GOMPA ROHIT NAIDU 5A

I. Answer the following questions:

1. Non-opioid analgesics used as anti-inflammatory agents. Pharmacologic

characteristics of agents. Comparative characteristics, and adverse effects.

Non-opioid analgesics including both selective and non-selective cyclooxygenase (COX)

inhibitors and acetaminophen are the most widely used treatments for pain. Inhibition of COX is
thought to be largely responsible for both the therapeutic and adverse effects of this class of
drugs.

Non-opioid analgesics include nonsteroidal anti-inflammatory drugs (NSAIDs), selective COX-

2 inhibitors, and acetaminophen. NSAIDs inhibit cyclooxygenases (COX-1 and COX-2), thereby
disrupting the production of prostaglandin, an important mediator of pain and inflammation.

Consequently, NSAIDs possess antipyretic, analgesic, and anti-inflammatory effects, and are
particularly effective in the management of musculoskeletal pain (e.g., rheumatic disorders,
inflammatory joint pain).

Side effects include gastrointestinal ulcers and bleeding, increased risk of heart attacks, and renal
function impairment. The severity of these side effects is often underestimated because
most non-opioid analgesics are easily available OTC. Selective COX-2 inhibitors have similar
effects to NSAIDs, but show a lower risk for gastrointestinal side
effects. Acetaminophen possesses antipyretic and analgesic effects and is the most commonly
used over-the-counter (OTC) oral analgesic drug. It is generally well tolerated, but overdose can
result in significant hepatotoxicity with the risk of acute liver failure.

2. Nonsteroidal anti-inflammatory drugs (NSAIDs):classification,mechanism of action,

indications and contraindications to use.

Nonsteroidal Anti-inflammatory Drugs (NSAIDs):

A. Nonselective cyclooxygenase (COX) inhibitors:

➢ Derivatives of salicylic acid:

▪ Aspirin (Acetylsalicylic acid – tab. 0.5 g)
▪ Acelysin (Lysine acetylsalicylate – powder)
▪ Sodium salicylate (tab. 0.5 g), Salicylic acid
➢ Derivatives of pyrazolone:
▪ Analgin (Metamizole – tab. 0.5 g, amp. 25%-2 ml)
▪ Butadione (Phenylbutazone –tab. 0.15 g)
 ➢ Derivatives of antranyl acid: Mefenamic acid (tab. 0.25 g)
➢ Derivatives of indole-acetic acid:
▪ Indometacin (tab. 0.025 g)
▪ Sulindac (Clinoril – tab. 0.1 g)
➢ Derivatives of phenyl-acetic acid:
▪ Diclofenac Sodium (Voltaren – tab. 0.025 g; amp. 2.5%-3 ml)
▪ Aceclofenac (tab. 0.1 g)
➢ Derivatives of propionic acid:
▪ Ibuprophen (tab. 0.2 g)
▪ Naproxen (tab. 0.25 g)
▪ Ketoprofen (Ketonal)
➢ Oxicams:
▪ Piroxicam (tab. 0.02 g)
▪ Tenoxicam (Tenoktil – tab. 0.02 g)
➢ Derivatives of isonicotinic acid:
▪ Amizon

➢ B. Selective COX-2 inhibitors:

▪ Meloxicam (tab. 0.015 g)
▪ Celecoxib (caps. 0.1 and 0.2 g)
▪ Nimesulide.

Mechanism of action - The main mechanism of action of NSAIDs is the inhibition of the
enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into
thromboxanes, prostaglandins, and prostacyclins. The therapeutic effects of NSAIDs are
attributed to the lack of these eicosanoids.

Indications of Use - NSAIDs are frequently used to treat inflammatory conditions such as
arthritis, bursitis and tendonitis. NSAIDs are relatively inexpensive and are frequently the
first line of medication used to relieve pain and reduce inflammation. Very low doses
of NSAIDs may be prescribed for people with cardiac disease.

Contraindications - NSAIDs should usually be avoided by people with the following

conditions:
• Peptic ulcer or stomach bleeding.
• Uncontrolled hypertension.
• Kidney disease.
• People that suffer with inflammatory bowel disease (Crohn's disease or ulcerative colitis)
• Past transient ischemic attack (excluding aspirin).
• Past stroke (excluding aspirin).

3. Comparative characteristics of NSAIDs according to a degree of inhibition of the

cyclooxygenases (COX) – COX-1 and COX-2, and degree of anti-inflammatory
action. Adverse effects and their prevention.

The majority of NSAIDs are non-selective inhibitors of cyclo-oxygenase isozymes - COX-

1 and COX-2. COX-1 is structural and responsible for protective properties of GIT.

COX-2 is induced and responsible for PG production by cells involved in inflammation.

Selective inhibitors of COX-2 generally inhibit activity of enzyme that is formed in focus
of inflammation (COX-2). Therefore such agents rarely induce adverse effects that are
typical for non-selective inhibitors of COX-1 and COX-2 (from side of GIT, kidney,
platelets aggregation).These agents increase BP if given with antihypertensive drugs.

Uses - COX-1 is structural and responsible for protective properties of GIT.

COX-2 is induced and responsible for PG production by cells involved in inflammation.

Considerable attention is now given to selective inhibitors of COX-2. They generally inhibit
activity of enzyme that is formed in focus of inflammation (COX-2). Therefore such agents
rarely induce adverse effects that are typically for non-selective inhibitors of COX-1 and COX-
2 (from side of GIT, kidney, platelets aggregation).

Adverse effects - they may have prothrombotic effect, leading to a higher incidence of
cardiovascular events.

Other adverse effects include renal toxicity – decrease in renal blood flow, edema;
hypertension. Studies suggest that COX-2 inhibitors may interfere with wound (ulcer) healing, bone
remodeling, ovulation and prenatal renal development.

Their use is not recommended in children and women of child-bearing age. Nor should they be used
to lactating mothers, as they are excreted in breast milk. Use of the selective COX-2 agents may
increase cardiovascular risk.

Like the COX-1 inhibitors, these COX-2-selective agents also reduce glomerular filtration
rates in elderly individuals.
 II. Write out a prescription and conduct a pharmacotherapeutic analysis (specify the
class, mechanism of action, indications for use, possible complications) of the following
drugs:

1. Acetylsalicylic acid in tablets:

Rx. Tab Acetylsalicylic acid 0.5 N10
D.S. Used for treatment of cold.

Class – Non-steroidal anti-inflammatory drugs. (COX) Inhibitors.

Mechanism of action – Aspirin is non-selective and irreversibly inhibits both forms (but is
weakly more selective for COX-1). It does so by acetylating the hydroxyl of a serine residue.

Indications for use-

• Angina pectoris.
• Angina pectoris prophylaxis.
• Fever.

Complications –
• Gastrointestinal bleeding.
• Allergic reaction.

2. Paracetamol in tablets:
Rx . Tab Paracetamol 0.2 N10
D.S. To reduce high temperatures.

Class – Aniline analgesic ( Derivative of para aminophenol that acts by central mechanism)
Mechanism - . Paracetamol has a central analgesic effect that is mediated through
activation of descending serotonergic pathways.

Its primary site of action, is through inhibition of prostaglandin (PG) synthesis or through
an active metabolite influencing cannabinoid receptors.

Indications for use –

• Menstrual pains
• Migraine headaches.
• Dental pain.
• Post operative pain.

Complications -
• Vomiting.
• Constipation.
• Nausea.
 3. Diclofenac -sodium in tablets:
Rx. Tab Voltareni 0.025 N10
D.S For treatment of arthritis.

Class – Non steroidal anti-inflammatory drugs. ( COX inhibitor, derivative of phenyl acetic acid.)
Mechanism - Diclofenac inhibits cyclooxygenase-1 and -2, the enzymes responsible for
production of prostaglandin (PG) G2 which is the precursor to other PGs. These molecules have
broad activity in pain and inflammation and the inhibition of their production is the
common mechanism linking each effect of diclofenac.
Indications of use –
• Pain
• Swelling ( inflammation )
• Joint swiftness caused due to arthritis.

Complications -
• Indigestion, gas, stomach pain, nausea, vomiting;
• Diarrhea, constipation;
• Headache, dizziness, drowsiness;
• Stuffy nose

4.Celecoxib in tablets :
Rx. Tab Celecoxib 0.1 N10
D.S. Used for treatment of pain and inflammation

Class – Non steroidal anti-inflammatory drugs. ( Selective COX-2 Inhibitors)

Mechanism - The mechanism of action of celecoxib is due to selective inhibition of
cyclooxygenase-2 (COX-2), which is responsible for prostaglandin synthesis, an integral part of
the pain and inflammation pathway.
Indications of use - Is indicated for the management of the signs and symptoms of osteoarthritis,
rheumatoid arthritis and ankylosing spondylitis.
Complications -
• Constipation.
• Diarrhea.
• Gas.
• Stomach pain.

5. Ketorolac in tablets:
Rx. Tab Ketorolac 0.01 N10
 D.S. Used for the treatment of fever.

Class – Non steroidal anti- inflammatory drugs.

Mechanism -
Works by the inhibition of prostaglandin synthesis by competitive blocking of the enzyme
cyclooxygenase (COX). Ketorolac is a non-selective COX inhibitor. It works by blocking your
body's production of certain natural substances that cause inflammation.
Indications of use -
Used before or after medical procedures or after surgery.
Complications –
• Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation.
• Hemorrhage.
• Renal Effects