Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of medications commonly used to relieve By inhibiting COX enzymes, NSAIDs reduce

reduce the synthesis of prostaglandins, leading to decreased

pain, reduce inflammation, and lower fever. They work by inhibiting enzymes called cyclooxygenases inflammation, pain, and fever.
(COX-1 and COX-2) that are involved in the production of prostaglandins, which are chemicals in the
body that promote inflammation, pain, and fever. Anti-Inflammatory Effects:
Classification  Nonselective COX Inhibitors: Most NSAIDs inhibit both COX-1 and COX-2. This leads to
Classification Examples reduced inflammation by decreasing the production of prostaglandins that promote
A. Nonselective COX Inhibitors inflammatory responses.
Salicylates Aspirin  Selective COX-2 Inhibitors: These drugs preferentially inhibit COX-2, aiming to provide anti-
Para-aminophenol Derivatives Paracetamol (Acetaminophen) inflammatory effects while minimizing gastrointestinal side effects associated with COX-1
Propionic Acid Derivatives Ibuprofen, Fenoprofen, Ketoprofen, Flurbiprofen, Oxaprozin, inhibition.
Naproxen  Analgesic (Pain-Relieving) Effects:
Acetic Acid Derivatives Ketorolac, Tolmetin, Indomethacin, Sulindac  By reducing prostaglandin levels, NSAIDs decrease the sensitivity of pain receptors, thereby
Fenamates (Anthranilic Acids) Mefenamic Acid, Meclofenamic Acid alleviating pain.
Pyrazolone Derivatives Phenylbutazone, Azapropazone  Antipyretic (Fever-Reducing) Effects:
 NSAIDs lower fever by inhibiting prostaglandin E2 (PGE2) in the hypothalamus, which is
Oxicams (Enolic Acid Piroxicam, Tenoxicam
Derivatives) involved in the regulation of body temperature.
Pharmacological Actions
B. Preferential COX-2 Inhibitors Diclofenac, Aceclofenac, Etodolac, Meloxicam, Nabumetone,
Salicylates, including acetylsalicylic acid (aspirin), have several important effects:
Nimesulide
Analgesia:
C. Selective COX-2 Inhibitors Celecoxib, Parecoxib, Etoricoxib
Mechanism: Inhibits prostaglandin (PG) synthesis, reducing pain sensitivity.
Mechanism of Action (MOA) of NSAIDs
Effectiveness: Relieves pain from muscles, bones, joints, and connective tissues but is less
effective for visceral pain. Weaker than morphine.
Antipyretic Action:
Mechanism: Lowers fever by inhibiting PG synthesis in the hypothalamus, resetting the
temperature set point.
Effectiveness: Effective in reducing fever; no effect on normal body temperature.
Anti-inflammatory Action:
Dosage: High doses (4–6 grams/day) required.
Mechanism: Reduces inflammation by inhibiting PG synthesis and affecting other inflammatory
mediators.
Effectiveness: Reduces inflammation but does not alter disease progression in chronic
conditions.
Respiration:
Mechanism: Increases respiration rate and depth due to increased CO2 production and direct
stimulation of the medullary respiratory center.
Effects: Therapeutic doses can cause respiratory alkalosis; toxic doses may lead to respiratory
depression.
 Cyclooxygenase (COX) Inhibition:
Acid–Base and Electrolyte Balance:
COX Enzymes: NSAIDs primarily exert their effects by inhibiting cyclooxygenase (COX)
Anti-inflammatory Doses: Induce compensated respiratory alkalosis.
enzymes, which are crucial for the conversion of arachidonic acid to prostaglandins.
Toxic Doses: Cause uncompensated respiratory acidosis and metabolic acidosis, along with
COX-1: Generally involved in the production of prostaglandins that protect the gastric mucosa,
dehydration.
maintain renal blood flow, and support platelet aggregation.
Metabolic Effects:
COX-2: Induced during inflammation and primarily responsible for the production of
Mechanism: Enhances cellular metabolism, leading to increased heat production and glucose
prostaglandins that mediate pain, fever, and inflammation.
utilization.
 Reduction in Prostaglandin Synthesis:
 Effects: Can cause hyperpyrexia, aminoaciduria, and hypoglycemia or hyperglycemia at high  Pregnancy: Can delay labor and cause premature ductus arteriosus closure; avoid during late
doses. pregnancy.
Gastrointestinal Tract:  Salicylism: Chronic toxicity symptoms include headache, tinnitus, nausea, and confusion;
Effects: Causes gastric irritation, epigastric distress, and potential for ulcers and bleeding. reversible upon discontinuation.
Mechanism: Unionized salicylates irritate mucosa; inhibit protective PGs in the stomach.  Acute Intoxication: Symptoms include dehydration, hyperpyrexia, GI irritation, metabolic
Cardiovascular System (CVS): acidosis, and respiratory failure. Treatment involves gastric lavage, IV fluids, cooling, and forced
Therapeutic Doses: Minimal effects. alkaline diuresis.
Toxic Doses: May depress circulation.
Immunological Effects: Precautions and Contraindications:
Higher Doses: Suppress antigen-antibody reactions, which may help in conditions like rheumatic  Contraindications: Peptic ulcer, liver diseases, bleeding tendencies, and viral fever in children.
fever.  Pregnancy: Avoid due to risks of premature ductus arteriosus closure.
Uric Acid Excretion:  Surgery: Discontinue NSAIDs one week prior to prevent bleeding risks.
Low Doses: Increase urate levels due to retention. Uses:
High Doses: Increase urate excretion, but high doses cause significant side effects.  Analgesic: For pain relief in headache, backache, myalgias, and dysmenorrhea.
Blood:  Fever: Provides symptomatic relief.
Mechanism: Irreversibly inhibits platelet COX-1, affecting thromboxane A2 (TXA2) synthesis and  Inflammatory Conditions: Effective for arthritis, fibromyositis.
prolonging bleeding time.
 Acute Rheumatic Fever: High doses (4–6 g/day) provide relief.
Local Effects:
 Rheumatoid and Osteoarthritis: Symptomatic relief.
Application: Acts as a keratolytic and has mild antiseptic properties; can be irritating to broken skin.
 Cardiovascular Protection: Low doses help prevent reinfarction and TIA.
 Inflammatory Bowel Disease: Mesalamine and sulfasalazine used for ulcerative colitis.
 Other Uses: Delays labor, may prevent colon cancer, helps close PDA in newborns, and treats
Pharmacokinetics:
certain rare conditions.
 Absorption: Rapid from the stomach and upper small intestine. Aspirin’s absorption improves
Drug Interactions:
with microfine particle formulations. Influenced by particle size, gut pH, solubility, and food
 Protein Binding: Displacement interactions with warfarin, heparin, and other drugs.
presence.
 Uricosuric Effect: Countered by salicylates.
 Distribution: Extensively bound to plasma proteins. Aspirin is metabolized to salicylic acid, the
 Antihypertensives: May reduce effectiveness.
active form, in the liver and tissues.
 Nephrotoxicity: Can exacerbate effects of other nephrotoxic drugs.
 Metabolism and Elimination: Aspirin has a plasma half-life of 3–5 hours, extending to 12 hours
at higher doses. Salicylates follow first-order kinetics at low doses and zero-order kinetics at high
Para-Aminophenol Derivatives
doses. Excreted in urine; alkaline urine accelerates excretion.
Paracetamol (Acetaminophen)
Adverse Effects:
Mechanism of Action of Paracetamol (Acetaminophen)
 Gastrointestinal (GI) Tract: Common issues include nausea, epigastric distress, vomiting, erosive
1. Inhibition of Cyclooxygenase (COX) in the Brain:
gastritis, peptic ulcer, and occult blood loss due to gastric irritation and PG inhibition.
 Paracetamol exerts its analgesic and antipyretic effects primarily through the inhibition of
 Nephrotoxicity: Long-term use can lead to analgesic nephropathy, salt and water retention,
cyclooxygenase (COX) enzymes in the central nervous system (CNS).
hypertension, and acute interstitial nephritis.
 It inhibits COX-3, a variant of COX-1, in the brain. This reduces the synthesis of prostaglandins,
 Central Nervous System (CNS): Symptoms include headache, dizziness, and confusion.
which are involved in pain and fever regulation.
 Allergic Reactions: Rare but may include rashes, urticaria, pruritus, photosensitivity, and
2. Effect on Prostaglandin Synthesis:
asthma.
 Inflammatory sites are rich in peroxides produced by leukocytes. Paracetamol is a weak COX
 Respiratory System: Can worsen bronchial asthma due to increased leukotriene production.
inhibitor in the presence of these peroxides, which explains its poor anti-inflammatory action.
 Hemolysis: Risk in patients with G6PD deficiency; may also cause rare thrombocytopenia and
 It does not significantly inhibit COX-1 or COX-2 in peripheral tissues, leading to minimal anti-
neutropenia.
inflammatory effects compared to NSAIDs.
 Hepatotoxicity: Potential for hepatic necrosis and cholestatic jaundice with high doses over long
periods.
 Reye’s Syndrome: Serious condition in children post-viral infection; contraindicated in children
3. Lack of Impact on Other Systems:
with viral fever.
  Unlike NSAIDs, paracetamol does not significantly impact respiration, acid-base balance, cellular o Properties: Longer-acting than ibuprofen.
metabolism, cardiovascular function, or platelet aggregation. o Dose: 250–500 mg BD.
 It does not act as a uricosuric agent, nor does it cause significant gastric irritation. o Uses: Pain relief, fever, inflammatory conditions.
4. Detoxification Mechanism: 2. Acetic Acid Derivatives:
 A small portion of paracetamol is metabolized to a highly reactive intermediate, N-acetyl-  Ketorolac:
benzoquinone-imine. o Properties: Good analgesic and anti-inflammatory.
 In normal doses, this intermediate is detoxified by conjugation with glutathione in the liver. o Forms: Mostly parenteral, also oral.
 In overdose situations, glutathione stores are depleted, leading to binding of the toxic metabolite o Uses: Postoperative pain relief.
to hepatic proteins, resulting in liver damage.  Indomethacin:
Pharmacokinetics: o Properties: Potent anti-inflammatory, analgesic, antipyretic. High protein binding,
 Absorption: Well-absorbed orally. undergoes enterohepatic circulation.
 Protein Binding: 30%. o Adverse Effects: GI irritation, nausea, vomiting, peptic ulcers, CNS effects,
 Metabolism: Primarily in the liver via glucuronide conjugation (60%) and glutathione hypersensitivity, bleeding risks.
conjugation (20%). o Drug Interactions: Blunts diuretic and antihypertensive actions, increases bleeding risk
Dosing: with warfarin.
 Common Preparations: CROCIN (500, 650 mg tablets; 120 mg/5 ml suspension), DOLO (500, 650 o Uses: Closure of patent ductus arteriosus (PDA) in infants, RA, ankylosing spondylitis,
mg tablets; 156 mg/5 ml suspension). gout, psoriatic arthritis, topical applications.
Adverse Effects:  Sulindac:
 At Therapeutic Doses: Generally safe; may cause nausea and rashes. o Properties: Weaker analgesic, antipyretic, anti-inflammatory; less toxic.
 At High Doses: Risk of acute toxicity, especially in children. Symptoms include nausea, o Uses: Alternative for inflammatory conditions.
vomiting, anorexia, and abdominal pain within 24 hours. 3. Fenamates (Anthranilic Acid Derivatives):
o Hepatotoxicity: Severe liver damage with increased serum transaminases, jaundice, and  Mephenamic Acid:
potential liver failure. Hepatic lesions are reversible with prompt treatment. o Properties: Analgesic, antipyretic, anti-inflammatory, less preferred due to toxicity.
o Nephrotoxicity: Possible acute renal failure. o Adverse Effects: GI issues, diarrhea.
 Mechanism of Toxicity: High doses deplete hepatic glutathione, leading to accumulation of toxic o Uses: Myalgias, dysmenorrhea.
metabolite (N-acetyl-benzoquinone-imine) which damages liver proteins. 4. Pyrazolone Derivatives:
Treatment of Overdose:  Phenylbutazone:
 Immediate Actions: Stomach wash and activated charcoal to prevent absorption. o Properties: Potent anti-inflammatory, uricosuric, but highly toxic.
 Antidote: N-acetylcysteine (150 mg/kg IV infusion over 15 min, repeated as needed; oral loading o Adverse Effects: GI issues, hematological toxicity, CNS effects.
dose 140 mg/kg followed by 70 mg/kg every 4 hours for 17 doses). Effective when administered o Status: Withdrawn in most countries.
early, replenishes liver glutathione and prevents toxic metabolite binding.  Metamizole (Dipyrone):
Uses: o Properties: Potent analgesic and antipyretic, poor anti-inflammatory.
 Analgesic: For pain relief in conditions like toothache, headache, and myalgia. o Adverse Effects: Not recommended in children up to 6 years.
 Antipyretic: To reduce fever o Uses: Limited due to toxicity, no major advantages over aspirin.
Propionic Acid Derivatives: 5. Oxicams (Enolic Acid Derivatives):
 Piroxicam:
 Ibuprofen:
o Properties: Good anti-inflammatory, analgesic, antipyretic. Long-acting, well-tolerated,
o Properties: Analgesic, antipyretic, mild anti-inflammatory. Well-tolerated compared to
less ulcerogenic.
aspirin.
o Pharmacokinetics: 99% plasma protein-bound, almost completely absorbed.
o Pharmacokinetics: 99% plasma protein-bound, well-absorbed, crosses BBB and synovial
o Uses: RA, osteoarthritis, ankylosing spondylitis, acute musculoskeletal pain,
fluid. Metabolized in the liver, excreted via bile and kidneys.
postoperative pain, dental pain.
o Forms: Oral, parenteral, topical.
Preferential COX-2 Inhibitors
o Adverse Effects: Nausea, vomiting, gastric discomfort, CNS effects, hypersensitivity,
1.1 Diclofenac
fluid retention.
 Mechanism of Action: Diclofenac primarily inhibits COX-2, but it also affects COX-1 to a lesser
o Uses: Pain relief (e.g., toothache, headache), fever, soft tissue injuries, osteoarthritis, gout.
extent. It has strong anti-inflammatory, analgesic, and antipyretic properties.
 Naproxen:
  Pharmacokinetics:  Mechanism of Action: Highly selective COX-2 inhibitor with long duration of action.
o Absorption: Well absorbed but has 50% bioavailability due to first-pass metabolism.  Dosage: 60, 90, or 120 mg once daily.
o Distribution: Extensively protein-bound.  Adverse Effects: Similar to other COX-2 inhibitors, including cardiovascular risk.
o Metabolism: Metabolized by liver microsomal enzymes.  Uses: Osteoarthritis, rheumatoid arthritis, acute pain, and gout.
o Excretion: Primarily via the kidneys. 2.3 Parecoxib
 Dosage Forms: Oral tablets, extended-release formulations, topical gel, ophthalmic drops, rectal  Mechanism of Action: Prodrug of valdecoxib, converted in the body to its active form. Given
suppositories, and mouthwashes. parenterally.
 Adverse Effects: Similar to other NSAIDs but generally milder. Includes gastrointestinal issues  Uses: Short-term management of pain and inflammation.
and potential liver effects. 3. Topical NSAID Preparations
 Uses: Chronic inflammatory conditions (e.g., rheumatoid arthritis, osteoarthritis), acute  Examples: Diclofenac, ibuprofen, and paracetamol in ointments or transdermal patches. Used for
musculoskeletal pain, postoperative pain, and ocular inflammation. localized pain to reduce systemic side effects.
1.2 Aceclofenac  Uses: Joint pain, muscular pain, and other localized conditions. May also be used as eye drops.
 Mechanism of Action: More selective for COX-2 compared to diclofenac, providing reduced 4. Drugs That Inhibit Both COX and Lipoxygenase
gastric irritation and longer duration of action.  Examples: Diclofenac, ketoprofen, and indomethacin. They also inhibit leukotriene synthesis,
 Dosage: 100 mg twice daily. reducing the risk of asthma exacerbations.
 Uses: Similar to diclofenac but preferred due to better gastric tolerance. 5. Atypical NSAID
1.3 Nabumetone Diacerin
 Mechanism of Action: A prodrug that is converted to its active form, which preferentially  Mechanism of Action: Inhibits interleukin-1β (IL-1β), involved in inflammation and cartilage
inhibits COX-2, leading to reduced ulcerogenic effects. destruction in osteoarthritis.
 Dosage: 500 mg to 750 mg tablets.  Dosage: Used long-term (6–8 months).
 Uses: Rheumatoid arthritis and osteoarthritis.  Adverse Effects: Mild diarrhea and deep yellow urine discoloration.
 Adverse Effects: Lower incidence of gastrointestinal issues compared to traditional NSAIDs.  Uses: Osteoarthritis.
1.4 Meloxicam
 Mechanism of Action: Preferentially binds to COX-2 but has some COX-1 inhibition at higher
doses. Generally has less gastric irritation compared to piroxicam.
 Dosage: 7.5–15 mg once daily.
 Uses: Osteoarthritis, rheumatoid arthritis.
 Adverse Effects: Similar to other NSAIDs but less severe gastrointestinal issues.
1.5 Nimesulide
 Mechanism of Action: Selectively inhibits COX-2 and has additional antihistaminic and
antiallergic properties.
 Adverse Effects: Nausea, epigastric pain, rashes, drowsiness, dizziness, nephrotoxicity, and
hepatotoxicity. Banned in several countries due to hepatotoxicity.
 Uses: Analgesic, antipyretic, anti-inflammatory, particularly where other NSAIDs are
contraindicated.
2. Selective COX-2 Inhibitors (Coxibs)
2.1 Celecoxib
 Mechanism of Action: Highly selective for COX-2 (10–20 times more than COX-1). Provides anti-
inflammatory, analgesic, and antipyretic effects while minimizing gastric irritation.
 Dosage: 100–200 mg once or twice daily.
 Adverse Effects: Can cause hypertension and edema; increased risk of cardiovascular events
(e.g., myocardial infarction, stroke).
 Uses: Acute pain, dysmenorrhea, osteoarthritis, rheumatoid arthritis, and in patients who cannot
tolerate other NSAIDs.
2.2 Etoricoxib
Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disorder primarily affecting the Glucocorticoids, such as prednisone and dexamethasone, are synthetic drugs that mimic the effects of
joints and surrounding tissues. The disease begins with the formation of antigen-antibody complexes that cortisol, a natural hormone produced by the adrenal glands. Their primary mechanisms of action include:
initiate an inflammatory response. This response starts with vasculitis (inflammation of the blood vessels) 1. Anti-Inflammatory Effects:
and progresses to synovial edema (swelling of the joint lining) and infiltration with inflammatory cells. o Inhibition of Proinflammatory Cytokines: Glucocorticoids suppress the production of
In the affected joints, inflammatory mediators such as prostaglandins and leukotrienes are produced. cytokines like IL-1, IL-6, and TNF-alpha, which are involved in the inflammatory process.
Prostaglandins contribute to vasodilation (widening of blood vessels) and pain, while leukotrienes are o Inhibition of Immune Cells: They reduce the activation and proliferation of immune
involved in the inflammatory response. Additionally, the inflammatory cells release lysosomal enzymes, cells, including T lymphocytes and macrophages.
which lead to damage of bones and cartilage within the joints. This damage contributes to the progressive 2. Gene Regulation:
joint destruction characteristic of RA. o Transcriptional Control: Glucocorticoids bind to glucocorticoid receptors in the
Drug Class Purpose/Mechanism Examples/Notes cytoplasm, which then translocate to the nucleus. They regulate the expression of various
Nonsteroidal Anti- Reduce pain and - Ibuprofen genes involved in inflammation and immune response.
Inflammatory Drugs inflammation - Naproxen Pharmacokinetics
(NSAIDs) - Diclofenac  Absorption: Glucocorticoids are well absorbed when administered orally, topically, or
Disease-Modifying Slow disease - Methotrexate
parenterally.
Antirheumatic Drugs progression and - Sulfasalazine
(DMARDs) reduce joint damage - Hydroxychloroquine  Distribution: They are widely distributed throughout the body, including crossing the blood-
- Leflunomide brain barrier.
Biologic DMARDs Target specific - Tumor Necrosis Factor (TNF) Inhibitors:  Metabolism: Metabolized primarily in the liver.
immune system - Etanercept  Excretion: Excreted mainly via the kidneys.
components to reduce - Adalimumab Adverse Effects (ADRs)
inflammation - Infliximab
Long-term or high-dose use of glucocorticoids can lead to several adverse effects, including:
Interleukin-6 (IL-6) Inhibitors: 1. Metabolic Effects:
- Tocilizumab o Weight Gain: Increased appetite and altered metabolism.
- B-Cell Inhibitors: o Hyperglycemia: Can lead to steroid-induced diabetes.
- Rituximab 2. Musculoskeletal Effects:
T-Cell Co-Stimulation Modulators: o Osteoporosis: Increased risk of bone loss and fractures.
- Abatacept
o Muscle Weakness: Catabolic effects on muscle tissue.
Janus Kinase (JAK) Inhibit enzymes - Tofacitinib
3. Gastrointestinal Effects:
Inhibitors involved in the - Baricitinib
inflammatory process - Upadacitinib o Peptic Ulcers: Increased risk of gastrointestinal bleeding and ulcers.
Glucocorticoids Reduce inflammation - Prednisone 4. Cardiovascular Effects:
(Corticosteroids) and suppress immune - Methylprednisolone o Hypertension: Fluid retention and increased blood pressure.
response 5. Infection Risk:
Analgesics Provide pain relief, - Acetaminophen o Immunosuppression: Increased susceptibility to infections.
but do not affect - Tramadol 6. Psychiatric Effects:
inflammation
o Mood Changes: Can cause euphoria, depression, or psychosis.
Uses in Rheumatoid Arthritis (RA)
In rheumatoid arthritis (RA), NSAIDs provide symptomatic relief by reducing pain and inflammation in
Glucocorticoids are used in RA primarily for their potent anti-inflammatory effects. Their roles include:
the joints. They are effective for managing acute flare-ups and improving joint function but do not alter
1. Management of Acute Flare-Ups:
the disease's progression. NSAIDs are often used alongside disease-modifying treatments like DMARDs
o Rapid Symptom Relief: Effective for controlling severe inflammation and pain during
or biologics. Long-term use carries risks such as gastrointestinal issues, cardiovascular problems, and
flare-ups.
kidney damage, so their use should be monitored carefully.
2. Bridging Therapy:
o Before DMARDs Take Effect: Used temporarily while waiting for disease-modifying
antirheumatic drugs (DMARDs) or biologics to become effective.
Glucocorticoids: Overview for Rheumatoid Arthritis (RA)
3. Disease Control:
Mechanism of Action (MOA)
o In Combination Therapy: Used in conjunction with DMARDs to achieve better control
of inflammation and disease activity.
 Classification of drugs used in gout Receptors: Histamine acts through four main types of receptors:
H1 Receptors: Involved in allergic responses, smooth muscle contraction, and increased vascular
permeability.
H2 Receptors: Regulate gastric acid secretion in the stomach.
H3 Receptors: Located primarily in the CNS; involved in modulating neurotransmitter release.
H4 Receptors: Found in the bone marrow and white blood cells; involved in immune response and
inflammation.

Serotonin
Serotonin (5-hydroxytryptamine or 5-HT) is a monoamine neurotransmitter and hormone involved in
various physiological processes including mood regulation, gastrointestinal function, and platelet
aggregation.
Synthesis:

Histamine
Histamine is a biogenic amine that acts as both a neurotransmitter in the central nervous system and a
mediator in the peripheral immune response. It is known for its role in allergic reactions and its
physiological functions in various systems of the body.
Synthesis:
Precursor: Histidine. Precursor: Tryptophan.
Enzyme: Histidine decarboxylase. Enzyme Pathway:
Histidine decarboxylase catalyzes the decarboxylation of histidine to form histamine. Tryptophan Hydroxylase: Converts tryptophan to 5-hydroxytryptophan (5-HTP).
Storage and Release: Aromatic L-Amino Acid Decarboxylase: Converts 5-HTP to serotonin.
Mast Cells and Basophils: Histamine is stored in granules and released upon degranulation Storage and Release:
in response to allergens or inflammatory signals. Neurons: Serotonin is stored in vesicles in serotonergic neurons and released into the
Enterochromaffin-like Cells: In the stomach, histamine is stored and released to regulate synaptic cleft upon activation.
gastric acid secretion. Platelets: Serotonin is taken up from the bloodstream and stored in platelets, where it plays a
Physiological Roles: role in hemostasis.
Immune Response and Inflammation:
Enterochromaffin Cells: Located in the gastrointestinal tract, these cells release serotonin to
Vasodilation: Histamine acts on H1 receptors located on the endothelial cells of blood
regulate gut motility.
vessels, leading to increased vascular permeability and vasodilation. This causes redness,
Physiological Roles:
swelling, and heat in the inflamed area. Mood Regulation:
Bronchoconstriction: Histamine can cause constriction of bronchial smooth muscle, Central Nervous System: Serotonin modulates mood, anxiety, and overall emotional state.
contributing to asthma symptoms. Low levels of serotonin are associated with depression, anxiety disorders, and other mood
Allergic Reactions: In allergies, histamine release from mast cells results in symptoms such disorders. Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine increase serotonin
as itching, hives, and nasal congestion. levels in the brain and are commonly used to treat depression and anxiety.
Gastric Acid Secretion: Gastrointestinal Function:
Stimulation of Parietal Cells: Histamine binds to H2 receptors on gastric parietal cells, Motility: In the GI tract, serotonin regulates bowel movements by influencing the motility of
stimulating the secretion of hydrochloric acid (HCl) in the stomach, which aids digestion. the intestines. It stimulates peristalsis and can affect the secretion of digestive enzymes.
Neurotransmission: Platelet Aggregation:
Central Nervous System: In the brain, histamine acts as a neurotransmitter involved in Hemostasis: Serotonin released from platelets contributes to platelet aggregation and blood
regulating arousal, sleep-wake cycles, and cognitive functions. It acts on H1 and H3 receptors clot formation, which is essential for wound healing.
in the CNS, where it influences alertness and feeding behaviors. Vascular Tone:
 Vasoconstriction: Serotonin can induce vasoconstriction and influence blood pressure
through its action on smooth muscle cells in blood vessels.
Receptors: Serotonin acts through a range of receptors, classified into seven main families (5-
HT1 to 5-HT7), each with subtypes:
5-HT1 Receptors: Involved in inhibiting neurotransmitter release, mood regulation, and
vasoconstriction.
5-HT2 Receptors: Affect smooth muscle contraction and are implicated in platelet aggregation.
5-HT3 Receptors: Ion channels involved in nausea and vomiting.
5-HT4 Receptors: Influence gastrointestinal motility and secretion.
5-HT5-7 Receptors: Involved in various functions including mood regulation and cognition.