1 Practice Questions Gastro-Intestinal

1 – A 28-year-old male complains of nighttime abdominal pain that is relieved by food. He has no significant past medical history and does not take any medications. Upper gastrointestinal endoscopy reveals a deep mucosal defect in the first portion of the duodenum. Which of the following is most likely to provide long-term relief in this patient?

A. Ranitidine B. Sucralfate C. Metoclopramide D. Misoprostol E. Antibiotics F. NSAIDs

2 – A 50-year-old male has had increasingly severe epigastric pain that failed to resolve with over-the-counter antacids. Upper 01 endoscopy shows multiple ulcerations in the stomach, duodenum, and jejunum. Fasting serum gastrin levels are elevated. Imaging studies show a pancreatic tumor with diffuse metastasis. Which of the following is the most effective acid suppressive therapy for this patient?

A. Proton pump inhibitor B. High dose H2 receptor blockers C. Combination of antacids and H2 receptor blockers D. Sucralfate and H2 receptor blocker therapy E. Octreotide

3 – A patient with multiple medical problems is taking theophylline, warfarin, quinidine, and phenytoin. Despite the likelihood of interactions, dosages of each are adjusted carefully so their serum concentrations and effects are acceptable. However, the patient suffers some GI distress and starts taking a drug provided by one of his “well-intentioned” friends. He presents with excessive or toxic effects from all other medications & blood tests reveal that their serum concentrations are high. Which drug was most likely self-prescribed?

A. Cimetidine B. Esomeprazole C. Famotidine D. Nizatidine E. Ranitidine F. Misoprostol

4 – A new medication ‘Drug A1 has the following effects on HCI output by the stomach mucosa:

Drug A is most similar to which of the following substances? A. Atropine B. Cimetidine C. Lansoprazole D. Sucralfate E. Bethanechol

Consumption aka “Consumption”

 TB is an ancient infectious disease caused mainly by Mycobacterium tuberculosis. Known since 3000 – 2000 BC  TB is a disease of respiratory transmission, optimal conditions for transmission include:  overcrowding  poor personal hygiene  poor public hygiene  Malnutrition  Poverty

 Pulmonary tuberculosis is a disease of respiratory transmission, Patients with active TB (bacilli) expel them into the air by:  Coughing,  Sneezing,  Shouting,  Spitting,  or any other way that will expel bacilli into the air

TB Case Rates in U.S.-born vs. Foreign-born Persons, United States, 1993 – 2013* *Updated as of June 11, Cases per 100,000

DC *Updated as of June 11, Percentage of TB Cases Among Foreign-born Persons, United States* DC >50% 25%–49% <25% No cases

TB Case Rates by Race/Ethnicity,* United States, 2003–2013** *All races are non-Hispanic. **Updated as of June 11, Cases per 100,000

 TB- 2 nd to HIV/AIDS as worldwide greatest killer due to a single infectious agent.  In 2013, 9 million people fell ill with TB & 1.5 million died from the disease.  > 95% of TB deaths in low- & middle-income countries & among the top 5 causes of death for women 15 – 44yrs old.  2013, an estimated children became ill with TB & 80, 000 HIV-ve children died of TB.  TB is a leading killer of HIV+ patients causing 1/4 of all HIV-related deaths.

 Are slender, rod-shaped bacteria with lipid-rich cell wall that stain poorly with Gram stain, but once stained, the walls cannot be easily decolorized. “acid-fast”  Mycobacterial infections are intracellular & result slow-growing granulomatous lesions that cause major tissue destruction eg: granuloma necrosis.  The most common mycobacterial infection: TB  Mycobacteria also cause leprosy

A. Microscopy – B. PPD / Mantoux C. Chest X-ray A. Microscopy – auramine-rhodamine stain (fluorescent apple-green ) - very sensitive - if positive, followed by acid fast stain

B. Mantoux Skin Test – ) - Tuberculin (0.1 ml) injected intra-dermally & read 48 to 72 hrs - > 5mm in HIV & recent TB contact - > 10 mm in high risk population - > 15 mm no recent TB contact PPD  - if current infection, past exposure, or BCG vaccinated. PPD  - if no infection or anergic (steroids, malnutrition, immuno-compromise) & in sarcoidosis.

C. X-Ray – What are we looking for ?? - enlarged lymph nodes (  density) - regions of excavation - calcifications

 Reactivation of M. tuberculosis (e.g., after immune compromise or TNF-α inhibitor use)  has a predilection for the apices of the lung, which have the highest PO 2.

 Counselling & Testing for HIV +  CD4+ T-cell count in HIV+ ( how much ? )  AST / ALT testing, AlkP, platelet count, bilirubin  Visual acuity & colour vision testing (EMB)

 Treating tuberculosis as well as other mycobacterial infection poses therapeutic problems.  The organism grows slowly, thus the disease may have to be treated for six moths to two years.

 Seen in pts who have had prior therapy  Those who fail to comply (e.g. rifampin)  Treatment with a single drug  MDR – TB:

 Multi drug therapy with a minimum of two drugs preferably bactericidal.  Direct observed therapy (DOT) to address the problem of noncompliance

 Based on degree of effectiveness and potential side effect.  FIRST-LINE DRUGS: Ethambutol, isoniazid, rifampin, streptomycin and pyrazinamide - (RIPE)  Most effective and less toxic  SECOND-LINE DRUGS: Fluoroquinolones, macrolides, aminosalicylic acid, cycloserine, ethionamide etc.  Second line drugs are less effective and more toxic.

 Considered the first drug of choice for the chemotherapy of TB. discovered in 1945 the hydrazide of isonicotonic acid, therefore called INH  Is a synthetic analog of pyridoxine (vit B6)  Only drug that can be used solo with TB

 INH is a prodrug that is activated by a mycobacterial catalase-peroxidase (KatG) which inhibits the synthesis of mycolic acid which is part of the bacteria cell wall structure.  is bacteriostatic for resting / slow growing bacilli,  bactericidal for growing/dividing bacilli.

 Organism eventually develops resistance.  The mechanism of resistance is related to mutation or deletion of KatG leading to inability to activate the prodrug.

 Absorption: INH rapidly absorbed either oral or parenteral route.  Liver metabolized via acetylation resulting in the production of inactive but toxic metabolite called monoacetylhydrazine that is excreted in the urine.  This acetylation is genetically regulated resulting in two types of acetylators: fast and slow acetylators.  Fast-acetylators: have a short half-life(~1 hr)  Slow-acetylators: have a long half-life (~3hrs)

 Induced Hepatitis (2% of Population) due to the buildup of toxic metabolic products of acetylisoniazid --> acetylhydrazine. Common in fast acetylators.  Hepatic reactions to Isoniazid ↑es with age.  Peripheral neuritis : common adverse effect due to Vit B6 def. & thus can be corrected by supplementation with B6  Others: sideroblastic anemia, SLE(slow acetylators)  INH – Injures Neurons & Hepatocytes

 INH interferes with metabolism of phenytoin, therefore increasing the activity of phenytoin and potentiating the adverse effect of phenytoin.  Blocks P450  Prolongs the effect of P450 metabolite dependent drugs (eg: warfarin..etc )

Mechanism of Action  Rifampin inhibits DNA dependent RNA polymerase of the bacilli thereby affecting transcription.  Rifampin’s 4 R’s: I. RNA polymerase inhibitor II. Ramps up microsomal cytochrome P-450 III. Red/orange body fluids (SE) IV. Rapid resistance if used alone V. Rifampin ramps up cytochrome P-450, but rifabutin does no

 Due to alteration of the target enzyme (DNA dependent RNA polymerase) of the drug

 Does not cause many side effects in any great frequency.  G.I. upset: Anorexia, Nausea, Vomiting, Mild abdominal pain,  Hepatitis  Red-orange discoloration of body fluid ( sweat, saliva, stool, urine etc…)

 Is an inducer of cytP450, so can decrease the half life of certain drugs that require P450 for their metabolism e.g., warfarin, sulfonyurea, oral contraceptives etc.

 Treatment of leprosy  Prophylaxis for individuals exposed to meningitis caused by meningococci or H. influenza

 Capreomycin  Viomycin  Kanamycin  STREPTOMYCIN

 The first drug used clinically to treat TB ; was the only drug available at that time.  is an aminoglycoside antibiotic  acts by protein synthesis inhibitor and decreases the fidelity mRNA & garbles the message, leading to nonsense proteins.  Streptomycin only binds to the 30s subunit

 These drugs are: Nephrotoxic - will cause Proteinuria, Hematuria, Nitrogen metabolism, and Electrolyte disturbances  Ototoxic: involving both hearing and balance.  Hearing is irreversible but balance is reversible once drug is stopped.

 Bactericidal antitubercular drug.  mechanism of action is not understood. Used in combination with isoniazid and rifampin.  Must be enzymatically hydrolyzed to pyrazinoic acid(active form) by pyrazinamidase  Active against tubercle bacilli in lysosomes and in macrophages.  Adverse effect: gout (DOC ??)

 MOA: Inhibition of arabinogalactan, a component of the bacteria cell wall  Adverse effect: inhibits urate excretion – GOUT  OPTIC NEURITIS - vision changes (e.g., blurring, inability to distinguish between red-green color blindness)

.  Aminosalicylic acid  Capreomycin  Cycloserine  Ethionamide  Fluoroquinolones  macrolides

 a structural analog of PABA (p-aminobenzoic acid) is bacteriostatic inhibits de novo folate synthesis

 GI irritation due to the amount of drug given (high doses) nausea, vomiting, bleeding, occurs in 30-40% of the patients.  Hypersensitivity reactions Rash, Fever  hepatotoxicity  All will disappear when the drug is stopped 

 Structural analog of isoniazid but not believed to act by the same mechanism  Oral administration  Widely distributed throughout the body  Adverse effects- hepatotoxicity, optic neuritis,  Peripheral neuropathy.

 Also called Hansen disease  Caused by Mycobacterium leprae, (acid-fast bacillus); likes cool temperatures (infects skin & superficial nerves —“glove & stocking” loss of sensation)  Not grown in culture  Treated with a triple drug regimen of dapsone, clofazimine and rifampin for 6 to 24 months to decrease prevalence

 Structurally related to sulfonamides  It is bacteriostatic  MOA: acts as a PABA antagonist to inhibit folate synthesis  Undergoes hepatic acetylation  Excreted through urine  Adverse effects: hemolysis in pts with G6PD def, metHb, peripheral neuropathy and erythema nodosum leprosum

 X-linked recessive disorder;  most common human enzyme deficiency; more prevalent among African descent  ↓↓ NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents  Microscopy – Heinz Bodies & Bite Cells

 A serious and severe skin complication of leprosy which is due to inflammation of fat cells in the face, arms and shins of pts treated with dapsone  Treatment: corticosteroid or thalidomide

 MOA: Binds to DNA and prevents it from serving as a template for future DNA replication.  Also has redox properties → production of oxygen free radicals.  Is bactericidal  Adverse effect: red-brown discoloration of the skin, eosinophilic enteritis  No erythema nodosum leprosum.

Caused byAdverse ReactionSigns and Symptoms Any drugAllergySkin rash EthambutolEye damageBlurred or changed vision Changed color vision Isoniazid, Pyrazinamide, or Rifampin HepatitisAbdominal pain Abnormal liver function test results Fatigue Lack of appetite Nausea Vomiting Yellowish skin or eyes Dark urine Common Adverse Reactions to Drug Treatment (1)

Common Adverse Reactions to Drug Treatment (2) Caused byAdverse ReactionSigns and Symptoms IsoniazidPeripheral neuropathy Tingling sensation in hands and feet PyrazinamideGastrointestinal intolerance Arthralgia Arthritis Upset stomach, vomiting, lack of appetite Joint aches Gout (rare) StreptomycinEar damage Kidney damage Balance problems Hearing loss Ringing in the ears Abnormal kidney function test results

Common Adverse Reactions to Drug Treatment (3) Caused byAdverse ReactionSigns and Symptoms Rifamycins Rifabutin Rifapentine Rifampin Thrombocytopenia Gastrointestinal intolerance Drug interactions Easy bruising Slow blood clotting Upset stomach Interferes with certain medications, such as birth control pills, birth control implants, and methadone treatment