PHEENT flashcards

Antihistamines and PGs, asthma drugs, Pathology of Lung Tumors, Granulomatous and pulmonary vessel disease,

First Generation (Sedative)

Diphenhydramine, Promethazine, Chloropheniramine, Meclinzine, Dimenhydrinate, Hydroxyzine, Cyclinzine, Doxylamine

First Generation Antihistamine about

• Lipophillicity = High (cross BBB)

• Sedation = Strong

• Anticholinergic Effects = Present (dry mouth, urinary retention)

• Anti-motion sickness = Effective (esp Promethazine, Meclinzine)

• Duration of Action = Short (T1/2 = 4-12 hours)

• Clinical Uses = Allergies, motion sickness, insomnia, nausea, vertigo, urticaria

• Special Uses = Diphenhydramine: Parkinsonism, Promethazine: local anesthetic, Doxycycline + Pyidoxine: morning sickness

• AE = sedation, CNS depression, anticholinergic side effects, paradoxical agitation (children), seizures

• Contraindications/Caution = avoid in young children, caution in pregnancy (except Doxylamine combo)

• Drug Interactions = CNS depressants (alcohol, benzodiazepines), MAOIs, CYP3A4 inhibitors (grapefruit juice, azoles)

Second Generation (Non-Sedative)

Loratadine, Desloratadine, Cetrizine, Fexofenadine

Second Generation Antihistamine about

• Lipophilicity = Low (does not cross BBB)

• Sedation = None or minimal (Cetrizine: mild)

• Anticholinergic Effects Present= Absent

• Anti-motion sickness = Ineffective

• Duration of Action = Long (T1/2 = 12-24 hours)

• Clinical Uses = allergic rhinitis, urticaria, conjunctivitis

• Special Uses = Cetrizine: mast cell stabilizer, pregnancy-safe

• AE = minimal sedation, no anticholinergic side effects

• Contraindications/Caution = Safe in pregnancy and children

• Drug Interactions = CYP3A4 metabolism; fewer interactions

Alprostadil

• Type: PGE1 analog

• Clinical Use: ED, maintain ductus arteriosus (neonates)

• Mechanism/Notes: Vasodilator; intracavernosal injection, used in congenital heart disease

Misoprostol

• Type: PGE1 analog

• Clinical Uses: NSAID-induced ulcers, abortion, labor induction

• Mechanism/Notes: Cytoprotective; uterotonic; risk of uterine rupture

Dinoprostone

• Type: PGE2

• Clinical Uses: Cervical ripening, labor induction

• Mechanism/Notes: less risk of uterine rupture; vaginal insert/gel

Carboprost

• Type: PGF2a analog

• Clinical Uses: Postpartum hemorrhage, abortion

• Mechanism/notes: strong uterine contraction

Epoprostenol

• Type: PGI2 analong

• Clinical Uses: Pulmonary hypertension, dialysis (platelet aggregation prevention), Raynaud’s

• Mechanism/notes: potent vasodilator; IV infusion only; short T1/2 (3-5 min)

Latanoprost

• Type: PGFalpha analog

• Clinical Uses: Open-angle glaucoma

• Mechanism/notes: increase aqueous humor outflow; topical use; minimal systemic effects

Other PGs (Bimatoprost, Travoprost)

• Type: PGFalpha derivatives

• Clinical Uses: Glaucoma

• Mechanism/Notes: Same as latanoprost

Side effects

• Clinical Uses: GI - nausea, diarrhea (especially misoprostol); eye - pigmentation, irritation (latanoprost)

• Mechanism/Notes: Misoprostol contraindicated in pregnancy (unless inducing labor)

B2-agonists (SABA)

• Examples: Albuterol, Levalbuterol, Terbutaline, Pirbuterol, Bitolterol, Metaproterenol

• MOA: Stimulate B2 receptor —> increase cAMP —> relax bronchial smooth muscle

• Uses: rescue inhaler for acute attacks

B2 - Agonists (LABA)

• Examples: Salmeterol, Formoterol

• MOA: stimulate B2R —> increase cAMP —> relax bronchial smooth muscle (slower onset, longer duration)

• Uses: adjunct maintenance w/ corticosteroids (not monotherapy)

Inhaled Corticosteroids

• Examples: Fluticasone, Budesonide, Mometasone, Beclomethasone, Triamcinolone, Flunisolide)

• MOA: Block PLA2 —> inhibit inflammation, decrease mucus, increase B2R

• Uses: maintenance therapy in persistent asthma

Systemic Corticosteroids

• Examples: methylprednisolone, prednisolone, prednisone

• MOA: block PLS2 —> systemic anti-inflammatory

• Uses: sever asthma attacks

Muscarinic Antagonists (SAMA)

• Examples: Ipratropium

• MOA: Block Muscarinic M1-M3 —> decrease bronchoconstriction

• Uses: Adjunct w/ albuterol in exacerbations (not acute attacks)

Muscarinic Antagonists (LAMA)

• Examples: Tiotropium

• MOA: Block Muscarinic M1 & M3 —> decrease bronchoconstriction

• Uses: Maintenance (esp COPD); less in asthma

Leukotriene Modifiers

• Examples: Montelukast, Zafirlukast, Zileuton

• MOA: Montelukast/Zafirlukast: block leukotriene receptor; Zileuton: inhibit 5-LOX —> decrease leukotrienes

• Uses: Adjunct/alternative to ICS (not monotherapy)

Mast Cell Stabilizers

• Examples: Cromolyn, Nedocromil

• MOA: Stabilize mast cells —> inhibit degranulation (block Ca influx)

• Uses: Prophylaxis: seasonal, exercise-induced asthma

Methylxanthines

• Examples: Theophylline, Caffeine

• MOA: Inhibit PDE ¾ —> increase cAMP —> relax smooth muscle, decrease TNF-alpha and leukotrienes

• Uses: Limited role; nocturnal asthma (sustained release)

Monoclonal Ab - Benralizumab

• Examples: Benralizumab (Fasenra)

• MOA: Bind IL-5R —> recruit NK cells —> eosinophilia apoptosis

• Uses: Add-on for eosinophilic asthma

Monoclonal Ab - Omalizumab

• Examples: Omalizumab (Xolair)

• MOA: Bind IgE —> form inert IgE - drug complexes

• Uses: Severe allergic asthma (allergen - driven)

Monoclonal Ab - Dupilumab

• Examples: Dupilumab (Dupixent)

• MOA: Block IL-4/IL-13 pathway —> decrease type 2 inflammation

• Uses: Moderation-severe eosinophilic asthma (>= 12 years)

Monoclonal Ab - Reslizumab/Mepolizumab

• Examples: Reslizumab (Cinqair), Mepolizumab (Nucala)

• MOA: Bind IL-5 —> prevent receptor binding —> decrease eosinophils

• Uses: Severe asthma, EGPA

Interstitial Lung Disease

• Patchy pulmonary fibrosis mainly affecting the walls of alveoli and progressive scarring

• Cough and progressive exertional dyspnea are the most common symptoms

• Reduced compliance

• V/Q mismatch, leading to hypoxia

• Ground-glass opacities

• Honeycombing

• Common types: idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, Sarcoidosis, smoking-related ILD, pneumoconiosis

Sarcoidosis

• Multisystem disease of unknown etiology characterized by noncaseating granulomatous inflammation in many tissues and organs

• Epithelioid cells of granulomas produce ACE

• Activated pulmonary alveolar macrophages —> increase 1-alpha hydroxylase expression and activity —> increase 1,25 - dihydroxyvitamin D (calcitriol) —> hypervitaminosis D —> hyperphosphatemia and hypercalcemia

Manifestations of Sarcoidosis

• Pulmonary: Interstital granulomas

• Hilar lymphadenopathy: up to 90% of patients

• Skin lesions: erythema nodosum, tender nodules on anterior aspects of legs

• Eyes: anterior and posterior uveitis

• Endocrine: hypercalcemia

• Elevated CD4/CD8 ration

• A nerdy to PPD

• TB MUST BE EXCLUDED

Lupus pernio - a pathognomonic manifestations of sarcoidosis characterized by extensive, violaceous skin plaques on nose, cheeks, chin, and/or ears

Loggers Syndrome

• acute form of sarcoidosis

• Erythema nodosum

• Hilar adenopathy

• Polyarthralgia and fever

Hypersensitivity pneumonitis

Immunologically mediated lung disease that primarily affects the alveoli —> allergic alveolitis —> restrictive lung disease

Increase CD4+ and CD8+

Sources: mushrooms, fungi, yeast, bacteria, MAC, birds, chemicals

Smoking-related interstitial disease

macrophages contain dusty-brown pigment (smokers’ macrophages) in airspace and they contain various substances like tar, nicotine, carbon, etc —> result in increase of risk of respiratory infections

Pulmonary Eosinophilia

Most often are idiopathic or have associations with helminth infections, drugs such as Allopurinol

Loffler syndrome

eosinophilic lung disease, eosinophils accumulate in the lung in response to a parasitic infections, helminth larvae migrate through lung —> eosinophilic inflammation —> transient migratory infiltrates

Drug & Radiation Induced Pulmonary Disease

Bleomycin —> pneumonitis and fibrosis

Amiodarone —> pneumonitis and fibrosis

Busulphan —> pulmonary fibrosis

Radiation pneumonitis —> pulmonary fibrosis

Allopurinol —> eosinophilic pneumonia

Aspirin —> eosinophilic pneumonia and bronchospasm

Beta blockers —> hypersensitivity pneumonia and bronchospasm

Acute Respiratory Distress Syndrome

acute lung injury characterized by abrupt onset of hypoxemia and bilateral pulmonary edema and in absence of cardiac failure

ARDS pathogenesis

Hyaline membrane - consisting of fibrin, edema fluid, necrotic epithelial cells

Exudative phase (0-7 days) —> injury of alveolar & endothelial injury —> increased pulmonary capillaries permeability → leakage of protein-rich fluid into alveoli → pulmonary edema _→ formative of hyaline membrane

Proliferation phase: 1-2 weeks

Fibrotic phase: endothelial cells, pneumocystis, and fibroblasts proliferate in an attempt to repair damage —> collagen deposition —> scarring

Pulmonary hypertension

Plexiform Lesions

Increase pulmonary vascular resistance —> increase in right ventricular pressure —> structural changes or impaired function of right ventricle —> cor pulmonale

Pulmonary Hypertension —> medial hypertrophy of pulmonary arteries that —> narrowing the lumens to pinpoint channels

Idiopathic Pulmonary Fibrosis

Unknown etiology —> repeated injury and defective repair of the alveolar epithelium, diagnosis of exclusion

Subpleural fibrosis is characteristic histologic finding

Patchy, progressive bilateral interstitial fibrosis

Honeycomb pattern of fibrosis

Pneumoconiosis

Asbestosis is a type!

PALM = conditions associated with asbestos exposure —> Pleural plaques, asbestosis (diffuse pulmonary interstitial fibrosis), lung carcinoma, malignant mesothelioma

Pathophysiology - macrophages phagocytoses asbestos fibers → activate the inflammation and apoptosis —> stimulating the release of pro-inflammatory factors and fibrogenic mediators —> fibroblast activation —> collagen deposition —> interstitial pulmonary fibrosis

Asbestosis - Diffuse Pulmonary Intersitial Fibrosis

• Presence of ferruginous bodies

• Severe in lower lobes

• Bronchogenic carcinoma - most common cancer related to asbestosis

Silicosis

• Sandblasting and hard-rock mining

• Upper zones of the lungs

• Characteristic whorled or onion-skin fibers

• Polarized microscopy reveals weakly birefringent silica particles

• Eggshell calcification

• Advanced = risk of TB

Coal Workers’ Pneumonoconiosis

coal miners

Ranges from asymptomatic pulmonary anthracosis —> simple coal worker pneumoconiosis —> complicated CWP

Coal macules and coal nodules —> upper lobes

Caplan Syndrome

pneumoconiosis + rheumatoid arthritis

Berylliosis

Aerospace and microchip manufacturing

Macrophages phagocytose beryllium —> form noncaseating granulomas and cause Hilar lymphadenopathy

Benign lung lesions

Hamartoma —> coin-like lesion, looks like mixed-up jigsaw puzzle piece within a completed puzzle

Located in heart, brain, and lungs

Adenocarcinoma

• epithelial in origin, comes from glands

• Tumor feels firm or hard grossly

• Tumor cells release TGF-Beta, PDGF, FGF

• Lymphatic spread is common route of spread

• Classically peripheral tumors

• Tendency to form glands that may or may not produce mucin

• IN NON-SMOKERS AND SMOKERS ADENOCARCINOMA IS ASSOCIATED WITH MUTATIONS OF EGFR MUTATIONS (or it’s pathway, KRAS) and ALK gene rearrangements

• Napsin A and TTF-1 are immunohistochemical markers

Thrombophlebitis Migrans (Trousseau syndrome)

• form of superficial thrombophlebitis

• Tumor release mucin —> reacts with platelets —> platelet microthrombi

Squamous Cell Carcinoma

• Centrally located, appears as a hilar mass

• Hypercalcemia

• Intercellular bridges (desmosomes)

• Keratin pearls

Small Cell Lung Carcinoma

• small round/oval blue cells with minimal cytoplasm

• Nuclear features: finely dispersed chromatin, no distinct nucleoli

• IH markers: chromogranin A, neuron-specific enclave, synaptophysin, Insulinoma-associated protein 1, neural cell adhesion molecule

• Associated with several paraneoplastic syndromes: ACTH, SIADH, Lambert-Eaton Syndrome

• Associated mutations: TP53 and RB, L-myc

Bronchial carcinoid tumor

• Central/peripheral

• Well-differentiated NE tumor

Hypertrophic Pulmonary Osteoarthropathy

• digital clubbing

• Adenocarcinomas —> increase TGF-beta, VEGF, and PDGF

Pancoast Tumors

• apical lung carcinoma

• Horner syndrome - ipsilateral mitosis, ptosis, and antisepsis

• Brachial plexus compression

• Compression of recurrent laryngeal nerve

• SVC compression —> facial swelling

• Phrenic nerve —> paralysis of the hemidiaphragm (visible as elevated hemidiaphragm on chest X-ray)

Superior Vena Cava Syndrome

• compression of the superior vena cava mediastinum or apex

• Compression —> severe reduction in venous return from head, neck, and upper extremities —> results in venous congestion

• Neck, facial swelling

• Hoarseness —> compression of recurrent laryngeal nerve

Mesothelioma

• malignant tumor from mesothelial cells

• Secondary to asbestos exposure

• Biopsy reveals mesothelioma cells and psammoma bodies

• Stains positive for mesothelin and cytokeratin

Laryngeal tumors - benign

• Nonmalignant lesions - vocal cord nodules —> common in heavy smokers or slingers

• Non malignant lesions - laryngeal papilloma —> caused by HPV types 6 and 11

Laryngeal cancers

• almost always Squamous cell cancers

• HPV 16 and 18

• Unexplained hoarseness for longer than 3 weeks should always be investigated by laryngoscopy

Nasopharyngeal Carcinoma

strong association with EBV

Bacterial Pneumonias

• Consolidation - solidification of the lung due to replacement of the air by exudate in the alveoli

• Lobar pneumonia - generally confined to a single lobe, and that entire lobe becomes consolidated

• Bronchopneumonia - is characterized by patchy consolidation surrounding the airways and can involve multiple lobes

• Tissue destruction and necrosis, causing abscess formation

Stages of Pneumonia

1. Congestion (first stage) - lung is heavy, wet & red with interalveolar fluid

2. Red hepatization - more neutrophils arrive and fill the alveolar space, massive confluent exudation: neutrophils, red cells, and fibrin - lobe is red, firm, and airless (consolidation and hepatization are synonymous

3. Gray hepatization - RBS disintegration

4. Resolution - macrophages arrive, restore alveolar spaces with air

Viral Pneumonia

• Alveolar spaces in viral pneumonias are free of cellular exudate - no consolidation on chest x ray

• Lymphocyte accumulation —> inflammation within the septa —> interstitial inflammatory reaction in which the alveolar septa are widened and edematous

• Mycoplasma also causes interstitial inflammation —> atypical pneumonia

Pathogenesis of TB

1. Ghon focus = caseating granuloma typically located in middle/lower lung lobes

2. Ghon complex = Ghon focus + involved hilar lymph nodes

Majority of patients infected progress to asymptomatic latent disease

Th1 lymphocytes

TB Histopathology

Epithelioid macrophages are elongated with long, pale nuclei and pink cytoplasm

Miliary TB

Hematogenous transmission of the organism to the remaining lung and more distant sites during fulminant infections

“Miliary” pattern - many small tan granulomas scattered throughout lung parenchyma

Pott Disease

• Spondylitis - inflammation of spinal bones

• Pitt disease - destructive infection of vertebrae

• Psoas abscess - painful collection of pus in psoas muscle of the spine - Pott’s disease is the most frequent cause of secondary psoas abscess in developing countries