo effect

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Weak – Codeine
Codeine
❑Well absorbed orally
❑Metabolised in liver, excreted in urine
Opioid: ❑Indication: mild to moderate pain, diarrhoea, cough
Analgesic ❑half life: 4 - 6 hrs
Potency
Strong – Oxycodone,
Morphine, Pethidine,
Methadone, Buprenorphine,
Fentanyl, Heroin, Etorphione

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Oxycodone Morphine
❑10 x potency of codeine ❑Bioavailability 25%
❑Metabolised in liver to M3G and M6G, excreted in urine
❑Indication: mild to moderate pain, antitussive ❑Indication: Moderate and severe pain, cancer-related pain, post operative pain
❑Half life: 2 - 4 hrs
❑Half life: 2-3 hrs

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Methadone Buprenorphine
❑Bioavailability > 85% ❑Partial opioid agonist

❑Metabolised in liver, mainly excreted in urine ❑Bioavailability 16%

❑Metabolised in liver, excreted in bile and urine
❑Indication: moderate to severe pain, opioid maintenance programs (decreases
rapid lows and highs seen with heroin) ❑Indication: moderate pain

❑Half life: 13 - 58 hrs ❑May be used for opioid withdrawal

❑Half life: 6 - 9 hrs

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Heroin
Fentanyl • Diacetylmorphine
❑50 – 100 X potency of morphine • Greater ability to cross BBB
• Converted to morphine and
❑Metabolised in liver, excreted in urine monoacetylmorphine in the
brain
• Not approved for medicinal
❑Indication: moderate to severe pain, child birth, anaesthetic/analgesic use in Australia
• Indication: Cancer-related Heroin: Inactive Morphine: active

❑Half life: 1hr (high lipid solubility) pain

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- a) on recurrence of pain
On demand
- b) fixed intervals

Morphine 10 mg oral, s.c. or i.m. will control pain

in 70% of patients with mild - moderate pain

Administration Patient controlled Analgesia (PCA)

– infusion systems
Pain Control
Severe pain may require i.v. morphine via
intermittent or continuous infusion. May also use
PCA

oral, transdermal, rectal, iv, sc, im,

epidural, intrathecal

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Which Opioid (if any) is indicated

depends on the level and type of
pain

eTG: Analagesic

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