B Pharmacy Sem 6: Pharmacology III

Subject 2. Pharmacology III

Unit 1 – Drugs for Respiratory & GI Systems
                  o Anti asthmatics, COPD therapies, expectorants, antitussives, decongestants, stimulants
                o Anti ulcer, laxatives, anti diarrheals, appetite regulators, digestants, anti emetics
 Unit 2 – Chemotherapy I (Sulfonamides, Penicillins, Cephalosporins, Chloramphenicol, Macrolides, Quinolones, Tetracyclines, Aminoglycosides)
 Unit 3 – Chemotherapy II (Anti tuberculosis, -leprosy, -fungal, -viral, -malarial, -amoebic, -helmintic)
Unit 4 – Further Chemotherapy & Immunopharmacology (UTI/STI agents, anticancer drugs, immunostimulants, immunosuppressants, monoclonal antibodies, biosimilars)
 Unit 5 – Toxicology & Chronopharmacology (Acute/chronic toxicity, heavy metal poisonings, dosing time rhythms) 

Unit 1: Drugs for Respiratory & Gastrointestinal (GI) Systems

This unit examines agents that modify airway function (asthma, COPD, mucus clearance) and GI motility/secretion (ulcer management, bowel habits, nausea). Focus is on mechanisms, clinical uses, and major side effects—presented in a concise, memorable manner.

2.1 Respiratory System Drugs

2.1.1 Anti‑Asthmatic Agents

• β₂‑Adrenergic Agonists

  • Salbutamol, Terbutaline (short‑acting) / Salmeterol, Formoterol (long‑acting)

  • Mechanism: Stimulate β₂‑receptors → bronchial smooth muscle relaxation

  • Use: Relief/prevention of bronchospasm

  • Side Effects: Tremor, tachycardia, hypokalemia

• Inhaled Corticosteroids

  • Beclomethasone, Budesonide, Fluticasone

  • Mechanism: Anti‑inflammatory via glucocorticoid receptor → ↓ cytokines, eosinophils

  • Use: Maintenance therapy in asthma

  • Side Effects: Oral candidiasis, dysphonia

• Leukotriene Receptor Antagonists

  • Montelukast, Zafirlukast

  • Mechanism: Block CysLT₁ receptor → reduce bronchoconstriction & inflammation

  • Use: Add‑on in mild persistent asthma; allergic rhinitis

  • Side Effects: Headache, neuropsychiatric (rare)

• Methylxanthines

  • Theophylline

  • Mechanism: Phosphodiesterase inhibition + adenosine receptor antagonism → bronchodilation

  • Use: Oral maintenance in severe asthma/COPD

  • Side Effects: Narrow therapeutic index: nausea, arrhythmias, seizures

2.1.2 COPD Therapies

• Antimuscarinic Agents

  • Ipratropium (short‑acting), Tiotropium (long‑acting)

  • Mechanism: Block M₃ receptor → reduce bronchoconstriction & secretions

  • Use: COPD maintenance; alternative/add‑on in asthma

  • Side Effects: Dry mouth, blurred vision

• Combination Inhalers

  • ICS + LABA or LAMA + LABA

  • Maximize bronchodilation and control inflammation

2.1.3 Expectorants & Mucolytics

• Guaifenesin (Expectorant)

  • Mechanism: Increases respiratory tract fluid → thins mucus

  • Use: Productive cough

  • Side Effects: GI upset

• N‑Acetylcysteine (Mucolytic)

  • Mechanism: Breaks disulfide bonds in mucus → lowers viscosity

  • Use: COPD, acetaminophen overdose (IV form)

  • Side Effects: Bronchospasm (inhaled form)

2.1.4 Antitussives

• Dextromethorphan

  • Mechanism: NMDA receptor antagonist → cough reflex suppression

  • Use: Dry, non‑productive cough

  • Side Effects: Dizziness, serotonin syndrome (with SSRIs)

• Codeine

  • Mechanism: Opioid receptor agonist → reduces cough center sensitivity

  • Use: Severe cough

  • Side Effects: Sedation, constipation, dependence

2.1.5 Decongestants & Stimulants

• Oral/Topical α₁‑Agonists

  • Pseudoephedrine (oral), Phenylephrine (topical)

  • Mechanism: Vasoconstriction of nasal mucosa → reduces congestion

  • Use: Rhinitis, sinusitis

  • Side Effects: Hypertension, rebound congestion (topical)

• Respiratory Stimulants

  • Doxapram

  • Mechanism: Stimulates carotid chemoreceptors → increases respiratory drive

  • Use: Acute respiratory failure (ICU)

  • Side Effects: Hypertension, arrhythmias

2.2 Gastrointestinal System Drugs

2.2.1 Anti‑Ulcer Agents

• Proton Pump Inhibitors (PPIs)

  • Omeprazole, Pantoprazole

  • Mechanism: Irreversible H⁺/K⁺‑ATPase inhibition → profound acid suppression

  • Use: Peptic ulcer disease, GERD

  • Side Effects: Risk of C. difficile, hypomagnesemia

• H₂‑Receptor Antagonists

  • Ranitidine, Famotidine

  • Mechanism: Block H₂ receptors on parietal cells → reduce acid secretion

  • Use: Mild to moderate ulcer/GERD

  • Side Effects: Headache, rare CNS effects

• Antacids

  • Mg(OH)₂, Al(OH)₃

  • Mechanism: Neutralize gastric acid

  • Use: Symptomatic relief

  • Side Effects: Diarrhea (Mg), constipation (Al)

2.2.2 Laxatives

• Bulk‑Forming

  • Psyllium, Methylcellulose

  • Mechanism: Absorb water → increase stool bulk

  • Use: Chronic constipation

  • Side Effects: Bloating, gas

• Osmotic

  • Lactulose, Polyethylene glycol

  • Mechanism: Draws water into lumen

  • Use: Constipation, hepatic encephalopathy (lactulose)

  • Side Effects: Cramping, electrolyte imbalance

• Stimulant

  • Senna, Bisacodyl

  • Mechanism: Irritates mucosa → increased peristalsis

  • Use: Short‑term relief

  • Side Effects: Cramping, electrolyte loss

2.2.3 Anti‑Diarrheal Agents

• Opioid‑Derivatives

  • Loperamide, Diphenoxylate

  • Mechanism: μ‑Receptor agonism in gut → ↓ motility

  • Use: Acute non‑infectious diarrhea

  • Side Effects: Constipation, potential CNS effects (high dose)

• Adsorbents

  • Kaolin‑pectin

  • Mechanism: Binds toxins and fluid

  • Use: Mild diarrhea

  • Side Effects: Minimal

2.2.4 Appetite Regulators & Digestants

• Appetite Stimulants

  • Megestrol acetate

  • Mechanism: Progesterone receptor agonist → increases appetite

  • Use: Cachexia in cancer/AIDS

  • Side Effects: Thrombosis, adrenal suppression

• Digestants

  • Pancrelipase

  • Mechanism: Exogenous pancreatic enzymes → aid digestion

  • Use: Pancreatic insufficiency (CF, pancreatitis)

  • Side Effects: GI upset, fibrosing colonopathy (high doses in children)

2.2.5 Anti‑Emetics

• 5‑HT₃ Antagonists

  • Ondansetron

  • Mechanism: Blocks 5‑HT₃ receptors centrally & peripherally

  • Use: Chemotherapy/radiation‑induced nausea

  • Side Effects: Headache, constipation

• Dopamine Antagonists

  • Metoclopramide, Prochlorperazine

  • Mechanism: D₂‑receptor blockade in CTZ → antiemetic & prokinetic

  • Use: Post‑operative/chemotherapy nausea, gastroparesis (metoclopramide)

  • Side Effects: Extrapyramidal symptoms, sedation

Key Exam Tips

• Group respiratory drugs by bronchodilators versus anti‑inflammatories.

• In GI, distinguish acid‑reducing agents (PPI vs. H₂‑blocker vs. antacid) by onset/duration.

• Laxatives: bulk, osmotic, stimulant—know mechanism and main side effect.

• Anti‑emetics: classify by receptor (5‑HT₃ vs. D₂).

Unit 2: Chemotherapy I

This unit covers primary antibacterial classes—sulfonamides, β‑lactams, protein‑synthesis inhibitors, and DNA‑damaging agents—highlighting mechanisms, key examples, clinical uses, and main adverse effects in a clear, memorization‑friendly format.

2.2.1 Sulfonamides

• Mechanism: Competitive inhibition of dihydropteroate synthase → ↓ folate synthesis

• Key Drugs: Sulfamethoxazole (often combined with trimethoprim)

• Use: UTIs, Nocardia, Pneumocystis jirovecii pneumonia (with TMP)

• Side Effects: Hypersensitivity (rash, Stevens–Johnson), kernicterus in neonates

2.2.2 Penicillins

• Mechanism: Inhibit penicillin‑binding proteins (PBPs) → block cell wall cross-linking → bacterial lysis

• Classes & Examples:

  • Natural: Penicillin G/V (Gram‑positive cocci)

  • Aminopenicillins: Ampicillin, Amoxicillin (extended to some Gram‑negatives)

  • β‑Lactamase–Resistant: Cloxacillin, Oxacillin (staphylococcal infections)

• Resistance: β‑lactamases, altered PBPs (e.g., MRSA)

• Side Effects: Allergic reactions (anaphylaxis), diarrhea

2.2.3 Cephalosporins

• Mechanism: Same as penicillins (PBP inhibition) but broader spectrum and β‑lactamase stability

• Generations:

  1. Cefazolin, Cephalexin – Gram‑positive

  2. Cefuroxime – + some Gram‑negative

  3. Ceftriaxone, Ceftazidime – serious Gram‑negative, CSF penetration

  4. Cefepime – enhanced β‑lactamase resistance

  5. Ceftaroline – anti‑MRSA activity

• Side Effects: Cross‑reactivity in penicillin‑allergic patients, GI upset

2.2.4 Chloramphenicol

• Mechanism: Inhibits 50S peptidyl transferase → blocks peptide bond formation

• Spectrum: Broad (aerobes & anaerobes)

• Use: Severe infections (e.g., meningitis) when other agents fail

• Side Effects: Aplastic anemia (idiosyncratic), “gray baby” syndrome

2.2.5 Macrolides

• Mechanism: Bind 50S subunit → block translocation of peptide chain

• Key Drugs: Erythromycin, Azithromycin, Clarithromycin

• Use: Atypical pneumonia (Mycoplasma, Chlamydia), pertussis, diphtheria

• Side Effects: GI cramps, QT prolongation, CYP3A4 inhibition

2.2.6 Quinolones

• Mechanism: Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → prevent DNA replication

• Examples: Ciprofloxacin, Levofloxacin, Moxifloxacin

• Use: UTIs, GI infections, some respiratory infections

• Side Effects: Tendon rupture, QT prolongation, photosensitivity

2.2.7 Tetracyclines

• Mechanism: Bind 30S subunit → block tRNA attachment → inhibit protein synthesis

• Key Drugs: Tetracycline, Doxycycline, Minocycline

• Use: Acne, Lyme disease, Chlamydia, Rickettsia

• Side Effects: Tooth discoloration (children), photosensitivity, GI upset

2.2.8 Aminoglycosides

• Mechanism: Bind 30S subunit → cause misreading of mRNA → faulty proteins & cell death

• Examples: Gentamicin, Amikacin, Tobramycin, Streptomycin

• Use: Serious Gram‑negative infections, synergy with β‑lactams against Gram‑positives

• Side Effects: Nephrotoxicity, ototoxicity, neuromuscular blockade

Key Exam Pointers

• β‑Lactams: Remember “cillin” vs. “cef–” generations and resistance mechanisms.

• Protein synthesis inhibitors: Group by ribosomal subunit (30S vs. 50S).

• Quinolone safety: Tendon risk in elderly.

• Sulfonamide combo: Always think SMX + TMP synergy.

Unit 3: Chemotherapy II

This unit covers second-tier antimicrobial and antiparasitic agents used against resistant infections and specialized pathogens. Focus is on mechanisms, key uses, and major toxicities.

2.3.1 Anti‑Tuberculosis Agents

• Streptomycin

  • Mechanism: Aminoglycoside → binds 30S ribosome → misread mRNA

  • Use: MDR‑TB in combination regimens

  • Side Effects: Ototoxicity, nephrotoxicity

• Ethionamide

  • Mechanism: Prodrug → inhibits mycolic acid synthesis

  • Use: Second-line TB

  • Side Effects: Hepatotoxicity, gastrointestinal upset

• Para‑Aminosalicylic Acid (PAS)

  • Mechanism: Competes with PABA → disrupts folate pathway

  • Use: TB when first-line agents fail

  • Side Effects: GI distress, hypersensitivity

• Capreomycin

  • Mechanism: Cyclic polypeptide → inhibits protein synthesis

  • Use: Drug‑resistant TB

  • Side Effects: Nephrotoxicity, hearing loss

2.3.2 Anti‑Leprosy Agents

• Dapsone

  • Mechanism: Sulfone → inhibits dihydropteroate synthase

  • Use: Leprosy (with rifampicin, clofazimine)

  • Side Effects: Hemolysis (G6PD deficiency), methemoglobinemia

• Clofazimine

  • Mechanism: Binds mycobacterial DNA → blocks growth

  • Use: Multidrug therapy for leprosy

  • Side Effects: Skin discoloration, GI upset

2.3.3 Antifungal Agents (Systemic)

• Amphotericin B Lipid Formulations

  • Mechanism: Binds ergosterol → pores in membrane

  • Use: Severe systemic fungal infections

  • Side Effects: Reduced nephrotoxicity vs. conventional

• Voriconazole

  • Mechanism: Inhibits 14‑α‑demethylase → ergosterol synthesis block

  • Use: Invasive aspergillosis

  • Side Effects: Visual disturbances, hepatotoxicity

• Flucytosine

  • Mechanism: Converted to 5‑FU → inhibits DNA/RNA synthesis

  • Use: Cryptococcal meningitis (with AMB)

  • Side Effects: Bone marrow suppression

2.3.4 Antiviral Agents

• Ganciclovir

  • Mechanism: Guanine analog → inhibits viral DNA polymerase

  • Use: CMV retinitis

  • Side Effects: Bone marrow suppression

• Foscarnet

  • Mechanism: Pyrophosphate analog → directly inhibits viral polymerases

  • Use: CMV, acyclovir‑resistant HSV/VZV

  • Side Effects: Nephrotoxicity, electrolyte imbalance

• Adefovir

  • Mechanism: Nucleotide analog → inhibits HBV DNA polymerase

  • Use: Chronic hepatitis B

  • Side Effects: Nephrotoxicity

2.3.5 Antimalarial & Antiamoebic Agents

• Artemisinin Derivatives (e.g., Artesunate)

  • Mechanism: Generates free radicals in parasite → damages proteins

  • Use: Severe falciparum malaria

  • Side Effects: Neurotoxicity (rare)

• Emetine

  • Mechanism: Inhibits protein synthesis in Entamoeba

  • Use: Amoebic dysentery (second‑line)

  • Side Effects: Cardiotoxicity, myopathy

Key Exam Tips

• Resistant TB: Remember streptomycin vs. capreomycin nephro‑oto profiles.

• Leprosy: Dapsone hematologic risks; clofazimine’s skin effects.

• Systemic antifungals: Lipid amphotericin reduces toxicity; flucytosine → marrow suppression.

• Viral: Foscarnet bypasses kinase activation (useful in resistant strains).

• Artemisinins: Fast action in severe malaria; radical formation is key.

Unit 4: Further Chemotherapy & Immunopharmacology

This unit explores specialized anti-infectives, anticancer drugs, and immune-modulating therapies. Each section highlights mechanism, clinical use, and key adverse effects in an easy-to-remember format.

2.4.1 UTI & STI Agents

• UTI Agents

  • Nitrofurantoin

    • Mechanism: Bacterial enzyme–mediated reduction → reactive intermediates damage DNA

    • Use: Uncomplicated cystitis

    • Side Effects: GI upset, pulmonary fibrosis (long-term)

  • Fosfomycin

    • Mechanism: Inhibits MurA → blocks peptidoglycan synthesis

    • Use: Single-dose UTI

    • Side Effects: Headache, diarrhea

• STI Agents

  • Penicillin G

    • Mechanism: PBP inhibition → cell wall lysis

    • Use: Syphilis (Treponema pallidum)

    • Side Effects: Hypersensitivity reactions

  • Azithromycin

    • Mechanism: 50S ribosome blockade → protein synthesis inhibition

    • Use: Chlamydia trachomatis, gonorrhea (with cephalosporin)

    • Side Effects: GI upset, QT prolongation

2.4.2 Anticancer Drugs

• Alkylating Agents

  • Cyclophosphamide

    • Mechanism: DNA cross-linking → prevents replication

    • Use: Lymphomas, breast cancer

    • Side Effects: Myelosuppression, hemorrhagic cystitis

• Antimetabolites

  • 5-Fluorouracil (5-FU)

    • Mechanism: Thymidylate synthase inhibition → DNA synthesis blockade

    • Use: Colorectal, breast cancers

    • Side Effects: Mucositis, myelosuppression

• Plant Alkaloids

  • Paclitaxel

    • Mechanism: Stabilizes microtubules → mitotic arrest

    • Use: Ovarian, breast cancers

    • Side Effects: Neuropathy, myelosuppression

• Monoclonal Antibodies (mAbs)

  • Trastuzumab

    • Mechanism: Binds HER2 → blocks signaling, mediates ADCC

    • Use: HER2-positive breast cancer

    • Side Effects: Cardiotoxicity

  • Rituximab

    • Mechanism: Targets CD20 on B cells → cell lysis

    • Use: Non-Hodgkin lymphoma, CLL

    • Side Effects: Infusion reactions, immunosuppression

2.4.3 Immunostimulants & Immunosuppressants

• Immunostimulants

  • Interferon-α

    • Mechanism: Activates antiviral genes, enhances NK cell activity

    • Use: Hepatitis B/C, certain leukemias

    • Side Effects: Flu-like symptoms, depression

  • Levamisole

    • Mechanism: Enhances T-cell function

    • Use: Colon cancer adjuvant, used in veterinary practice

    • Side Effects: Agranulocytosis

• Immunosuppressants

  • Cyclosporine

    • Mechanism: Inhibits calcineurin → ↓ IL-2 transcription

    • Use: Transplant rejection prophylaxis

    • Side Effects: Nephrotoxicity, hypertension

  • Azathioprine

    • Mechanism: Purine analog → inhibits lymphocyte proliferation

    • Use: Autoimmune diseases, transplant

    • Side Effects: Myelosuppression, hepatotoxicity

2.4.4 Monoclonal Antibodies & Biosimilars

• Monoclonal Antibodies (mAbs)

  • Mechanism: Highly specific binding to target antigens → block signaling or recruit immune effector functions

  • Examples:

    • Infliximab (anti-TNFα for rheumatoid arthritis)

    • Bevacizumab (anti-VEGF for colorectal cancer)

  • Side Effects: Infusion reactions, increased infection risk

• Biosimilars

  • Definition: Highly similar to an approved mAb (“reference product”) with no clinically meaningful differences in safety/efficacy

  • Benefits: Lower cost, increased access

  • Examples:

    • Etanercept biosimilars for autoimmune diseases

    • Trastuzumab biosimilars for breast cancer

Key Exam Tips

• UTI vs. STI: UTI drugs concentrate in urine; STI drugs target specific pathogens.

• Anticancer classes: Remember mechanism first (alkylator vs. antimetabolite vs. mitotic inhibitor).

• Immune drugs: “Stimulate” vs. “suppress” — match to clinical context.

• mAbs vs. biosimilars: Biosimilars are “generic” biologicals — same efficacy, lower cost.

Unit 5: Toxicology & Chronopharmacology

This unit examines toxic effects of chemicals, heavy metal poisonings, and how biological rhythms influence drug action. Definitions are concise for easy recall.

2.5.1 Toxicology

Study of adverse effects of chemicals on living organisms.

• Acute Toxicity

  • Definition: Harmful effects within 24 hours of a single dose.

  • Key Parameter: LD₅₀ (dose lethal to 50% of test animals).

  • Example: Acute acetaminophen overdose → centrilobular hepatic necrosis.

• Chronic Toxicity

  • Definition: Adverse effects from repeated or long‑term exposure.

  • Example: Prolonged benzene exposure → aplastic anemia, leukemia.

• Toxicokinetics vs. Toxicodynamics

  • Toxicokinetics: ADME of toxins.

  • Toxicodynamics: Molecular/cellular effects of toxins.

2.5.2 Heavy Metal Poisonings

Metals that disrupt enzyme function or generate ROS.

• Lead

  • Mechanism: Inhibits δ‑aminolevulinic acid dehydratase → ↓ heme synthesis.

  • Clinical: Anemia, neuropathy, developmental delay in children.

  • Treatment: EDTA chelation, succimer.

• Mercury

  • Forms: Elemental, inorganic, organic (methylmercury).

  • Mechanism: Binds sulfhydryl groups → enzyme inhibition, neurotoxicity.

  • Clinical: Peripheral neuropathy, cognitive deficits.

  • Treatment: Dimercaprol, DMSA (succimer).

• Arsenic

  • Mechanism: Binds lipoic acid on pyruvate dehydrogenase → disrupts ATP production.

  • Clinical: GI distress, QT prolongation, hyperkeratosis.

  • Treatment: Dimercaprol, DMSA.

2.5.3 Chronopharmacology

Study of how biological rhythms (circadian, ultradian) affect drug response.

• Circadian Rhythms

  • Definition: ~24 hour cycles in physiology (e.g., cortisol peaks morning).

  • Implication: Time‑dependent variation in drug efficacy/toxicity.

    • Example: Morning administration of statins aligns with peak HMG‑CoA reductase activity.

• Chronotherapy

  • Concept: Timing drug delivery to maximize benefit and minimize harm.

  • Example: Administering antihypertensives at bedtime to control nocturnal BP surge.

Key Exam Tips

• Toxicity classifications: Acute vs. chronic—remember LD₅₀ for acute.

• Heavy metals: Know each metal’s mechanism and chelator (EDTA for lead; dimercaprol/DMSA for arsenic & mercury).

• Chronopharmacology: Match drug timing to physiological peaks (e.g., statins at night).