Pharmacokinetics describes “what the body does to the drug” (ADME).

Generic name (INN) is the official non-proprietary name.

Oral route is safest, most convenient, and economical, making it most commonly used.

Orally administered drugs pass through the portal circulation to the liver before reaching systemic circulation, where hepatic enzymes metabolize them.

IV administration delivers the entire dose directly into systemic circulation, bypassing absorption barriers and first-pass metabolism, giving 100% bioavailability.

Vd is a theoretical/apparent volume relating total drug in body to plasma concentration.

Loading dose = Vd × Desired concentration.

Brain capillary endothelial cells have tight junctions preventing passage of polar/large molecules.

Phase I (functionalization) adds or exposes functional groups via oxidation, reduction, or hydrolysis, mainly by cytochrome P450.

Cytochrome P450 (CYP) enzymes metabolize >75% of drugs, primarily in liver microsomes.

Rifampicin is a potent CYP450 inducer, accelerating metabolism of estrogen/progesterone, reducing contraceptive efficacy.

Ketoconazole is a potent CYP3A4 inhibitor, increasing levels of drugs metabolized by this enzyme (cyclosporine, statins).

Kidneys excrete most drugs and metabolites via glomerular filtration, tubular secretion, and reabsorption.

Maintenance dose = Clearance × Desired concentration.

Half-life (t½) is time for plasma concentration to fall by 50%.

Steady-state occurs when drug input equals elimination, reached after 4-5 half-lives regardless of dose or frequency.

First-order kinetics: elimination rate ∝ plasma concentration (constant fraction eliminated per unit time).

Phenytoin exhibits saturation kinetics–at high doses, metabolizing enzymes saturate, shifting from first-order to zero-order (constant amount eliminated).

Pharmacodynamics = “what the drug does to the body” (mechanism, effects, dose-response).

Dose-response curves show relationship between drug dose (x-axis) and response magnitude (y-axis), typically sigmoidal.

Therapeutic index = LD50/ED50 (lethal dose 50%/effective dose 50%).

Narrow therapeutic window means small difference between therapeutic and toxic concentrations (digoxin, lithium, warfarin).

Potency = amount (dose) needed to produce a given effect; lower dose = higher potency.

Efficacy = maximum therapeutic effect a drug can produce regardless of dose.

Competitive antagonists bind reversibly to same receptor site as agonist, causing rightward shift of dose-response curve (reduced potency) without reducing maximum response.

Non-competitive antagonists bind irreversibly or at allosteric sites, reducing number of functional receptors, decreasing maximum achievable response (Emax).

Synergism (potentiation): combined effect > sum of individual effects (1+1=3).

Tachyphylaxis = rapid tolerance developing within minutes to hours (ephedrine, nitrates).

Type A reactions are augmented pharmacological effects, dose-dependent, predictable, and common (80% of ADRs).

Idiosyncratic (Type B) reactions are unpredictable, not dose-dependent, often genetically determined (pharmacogenetic), rare but potentially serious.

Pharmacokinetic interactions affect ADME (absorption, distribution, metabolism, excretion).

Tolerance = decreased response requiring dose escalation for same effect.

ED50 (effective dose 50) produces therapeutic effect in 50% of population.

Partial agonists bind receptors but produce submaximal response even at full receptor occupancy (lower intrinsic activity/efficacy).

Protective index = TD50/ED50, using toxic dose instead of lethal dose–more relevant for human therapeutics.

NSAIDs inhibit cyclooxygenase (COX-1 and/or COX-2), blocking prostaglandin synthesis.

COX-1 is constitutive, maintaining gastric mucosa (cytoprotective prostaglandins), platelet function, and renal blood flow.

Celecoxib selectively inhibits COX-2, reducing inflammation with less GI toxicity than traditional NSAIDs.

Paracetamol acts centrally (CNS COX inhibition) providing analgesia and antipyresis but lacks peripheral anti-inflammatory action.

N-acetylcysteine (NAC) replenishes glutathione, detoxifying toxic metabolite NAPQI (N-acetyl-p-benzoquinone imine) formed in paracetamol overdose, preventing hepatotoxicity.

First-generation antihistamines (diphenhydramine, chlorpheniramine) are lipophilic, cross BBB, and block central H1 receptors causing sedation.

Cetirizine is a second-generation H1 antihistamine–less sedating, longer-acting, with peripheral selectivity.

Sumatriptan is a 5-HT1B/1D agonist causing cranial vasoconstriction and inhibiting neurogenic inflammation, aborting migraine.

Ondansetron blocks 5-HT3 receptors in CTZ and vagal afferents, highly effective for chemotherapy-induced and postoperative nausea/vomiting.

Misoprostol (PGE1 analog) replaces protective prostaglandins inhibited by NSAIDs, reducing gastric acid and enhancing mucus/bicarbonate.

Aspirin irreversibly acetylates platelet COX-1; since platelets lack nuclei, they cannot synthesize new enzyme.

Naproxen has relatively balanced COX-1/COX-2 inhibition with lower cardiovascular risk than selective COX-2 inhibitors (etoricoxib) or diclofenac.

Reye’s syndrome (hepatic encephalopathy) occurs in children given aspirin during viral infections (influenza, varicella).

Montelukast blocks CysLT1 receptors, preventing leukotriene-mediated bronchoconstriction.

Ibuprofen (NSAID) has antipyretic, analgesic, and anti-inflammatory actions via COX inhibition.

Penicillins are β-lactams that inhibit transpeptidase (penicillin-binding proteins), blocking peptidoglycan cross-linking in bacterial cell walls, causing cell lysis.

Clavulanic acid + amoxicillin = Augmentin/Co-amoxiclav.

Ceftazidime (3rd gen) and cefepime (4th gen) cover Pseudomonas aeruginosa.

Cilastatin inhibits renal dehydropeptidase-1 (DHP-1), which would otherwise inactivate imipenem in kidneys, increasing urinary levels and reducing nephrotoxicity.

Aztreonam is a monobactam (monocyclic β-lactam) active only against aerobic gram-negative bacteria including Pseudomonas.

Vancomycin (glycopeptide) binds D-Ala-D-Ala terminal of peptidoglycan precursors, blocking transglycosylation and transpeptidation.

Red man syndrome (flushing, pruritus, hypotension) results from histamine release due to rapid vancomycin infusion–not true allergy.

Tetracyclines bind 30S subunit, blocking aminoacyl-tRNA attachment to ribosome A site, inhibiting protein synthesis.

Tetracyclines deposit in developing teeth and bones, causing permanent yellow-brown discoloration and affecting bone growth.

Aminoglycosides (gentamicin, amikacin) cause dose-dependent nephrotoxicity (reversible) and ototoxicity (often irreversible–vestibular and cochlear).

Macrolides (erythromycin, azithromycin, clarithromycin) bind 50S ribosomal subunit, blocking translocation.

Azithromycin has long tissue half-life (~68 hours), allowing short courses (3-5 days) with once-daily dosing.

Linezolid is an oxazolidinone that inhibits 50S ribosome formation initiation.

Clindamycin has excellent anaerobic coverage (Bacteroides fragilis) and gram-positive activity.

Fluoroquinolones (ciprofloxacin, levofloxacin) inhibit DNA gyrase (topoisomerase II) in gram-negatives and topoisomerase IV in gram-positives, blocking DNA replication.

Fluoroquinolones cause arthropathy and cartilage damage in weight-bearing joints in juvenile animals and potentially children.

Sulfonamides are structural analogs of PABA, competitively inhibiting dihydropteroate synthase in folic acid synthesis.

TMP inhibits dihydrofolate reductase; SMX inhibits dihydropteroate synthase–sequential steps in folate synthesis pathway.

Chloroquine kills blood stages of P. vivax.

Amphotericin B (polyene antifungal) binds ergosterol in fungal cell membranes, creating pores causing leakage and cell death.

Azoles (fluconazole, itraconazole, voriconazole) inhibit lanosterol 14-α-demethylase (CYP51), blocking ergosterol synthesis, disrupting fungal membrane.

Amphotericin B + flucytosine for 2 weeks is preferred induction for cryptococcal meningitis, followed by fluconazole consolidation/maintenance.

Acyclovir requires phosphorylation by viral thymidine kinase (HSV, VZV) to become active triphosphate form, which inhibits viral DNA polymerase.

Acyclovir is first-line for HSV (genital, oral, encephalitis) and VZV (chickenpox, shingles).

NRTIs (nucleoside reverse transcriptase inhibitors: zidovudine, lamivudine) are incorporated into viral DNA, causing chain termination due to lacking 3′-OH group.

HIV protease inhibitors end in “-navir” (ritonavir, lopinavir, atazanavir, darunavir).

Chloramphenicol causes dose-independent, idiosyncratic aplastic anemia (rare but fatal) and dose-dependent reversible bone marrow suppression.

Grey baby syndrome occurs in neonates given chloramphenicol–immature liver cannot glucuronidate the drug, causing accumulation, cardiovascular collapse, and grey discoloration.

Bactericidal drugs kill bacteria: β-lactams, aminoglycosides, fluoroquinolones, vancomycin.

Aminoglycosides (gentamicin) are renally excreted and nephrotoxic–require dose adjustment and monitoring in renal impairment.

The hepatic first-pass effect refers to the metabolism of a drug by the liver before it reaches systemic circulation, significantly reducing bioavailability.

Bioavailability is the fraction of administered drug that reaches systemic circulation in unchanged form.

A loading dose is a higher initial dose given to rapidly achieve therapeutic plasma concentration, especially important for drugs with long half-lives.

Volume of distribution (Vd) exceeding total body water (~42L) indicates extensive tissue distribution and binding.

Phenobarbital is a potent inducer of hepatic CYP450 enzymes, increasing warfarin metabolism and reducing its anticoagulant effect.

Plasma half-life is prolonged in renal impairment for drugs primarily eliminated by kidneys, like gentamicin.

In zero-order kinetics, a constant amount of drug is eliminated per unit time regardless of plasma concentration (enzyme saturation).

CYP3A4 metabolizes approximately 50% of clinically used drugs, making it the most common site of drug-drug interactions.

Therapeutic index (TI) = TD50/ED50 or LD50/ED50.

Efficacy refers to the maximum effect a drug can produce regardless of dose.

Tolerance is a gradual decrease in drug response with repeated administration over days to weeks, reversible after drug-free period.

Tachyphylaxis is rapid tolerance developing within minutes to hours of repeated dosing, common with nitroglycerin due to depletion of sulfhydryl groups.

Potency refers to the amount of drug needed to produce a given effect.

Partial agonists have lower intrinsic activity, producing submaximal response even at 100% receptor occupancy.

Competitive antagonists bind reversibly to the same receptor site as agonists, and their effect can be overcome by increasing agonist concentration.

Synergism occurs when combined effect of two drugs exceeds the sum of individual effects, often seen when drugs work through different mechanisms.

Phase I reactions (functionalization) include oxidation, reduction, and hydrolysis, introducing or exposing functional groups.

Vd of 5 liters approximates plasma volume (3-5L), indicating drug is largely confined to plasma, likely due to high plasma protein binding or large molecular size.

Steady-state is reached after approximately 4-5 half-lives.

Type B (Bizarre) reactions are unpredictable, dose-independent, and often immunological (allergic reactions).

Celecoxib selectively inhibits COX-2, sparing COX-1 which protects gastric mucosa, thus reducing GI ulceration risk.

Aspirin is contraindicated in children with viral infections due to risk of Reye’s syndrome (hepatic failure and encephalopathy).

Paracetamol inhibits prostaglandin synthesis primarily in the CNS, particularly the hypothalamus (thermoregulatory center), explaining its antipyretic and analgesic effects without significant peripheral anti-inflammatory action.

Aspirin irreversibly acetylates platelet COX-1, preventing thromboxane A2 synthesis for the platelet’s entire lifespan (7-10 days).

Selective COX-2 inhibitors reduce prostacyclin (PGI2, vasodilator and antiplatelet) without affecting thromboxane A2 (proaggregatory), creating a prothrombotic imbalance.

At therapeutic doses, paracetamol undergoes glucuronidation and sulfation.

N-acetylcysteine (NAC) is the antidote for paracetamol poisoning.

Aspirin-exacerbated respiratory disease (AERD) results from COX inhibition, shunting arachidonic acid metabolism toward the lipoxygenase pathway, increasing bronchoconstrictive leukotrienes.

Second-generation antihistamines (cetirizine, loratadine, fexofenadine) are more polar and have limited CNS penetration due to P-glycoprotein efflux pumps, causing less sedation.

Terfenadine (prodrug of fexofenadine) was withdrawn due to QT prolongation and fatal arrhythmias when combined with CYP3A4 inhibitors.

Sumatriptan is a 5-HT1B/1D agonist causing cerebral vasoconstriction and inhibiting trigeminal nerve nociceptive transmission, aborting migraine attacks.

Serotonin syndrome results from excessive serotonergic activity, characterized by hyperthermia, autonomic instability, neuromuscular changes (rigidity, clonus), and altered mental status.

Misoprostol replaces cytoprotective prostaglandins depleted by NSAIDs, reducing gastric acid secretion and enhancing mucosal defense.

Ondansetron is a 5-HT3 antagonist blocking serotonin receptors in the chemoreceptor trigger zone and vagal afferents, preventing chemotherapy-induced emesis.

Ibuprofen reversibly binds to COX-1 at the same site as aspirin, competitively preventing aspirin’s irreversible acetylation.

Penicillins inhibit transpeptidase (PBP – penicillin-binding proteins), preventing peptidoglycan cross-linking in bacterial cell walls.

Penicillin allergy causing anaphylaxis is a Type I hypersensitivity reaction mediated by IgE antibodies bound to mast cells, triggering histamine release.

Ampicillin is an aminopenicillin with extended gram-negative coverage including E. coli, H. influenzae, Proteus, and Salmonella.

Piperacillin is an antipseudomonal penicillin with activity against P. aeruginosa.

Clavulanic acid is a β-lactamase inhibitor with minimal intrinsic antibacterial activity.

MRSA resistance is due to the mecA gene encoding altered PBP2a with low affinity for all beta-lactams including cephalosporins.

Third-generation cephalosporins (ceftriaxone, cefotaxime) have excellent CSF penetration, making them first-line for bacterial meningitis.

Ceftazidime and cefepime (4th gen) have antipseudomonal activity.

Aztreonam is active only against aerobic gram-negative bacteria and has minimal cross-reactivity with penicillins, making it safe in penicillin-allergic patients.

Cilastatin inhibits renal dehydropeptidase-I (DHP-I), which degrades imipenem in renal tubules, thereby increasing drug levels and reducing nephrotoxic metabolites.

Oral vancomycin is not absorbed from the GI tract, achieving very high concentrations directly in the gut lumen where C. difficile resides.

Red Man Syndrome is a non-allergic, direct histamine release reaction from rapid vancomycin infusion, not IgE-mediated.

Fosfomycin inhibits early cell wall synthesis (MurA enzyme) and achieves very high urinary concentrations.

Cycloserine is a D-alanine analog that inhibits alanine racemase and D-Ala-D-Ala ligase, preventing peptidoglycan synthesis.

Bacitracin causes significant nephrotoxicity when given systemically, limiting use to topical application for skin and eye infections.

Tetracyclines bind reversibly to the 30S ribosomal subunit, blocking aminoacyl-tRNA attachment to the acceptor (A) site, inhibiting protein synthesis.

Tetracyclines chelate with divalent and trivalent cations (Ca²⁺, Mg²⁺, Al³⁺, Fe²⁺) in dairy products, antacids, and iron supplements, forming insoluble complexes that reduce absorption.

Aminoglycosides exhibit concentration-dependent killing (higher peak = more killing) and significant post-antibiotic effect.

Aminoglycosides accumulate in cochlear and vestibular hair cells causing irreversible ototoxicity.

Erythromycin inhibits CYP3A4 and prolongs QT interval.

Azithromycin has longer half-life (68 hours), better tissue penetration (concentrates intracellularly), and fewer drug interactions (minimal CYP450 inhibition).

Neonates, especially premature infants, have immature hepatic glucuronyl transferase and reduced renal function, causing chloramphenicol accumulation.

Chloramphenicol causes two types of bone marrow toxicity: dose-related reversible suppression (common) and idiosyncratic aplastic anemia (rare, dose-independent, irreversible, often fatal).

Linezolid (oxazolidinone) binds to 23S rRNA of the 50S subunit, preventing formation of the 70S initiation complex (unique mechanism).

Prolonged linezolid use (>28 days) can cause peripheral neuropathy (numbness, tingling) and optic neuropathy (vision changes), likely due to mitochondrial toxicity.

Clindamycin is strongly associated with Clostridioides difficile-associated pseudomembranous colitis due to disruption of normal gut flora.

Quinupristin and dalfopristin are streptogramins that synergistically bind different sites on the 50S ribosome.

Fluoroquinolones inhibit DNA gyrase (topoisomerase II) in gram-negatives and topoisomerase IV in gram-positives, preventing DNA supercoiling and replication.

Concurrent corticosteroid use significantly increases fluoroquinolone-associated tendinopathy and rupture risk, especially in elderly patients.

Sulfonamides inhibit dihydropteroate synthase (compete with PABA), while trimethoprim inhibits dihydrofolate reductase.

Chloroquine accumulates in the acidic food vacuole of intraerythrocytic parasites, preventing heme polymerization (toxic heme accumulates).

Primaquine can cause severe hemolysis in G6PD-deficient patients (oxidant-induced hemolytic anemia).

Artemisinin compounds provide rapid parasite clearance (fastest-acting antimalarials) but have short half-lives (1-3 hours).

Amphotericin B binds to ergosterol in fungal cell membranes, creating pores that lead to ion leakage and cell death.

Infusion-related reactions (fever, chills, rigors) are common with amphotericin B due to cytokine release.

Fluconazole achieves excellent CSF levels (70-80% of plasma), is orally bioavailable, and has fewer adverse effects than amphotericin B, making it ideal for long-term suppression.

Azoles inhibit fungal CYP51 (14-alpha-demethylase), preventing conversion of lanosterol to ergosterol.

Acyclovir is a prodrug requiring initial phosphorylation by viral thymidine kinase (HSV/VZV-specific), then cellular kinases convert it to active triphosphate.

Ganciclovir causes significant myelosuppression (neutropenia, thrombocytopenia) because it’s phosphorylated by cellular kinases more than acyclovir, affecting bone marrow cells.

Foscarnet directly inhibits viral DNA polymerase by blocking the pyrophosphate binding site, without requiring kinase activation.

NRTIs are nucleoside analogs that, after intracellular phosphorylation, incorporate into viral DNA during reverse transcription, causing chain termination (they lack 3′-OH for further elongation).

Protease inhibitors (ritonavir, lopinavir) are associated with metabolic syndrome: lipodystrophy, hyperlipidemia, insulin resistance, and increased cardiovascular risk.

Ritonavir is a potent CYP3A4 inhibitor.

Raltegravir, dolutegravir, and elvitegravir are integrase strand transfer inhibitors (INSTIs) that block HIV integrase, preventing viral DNA integration into host genome.

Enfuvirtide is a 36-amino acid peptide that binds to HIV gp41, preventing conformational change required for fusion of viral and host cell membranes (blocks viral entry).

Myopia (short-sightedness) causes difficulty with distant vision while near vision remains intact.

This presentation is classic presbyopia – age-related loss of accommodation.

Astigmatism results from unequal curvature of the cornea (or lens) in different meridians, causing blurred vision at all distances.

In myopia, the eyeball is too long or the refractive power too strong, causing parallel rays to converge in front of the retina.

Hypermetropia requires excessive accommodation to focus light on the retina.

The far point of a myopic eye equals the reciprocal of the lens power: 1/3.0 = 0.33 m = 33 cm.

This patient has axial myopia.

To read at 25 cm, the accommodation required is 1/0.25 = +4.0 D.

A small eyeball (short axial length) with a shallow anterior chamber and difficulty with near vision is classic hypermetropia.

In with-the-rule astigmatism, the vertical meridian is steeper (more refractive power) than the horizontal – the most common type in young people.

LASIK for myopia removes corneal stromal tissue centrally to flatten the central cornea, reducing its refractive power so that light focuses on the retina instead of in front of it.

Young hypermetropes can overcome their refractive error for distance by active accommodation – increasing lens curvature via ciliary muscle contraction.

When the principal meridian of astigmatism lies between 30°–60° or 120°–150°, it is classified as oblique astigmatism.

Low-dose atropine (0.01%) has been shown to slow the progression of myopia by reducing axial elongation of the eyeball.

In compound myopic astigmatism, both principal meridians are myopic, so both focal lines fall in front of the retina.

Retinoscopy under cycloplegia is the gold standard for objective refraction in young children.

Accommodation progressively decreases with age due to lens hardening (nuclear sclerosis).

In a young person with 6/6 distance vision but near vision symptoms (asthenopia), latent hypermetropia is the most likely cause.

The duochrome test exploits chromatic aberration.

Spectacle lenses sit ~12 mm from the cornea.

Persistent watery eye with mucopurulent discharge since birth is characteristic of congenital dacryocystitis caused by a blocked nasolacrimal duct (Hasner’s membrane persistence).

The first-line treatment for congenital NLDO is Crigler massage (hydrostatic massage over the lacrimal sac) combined with topical antibiotics for secondary infection.

Regurgitation test positive (mucopurulent reflux on pressing the lacrimal sac) confirms chronic dacryocystitis with nasolacrimal duct obstruction.

Dacryocystorhinostomy (DCR) creates a new passage between the lacrimal sac and nasal mucosa, bypassing the blocked nasolacrimal duct.

Chronic dacryocystitis harbors organisms (especially *Staphylococcus* and *Streptococcus*) in the lacrimal sac.

Schirmer’s test measures aqueous tear production.

Rheumatoid arthritis is associated with Sjögren’s syndrome, which causes keratoconjunctivitis sicca (dry eye).

Acute dacryocystitis presents as a painful, red, tender swelling over the lacrimal sac (below the medial canthal tendon) with purulent discharge expressible through the punctum.

Staphylococcus aureus is the most common organism causing acute dacryocystitis in adults.

In nasolacrimal duct obstruction, saline injected through the lower punctum cannot drain into the nose.

If conservative management (Crigler massage and topical antibiotics) fails to resolve congenital NLDO by age 12 months, the next step is probing of the nasolacrimal duct.

The FDDT assesses lacrimal drainage.

When the lacrimal drainage system is patent on syringing, epiphora in cold/windy conditions is due to reflex hypersecretion – the lacrimal gland overproduces tears in response to external irritation, overwhelming the normal drainage capacity.

A positive Jones I test means fluorescein has traveled from the eye through the entire lacrimal drainage system into the nose – confirming a patent (functional) system.

Ectropion is the outward turning of the eyelid margin, exposing the conjunctival surface and displacing the punctum away from the tear lake, causing epiphora (overflow tearing).

Normal TBUT is ≥10 seconds.

The classic triad of congenital glaucoma is epiphora, photophobia, and blepharospasm with an enlarged, cloudy cornea (buphthalmos = ox eye).

Crocodile tears (Bogorad syndrome) occur due to aberrant regeneration of facial nerve fibers after Bell’s palsy – salivatory fibers regenerate along the lacrimal pathway, causing tearing during eating.

The lacrimal gland is situated in the lacrimal fossa in the superolateral part of the orbit, beneath the orbital rim.

Punctal plugs (silicone or collagen) occlude the lacrimal puncta, preventing tear drainage and thereby increasing the tear film volume on the ocular surface.

Progressive painless vision loss with central yellowish-brown nuclear opacity is characteristic of nuclear sclerotic cataract – the most common age-related type.

“Second sight” occurs when progressive nuclear sclerosis increases the refractive index of the lens, creating a myopic shift.

Posterior subcapsular cataract (PSC) is common in diabetics and steroid users.

Chronic corticosteroid use (systemic or topical) is classically associated with posterior subcapsular cataract.

In children, dense cataract blocks visual stimulation during the critical period of visual development (up to ~8 years).

Retinoblastoma is the most important and dangerous cause of leukocoria in children.

In immature cataract, clear cortex remains between the iris and the opaque nucleus, casting an iris shadow (crescent-shaped shadow on oblique illumination).

In Morgagnian (hypermature) cataract, the cortex undergoes complete liquefaction, causing the dense brown nucleus to sink to the bottom of the capsular bag.

In phacomorphic glaucoma, the swollen intumescent lens pushes the iris forward, causing pupillary block and secondary angle-closure glaucoma.

Phacolytic glaucoma occurs in hypermature cataracts where high-molecular-weight lens proteins leak through the intact but permeable capsule.

Phacoemulsification is the current gold standard for cataract surgery.

Posterior capsule opacification (PCO), also called after-cataract, is the most common late complication of cataract surgery.

The SRK (Sanders-Retzlaff-Kraff) formula calculates IOL power: P = A − 2.5L − 0.9K, where A = lens constant, L = axial length, K = keratometry.

Diabetes mellitus is associated with two types of cataracts: posterior subcapsular cataract (common in all diabetics) and true diabetic “snowflake” cataract (widespread white cortical opacities, seen in young type 1 diabetics).

Sunflower cataract is a greenish-brown, petal-like anterior subcapsular opacity seen in Wilson’s disease (hepatolenticular degeneration) due to copper deposition in the lens.

Congenital rubella causes a characteristic pearly white, dense nuclear cataract, often bilateral.

The “oil droplet” cataract is pathognomonic of galactosemia.

“Christmas tree” (multicolored iridescent) cataract is classically seen in myotonic dystrophy – fine, polychromatic, needle-shaped crystals scattered throughout the lens cortex.

Severe pain, redness, hypopyon, lid edema, and vision loss within days of cataract surgery is classic postoperative endophthalmitis – a devastating intraocular infection.

Nd:YAG laser capsulotomy disrupts the posterior capsule, which can allow vitreous to prolapse forward and exert traction on the retina, increasing the risk of retinal detachment (especially in myopic eyes).

Pharmacodynamics is “what the drug does to the body.” Pharmacogenomics studies genetic influence on drug response.

Brand/trade names are company-specific marketing names.

IV is fastest but requires sterility.

Kidneys primarily excrete drugs.

Oral drugs have lower bioavailability due to incomplete absorption and hepatic metabolism.

It can exceed body volume if drugs distribute extensively into tissues.

It fills the distribution volume rapidly to achieve therapeutic levels immediately.

Fenestrated and sinusoidal capillaries (liver, kidney) allow easy passage.

Phase II involves conjugation (glucuronidation, acetylation).

CYP3A4 is the most abundant isoform.

Enzyme inhibitors increase drug levels.

It doesn’t primarily affect Phase II conjugation enzymes.

Liver metabolizes drugs; biliary excretion is secondary.

It replaces drug eliminated to maintain steady-state.

After 4-5 half-lives, ~97% of drug is eliminated.

At this point, plasma concentration fluctuates within a consistent range.

Zero-order kinetics: constant amount eliminated regardless of concentration (ethanol, phenytoin at high doses).

Small dose changes cause large concentration changes.

Pharmacokinetics covers ADME (absorption, distribution, metabolism, excretion).

They help determine potency, efficacy, and therapeutic window.

Higher TI means safer drug.

Requires frequent monitoring to avoid toxicity while maintaining efficacy.

Efficacy = maximum effect achievable.

Full agonists have high efficacy; partial agonists have lower maximal effect.

Non-competitive antagonists reduce Emax.

Cannot be overcome by increasing agonist concentration unlike competitive antagonism.

Additive: effects sum up (1+1=2).

Tolerance develops slowly over days-weeks.

Type B are idiosyncratic, unpredictable, not dose-related.

Examples: malignant hyperthermia with anesthetics, hemolysis in G6PD deficiency.

Rifampicin induces CYP450, increasing metabolism of other drugs.

Develops over days-weeks due to receptor downregulation or enhanced metabolism.

LD50 (lethal dose 50) causes death in 50%.

They can antagonize full agonists by competing for receptors.

Higher protective index indicates safer drug.

This produces anti-inflammatory, analgesic, and antipyretic effects.

COX-2 is inducible, mediating inflammation.

However, COX-2 inhibitors carry cardiovascular risks.

It doesn’t affect platelets or cause GI bleeding.

Flumazenil reverses benzodiazepines; naloxone reverses opioids.

Second-generation (cetirizine, loratadine) are less lipophilic with minimal CNS effects.

First-generation (diphenhydramine) causes sedation.

Contraindicated in coronary artery disease due to vasoconstriction.

Doesn’t cause extrapyramidal effects like dopamine antagonists.

Contraindicated in pregnancy (abortifacient).

Effect lasts platelet lifespan (7-10 days).

Rofecoxib was withdrawn for cardiovascular events.

Paracetamol or ibuprofen preferred in children.

Zileuton inhibits 5-lipoxygenase (leukotriene synthesis).

Paracetamol lacks anti-inflammatory action.

Bactericidal against dividing bacteria.

Clavulanate irreversibly inhibits β-lactamases, protecting amoxicillin.

Cefazolin (1st gen) covers gram-positives.

Cilastatin has no antibacterial activity.

Safe in penicillin allergy (minimal cross-reactivity).

Used for MRSA and C. difficile (oral).

Prevented by slow infusion (≥1 hour).

Aminoglycosides also bind 30S but are bactericidal.

Contraindicated in children <8 years and pregnancy.

Monitor levels and renal function.

Bacteriostatic (bactericidal at high concentrations).

Better tolerated (less GI upset) than erythromycin.

Active against MRSA, VRE, and resistant gram-positives.

Used for skin/soft tissue infections, dental infections, and aspiration pneumonia.

Generally avoided <18 years except for specific indications (cystic fibrosis, anthrax).

Trimethoprim inhibits dihydrofolate reductase (sequential blockade).

This produces synergistic bactericidal effect and reduces resistance development.

Primaquine is essential to eliminate hepatic hypnozoites preventing relapse (radical cure).

Liposomal formulations reduce toxicity.

CYP450 inhibitors causing drug interactions.

Flucytosine enhances amphotericin B penetration.

Selective toxicity–minimal effect on uninfected cells.

Valacyclovir (prodrug) has better oral bioavailability.

Foundation of antiretroviral therapy.

They block cleavage of viral polyproteins into functional proteins.

Reserved for serious infections (typhoid, bacterial meningitis when alternatives unavailable).

Avoid chloramphenicol in neonates.

Bacteriostatic drugs inhibit growth: tetracyclines, macrolides, sulfonamides, chloramphenicol.

Azithromycin and doxycycline are hepatically metabolized.

Volume of distribution describes drug distribution in body compartments, not metabolism.

Different formulations can have different bioavailability despite identical doses.

Maintenance dose sustains steady-state concentration after loading.

A Vd of 500L means the drug preferentially accumulates in tissues rather than plasma.

Enzyme induction increases drug clearance.

Extending the dosing interval compensates for slower elimination.

First-order kinetics shows proportional increase in elimination with concentration.

CYP2C9 metabolizes warfarin and some NSAIDs.

A higher TI indicates a wider margin between therapeutic and toxic doses, meaning greater safety.

Drug A has lower efficacy (80% max) than Drug B (100% max).

Tachyphylaxis is rapid tolerance developing within minutes to hours.

Drug allergy involves immune mechanisms.

A drug requiring lower dose (5 mg vs 50 mg) for equal effect is more potent.

Full agonists produce maximum response with full receptor occupancy.

Non-competitive antagonists cannot be overcome by increasing agonist dose.

Additive effect equals the sum of individual effects.

These reactions are primarily mediated by CYP450 enzymes.

Total body water is ~42L, tissue binding would show Vd >42L.

With t½ of 6 hours: 4-5 × 6 = 24-30 hours.

Type A (Augmented) reactions are predictable, dose-dependent extensions of pharmacological effects.

Ibuprofen, naproxen, and aspirin are non-selective NSAIDs inhibiting both COX-1 and COX-2, increasing GI bleeding risk.

Paracetamol and ibuprofen are safe alternatives.

Unlike NSAIDs, it lacks significant peripheral COX inhibition, hence minimal GI and antiplatelet effects.

This reduces platelet aggregation and thrombosis risk.

This increases MI and stroke risk.

A small fraction is converted to toxic NAPQI by CYP450, normally detoxified by glutathione conjugation.

It replenishes hepatic glutathione stores, allowing NAPQI to be safely conjugated and eliminated.

This is a pseudoallergic reaction, not IgE-mediated.

First-generation agents (diphenhydramine) are lipophilic, cross BBB easily.

Fexofenadine (active metabolite) lacks this cardiotoxicity.

5-HT3 antagonists (ondansetron) are antiemetics.

Combining triptans with SSRIs increases this risk.

It prevents NSAID-induced gastric ulcers.

Metoclopramide blocks D2 receptors.

Taking aspirin first allows irreversible platelet inhibition before ibuprofen competes for the site.

This leads to osmotic lysis and bacterial death.

Type II involves cytotoxic antibodies.

It’s not effective against penicillinase-producing staph (need anti-staphylococcal penicillins), MRSA (need vancomycin/linezolid), or B. fragilis (need metronidazole).

Amoxicillin and penicillin V lack antipseudomonal activity.

It irreversibly binds and inhibits β-lactamases, protecting amoxicillin from enzymatic destruction by resistant bacteria.

This isn’t primarily β-lactamase-mediated.

First and second generation cephalosporins have limited CNS penetration.

Ceftriaxone lacks reliable Pseudomonas coverage.

It has no activity against gram-positives (including MRSA) or anaerobes.

Cilastatin has no antibacterial activity or β-lactamase inhibition.

IV vancomycin doesn’t reach therapeutic colonic levels.

It’s prevented by slow infusion (over 1-2 hours).

Single-dose oral fosfomycin is approved for uncomplicated UTIs.

It’s reserved for MDR-TB due to significant CNS toxicity (seizures, psychosis).

It inhibits cell wall synthesis by blocking lipid carrier recycling.

Chloramphenicol inhibits 50S peptidyltransferase.

Fatty foods enhance absorption.

This allows once-daily dosing with high peaks and low troughs (reduces toxicity).

They also cause nephrotoxicity (reversible).

Combined with other QT-prolonging drugs (terfenadine, certain antiarrhythmics), it increases torsades de pointes risk.

However, erythromycin has equal or superior gram-positive activity.

Unconjugated chloramphenicol causes cardiovascular collapse (Gray Baby Syndrome).

The idiosyncratic reaction can occur weeks after treatment ends and isn’t related to dose.

This explains lack of cross-resistance with other protein synthesis inhibitors.

Serotonin syndrome occurs with concurrent MAOIs/serotonergics.

Treatment is oral vancomycin or fidaxomicin.

Dalfopristin blocks elongation (A site), quinupristin blocks peptide exit.

RNA polymerase is inhibited by rifampin.

Other risk factors include age >60, renal impairment, and prior tendon disorders.

Together they sequentially block bacterial folic acid synthesis, creating bactericidal synergy.

Hepatic stages lack this acidic vacuole mechanism.

G6PD testing before treatment is mandatory.

Combination with longer-acting partner drug (lumefantrine, mefloquine) prevents recrudescence and resistance.

Human cells contain cholesterol (lower affinity but still some binding, explaining toxicity).

Premedication with acetaminophen, diphenhydramine, and hydrocortisone reduces severity.

Amphotericin B is used for induction (more rapidly fungicidal).

This depletes ergosterol and causes toxic sterol intermediates to accumulate, impairing membrane function.

This selective activation explains specificity and low toxicity to uninfected cells.

Regular CBC monitoring is essential.

This makes it effective against thymidine kinase-deficient acyclovir-resistant HSV/VZV.

Zidovudine (AZT) was the first antiretroviral.

They inhibit HIV protease (polyprotein cleavage).

At low “boosting” doses, it increases plasma levels of other protease inhibitors (reduces dosing frequency, improves trough levels), without adding significant antiretroviral activity or toxicity at these doses.

They’re highly effective, well-tolerated, and have become preferred first-line agents.

As a peptide, it’s degraded orally and requires subcutaneous injection twice daily.

Concave (minus) lenses diverge light rays, correcting the focus onto the retina.

Convex (plus) lenses converge light rays and assist near focusing.

It is corrected with cylindrical lenses.

This results in a blurred distant image.

Since accommodation and convergence are neurally linked, excessive accommodation causes excessive convergence, leading to accommodative esotropia (convergent squint).

Objects at the far point are seen clearly without correction.

Increased axial length causes stretching and thinning of the retina, predisposing to retinal detachment, lattice degeneration, and vitreous detachment.

Available accommodation is +1.0 D.

Plus lenses (+4.0 D) converge rays onto the retina.

In against-the-rule, the horizontal meridian is steeper (common in elderly).

Increasing central curvature would worsen myopia.

This is called latent hypermetropia.

With-the-rule has the steepest meridian at or near 90° (vertical).

The exact mechanism may involve muscarinic receptors in the sclera.

In simple myopic astigmatism, one line is on the retina and the other in front.

Cycloplegic agents (atropine/cyclopentolate) paralyze accommodation, revealing the true refractive error.

It is approximately zero by age 60, after which the presbyopic correction stabilizes.

The ciliary muscle compensates for distance but fatigues during sustained near work.

Red wavelengths focus behind green.

When a minus lens moves closer to the eye (spectacles → contact lens), the effective power required decreases (less minus).

Ophthalmia neonatorum presents with purulent discharge and conjunctival injection within 28 days.