1. Module Outcome
Demonstrate integrated knowledge and understanding of the clinical
situation, appropriateness of use and the pharmacology of Antihistamines in
the nursing care plan
2. Learning unit
Learning unit 1.2: Analgesics (Nonsteroidal Anti-
Inflammatory) drugs used in the caring for patients
ILO : Demonstrate integrated knowledge and
understanding of the principles, rationale and
pharmacology of nonsteroidal anti-inflammatory
analgesics used in caring for patients.
3. Assessment Criteria
• The pharmacodynamics, contra indications,
interactions, therapeutic effects, side effects and
adverse reactions of Nonsteroidal Anti-inflammatory
Drugs are illustrated and applied in the context of
nursing specifics.
4. Inflammation
Inflammation is a normal and protective
response to tissue injury that may be
caused by physical trauma, noxious
chemicals or microbiological agents
The ROLE of inflammation:
Inactivate and destroy invading organisms
Remove irritants
Restore normal structure and function to
infected / damaged tissue
Inappropriate activation of immune
system or chronic inflammation can
result in unwanted conditions e.g.
rheumatoid arthritis
5. Inflammation
Prostaglandins (PGs) are chemical
mediators released during allergic and
inflammatory processes
Act locally
Tissues in which they are synthesised
Arachidonic acid (AA) [20-carbon
fatty acid] primary precursor of
PGs
Free AA is released from tissue
phospholipids by phospholipase
A2
2 major synthesising pathways:
CYCLOOXYGENASE AND
LIPOXYGENASE PATHWAYS
Rapidly metabolised to inactive products
NSAIDs Mechanism of action
Primarily : by inhibiting cyclooxygenase enzymes that
catalyses the first step in PGs biosynthesis
6. NSAIDs
Cycloxygenase-1 (COX-1)
PGs involved in normal housekeeping functions
Present in blood vessels, platelets, stomach,
intestines, kidneys
Constitutive enzyme
Physiological effects
Gastric protection
Platelet aggregation
Vascular homeostasis
Maintenance of blood pressure
7. NSAIDs
Cycloxygenase-2 (Cox-2)
Present at the site of inflammation (inducible enzyme)
Expressed by cells that are involved in the inflammatory
process
Macrophages, monocytes and synoviocytes
Tissues: kidneys, brain, uterus, bone and vascular endothelium
Induced by cytokines at the site of inflammation
Tumour necrosis factor (TNF) –α and Interleukin 1 & 2
Expressed in the CNS and plays a role in central meditation of
pain and fever
8. NSAIDs
Therapeutic effects and uses
Anti-inflammatory
Inhibits the release of PGs, histamine, thromboxane and leukotrienes at the site of tissue injury
Suppresses pain, swelling and increase blood flow associated with inflammation
Analgesic
Decrease production of PGs that sensitise nociceptors to bradykinin
Mild to moderate pain arising from inflammation/tissue damage
Arthritis, toothache and dysmenorrhoea
Post-operative pain- combine with opioids
Antipyretic properties
Normal body temperature is regulated by hypothalamus that controls balance between heat loss and heat
production
Inhibits the effects of PGs in the thermoregulatory centre in the hypothalamus
Anti-coagulants
Prolong clotting time by inhibiting clotting factors
Inhibit platelet aggregation
9. NSAIDs
Adverse effects
Gastrointestinal tract
Very common ADR
Inhibition of COX-1 decrease PGs that inhibit acid secretion and protect the mucosa
Abdominal pain, ulcerations, bleeding, anaemia, diarrhoea, N+V
Kidneys
No ADRs at therapeutic doses in health individuals
Renal insufficiency in susceptible patients- inhibition of PGE2 and PGI2 responsible for maintenance of
renal blood flow
Haematuria and renal necrosis
Skin conditions
Steven Johnsons syndrome: very rare but fatal skin reaction
Rashes associated with Mefenamic and sulindac
Central nervous system
Headaches, vertigo, depression
Haematopoietic effects
Thrombocytopenia, prolonged bleeding due to poor clotting, leukopenia
11. NSAIDs
Indomethacin
Potent anti-inflammatory agent that reversibly inhibits cyclogenases
Not used for its antipyretic activity
Toxicity limits its use for the treatment of acute gut and arthritis
Mefenamic acid
SE: diarrhoea and inflammation of the bowel
Rare cases are haemolytic anaemic have been reported
Piroxicam
Used to treat rheumatoid arthritis and osteoarthritis
Long half-life which permits single dose daily
SE: mainly associated with GIT disturbances
Ibuprofen
Anti-inflammatory, analgesic and antipyretic
Alter platelet function and prolong bleeding time
Chronic treatment of rheumatoid arthritis, osteoarthritis, fever and dysmenorrhea
GIT effects less severe than aspirin
12. NSAIDs
Aspirin
Commonly used drug worldwide
Inflammatory conditions in additions to cardiovascular disorders
Mechanism of action
Irreversible acetylation of COX-1 and COX-2 leading to inactivation
Inhibits synthesis of thromboxane
Inhibit platelet aggregation to decreased blood clotting
Pharmacokinetics
Admin: oral and suppositories
Absorption is delayed by food intake
Rapidly hydrolysed in plasma and tissues
Yields salicylate anti-inflammatory actions
Metabolised in the liver and excreted in kidneys
13. NSAIDs
Aspirin
Therapeutic uses
Analgesic: Mild to moderate pain
Synthesis of PG is inhibited
PGE2 sensitises nerve endings to action of bradykinin, histamine
and other chemical mediators
Antiplatelet activity
Inhibition of COX-1 enzyme prevents formation of thromboxane
A2
Preventing blood clotting
Cardiovascular conditions and used to prevent strokes
Anti-inflammatory
Inhibits cyclogenase activity diminishes PG formation
Rheumatoid arthritis: symptomatic relief
Reduce swelling and redness
14. NSAIDs
Aspirin
Therapeutic uses
Antipyretic
Rheumatic fever
Fever occurs when set point of hypothalamic
thermoregulatory centre is elevated
Reduce fever due to inhibition of PG synthesis
Rapidly lowers body temperature by increasing heat
dissipation
Peripheral vasodilation and sweating
15. NSAIDs
Aspirin
Adverse effects
Increased bleeding
Inhibition of platelet activation causing decreased blood clotting
Increased risk of bleeding
Exacerbates bleeding gastric ulcers
GIT
Inhibition of PG results in thinner mucous layer in the stomach which can result in peptic ulcer
Misoprostol is used to prevent ulcers (synthetic prostaglandin analogue)
Liver and kidney damage
Reye’s syndrome
Affects children than adults (approx. 30%)
Results in liver and brain damage
Symptoms: rash, vomiting, fever, convulsions and death
Associated with viral infections and aspirin
Teratogenic
Contraindicated in pregnancy can cross the placenta and enter breast milk
Birth defects in foetus and haemorrhage at birth
16. NSAIDs
Aspirin
Adverse effects
Allergic reactions
Rashes, wheezing, hives, swollen lips and tongue, shortness/loss of breath
which leads to anaphylactic shock
More prevalent in asthmatics
Drug-Drug interactions
Warfarin: Potentiates effects by displacing drug molecules from plasma
proteins
Probenecid and sulfinpyrazone- interferes with uricosuric agents and
reduces urate
Toxicity/ Overdose
Chronic overdose is fatal in 25% of cases
N+V, headaches, dizziness, impaired vision, hyperthermia
Administer: activated charcoal
17. NSAIDs
Paracetamol
Analgesic and antipyretic properties
Weak anti-inflammatory activity, does not have gastric and platelets effects
Not usually classified as an NSAID but combined with aspirin and various NSAIDs to
treat inflammation and fever
Therapeutic Effects
Analgesic and antipyretic activity inhibits PG synthesis in the CNS
Weak anti-inflammatory activity poor effects on COX enzymes in peripheral
tissues
No effect on platelet function or increase blood clotting time
Pharmacokinetics
Administered orally, absorbed in the GIT
Peak plasma concentration reached in 30-60min
Plasma half-life of therapeutic doses 2-4hours
Metabolism
Inactivated in the liver-conjugated to give glucuronide or sulphate
N-acetyl-p-benzoquinone imine accumulation leads to liver and kidney necrosis
18. NSAIDs
Paracetamol
Therapeutic Uses
Used as first-line of treatment for pain and where aspirin is contraindicated
Safe to use during pregnancy, nursing and children
Children with viral infections( no risk of Reye’s syndrome)
Patients with gastric complaints or are prone to gastric ulcers
Adverse Effects
No significant adverse effects at normal therapeutic doses
Fatal hepatotoxicity at toxicity doses
Rare: Renal tubular necrosis complication of prolonged, intake of large dose
therapy
Infrequent: Skin rash and minor allergic reactions
Contraindicated in patients with severe hepatic impairment
19. NSAIDs
Cycloxygenase-2 (COX-2) Inhibitors
COX-2 common to inflamed tissue
less gastric irritation associated with COX-2 inhibitors
-leading to decreased risk of peptic ulceration
E.g. Celecoxib, etoricoxib, valdecoxib
Serious Cardiovascular effects associated with COX-2
inhibitors have led to the withdrawal of Rofecoxib and
Valdecoxib
20. NSAIDs
Celecoxib
Mechanism of action
Significantly more selective for inhibition of COX-2 than COX-1
Does not inhibit platelet aggregation or increase bleeding time
Therapeutic uses
Rheumatoid arthritis, dysmenorrhea, pain
Adverse effects
Headache, dyspepsia, diarrhoea and abdominal pain
Proton pump inhibitors (PPIs) used with celecoxib in patients at high risk for
ulcers or history of peptic ulcers disease
Contraindication
Patients with sulphonamide allergies
Chronic renal insufficiency and hepatic failure
Celecoxib is an inhibitor of CYP2D6
Elevated levels of 𝝱-blockers, antidepressants and antipsychotics
21. Quiz time
1. Which of the following drugs is NOT an opioid receptor partial agonist
a) Pentazocine
b) Buprenorphine
c) Naloxone
d) Nalbuphine
2. Pharmacological effects of opioids include
a) Analgesia
b) Euphoria
c) Respiratory depression
d) All of the above
22. Quiz time
3. Which of the following drugs is an opioid receptor antagonist
a) Pentazocine
b) Buprenorphine
c) Naloxone
d) Nalbuphine
4. Therapeutic uses of codeine include
a) Analgesia
b) Diarrhoea
c) Cough suppression/ antitussive
d) All of the above
5. Naloxone is a preferred drug for treating opioid withdrawal symptoms. T/F
