308 NSAID's and opiates pharmacology

Question 1

What is the difference between an opiate and an opioid?

Answer 1

Opiate: naturally occurring substances

Opioid: includes natural, synthetic and semi-synthetic chemicals

Question 2

How long do NSAID’s take to have full effect when given for analgesia?

Answer 2

1 week
Eg. for osteoarthritis

Question 3

How long do NSAID’s take to have full effect when given for anti-inflammation?

Answer 3

3 weeks
Eg. for gout or rheumatoid arthritis

Question 4

How do NSIAD’s reduce fever?

Answer 4

IL-1 releases prostaglandins that elevate the hypothalamic temperature control, NSIAD’s prevent this

Question 5

Where are opiates metabolised?

Answer 5

In the kidneys

Question 6

Why is renal function important when prescribing NSAID’s?

Answer 6

NSIAD’s damage the kidneys

They reduce prostaglandins in the blood so there is less control of the afferent arteriole to the kidney which causes damage to the kidney over time

Question 7

What is prostacyclin for?

Answer 7

Vasodilation
Inhibition of platelet aggregation
Anti-inflammation

Question 8

Describe the WHO analgesic ladder

Answer 8

Step 1: non-opioid Eg. paracetamol, NSAID

Step 2: opioid for mild to moderate pain Eg. codeine phosphate

Step 3: Opioid for moderate to severe pain Eg. morphine sulphate

Question 9

What is Immediate-release oral morphine?

Answer 9

-Rapid onset – 20 minutes
-Need to administer 4 hourly for sustained effect
-Difficult to cover pain over 24 hours unless close supervision
-Useful for severe pain and rapid titration

-Morphine 5mg every hour as required for 24 hours

Question 10

What is Modified release morphine?

Answer 10

-Slower onset – 1-2 hours and later peak levels (4 hours)
-Cannot be rapidly titrated for severe pain
-Ideal for continuous analgesia and titration at home

Question 11

What is the effect of NSAIDs on COX1?

Answer 11

Undesirable inhibition of:

stomach PGE2 and PGI2
Intestine
Kidney PGE2 and PGI2
Platelet thromboxane A2

Causes acid reflux and lesions in stomach, imbalance in kidneys and other side effects

Question 12

What is the effect of NSAIDs on COX2?

Answer 12

Desirable inhibition that works on inflammation

Question 13

What is the effect of prostaglandins?

Answer 13

-Protect gastric mucosa
-Support renal function
-Support platelet function

-Inflammation and pain

Question 14

What are the issues and cautions with NSAIDs?

Answer 14

-Consider Gastro protection. History of ulcers?
-Elderly patients
-Duration of NSAID therapy
-Cardiac disease
-Renal and hepatic function
-Other medications

Avoid multiple NSAID’s

Question 15

What is PGD2 for?

Answer 15

Vasodilatation

Question 16

What is PGE2 for?

Answer 16

-Affect the hypothalamus temperature regulating system, produces fever

-Increases water electrolytes and mucus secretion in gastro-intestinal tract

Question 17

What is PG2-alpha for?

Answer 17

Produces contraction of uterine smooth muscles

Question 18

What is PGI2 for?

Answer 18

Vasodilatation and inhibition of platelet aggregation

Question 19

What is TXA2 for?

Answer 19

Vasoconstriction and stimulation of platelet aggregation

Question 20

What is LTC4 and LTD4 for?

Answer 20

Bronchoconstriction and increased capillary permeability

Question 21

Name some COX-2 inhibitors

Answer 21

Etoricoxib and Celecoxib

They have a reduced risk of serious upper GI events compared to non-selective NSAIDs

Not routinely recommended because they increase thrombotic events through PGI2 inhibition

Question 22

What is the opioid mechanism of action?

Answer 22

Opioid receptors at cellular level
Receptors distributed throughout CNS

Overall effect in reduction in neuronal cell excitability, resulting in reduced transmission of nociceptive impulses

Question 23

What are the side effects of opioids?

Answer 23

Confusion
Constipation
Drowsiness and sedation
Dizziness
Euphoric effect
Hallucination
Nausea and vomiting
Respiratory depression

Long term: tolerance/dependence and addiction

Question 24

What are the issues and cautions with opioids?

Answer 24

Allergy
Elderly patient
Renal and hepatic function

Question 25

What are the contraindications for opioids?

Answer 25

Acute respiratory depression
Comatose
Head injury

Question 26

What is the treatment for acute Gout?

Answer 26

First-line is high dose NSAID and gastro protection
Eg. Diclofenac, Indometacin, Ketoprofen, Naproxen

Colchicine is NSAIDs are contraindicated

Question 27

Why is aspirin not indicated for gout?

Answer 27

It reduces uric acid excretion

Question 28

What are the side effects of NSAIDs?

Answer 28

Common:
GI discomfort: nausea, diarrhoea, oesophagitis, gastritis
Renal impairment

Less common:
Upper GI-bleeding, peptic ulceration
Renal: fluid retention, papillary necrosis, interstitial nephritis
Increased BP and fluid retention (congestive heart failure)
Hypersensitivity rashes (erythema multiforme),angioedema, bronchospasm
Headache, dizziness
Blood disorders (phenylbutazone)
Cardiovascular events

Question 29

What are the drug interactions of NSAIDs?

Answer 29

Things that increase bleeding or risk of renal disease mostly

-Anticoagulants: ↑ risk of GI bleeding and
↑ anticoagulant effect
-Steroids: ↑ risk of GI bleeding
-ACE Inhibitors: ↑ risk of renal impairment, hyperkalaemia, antagonism of hypotensive effect
-Digoxin: May ↑ plasma concentration of digoxin, ↑ risk of heart failure, ↓renal function
-Antihypertensives: Antagonism of hypotensive effect
- Oral hypoglycaemics: Enhances effect of sulphonylureas
- Quinolone antibiotics: Possible ↑ risk of seizures
-Phenytoin: ↑ risk of phenytoin toxicity
- SSRI’s and venlafaxine: ↑ risk of bleeding
Diuretics: ↑ nephrotoxity risk, antagonism of diuretic effect