Test #19 (BMR Week 2N Block 2: Pulm)

Question 1

Role of following in allergic asthma tx: (1) Histamine receptor antagonists (2) LTD4 (3) Other drug that is efficacious

Answer 1

(1) Histamine may contribute to pathogenesis of asthmatic bronchoconstriction but its role appears to be relatively minor given that histamine antagonists lack efficacy in allergic asthma (2) Although numerous substances play role in pathogenesis of allergic asthma, only leukotrienes (LTC4, D4, AND E4) and acetylcholine have pharmacologic receptor antagonists that offer clear therapeutic benefit

Question 2

Major toxicities of theophylline

Answer 2

Seizures are major cause of morbidity and mortality from theophylline intoxication

Question 3

Rifampin monotherapy used for

Answer 3

N. meningitidis exposure

Question 4

(1) Dx: recurrent sinopulmonary and GI tract infections (2) Explain: blood transfusion with O negative packed red blood cells leads to diffuse itching, skin rash, bronchospasm, and death 30 min later

Answer 4

(1) Selective IgA defeciency (2) Assoc. w/ anaphylactic response to transfused blood products due to an immune response against transfused IgA which the patient’s body recognizes as foreign

Question 5

Dx: Patient’s flow-volume loop curve shows decrease in all lung volumes and significantly decreased expiratory flow rates

Answer 5

COPD - either chronic bronchitis or emphysema

Question 6

(1) Direct indicator of status of alveolar ventilation (2) Give examples/conditions of this

Answer 6

(1) Arterial paCO2 (2) Hypocapnia: ongoing alveolar hyperventilation (3) Hypercapnia: due to upper airway obstruction, reduced ventilatory drive, respiratory muscle fatigue, and/or decreased chest wall compliance

Question 7

(1) Use of monotherapy isoniazid for Tb (2) Risk/Outcome otherwise

Answer 7

(1) Isoniazid monotherapy may be used for patients who have a positive PPD and a negative chest x-ray (ie, no evidence of clinical disease) (2) Active tuberculosis NEVER treated with drug monotherapy due to fast emergence of mycobacterial antibiotic resistance from rapid, selective gene mutaitons.

Question 8

Mechanisms of following antifungals: (1) Amphotericin B (2) Itraconazole (3) Terbinafine (4) Griseofulvin (5) Caspofungin (6) Flucytosine

Answer 8

(1) Binds ergosterol in fungal membrane, leading to pore formation and cell lysis (2) Inhibits synthesis of ergosterol by fungal cytochrome P450 enzymes. Azoles also suppress human P450 system, resulting in may drug-drug interactions. (3) Inhibits fungal enzyme squalene-2,3-epoxidase, which ultimately results in decreased synthesis of ergosterol. Accumulates in skin and nails, so used to treat dermatophyses. (4) enters fungal cells and binds microtubules, inhibiting mitosis (5) (Echinocandin antifugals) Block glucan (1,3-beta-D glucan = major polysaccharide component of fungal cell wall) synthesis (6) Inhibits synthesis of both DNA (replication) and RNA (protein synthesis) in fungal cells. Mainly used as synergistic agent with amphotericin B. Drug combination particularly important in tx of crytococcal meningitis.

Question 9

c Flow rate in pulmonary versus systemic circuits

Answer 9

Pulmonary circulation continuous circuit with systemic circulation. Rate of blood flow thru pulmonary circulation must equal the rate of blood flow in the systemic circulation at all times. Arterial pressures and oxygen contents of the pulmonary and systemic arterial systems considerably different both at rest and during exercise.

Question 10

(1) Antituberculous agent most assoc. with decreased visual acuity (2) specific eye condition it causes & its presentation (3) Drug’s mechanism

Answer 10

(1) Ethambutol = most notorious for adverse visual changes (2) optic neuritis, which typically persents in conjuction with decreased visual acuity, central scotoma, and color blindness) (3) Inhibits carbohydrate polymerization, thereby preventing peptidoglycan wall synthesis

Question 11

(1) Mechanism of Amphotericin toxicity (2) Amphotericin most important adverse effects

Answer 11

(1) In addition to binding ergosterol of fungal cell membranes to exert its antifungal effects, also binds cholesterol to some degree, causing toxicity in human tissues (2) Nephrotoxicity, Hypokalemia, and Hypomagnesemia

Question 12

(1) 2 major risk factors for ARDS (2) Pathophysiology of ARDS

Answer 12

(1) Sepsis and shock 2 major risk factors for developing adult respiratory distress syndrome (ARDS, aka ‘shock lung’) (2) Produces non-cardiogenic pulmonary interstitial and intra-alveolar edema, inflammation, and alveolar hyaline membranes

Question 13

Mechanism of mycobaterial resistance to isoniazid

Answer 13

Non-expression of catalase-peroxidase enzyme or through genetic modification of isoniazid binding site on mycolic acid synthesis enzyme. Note: Mechanism not fully understood. It is know that Isoniazid must be processed by mycobacterial catalase-peroxidase for drug to be activated within bacteria, and that isoniazid requires a specific protein sequence in its enzyme target (an enzyme necessary for mycolic acid synthesis).

Question 14

Clinical use and mechanism of N-acetylcysteine

Answer 14

Mucolytic agent in tx of CF. Works by cleaving disulfide bonds within mucous glycoproteins, thus loosening thick sputum.

Question 15

(1) pO2 in left atrium versus pulmonary capillaries (2) explain

Answer 15

(1) pO2 in left atrium is lower than that in pulmonary capillaries because (2) deoxygenated blood originating from bronchial arteries mixes with oxygenated blood in pulmonary veins

Question 16

Preferred Beta-blockers in patients with COPD and/or asthma and why

Answer 16

Non-selective beta-adrenergic blockers cause bronchoconstriction, peripheral vasospasm, and can predispose diabetic patients to hypoglycemia. Selective Beta-blockers (metoprolol, atenolol, acebutolol, and esmolol) are preferred in patients with COPD and/or asthma

Question 17

Abscesses due to aspiration: (1) E.g.’s of anaerobes causing them (2) Risk factors

Answer 17

(1) Peptostreptococci and Fusobacteria are anaerobic bacteria normally found in oral cavity (2) Cause lung abscesses associated w/ aspiration. Risk factors include alcoholism, seizure disorder, CVA, and dementia

Question 18

Again, Ethambutol: (1) Major toxicity & its presentation (2) How to reverse it

Answer 18

(1) Optic neuritis that results in color blindness, central scotoma, & decreased visual acuity (2) Adverse side effect may be reversible with discontinuation of drug

Question 19

(1) Examples of Echinocandins (2) Their mechanism

Answer 19

(1) Echinocandins (e.g., caspofungin & micafungin) = newer group of antifungal medications that (2) inhibit synthesis of polysaccharide glucan, an essential component of fungal cell wall

Question 20

(1) Dx: Microscopic exam, tall, columar cells line alveolar septa without evidence of vascular or stromal invasion (2) Characterize Dx

Answer 20

(1) Bronchioalveolar carcinoma (2) is a subtype of lung adenocarcinoma. uncommon tumors occurs in non-smokers and arises from alveolar epithelium. It is located in peripheral parts of lung and is often multifocal. On micro exam, composed of tall, columnar cells that line alveolar septa without evidence of vascular or stromal invasion.

Question 21

Lung transplantation rejection: (1) Timeline if chronic rejection (2) Damaged area (3) Syndrome caused (4) Sx

Answer 21

(1) Months to years after tx (2) Small airways, (3) causing bronchiolitis obliterans (4) dyspnea and wheezing

Question 22

Immune cells that control Tb

Answer 22

Cd4+ th1 lymphocytes and macrophages - work together to contain M. tuberculosis within caseous granuloma, which offers macs inside an opportunity to kill remaining organisms if necrotic area is small enough

Question 23

(1) Dx: prolonged, burning substernal pain and ST segment elevation in leads 1 and V3-V6 (2) Common consequences of this dx

Answer 23

(1) Anterolateral left ventricle infarction (2) Left ventricular failure, Cardiogenic acute pulmonary edema, Pulmonary venous hypertension (congestion), & transudate of plasma into lung interstitium and alveoli

Question 24

Mechanism of Ipratropium on respiratory system

Answer 24

Antimuscarin agents (like ipratropium) only reverse vagally-mediated bronchoconstriction. No bronchodilatory effects.

Question 25

(1) Dx: low levels of circulating B cells, low levels of all immunoglobulins (2) Interpret additional findings: recurrent respiratory infections and persistent giardiasis (2) Cell surface markers of missing cells

Answer 25

(1) X-linked agammaglobulinemia (2) Deficient in all Ig, including IgA. Patients with IgA deficiency predisposed to recurrent respiratory infxs and persistent giardiasis. (3) CD19, 20, 21 are B cell surface markers