308 NSAID's and opiates pharmacology Flashcards
What is the difference between an opiate and an opioid?
Opiate: naturally occurring substances
Opioid: includes natural, synthetic and semi-synthetic chemicals
How long do NSAID’s take to have full effect when given for analgesia?
1 week
Eg. for osteoarthritis
How long do NSAID’s take to have full effect when given for anti-inflammation?
3 weeks
Eg. for gout or rheumatoid arthritis
How do NSIAD’s reduce fever?
IL-1 releases prostaglandins that elevate the hypothalamic temperature control, NSIAD’s prevent this
Where are opiates metabolised?
In the kidneys
Why is renal function important when prescribing NSAID’s?
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
What is prostacyclin for?
Vasodilation
Inhibition of platelet aggregation
Anti-inflammation
Describe the WHO analgesic ladder
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
What is Immediate-release oral morphine?
-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
What is Modified release morphine?
-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
What is the effect of NSAIDs on COX1?
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
What is the effect of NSAIDs on COX2?
Desirable inhibition that works on inflammation
What is the effect of prostaglandins?
-Protect gastric mucosa
-Support renal function
-Support platelet function
-Inflammation and pain
What are the issues and cautions with NSAIDs?
-Consider Gastro protection. History of ulcers?
-Elderly patients
-Duration of NSAID therapy
-Cardiac disease
-Renal and hepatic function
-Other medications
Avoid multiple NSAID’s
What is PGD2 for?
Vasodilatation
What is PGE2 for?
-Affect the hypothalamus temperature regulating system, produces fever
-Increases water electrolytes and mucus secretion in gastro-intestinal tract
What is PG2-alpha for?
Produces contraction of uterine smooth muscles
What is PGI2 for?
Vasodilatation and inhibition of platelet aggregation
What is TXA2 for?
Vasoconstriction and stimulation of platelet aggregation
What is LTC4 and LTD4 for?
Bronchoconstriction and increased capillary permeability
Name some COX-2 inhibitors
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
What is the opioid mechanism of action?
Opioid receptors at cellular level
Receptors distributed throughout CNS
Overall effect in reduction in neuronal cell excitability, resulting in reduced transmission of nociceptive impulses
What are the side effects of opioids?
Confusion
Constipation
Drowsiness and sedation
Dizziness
Euphoric effect
Hallucination
Nausea and vomiting
Respiratory depression
Long term: tolerance/dependence and addiction
What are the issues and cautions with opioids?
Allergy
Elderly patient
Renal and hepatic function
What are the contraindications for opioids?
Acute respiratory depression
Comatose
Head injury
What is the treatment for acute Gout?
First-line is high dose NSAID and gastro protection
Eg. Diclofenac, Indometacin, Ketoprofen, Naproxen
Colchicine is NSAIDs are contraindicated
Why is aspirin not indicated for gout?
It reduces uric acid excretion
What are the side effects of NSAIDs?
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
What are the drug interactions of NSAIDs?
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
