Pharmacodynamics of Analgesics, Antipyretics and Anti-inflammatory Drugs
Session 11: Pharmacodynamics of Analgesics, Antipyretics and Anti-inflammatory Drugs
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe mechanism of action of analgesics, antipyretics and anti-inflammatory drugs
Describe drug interactions associated with analgesics, antipyretics and anti-inflammatory drugs
Describe side effects of analgesics, antipyretics and anti-inflammatory drugs
Describe contraindications of analgesics, antipyretics and anti-inflammatory drugs
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
Computer and LCD projector
SESSION OVERVIEW
Step
Time
Activity/
Content
Step
Time
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
Introduction, Learning Tasks
PST 05104 Pharmacology & Therapeutics
PST 05104 Pharmacology & Therapeutics
PST 05104 Pharmacology & Therapeutics
PST 05104 Pharmacology & Therapeutics
PST 05104 Pharmacology & Therapeutics
PST 05104 Pharmacology & Therapeutics
PST 05104 Pharmacology & Therapeutics
PST 05104 Pharmacology & Therapeutics
89
89
NTA Level 5 Semester 1 Facilitator Guide
NTA Level 5 Semester 1 Facilitator Guide
2
45 minutes
Presentation/
Mechanism of Action of Analgesics,
2
45 minutes
Buzzing
Antipyretics and Anti-Inflammatory Drugs
Buzzing
Antipyretics and Anti-Inflammatory Drugs
Presentation/
Drug Interactions Associated With
3
20 minutes
Presentation/
Analgesics, Antipyretics and Anti-
3
20 minutes
brainstorming
Analgesics, Antipyretics and Anti-
brainstorming
Inflammatory Drugs
Inflammatory Drugs
4
20 minutes
Presentation
Side Effects of Analgesics, Antipyretics and
4
20 minutes
Presentation
Anti-Inflammatory Drugs
Anti-Inflammatory Drugs
5
20 minutes
Presentation/
Contraindications of Analgesics, Antipyretics
5
20 minutes
Brainstorming
and Anti-Inflammatory Drugs
Brainstorming
and Anti-Inflammatory Drugs
6
05 minutes
Presentation
Key Points
7
05 minutes
Presentation
Evaluation
PST 05104 Pharmacology & Therapeutics 90 NTA Level 5 Semester 1 Facilitator Guide
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Mechanism of Action of Analgesics, Antipyretics and Anti-Inflammatory Drugs (45 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
What are the mechanisms of actions of analgesics, antipyretics and anti-Inflammatory drugs?
ALLOW few pairs to respond and let other pairs add on points not mentioned
WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below
Anti-inflammatory, Antipyretic, Analgesics have different mechanisms of action:
Non-Steroidal Anti-Inflammatory Drugs
o Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin biosynthesis by inhibiting cyclo-oxygenase (COX).
o This is the basis of most of their therapeutic, as well as their undesired actions. COX is a key enzyme in the synthesis of prostaglandins and thromboxanes, important mediators of the erythema, oedema, pain and fever of inflammation.
o There are two main isoforms of the enzyme, namely a constitutive form (COX-1) that is present in platelets, stomach, kidneys and other tissues, and an inducible form, (COX-2), that is expressed in inflamed tissues as a result of stimulation by cytokines and is also present to a lesser extent in healthy organs, including the kidneys.
Drugs like Aspirin inhibits cyclooxygenase activity, it diminishes the formation of prostaglandins and thus modulates those aspects of inflammation in which prostaglandins act as mediators.
Acetaminophen, although a useful analgesic and antipyretic, has weak anti-inflammatory activity and is therefore not useful in the treatment of inflammation such as that seen with rheumatoid arthritis.
PST 05104 Pharmacology & Therapeutics 91 NTA Level 5 Semester 1 Facilitator Guide
Analgesic action
Prostaglandin E2 (PGE2) is thought to sensitize the nerve endings to the action of bradykinin, histamine, and other chemical mediators released locally by the inflammatory process.
Thus, by decreasing PGE2 synthesis, aspirin and other NSAIDs repress the sensation of pain.
NSAIDs are superior to opioids in the management of pain in which inflammation is involved; combinations of opioids and NSAlDs are effective in, treating pain in malignancy.
Antipyretic action
Fever occurs when the set-point of the anterior hypothalamic thermoregulatory centre is elevated.
This can be caused by PGE2 synthesis, stimulated when an endogenous fever-producing agent (pyrogen) such as a cytokine is released from white cells that are activated by infection, hypersensitivity, malignancy, or inflammation.
The salicylates and other NSAIDs lower body temperature in patients with fever by impeding PGE2 synthesis and release.
They reset the "thermostat" toward normal and rapidly lower the body temperature of febrile patients by increasing heat dissipation as a result of peripheral vasodilation and sweating.
These drugs have no effect on normal body temperature.
Glucocorticosteroids
Prednisolone and others
o These agents lack antipyretic and analgesic activity. o They only have anti-inflammatory activity.
o Inhibits expression of pro-inflammatory cytokines IL-2, 3 and 6, TNF, GM-CSF and IFN-γ;
o Inhibits production of adhesion molecules – ICAM-1,E-selectin and vascortin – leading to reduced vascular permeability.
o Reduces synthesis of arachidonic acid metabolites (prostaglandins, leukotrienes) and reduces histamine release.
Other (Slow Acting) Anti-Inflammatory Agents
Gold Compounds, Chloroquine and hydroxychloroquine, penicillamine
o In contrast to the NSAlDs drugs described earlier, remittive (remission inducing) arthritis drugs are slow-acting.
o They do not act by inhibiting cyclooxygenase and have no analgesic or primary anti-inflammatory activity.
o These drugs are used primarily for rheumatic disorders, especially in cases where the inflammation does not respond to cyclooxygenase inhibitors.
PST 05104 Pharmacology & Therapeutics 92 NTA Level 5 Semester 1 Facilitator Guide
They slow the course of the disease and may also induce a remission, preventing further destruction of the joints and involved tissues.
Gold compounds: like the other drugs in this group, cannot repair existing damage.
Rather, they can only prevent further injury.
o The currently available gold preparations are gold sodium thiomalate, aurothioglucose, and auranofin.
It is believed that gold salts are taken up by macrophages and suppress phagocytosis
and lysosomal enzyme activity.
This mechanism retards the progression of bone and articular destruction. o The mechanism of their anti-inflammatory activity is uncertain.
o Besides inhibiting nucleic acid synthesis, they are known to stabilize lysosomal membranes and trap free radicals.
o In treating inflammatory disorders, they are used for rheumatoid arthritis that has been unresponsive to NSAlDs or else they are used in conjunction with an NSAID.
STEP 3: Drug Interactions Associated with Analgesics, Antipyretics and Anti-Inflammatory Drugs (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are drug interactions associated with Analgesics, Antipyretics and Anti-Inflammatory Drugs occur?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Drug interactions of antipyretic, analgesics and anti-inflammatory are as follows:
Non-Steroidal Anti-Inflammatory Drugs
o NSAIDs are associated with drug interactions but only a proportion are clinically relevant.
o Many are due to displacement of a drug from its plasma protein binding sites by NSAIDs which are tightly protein-bound.
o They may not occur with all NSAIDs but might be selective
o Most NSAIDs do not have clinically important interactions with oral hypoglycemic agents whereas phenylbutazone, azaprozone & aspirin prolong their half-life.
o Similarly phenylbutazone and azaprozone prolong coumadin's half-life.
PST 05104 Pharmacology & Therapeutics 93 NTA Level 5 Semester 1 Facilitator Guide
Lithium clearance may be decreased by indomethacin, piroxicam, phenylbutazone and diclofenac. Methotrexate (MTX) may be displaced from its binding protein sites by NSAIDs.
This is generally not clinically relevant with low doses of MTX as utilized in rheumatoid arthritis patients with normal renal function.
NSAIDs also may reduce renal blood flow, tubular excretion of drugs & renal prostaglandin production and may attenuate the effect of anti-hypertensive drugs.
Renal failure & hyperkalemia have been reported in patients receiving triamterene & indomethacin.
STEP 4: Side Effects of Analgesics, Antipyretics and Anti-Inflammatory Drugs (20 minutes)
Anti-inflammatory, Antipyretic, Analgesics:
Non-Steroidal Anti-Inflammatory Drugs
o Non Selective: Gastrointestinal effects occur because of the inhibition of COX-1– mediated production of cytoprotective mucus in the stomach.
o Non selective: Edema: PGs inhibit the reabsorption of Na+ and the activity of ADH, so PG inhibition leads to salt and water retention. This can lead to edema and can be problematic in patients with conditions such as congestive heart failure.
o COX-2 Selective: Cardiovascular, cardiac failure with fluid retention and myocardial infarction: The mechanism is not confirmed, but cardiovascular effects are thought to be a result of disruption of the balance between the platelet-activating effects of COX-
1 and the platelet-inhibiting effects of COX-2.
o All: Central nervous system (CNS): Confusion, dizziness, depression, and hallucinations may occur. The mechanism is not confirmed, but COX-2 is the most abundant COX isoform in the CNS, and COX-2 may play a role in neurotransmission. The frequency of CNS side effects appears to be higher with COX-2–selective inhibitors and possibly with indomethacin.
Actions on the kidney: Cyclooxygenase inhibitors prevent the synthesis of PGE2 and PGl2 prostaglandins that are responsible for maintaining renal blood flow, particularly in the presence of circulating vasoconstrictors.
Decreased synthesis of prostaglandins can result in retention of sodium and water and may cause edema and hyperkalaemia in some patients. Interstitial nephritis can also occur with all of the IVSAIDs except aspirin.
Effect on platelets: TXA2 enhances platelet aggregation, whereas PGl2 decreases it. Low doses (60 to 80 mg daily) of aspirin can irreversibly inhibit thromboxane production in platelets. As a result of the decrease in TXA2, platelet aggregation (the first step in thrombus formation) is reduced, producing an anticoagulant effect with a prolonged bleeding time.
Gastrointestinal effects: Normally, prostacyclin (PGI2) inhibits gastric acid secretion, whereas PGE2 and PGF2 stimulate synthesis of protective mucus in both the stomach and small intestine.
PST 05104 Pharmacology & Therapeutics 94 NTA Level 5 Semester 1 Facilitator Guide
In the presence of aspirin, these prostanoids are not formed, resulting in increased gastric acid secretion and dirninished mucus protection. This may cause epigastric distress, ulceration, and/or hemorrhage.
Respiratory actions: At therapeutic doses, aspirin increases alveolar ventilation. Salicylates uncouple oxidative phosphorylation, which leads to elevated C02 and increased concentration.
Glucocorticosteroids
Adverse effects have been discussed in detail in session Pharmacodynamics of Drugs acting on Respiratory System
STEP 5: Contraindications of Analgesics, Antipyretics and Anti-Inflammatory Drugs (10 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are contraindications of Analgesics, Antipyretics and Anti-Inflammatory drugs? ALLOW few students to respond?
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Non-Steroidal Anti-Inflammatory Drugs o Active peptic ulcer
o Acetyl salicylic acid in Asthma
o Most drugs do not exhibit significant interactions
STEP 6: Key Points (5 minutes)
NSAIDs inhibit cyclo-oxygenase (COX) enzyme.
COX-2-selective drugs may have reduced gastric toxicity, but increase cardiovascular thrombotic events.
Drugs like Aspirin inhibits cyclooxygenase activity, it diminishes the formation of prostaglandins and thus modulates those aspects of inflammation in which prostaglandins act as mediators.
STEP 7: Evaluation (5 minutes)
What are the adverse effects of acetyl salicylic acid?
What are the indications for Gold compounds?
What is the mechanism of action of glucocorticosteroids in the treatment of inflammation?
PST 05104 Pharmacology & Therapeutics 95 NTA Level 5 Semester 1 Facilitator Guide
References
Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.
Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.
Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:
Jaypee Brothers Medical P.
Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.
Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.
School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).
Dar es Salaam, ARDHI University press.
The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.
The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.
PST 05104 Pharmacology & Therapeutics 96 NTA Level 5 Semester 1 Facilitator Guide
PST 05104 Pharmacology & Therapeutics 97 NTA Level 5 Semester 1 Facilitator Guide
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