Pharmacology Flashcards PDF

Lange® Pharmacology Flashcards Fourth Edition Series Editors Suzanne J. Baron, MD, MSc St. Luke’s Mid America Heart Institute Kansas City, Missouri Christoph I. Lee, MD, MS University of Washington School of Medicine Seattle, Washington Student Editors Tsion M. Aberra Yale University School of Me...

Lange® Pharmacology Flashcards Fourth Edition Series Editors Suzanne J. Baron, MD, MSc St. Luke’s Mid America Heart Institute Kansas City, Missouri Christoph I. Lee, MD, MS University of Washington School of Medicine Seattle, Washington Student Editors Tsion M. Aberra Yale University School of Medicine, New Haven, Connecticut Erik A. Levinsohn Yale University School of Medicine, New Haven, Connecticut New York / Chicago / San Francisco / Athens / London / Madrid Mexico City / Milan / New Delhi / Singapore / Sydney / Toronto  Notice Medicine is an ever-changing science. As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required. The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work. Readers are encouraged to confirm the information contained herein with other sources. For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration. This recommendation is of particular importance in connection with new or infrequently used drugs. Lange® Pharmacology Flashcards, Fourth Edition Copyright © 2018, 2013, 2009, 2005 by McGraw-Hill Education. All rights reserved. Printed in China. Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a data base or retrieval system, without the prior written permission of the publisher. 1 2 3 4 5 6 7 8 9 DSS 22 21 20 19 18 17 ISBN 978-1-259-83724-1 MHID 1-259-83724-6 ISSN 1555-9882 e-ISBN 978-1-259-83725-8 e-MHID 1-259-83725-4 This book was set in Times Roman by MPS Limited. The editors were Michael Weitz and Peter J. Boyle The production supervisor was Richard Ruzycka. Project management provided by Poonam Bisht, MPS Limited. The designer was Marsha Cohen. R. R. Donnelley Shenzhen was printer and binder. McGraw-Hill books are available at special quantity discounts to use as premiums and sales promotions, or for use in corporate training programs. To contact a representative, please e-mail us at bulksales@mcgraw- hill.com  Contents Preface Acknowledgments About the Authors Abbreviations 1 Anti-Bacterial Agents 2 Adrenergic Agents 3 Cholinergic Agents 4 Central Nervous System Agents 5 Cardiovascular Agents 6 Hematologic Agents 7 Endocrine and Metabolic Agents 8 Gastrointestinal Agents 9 Anti-Neoplastic Agents 10 Anti-Inflammatory Agents 11 General Pharmacology Principles and Miscellaneous Agents Bibliography Index  Preface When we began to review the pharmacology material covered in the USMLE Step 1 at the end of our second year at Yale Medical School, we had trouble finding one review source that covered this subject at just the appropriate level. Although we had taken introductory pharmacology during medical school, we found ourselves covering new material as well as reviewing old material from a different angle. Flipping through the highly rated pharmacology review sources, we realized that there was no gold standard review source for this high-yield topic that makes up nearly 20% of USMLE Step 1 questions. Lange Pharmacology Flashcards are the result of our struggles in studying these topics for Step 1 with the particular slant that the boards demand. These cards offer the most complete, concise, and high-yield information for the major drugs tested on Step 1 and in medical school basic science courses. With this fourth edition, we are confident that the content covered in these cards includes the most current and board relevant information that cannot be found in any other single clinical pharmacology review text. To ensure that these cards are high yield, we commissioned two current Yale Medical School student editors to help write this revised edition. We are pleased to present this information in a format modeled after Lange Flashcards: Pathology, our first publication in this series. Each card provides a structured presentation of a specific drug or drug class, and allows students to easily compare and contrast drugs. The introductory cards in each chapter describe the basic principles of that particular drug class that are board relevant and high yield. Each drug-specific card contains a clinical vignette on one side and important characteristics on the reverse side. These characteristics are organized into sections entitled mechanism of action, clinical uses, and side effects. Unlike other review cards on the market, only the information you need to know for the boards are on these cards. If certain drug-drug interactions or routes of administration are high yield, this information is included. Moreover, the most salient features of each drug are highlighted in bold for ease of rapid review. We would suggest using these cards as an adjunct to your pharmacology course in medical school. Being familiar with these cards early on will be very helpful during your Step 1 review. We also encourage you to jot down your own notes in the margins and to make these cards your personal pharmacology review for the boards. We are confident that the fourth edition of Lange Pharmacology Flashcards will be one of the most powerful tools to help prepare you for the boards and will serve as a resource that will bridge your basic science knowledge with the clinical aspects of disease. We wish you the best of luck on Step 1, and welcome your comments on how to improve this study tool in the next edition. Suzanne J. Baron [email protected] Christoph I. Lee [email protected]  Acknowledgments We would like to thank the many editors at McGraw-Hill for all of their support and hard work on this project as well as their constant encouragement of the Lange Flashcards series. A special thanks to Erik Levinsohn and Tsion Aberra for serving as student editors for this revised edition. We also acknowledge the many basic and clinical science teaching faculty of the Yale University School of Medicine who provided much of the foundation for the relevant content in these cards. To our family and friends, we thank you for your continuing support and love that have made this process even more meaningful. Special thanks to John and Jay Lee, Fran and Joe Baron, Paul B. Brennan III, Monique Mogensen, Bettina Lee, and Elena Lee.  About the Authors Suzanne J. Baron, MD, MSc, earned an AB magna cum laude in psychology and biology from Harvard University, her MD from Yale University School of Medicine, and her MSc from Harvard School of Public Health. She completed her internal medicine residency, cardiology fellowship, and interventional cardiology fellowship at Massachusetts General Hospital. She is currently practicing at St. Luke’s Mid America Heart Institute in Kansas City, Missouri, as an interventional cardiologist with an interest in structural heart disease. Dr. Baron is also involved in outcomes research aimed at evaluating the effects of new cardiac devices on quality of life and health economics. Her research has been published in several peer-reviewed journals, including JAMA and JACC. Christoph I. Lee, MD, MS, earned an AB cum laude in English from Princeton University, an MD cum laude from Yale University, and an MS in health policy and management research from UCLA. He completed his diagnostic radiology residency at Stanford University, a breast imaging fellowship at UCLA, and a national health policy fellowship as a Robert Wood Johnson Foundation Clinical Scholar. He is currently an associate professor of radiology and health services at the University of Washington. Dr. Lee is the author of five medical books spanning the basic sciences, evidence-based practice, and medical imaging. He has obtained extramural research funding from the National Institutes of Health, American Cancer Society, and Agency for Healthcare Research and Quality for imaging-related outcomes research, and has published more than 60 peer- reviewed journal articles.  Abbreviations 5-ASA: 5-Aminosalicylic acid 5-FU: 5-Fluorouracil 6-MP: 6-Mercaptopurine AC: adenylyl cyclase ACE: angiotensin-converting enzyme ACh: acetylcholine ACLS: advanced cardiac life support ADH: anti-diuretic hormone ALL: acute lymphoblastic leukemia AML: acute myelogenous leukemia AP: action potential ARB: angiotensin receptor blocker AV: atrioventricular BAL: British Antilewisite (dimercaprol) BNP: B-type natriuretic peptide BUN: blood urea nitrogen Ca2+: calcium ion cAMP: cyclic AMP CHF: congestive heart failure Cl−: chloride ion CML: chronic myelogenous leukemia CMV: cytomegalovirus CNS: central nervous system CO: cardiac output COPD: chronic obstructive pulmonary disease COX: cyclooxygenase CSF: cerebrospinal fluid CV: cardiovascular DAG: diacylglycerol DAP: dapsone DI: diabetes insipidus DKA: diabetic ketoacidosis DPP-4: dipeptidyl peptidase-4 DVT: deep vein thrombosis EBV: Epstein-Barr virus ECG: electrocardiogram ED: emergency department EDTA: ethylenediaminetetraacetic acid Epi: epinephrine ERP: effective refractory period ETH: ethambutol FH4: tetrahydrofolic acid FSH: follicle-stimulating hormone G6PD: glucose-6-phosphate dehydrogenase GABA: γ-aminobutyric acid GERD: gastroesophageal reflux disease GI: gastrointestinal GIST: gastrointestinal stromal tumors GLP-1: glucagon-like peptide-1 GnRH: gonadotropin-releasing hormone GU: genitourinary hBNP: human B-type natriuretic peptide HCO−3 : bicarbonate ion HDL: high-density lipoprotein HGPRT: hypoxanthine-guanine phosphoribosyl transferase HIT: heparin-induced thrombocytopenia HSV: herpes simplex virus HTN: hypertension IL: interleukin IMP: inositol monophosphate IP3: inositol triphosphate ITP: idiopathic thrombocytopenic purpura IV: intravenous K+: potassium ion LDL: low-density lipoprotein LFT: liver function test LH: luteinizing hormone LTB: leukotriene B LTC: leukotriene C LTD: leukotriene D M3: muscarinic MAC: minimal alveolar concentration MAO: monoamine oxidase MAOI: monoamine oxidase inhibitor MCP: metacarpophalangeal MCT: metacarpotarsal mRNA: messenger ribonucleic acid MRSA: methicillin-resistant Staphylococcus aureus Na+: sodium ion Na2HCO−3 : sodium bicarbonate NE: norepinephrine NMDA: N-methyl D-aspartate NNRTIs: non-nucleoside reverse transcriptase inhibitors NO: nitric oxide NRTI: nucleoside reverse transcriptase inhibitor NSAID: non-steroidal anti-inflammatory drug OCD: obsessive compulsive disorder PABA: para-aminobenzoic acid PBPs: penicillin-binding proteins PCP: Pneumocystis carinii pneumonia PFT: pulmonary function test PGE2: prostaglandin E2 PGI2: prostacyclin PIP: proximal interphalangeal PLC: phospholipase C PPAR: peroxisome proliferators-activated receptors PPD: purified protein derivative PSA: prostate-specific antigen PSVT: paroxysmal supraventricular tachycardia PT: prothrombin time PTT: partial thromboplastin time PYR: pyrazinamide RA: rheumatoid arthritis RNA: ribonucleic acid RPR: rapid plasma regain rRNA: ribosomal RNA SA: sinoatrial SIADH: syndrome of inappropriate ADH secretion SLE: systemic lupus erythematosus SSRI: selective serotonin reuptake inhibitor STD: sexually transmitted disease SVT: supraventricular tachycardia t1/2: half-life TFT: thyroid function test Thio-IMP: 6-thioinosinic acid TMP-SMX: trimethoprim-sulfamethoxazole TNF: tumor necrosis factor tRNA: transfer ribonucleic acid TSH: thyroid-stimulating hormone TXA2: thromboxane A2 URI: upper respiratory infection USMLE: United States Medical Licensing Examination UTI: urinary tract infection Vd: volume of distribution VB: vinblastine VC: vincristine VDRL: venereal disease research laboratory VIP: vasoactive intestinal peptide VLDL: very low-density lipoprotein VRE: vancomycin-resistant enterococcus VZV: varicella zoster virus WBC: white blood cell WPW: Wolff-Parkinson-White syndrome  1 CLASSES OF CEPHALOSPORINS AND THEIR ANTI-BACTERIAL ACTIVITY Generation Drug Names Anti-Bacterial Activity 1st Cefadroxil, cefazolin, cephalexin, Gram-positive cocci (pneumococci, cephalothin, cephapirin, cephradine streptococci, staphylococci), Proteus mirabilis, Escherichia coli, and Klebsiella pneumoniae 2nd Cefaclor, cefamandole, cefonicid, Gram-positive cocci, Proteus, E.  cefuroxime, cefprozil, loracarbef, coli, Klebsiella species, Enterobacter, ceforanide, cefoxitin, cefmetazole, Serratia, some anaerobes, and cefotetan Haemophilus influenzae 3rd Cefoperazone, cefotaxime, ceftazidime, Gram-negative bacteria (Serratia, ceftizoxime, ceftriaxone, cefixime, Pseudomonas, Enterobacter, H. cefpodoxime proxetil, cefditoren pivoxil, influenzae, Neisseria) ceftibuten, moxalactam 4th Cefepime Gram-negative bacteria (Serratia, Pseudomonas, Enterobacter, H. influenzae, Neisseria) Gram-positive bacteria (Staphylococcus aureus, Streptococcus pneumoniae) 5th Ceftaroline Gram-positive bacteria (Streptococcus, S. aureus [MSSA and MRSA]) Gram-negative bacteria (E. coli, Klebsiella, H. Influenzae) PROTEIN SYNTHESIS INHIBITORS Anti-Bacterial Type of Mechanism Class Inhibitor Aminoglycosides 30S Inhibits formation of initiation complex, causing the misreading of mRNA Tetracyclines 30S Prevents attachment of aminoacyl-tRNA to acceptor site Chloramphenicol 50S Inhibits peptidyl transferase (the enzyme responsible for incorporating new amino acid into growing peptide strand) Macrolides 50S Blocks aminoacyl-tRNA complex translocation step Clindamycin 50S Blocks initiation complex formation and inhibits aminoacyl-tRNA complex translocation step Linezolid 50S Blocks formation of initiation complex The protein synthesis inhibitors act by disrupting the bacterial 70S ribosomal mRNA complex that is responsible for bacterial protein synthesis. Since eukaryotes utilize a different ribosomal complex (80S), these drugs do not interfere with human cellular protein synthesis. The bacterial 70S ribosomal complex is composed of two subunits (30S and 50S), and the protein synthesis inhibitors act at one of these subunits. SULFONAMIDES AND TRIMETHOPRIM Sulfonamides are structural analogues of PABA, which is a precursor for dihydrofolic acid. High levels of PABA or a PABA analogue act to competitively inhibit dihydropteroate synthase, an enzyme needed for folic acid synthesis. Trimethoprim inhibits bacterial dihydrofolic acid reductase (DHFR), which is the subsequent enzyme needed for folic acid synthesis. Inhibition of folic acid synthesis results in the disruption of DNA synthesis and thus the inhibition of bacterial growth. Notably, trimethoprim is functionally analogous to other drugs (e.g., methotrexate, pyrimethamine) that inhibit the same synthetic reaction in other species. Methotrexate is an anti-neoplastic drug that selectively inhibits human DHFR, and pyrimethamine is an anti-parasitic agent that selectively inhibits DHFR in protozoa.  PRINCIPLES OF ANTI-VIRAL AGENTS Viruses are intracellular parasites that rely on the synthetic processes of the host cell in order to replicate. In order to act against viruses, anti-viral agents must either block the passages of viruses into or out of the cell or the anti-viral agents must be able to act inside the host cell to inhibit viral replication. Anti-viral agents can potentially target any of the steps of viral replication, which are the following: Entrance into host cells Uncoating of viral nucleic acid Synthesis of nucleic acid polymerases or nucleic acids (DNA or RNA) Synthesis or processing of viral proteins Assembly of viral particles Release of virus from the cell SITES OF ACTION OF SELECTED ANTI-VIRAL AGENTS Anti-Viral Agent Classes Site of Drug Action Guanosine analogues Blocks DNA synthesis Viral DNA polymerase Blocks DNA synthesis inhibitors Reverse transcriptase Block synthesis of DNA from RNA in CD4+ cell inhibitors and non-reverse transcriptase inhibitors Protease inhibitors Block assembly of HIV virions Integrase inhibitors Block HIV genome integration into host cell chromosomes Ribavirin Blocks synthesis of guanine Neuraminidase inhibitors Block release of viral particles from the host cell PRINCIPLES OF ANTI-FUNGAL AGENTS FUNGAL STRUCTURE Many anti-fungal agents take advantage of the difference in lipid composition between fungal and mammalian cell membranes. While cholesterol is found in most bacterial and human cell membranes, fungi have a sterol known as ergosterol that is only found in fungal cell membranes. Thus, most anti-fungal agents act by selectively targeting ergosterol synthesis and function. MECHANISMS OF ANTI-FUNGAL AGENTS Anti-Fungal Agent Mechanism of Action Amphotericin B, Nystatin Binds ergosterol and causes the formation of holes in the fungal cell membrane Flucytosine Converted to nucleotide analogues by fungal enzymes and then acts to inhibit DNA and RNA synthesis Azoles (e.g., fluconazole) Reduce ergosterol synthesis by inhibiting fungal cytochrome P- 450 enzymes Echinocandins (e.g., Disrupts fungal cell wall synthesis micafungin)  CLINICAL USES OF ANTI-PARASITIC AGENTS Drug Clinical Uses Pentamidine PCP pneumonia prophylaxis; alternate treatment of Trypanosoma brucei and Leishmaniasis Nifurtimox Chagas disease (Trypanosoma cruzi) Suramin T. brucei infection before CNS involvement Melarsoprol T. brucei infection after CNS involvement Sodium stibogluconate Leishmaniasis Ivermectin Onchocerciasis (river blindness) Mebendazole/albendazole/thiabendazole Roundworm (Ascaris), whipworm (Trichuris), hookworm (Necator, Ancylostoma), and pinworm (Enterobius) Pyrantel pamoate Roundworm (Ascaris), hookworm (Necator, Ancylostoma), and pinworm (Enterobius) Praziquantel Fluke (e.g., schistosomes, Clonorchis, Paragonimus), agent of choice for cysticercosis Pyrimethamine Toxoplasma, Plasmodium falciparum, and Plasmodium vivax malaria, and Isospora A 22-year-old man presents to your clinic complaining of a new lesion on his penis for 1 week. On physical examination, you find a single, painless ulceration with a firm border. Upon further questioning, you discover that he has been having unprotected sexual contact with several individuals over the last several months. Physical examination is also remarkable for enlarged lymph nodes in the groin, axilla, and supraclavicular regions. Suspecting a specific sexually transmitted disease, you send him to the laboratory for RPR and VDRL tests. When he returns from the laboratory, you empirically treat him with a shot of a common antibiotic and you warn him that a rare side effect of this medication is the development of a hemolytic anemia. Penicillin Similar Penicillin G (IV); penicillin V (oral). Drugs Mechanism Formation of bacterial peptidoglycan cell walls are mediated via of Action PBPs. Penicillin binds PBPs, thereby blocking peptidoglycan cross-linking, which leads to the inhibition of bacterial cell wall synthesis. Clinical Treatment of infections caused by gram-positive cocci Uses (streptococci), gram-negative cocci (Neisseria), and spirochetes (e.g., Treponema pallidum). Side Allergic reaction; drug-induced Coombs positive hemolytic Effects anemia. Other Penicillin and the other β-lactam drugs (ampicillin, methicillin, piperacillin, aztreonam, imipenem) have a structure that is characterized by a β-lactam ring. If the β-lactam ring is cleaved by bacterial enzymes (e.g., β-lactamases), the drug becomes inactive. Certain β-lactam drugs (e.g., penicillin, ampicillin, piperacillin) are more susceptible to bacterial β-lactamase cleavage than others. A 54-year-old man presents to your clinic complaining of a 3-week history of severe sinus congestion. He describes his sinus discharge as green and purulent and he also reports fevers to 100.4°F. He has been trying symptomatic therapy with nasal decongestants for the last 2 weeks with no improvement in his symptoms. You decide to prescribe him an antibiotic to cover the likely pathogens (i.e., Pneumococcus, H. influenzae, Moraxella) that may be causing his symptoms. Ampicillin  Similar Other aminopenicillins include Amoxicillin. Drugs Mechanism Formation of bacterial peptidoglycan cell walls are mediated via of Action PBPs. Ampicillin binds PBPs, thereby blocking peptidoglycan cross-linking, which leads to the inhibition of bacterial cell wall synthesis. Clinical Ampicillin has an extended spectrum of coverage as compared Uses to penicillin. It is used to treat infections caused by gram- negative rods (H. influenzae, E. coli, P. mirabilis, Salmonella), as well as infections caused by gram-positive cocci (Enterococci), gram-positive rods (Listeria monocytogenes), and gram-negative cocci. Amoxicillin is also indicated for treatment of H. Pylori as part of the triple-therapy regimen. Side Allergic reaction; non-allergenic skin rash; diarrhea. Effects Other Ampicillin and the other β-lactam drugs (penicillin, methicillin, piperacillin, aztreonam, imipenem) have a structure that is characterized by a β-lactam ring. If the β-lactam ring is cleaved by bacterial enzymes (e.g., β-lactamases), the drug becomes inactive. Certain β-lactam drugs (e.g., penicillin, ampicillin, piperacillin) are more susceptible to bacterial β-lactamase cleavage than others. Amoxicillin can be given in the oral form and thus is used more often for outpatient treatment. Clavulanic acid and sulbactam act to inactivate bacterial β- lactamases. They are often added to amoxicillin or ampicillin to broaden the spectrum of coverage against gram-negative organisms. A 54-year-old IV drug abuser is admitted to the hospital with suspected osteomyelitis in his lumbar spine. Blood cultures are taken in the emergency room and broad-spectrum antibiotics are started. After 2 days, his blood culture demonstrates growth of pan-sensitive S. aureus. In order to prevent overuse of stronger antibiotics that should be reserved for multidrug-resistant cases, you discontinue the current broad regimen of medications and you begin the patient on a more specific IV antibiotic. Methicillin Similar Nafcillin; oxacillin; dicloxacillin. Drugs Mechanism Formation of bacterial peptidoglycan cell walls are mediated via of Action PBPs. Methicillin binds PBPs, thereby blocking peptidoglycan cross-linking, which leads to the inhibition of bacterial cell wall synthesis. Clinical Methicillin is used to treat Staphylococcus infections including Uses S. aureus. It is inactive against enterococci, anaerobic bacteria, and gram-negative organisms. Side Allergic reaction; interstitial nephritis (methicillin); Effects neutropenia (nafcillin); hepatitis (oxacillin). Other Methicillin and the other β-lactam drugs (penicillin, ampicillin, piperacillin, aztreonam, imipenem) have a structure that is characterized by a β-lactam ring. If the β-lactam ring is cleaved by bacterial enzymes (e.g., β-lactamases), the drug becomes inactive. Methicillin is β-lactamase resistant due to its bulkier structure, which acts to sterically hinder access of the β-lactamase to the β-lactam ring. Methicillin-resistant S. aureus species have arisen, most often due to bacterial alteration of target PBPs. A 43-year-old burn victim is readmitted to the hospital for possible infection at his burn site. He had suffered a third-degree burn 2 months earlier and had just been released from the hospital after a failed skin graft procedure. The patient has a fever of 102°F, a blood pressure of 90/50 mm Hg, and his wound is oozing purulent discharge. You send a sample of the discharge for culture and you begin broad-spectrum antibiotic therapy. The culture grows out pan-sensitive Pseudomonas. You decide to change the patient’s antibiotic regimen to a medication that is commonly used to treat this aggressive organism. Piperacillin Similar Ticarcillin; carbenicillin. Drugs Mechanism Formation of bacterial peptidoglycan cell walls are mediated via of Action PBPs. Piperacillin binds PBPs, thereby blocking peptidoglycan cross-linking, which leads to the inhibition of bacterial cell wall synthesis. Clinical Piperacillin is used to treat infections caused by Pseudomonas Uses and gram-negative rods (e.g., Klebsiella). Side Allergic reactions. Effects Other Piperacillin and the other β-lactam drugs (penicillin, methicillin, ampicillin, aztreonam, imipenem) have a structure that is characterized by a β-lactam ring. If the β-lactam ring is cleaved by bacterial enzymes (e.g., β-lactamases), the drug becomes inactive. Certain β-lactam drugs (e.g., penicillin, ampicillin, piperacillin) are more susceptible to bacterial β-lactamase cleavage than others. Tazobactam acts to inactivate bacterial β-lactamases. It is often added to piperacillin to broaden the spectrum of coverage against gram-negative organisms and S. aureus infections. A 45-year-old white woman presents to the emergency room with increased urinary urgency and dysuria. She reports that this has occurred several times over the last year despite antibiotic treatment. Upon review of her medical records, you notice that she has been treated with both first- and second-line pharmacologic agents for her recurrent urinary tract infections, which have been caused by drug-resistant strains of Klebsiella and Serratia in the past. Her medical history is also notable for an allergy to penicillins and cephalosporins. On physical examination, she is febrile to 101°F and has a blood pressure of 90/50 mm Hg. You draw urine and blood cultures and you decide to put the patient on a broad-spectrum β-lactam drug that is both effective against gram- negative rod infections and can be used in penicillin-allergic patients. Aztreonam Similar Belongs to the monobactam class of anti-bacterial agents. Drugs Mechanism Formation of bacterial peptidoglycan cell walls are mediated via of Action PBPs. Aztreonam is a drug with a monocyclic β-lactam ring that acts to bind PBPs, thereby blocking peptidoglycan cross- linking, which leads to the inhibition of bacterial cell wall synthesis. Clinical Aztreonam is used to treat infections caused by gram-negative Uses rods (Klebsiella, Pseudomonas, Serratia). It has no activity against gram-positive bugs or anaerobes. Side GI upset; skin rash; elevated LFTs; not a cross-allergen of Effects penicillin. Other Aztreonam and the other β-lactam drugs (penicillin, methicillin, ampicillin, piperacillin, imipenem) have a structure that is characterized by a β-lactam ring. If the β-lactam ring is cleaved by bacterial enzymes (e.g., β-lactamases), the drug becomes inactive. Like methicillin, aztreonam is relatively resistant to the actions of β-lactamases. Aztreonam can be used to treat severe gram-negative infections in patients allergic to penicillin or in patients who are renally insufficient and thus cannot tolerate aminoglycosides. A 72-year-old man presents to the emergency room complaining of right upper quadrant abdominal pain. On examination, he has significant right upper quadrant tenderness as well as fever up to 102°F and a blood pressure of 88/50 mm Hg. Blood cultures reveal Klebsiella. You decide to start the patient on a combination of two medications—one drug to treat the infection and the second drug to keep the first medication potent in the renal tubules. Imipenem Similar Other carbapenems include meropenem, ertapenem, and Drugs doripenem. Mechanism Formation of bacterial peptidoglycan cell walls are mediated via of Action PBPs. Imipenem binds PBPs, thereby blocking peptidoglycan cross-linking, which leads to the inhibition of bacterial cell wall synthesis. Clinical Imipenem is a broad-spectrum antibiotic, which can be used to Uses treat infections caused by Enterobacter, gram-positive cocci, enterococci, gram-negative rods (especially drug-resistant Klebsiella), anaerobes, and Pseudomonas species. Imipenem cannot treat infections caused by VRE or MRSA. Side GI upset; allergic reaction (rash); seizures at high serum levels, Effects especially in renally insufficient patients. Other Imipenem and the other β-lactam drugs (penicillin, methicillin, ampicillin, piperacillin, aztreonam) have a structure that is characterized by a β-lactam ring. If the β-lactam ring is cleaved by bacterial enzymes (e.g., β-lactamases), the drug becomes inactive. Like aztreonam, imipenem is relatively resistant to the actions of β-lactamases. Cilastatin inhibits renal dihydropeptidase I, which is an enzyme that inactivates imipenem in the renal tubules. Thus, imipenem is usually administered with cilastatin in order to increase imipenem’s duration of action. A 28-year-old Caucasian man presents to the emergency room complaining of flushing, nausea, vomiting, and headache. He reports that he was feeling fine until he drank a beer 1 hour ago at a local bar. He also tells you that he has been taking an antibiotic for the last 5 days for the treatment of simple cellulitis of the leg. Physical examination is unremarkable and his symptoms have improved while he was waiting in the emergency room. You suspect that he has had a disulfiram-like reaction due to the combination of his antibiotic and his alcohol intake and you instruct the patient not to ingest alcohol until his antibiotic regimen has been completed. Cephalosporins Similar Please see card 1 for a list of the different cephalosporins. Drugs Mechanism Formation of bacterial peptidoglycan cell walls are mediated via of Action PBPs. The cephalosporins bind PBPs, thereby blocking peptidoglycan cross-linking, which leads to the inhibition of bacterial cell wall synthesis. Clinical 1st generation: Effective against gram-positive cocci, P. Uses mirabilis, E. coli, and K. pneumoniae; usually used for surgical prophylaxis or treatment of cellulitis. 2nd generation: Effective against gram-positive cocci, Proteus, E. coli, Klebsiella, Serratia, some anaerobes, and H. influenzae; used to treat sinusitis, otitis, and pneumonia. 3rd generation: Effective against gram-negative bacteria (Serratia, Pseudomonas, Enterobacter, H. influenzae, Neisseria); used to treat serious gram-negative infections. 4th generation: Effective against gram-negative bacteria (Serratia, Pseudomonas, Enterobacter, H. influenzae, Neisseria), as well as against some gram-positive bacteria (S. aureus, S. pneumoniae); used to treat serious gram- negative infections (e.g., meningitis, Pseudomonas, and Enterobacter infections). 5th generation: Effective against gram-positive bacteria (including MRSA) as well as gram-negative bacteria (though notably not pseudomonas).  Side Hypersensitivity reaction (10% of patients with penicillin Effects allergy will have a cephalosporin allergy); disulfiram-like reaction with ethanol (cefamandole, cefotetan, and cefoperazone); nephrotoxicity. Other The cephalosporins have a structure that is characterized by a β- lactam ring. While other β-lactam drugs (e.g., penicillin) are inactivated by the cleavage of the β-lactam ring by bacterial β- lactamases, the cephalosporins are relatively resistant to β- lactamases. A 74-year-old man with a history of mitral regurgitation presents to the emergency room with a temperature of 102.5°F over the last 3 days. Physical examination is significant for a loud systolic murmur at the apex as well as the presence of splinter hemorrhages on several nail beds. Blood cultures are drawn and he is started on broad-spectrum antibiotics. Given his antibiotic regimen, he will need to be carefully monitored for renal failure. Gentamicin Similar Other aminoglycosides include neomycin, amikacin, Drugs tobramycin, and streptomycin. Mechanism Gentamicin is a protein synthesis inhibitor. It binds the 30S of Action bacterial ribosomal subunit and acts to inhibit the formation of the initiation complex, causes mRNA misreading leading to non-functional proteins. It also induces the dissolution of polyribosomes during protein synthesis. Clinical The aminoglycosides are used to treat severe infections with Uses gram-negative rods (e.g., sepsis, chronic urinary tract infections, endocarditis [when given in conjunction with vancomycin], pneumonia, Pseudomonas infections). Neomycin is used for preparation for bowel surgery (kills bowel flora, thereby reducing chances of infection after surgery). Streptomycin is used as a second-line agent to treat tuberculosis  as well as to treat tularemia. Side Nephrotoxicity (acute tubular necrosis, especially with Effects cephalosporin use); neuromuscular blockade; ototoxicity (especially with loop diuretic use); teratogen. Other Aminoglycosides require oxygen for uptake into the bacterial cell. Thus, they are only active against aerobes. A 24-year-old graduate female student presents to the clinic complaining of a severe toothache in her left upper palate. She reports feeling slightly feverish and has noticed increased swelling where her wisdom tooth is erupting. Plain films show that there is no wisdom tooth impaction, but that the soft tissue swelling is consistent with a dental abscess. You prescribe her an antibiotic that will be effective against mouth flora (anaerobes and gram-positive organisms) to treat her infection. Clindamycin Similar Drugs Mechanism Clindamycin is a protein synthesis inhibitor. It binds the 50S of Action bacterial ribosomal subunit and acts to inhibit the formation of the initiation complex. It also inhibits the translocation of the aminoacyl peptide during protein synthesis. Clinical Clindamycin is effective against some anaerobes (e.g., Uses Bacteroides fragilis, Clostridium perfringens) as well as against some gram-positive cocci (streptococci, staphylococci). It is used to treat severe anaerobic infections above the diaphragm (e.g., aspiration pneumonia, lung abscess) and for endocarditis prophylaxis before dental procedures in patients with prosthetic heart valves. Side Pseudomembranous colitis (Clostridium difficile overgrowth), Effects nausea; diarrhea; skin rashes; impaired liver function.  Other Chloramphenicol is a protein synthesis inhibitor that binds the 50S ribosomal subunit and prevents chain elongation by peptidyl transferase. It has broad-spectrum coverage for both gram- positive and gram-negative bacteria, and is most commonly used to treat meningitis and Rocky Mountain spotted fever. It is rarely used now due to significant side effects, which include myelosuppression (both a dose-dependent anemia and dose- independent aplastic anemia) and gray baby syndrome (characterized by vomiting, flaccidity, gray skin hue, and shock in newborns, due to lack of UDP-glucuronyl transferase in newborn liver). A 69-year-old male is admitted to the MICU with septic shock. His past medical history is significant for prior staphylococcal skin infections as well as colorectal cancer. He is status-post colectomy 1 week ago. In addition to providing pressor support, you draw blood cultures and start him on broad-spectrum antibiotics. Within 24 hours, the blood cultures return demonstrating vancomycin-resistant enterococcus (VRE). You subsequently adjust his antibiotic regimen to include a bacterial protein synthesis inhibitor commonly used to treat VRE. Linezolid Similar Linezolid belongs to the oxazolidinone class of anti-bacterial Drugs agents. Mechanism Linezolid is a protein synthesis inhibitor. It binds the 50S of Action bacterial ribosomal subunit and acts to inhibit the formation of the initiation complex. Clinical Used to treat gram-positive infections, including MRSA and Uses VRE infections, as well as infections caused by other gram- positive cocci and Listeria. Side Bone-marrow suppression (especially thrombocytopenia); Effects peripheral neuropathy; fungal infections.  Other The combination drug of quinupristin and dalfopristin fall into a category of antibiotics known as the streptogramins. Quinupristin and dalfopristin are protein synthesis inhibitors that act at the 50S ribosomal unit. As with linezolid, this combination of drugs can be used to treat infections caused by MRSA and VRE. A 34-year-old woman with a history of IV drug abuse presents with a 2-week history of fever, weight loss, and chills. Her physical examination is notable for a temperature of 103.1°F, clear lungs, and a new systolic murmur heard best at the left sternal border. You also notice several small red streaks along her fingernails. Initial blood cultures reveal S. aureus, confirming your suspicion of endocarditis. While you await the blood culture susceptibilities, you consider your choices of anti-microbial agents to treat her infection, including an agent that is a lipopeptide antibiotic that disrupts bacterial cell membranes and can be effective against methicillin-resistant S. aureus. Daptomycin Similar Drugs Mechanism Daptomycin is a lipopeptide antibiotic that works primarily by of Action directly disrupting bacterial cell membranes, causing cellular depolarization and arrest of protein synthesis. Clinical Used to treat severe skin and bloodstream infections caused by Uses gram-positive cocci (including MRSA and VRE). Side Skeletal muscle toxicity; eosinophilia. Effects Other Daptomycin cannot be used for pneumonia, as it complexes with and is inactivated by pulmonary surfactant. Other medications used for severe MRSA infections include vancomycin, linezolid, tigecycline (a tetracycline derivative  with broad gram-positive, gram-negative, and anaerobic coverage), and ceftaroline (fifth-generation cephalosporin). A 24-year-old man presents to your clinic complaining of a 4-day history of a dry cough and a low-grade fever. On physical examination, his temperature is 99.9°F, and you note that there are decreased breath sounds and rales throughout his lung fields. You send the patient for a chest x-ray, the results of which suggest the presence of an atypical pneumonia. You decide to start the patient on a medication that covers the most common infectious agents responsible for such community-acquired atypical pneumonias. Erythromycin Similar Other macrolides include clarithromycin and azithromycin. Drugs Mechanism Erythromycin is a protein synthesis inhibitor. It binds to the of Action 50S ribosomal subunit and inhibits the formation of the initiation complex. It also inhibits the translocation of the aminoacyl peptide during protein synthesis. Clinical The macrolides are effective against gram-positive cocci Uses (streptococci, staphylococci), Corynebacteria species, atypical organisms (Mycoplasma, Legionella, Chlamydia species), Ureaplasma, Listeria species, Rickettsia species, and some gram-negative organisms (Neisseria species, Bordetella pertussis, Bartonella henselae). The macrolides are generally used to treat upper respiratory infections (e.g., Mycoplasma, Legionnaires disease), some STDs (Neisseria, Chlamydia, syphilis in patients allergic to penicillin), Helicobacter pylori infections, Corynebacteria infections (e.g., diphtheria), and infections caused by gram- positive cocci in penicillin-allergic patients. Side GI upset (macrolides have a pro-motility effect on the gut, Effects which can be exploited therapeutically for patients with motility  disorders); acute cholestatic hepatitis; skin rash; eosinophilia. Other Erythromycin inhibits cytochrome P-450 enzymes, thereby resulting in increased serum levels of other drugs, such as warfarin, cyclosporine, and theophylline. A 32-year-old woman presents to your office complaining of a rash. She reports that she was out gardening the day before and woke up this morning with lesions on the back of her neck and forearms. On physical examination, the patient has maculopapular lesions over the sun-exposed areas of her body. Her past medical history is significant for Lyme disease, diagnosed 1 week ago, for which she is currently being treated with antibiotics. You inform the patient that the rash is most likely due to a medication side effect and that she should avoid the sun until her antibiotic treatment is complete. Tetracycline Similar Doxycycline; minocycline; demeclocycline. Drugs Mechanism Tetracycline is a protein synthesis inhibitor. It binds to the 30S of Action subunit and blocks the aminoacyl-tRNA from binding to the ribosome, thereby inhibiting protein synthesis. Clinical Tetracycline and other drugs of this class are broad-spectrum Uses antibiotics that are effective against many gram-positive and gram-negative organisms, including Vibrio cholerae, Chlamydia species, rickettsiae, mycoplasmas, spirochetes, and some anaerobes. These drugs are used to treat pneumonia caused by Mycoplasma or Chlamydia, Rocky Mountain spotted fever and other rickettsial infections, Lyme disease, cholera, and sexually transmitted Chlamydia infections. These drugs can also be used in combination with other agents to treat H. pylori infections (as part of quadruple therapy), tularemia, and brucellosis.  Side GI upset; relatively contraindicated in pregnancy (causes teeth Effects discoloration and bone deformity in children); Fanconi syndrome (aminoaciduria, phosphaturia, acidosis, and glycosuria); photosensitivity. Other Doxycycline can be used in renally insufficient patients since it is fecally eliminated. Drugs in the tetracycline family should not be taken with antacids, milk, or iron-containing substances since divalent cations present in these substances inhibit absorption of tetracyclines in small intestine. Demeclocycline also acts as a competitive antagonist at the V2 receptors and can be used to treat SIADH. A 42-year-old HIV-positive man presents to the emergency room with a fever and cough. He says that he has been compliant with his medication regimen, but he developed a cough 2 weeks ago and now he finds himself feeling short of breath upon exertion. On physical examination, you hear diffuse rhonchi and the chest x-ray shows bilateral infiltrates consistent with Pneumocystis carinii pneumonia. You begin antibiotic therapy immediately and inform the patient that he will need to take a prophylactic antibiotic after discharge to ward off future recurrences of this infection. Trimethoprim-Sulfamethoxazole (TMP-SMX) Similar Other sulfonamides include sulfisoxazole, sulfamethizole, Drugs sulfadoxine, and sulfadiazine. Mechanism Trimethoprim is a protein synthesis inhibitor that inhibits folic of Action acid synthesis by inhibiting dihydrofolate reductase. Sulfamethoxazole is a structural analogue of PABA, which is a dihydrofolic acid precursor. High levels of a PABA analogue acts to competitively inhibit dihydropteroate synthase, an enzyme needed for folic acid synthesis. Inhibition of folic acid synthesis by both drugs results in DNA  synthesis disruption. Clinical TMP-SMX is effective against both gram-positive and gram- Uses negative bacteria, including enteric bacteria (e.g., E. coli; Enterobacter, Klebsiella, Salmonella species), Chlamydia trachomatis, Nocardia species, and P. carinii. It is used to treat urinary tract infections (caused by E. coli), sinus tract infections, P. carinii pneumonia, and ocular chlamydial infections. Side Allergic reactions (including Stevens-Johnson syndrome); Effects hemolytic anemia; granulocytopenia (alleviated with folinic acid supplementation); nephrotoxicity; kernicterus in newborns. Other A 56-year-old diabetic woman was admitted for diabetic ketoacidosis and a urinary tract infection. The urine culture grew out an E. coli species and the patient was put on appropriate antibiotic therapy. A few days after admission, the patient begins to complain about some tenderness in her elbow and knee joints. You immediately become concerned that her new symptoms may be a rare complication of her antibiotic treatment. Ciprofloxacin Similar Other fluoroquinolones include norfloxacin, ofloxacin, Drugs sparfloxacin, gemifloxacin, gatifloxacin, moxifloxacin, and levofloxacin. Mechanism Ciprofloxacin and the other fluoroquinolones inhibit bacterial of Action DNA topoisomerase II, thereby inducing DNA strand breakage and cell death. Clinical Fluoroquinolones are effective against gram-negative species, Uses including Neisseria, Haemophilus species, Klebsiella, E. coli, and Enterobacter, as well as against Mycoplasma and Legionella species. The newer fluoroquinolones (e.g., gatifloxacin, levofloxacin, moxifloxacin) also have increased activity  against some gram-positive organisms (S. pneumoniae, some staphylococci species). Fluoroquinolones are used to treat UTIs, GI infections, respiratory tract infections (e.g., pneumonias), and gonococcal infections. Side GI upset; skin rash; headache; tendonitis and tendon rupture Effects in adults. Other Fluoroquinolones are contraindicated in pregnant women and in children as they have been shown to damage growing cartilage. Nitrofurantoin is an agent that is metabolized to a compound, which then acts to damage bacterial DNA. Clinically, it is used for recurrent UTIs. Side effects include GI upset, neuropathy, pulmonary fibrosis, and hemolytic anemia in G6PD-deficient patients. You are called to evaluate a 32-year-old male patient in the hospital who has been admitted for endocarditis. He is complaining of a red flushing over his entire body. The patient’s blood culture had grown out methicillin-resistant S. aureus and the intern had started him on the proper antibiotic therapy several hours beforehand. On physical examination, the patient is diffusely flushed from his face down to his legs. You inform the patient that he has had a reaction to the antibiotic and that this reaction can be prevented in the future by slowing the infusion rate of the medication and by administering anti-histamines simultaneously with the medication. Vancomycin Similar — Drugs Mechanism Vancomycin binds the D-ala D-ala terminus of bacterial cell wall of Action precursors, thereby inhibiting transglycosylase, which is an enzyme involved in peptidoglycan elongation and cross-linking. The inhibition of transglycosylase results in weakened  peptidoglycans in the cell wall, thereby leading to cell wall damage and lysis. Clinical Vancomycin is effective against gram-positive bacteria (e.g., Uses staphylococci, enterococci, streptococci). It is used to treat serious gram-positive multidrug-resistant infections (e.g., sepsis, endocarditis) including MRSA infections. It is also used to treat C. difficile pseudomembranous colitis. Side Nephrotoxicity; “red man syndrome” (flushing of the skin; Effects this reaction is not IgE-dependent and can be prevented with simultaneous anti-histamine administration and a slow infusion rate); ototoxicity (seen with early formulations of drug but less common currently). Other Polymyxins (B and E) are compounds that bind to bacterial cell membranes and increase the permeability of the cell membrane to polar molecules. They are effective against many gram- negative rods; however, because of significant toxicity (e.g., nephrotoxicity, neurotoxicity), they are currently only used topically to treat infected skin lesions. A 21-year-old college senior presents to the student health clinic. She has just returned from a spring break trip to Costa Rica, where she backpacked along the hillsides for several days. She complains of a watery, non-bloody diarrhea that has lasted for 5 days now. On further history, you learn that she had been drinking stream water during her backpacking trip. She denies any strange food consumption. You are confident that the patient has a protozoal infection and you send away for stool cultures to confirm your suspicions. In the meantime, you start the patient on an agent that kills protozoa by forming cytotoxic byproducts and you recommend that the patient abstain from drinking alcoholic beverages while taking this medication. Metronidazole Similar Drugs  Mechanism Metronidazole is metabolized by bacterial proteins into reduced of Action reactive compounds that serve to damage bacterial DNA, proteins, and membranes, thereby leading to cell death. Clinical Metronidazole is active against anaerobic bacteria (e.g., Uses Clostridium species, Bacteroides species) as well as against protozoans including Giardia, Entamoeba, Trichomonas, and Gardnerella vaginalis. It is used to treat giardiasis, trichomoniasis, and Entamoeba histolytica infections. It is the agent of choice for anaerobic infections below the diaphragm (i.e., C. difficile colitis, diverticulitis). It is also used in combination with a proton- pump-inhibitor, bismuth, and amoxicillin (or tetracycline) as quadruple therapy for treatment of H. pylori infection. Side Disulfiram-like effect with alcohol; metallic taste. Effects Other Metronidazole is an inhibitor of the P-450 system and hence can lead to increased levels of warfarin and phenytoin. A 34-year-old foreign-born farm worker presents to your clinic complaining of dark orange-red urine over the past several weeks. On further history, you learn that he had a positive PPD 2 months ago. At that time, a chest x-ray indicated a lesion in the right upper lobe, consistent with tuberculosis. He was started on multidrug therapy to eradicate the infection, which he states that he is currently taking. The patient’s physical examination is completely within normal limits. You reassure the patient that the urine discoloration is a harmless side effect of his medication, and you order serum and urine studies to ensure that there is no indication of damage to the liver or kidneys. Rifampin Similar Other rifamycins include rifabutin. Drugs  Mechanism Rifampin inhibits bacterial DNA-dependent RNA polymerase, of Action thereby leading to decreased RNA synthesis in bacterial cells. Clinical Rifampin is active against mycobacteria as well as against Uses certain gram-negative bacteria (e.g., Neisseria meningococcus, H. influenzae). It is used in combination with other drugs in the treatment of tuberculosis and leprosy. It is also used as prophylaxis for contacts of patients with meningococcal meningitis and H. influenzae type B infection and as part of a combination treatment of prosthetic valve endocarditis and osteomyelitis. Side Harmless orange color to urine and sweat; rash; Effects thrombocytopenia; nephritis; hepatitis. Other Rifampin has been shown to induce the cytochrome P-450 system, thereby increasing the metabolism and elimination of several other drugs (e.g., warfarin, oral contraceptives, prednisone, ketoconazole, digoxin, glyburide). A 14-year-old foreign-born Hispanic woman arrives at your pediatric clinic for an annual physical examination. She immigrated to the United States 2 years ago and she lives with her parents, younger brother, and maternal grandmother. Of note, the grandmother was just hospitalized 2 days ago for fevers, chills, and a productive cough with sputum that demonstrated acid-fast bacteria. The patient’s parents note that the patient’s PPD has been positive in the past due to a BCG vaccination as an infant. She reports no concerning symptoms and her physical examination is unremarkable. Nevertheless, given the grandmother’s history, you decide to place the child on a prophylactic pharmacologic regimen to prevent active tuberculosis and you suggest that her brother and parents also consider prophylactic medication as well. Isoniazid Similar Drugs  Mechanism Isoniazid acts to inhibit the synthesis of mycolic acids, which of Action are major components of mycobacterial cell walls. Clinical Isoniazid is used in combination with other medications in the Uses treatment of Mycobacterium tuberculosis. It is also used as prophylaxis against active tuberculosis in patients with a positive PPD. Side Peripheral neuropathy (pyridoxine, or vitamin B6, is given to Effects prevent peripheral neuropathy in patients taking isoniazid); G6PD-deficient hemolytic anemia; drug-induced lupus; hepatitis. Other Some patients metabolize isoniazid faster than others, due to a genetic difference in the rate of action of a liver enzyme (N- acetyltransferase). Thus, serum levels of isoniazid should be monitored initially to ensure therapeutic levels of the drug in patients who are rapid metabolizers. A 28-year-old foreign-born man comes to your clinic complaining of eye pain over the last week. Besides eye pain, he also reports to you that he has noticed transient spots in the center of his visual fields and that he feels as if he is unable to see as well as he used to. His medical history is significant for active tuberculosis, for which he has been taking several medications for the past 3 weeks. He denies fevers, chills, night sweats, or current productive cough, and he tells you that he has been diligent about his drug regimen. You tell the patient that you believe his symptoms are related to one of the medications that he is taking to treat his tuberculosis and you decide to refer the patient to an ophthalmologist. Other Anti-Mycobacterial Agents Similar Other medications used to treat mycobacterial infections include Drugs dapsone (DAP), ethambutol (ETH), and pyrazinamide (PYR).  Mechanism DAP: PABA antagonist that acts to inhibit folic acid synthesis; of Action behaves similarly to the sulfonamides. ETH: Inhibits mycobacterial arabinosyl transferase, which is an enzyme involved in the synthesis of the mycobacterial cell wall. PYR: Known to lower pH of mycobacteria, but the exact mechanism of action is unknown. Clinical DAP: Used in combination with rifampin and clofazimine to Uses treat M. leprae infection (leprosy); also used as prophylaxis against P. carinii infection in HIV patients. ETH and PYR: Used in combination with other medications to treat M. tuberculosis infection. Side DAP: G6PD-deficient hemolytic anemia; GI intolerance; rash. Effects ETH: Retrobulbar neuritis resulting in decreased visual acuity and red-green color blindness. PYR: GI intolerance; fever; hepatotoxicity; hyperuricemia (gout). Other Streptomycin (an aminoglycoside) is also used as second-line treatment of M. tuberculosis infection. A 36-year-old man with HIV presents to the urgent care clinic with epigastric pain that is sharp and radiates toward his back. He states that he is very compliant with his anti-viral medications and was feeling fine 3 days ago. He does not drink alcohol. His laboratory studies demonstrate a markedly elevated lipase. You suspect that his acute pancreatitis is likely secondary to his drug regimen and you order an abdominal ultrasound to confirm your suspicion and to assess for any other cause for his pancreatitis. Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Similar NRTIs include zidovudine (AZT or ZDV), didanosine (ddI), Drugs zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), emtricitabine (FTC), and abacavir.  Mechanism NRTIs inhibit HIV reverse transcriptase, thereby inhibiting of Action DNA synthesis. NRTIs can also compete with nucleoside triphosphates (e.g., dTTP, dATP, dCTP, dGTP) to be added to the newly synthesized viral DNA strand. Incorporation of an NRTI into the viral DNA strand leads to a defective viral particle. Clinical NRTIs are used in the treatment of HIV infection. Uses Lamivudine is also used in the treatment of chronic hepatitis B. Side Neutropenia; megaloblastic anemia (AZT); pancreatitis (ddI); Effects peripheral neuropathy (ddC, d4T); hypersensitivity reactions (rash); lactic acidosis (abacavir); GI upset. Other The use of AZT during pregnancy and in neonates with HIV+ mothers has been shown to significantly reduce the risk of viral transmission from mother to child. Nucleotide analogue reverse transcriptase inhibitors include tenofovir and adefovir. These drugs also work by inhibiting viral reverse transcriptase. They are used to treat HIV infection and hepatitis B infection (adefovir). A 36-year-old HIV-positive man presents to the AIDS clinic complaining of having vivid nightmares and delusional thoughts during the day. His current CD4 count is within acceptable range and his viral load is nearly undetectable. He has no other complaints other than the delusions and vivid nightmares, but he is concerned that he may be becoming schizophrenic. Upon reviewing his chart, you see that he was recently switched to a protease-sparing drug regimen and you begin to believe that the medication substituted for the protease inhibitor is the cause of the patient’s current symptoms as opposed to a primary psychiatric disorder. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)  Similar NNRTIs include nevirapine, efavirenz, and delavirdine. Drugs Mechanism The NNRTIs bind specifically to HIV reverse transcriptase, of Action thereby blocking DNA synthesis. Clinical NNRTIs are used in the treatment of HIV infection. Uses Side Nevirapine: Stevens-Johnson syndrome; fulminant hepatitis; Effects induction of cytochrome P-450 activity, which results in the increased metabolism of several drugs, including oral contraceptives, warfarin, metronidazole, ketoconazole, and some protease inhibitors. Delavirdine: Elevated LFTs; teratogenic compound. Efavirenz: CNS disturbances including insomnia, dizziness, delusions, and nightmares. Other A 32-year-old HIV-positive man presents to your AIDS clinic for a routine checkup. Although his CD4 count and viral load are within acceptable limits, you find that serum studies have demonstrated markedly elevated cholesterol and triglyceride levels. Upon physical examination, you find that the patient has truncal obesity and a buffalo hump, which he reports has developed only since beginning his drug regimen several months ago. Although the patient feels fine, he is concerned about his appearance and asks what is happening. You report that this altered body fat distribution, as well as his hyperlipidemia, is a common side effect of one of his HIV medications. Protease Inhibitors Similar Protease inhibitors include saquinavir, ritonavir, indinavir, Drugs nelfinavir, lopinavir, atazanavir, fosamprenavir, tipranavir, darunavir, and amprenavir.  Mechanism The protease inhibitors act to inhibit the HIV protease enzyme, of Action which is responsible for cleaving precursor proteins into mature proteins that are involved in forming the core of the viral particle. If the protease enzyme is inhibited, the virus is unable to replicate. Clinical Protease inhibitors are used in the treatment of HIV infection. Uses Side All protease inhibitors have been associated with altered Effects distribution of body fat (often formation of a buffalo hump or increased truncal obesity), insulin resistance, and hyperlipidemia. Other side effects include GI discomfort and paresthesias (associated with ritonavir, nelfinavir, and amprenavir), and elevated bilirubin levels and kidney stones (both associated with indinavir). Other Ritonavir has been shown to inhibit cytochrome P-450, thus leading to increased serum levels of certain drugs (e.g., other protease inhibitors, ketoconazole, rifampin, erythromycin, some anti-arrhythmic agents, some benzodiazepines, and some CNS drugs such as clozapine, fluoxetine, and haloperidol). Ritonavir is often used in combination with other anti-retroviral therapy since its effect on cytochrome P-450 can be therapeutically exploited to maximize the half-life of other anti-retroviral agents. A 28-year-old woman, who was diagnosed with HIV 7 years ago, presents to your infectious disease clinic for follow-up. While she was able to maintain a stable CD4 count and avoid opportunistic infections previously, her lab results today demonstrate both a falling CD4 count as well as an increase in her viral load compared to prior visits. The patient insists that she has been compliant with her medications. After discussing options with the patient, you both agree to try a different class of medication that is sometimes used in conjunction with two nucleoside reverse transcriptase inhibitors as an alternative triple therapy that works by incorporating viral DNA into the host cell genome. Integrase Inhibitors Similar Integrase inhibitors include raltegravir, elvitegravir, and Drugs dolutegravir. Mechanism The integrase inhibitors act to reversibly inhibit HIV integrase, of Action which works to incorporate viral DNA (produced via reverse transcription) into the host cell genome. Without the integrase enzyme, HIV is unable to replicate. Clinical Integrase inhibitors are primarily used in the treatment of HIV Uses infection. Side Integrase inhibitors are generally well-tolerated. Side effects Effects include rash, diarrhea, and insomnia. Other Entry inhibitors, including maraviroc and enfuvirtide, work by preventing viral entrance into the host cell. Maraviroc blocks the binding of the HIV gp120 protein to the CCR5 co-receptor on the host cell, and enfuvirtide inhibits membrane fusion through blocking the HIV gp41 protein. Maraviroc carries the risk of hepatotoxicity. A 35-year-old man comes to the urgent care clinic complaining of a painful lesion on his penis. Upon further questioning, the patient admits to having unprotected sexual intercourse with several different partners over the past several months. Physical examination reveals a vesicular lesion on the glans of the penis. You explain to the patient that he has contracted a viral sexually transmitted disease and you prescribe a medication to treat his condition and to suppress future outbreaks of this infection. Acyclovir Similar Valacyclovir; penciclovir; famciclovir. Drugs Mechanism Acyclovir is phosphorylated by viral thymidine kinase into an  of Action analogue of dGTP. After conversion, the drug acts to inhibit DNA synthesis through incorporation into the growing viral DNA strand, thereby leading to chain termination. Clinical Acyclovir is used to treat genital herpes, herpes meningitis Uses and encephalitis, acute VZV infection, and oral hairy leukoplakia (associated with EBV infection). Because acyclovir targets DNA replication, it is inactive against latent herpes virus infections. Side Nephrotoxicity (may crystallize in urinary tract), neurotoxicity Effects (tremor, delirium). Other Valacyclovir has better bioavailability than acyclovir. Resistance to acyclovir can occur if the virus lacks thymidine kinase. A 46-year-old AIDS patient presents to the clinic complaining of progressive decreased visual acuity and loss of peripheral vision. He reports that his symptoms started initially in his left eye, but that the symptoms quickly spread to the right eye as well. Your ophthalmologic examination, combined with serum studies that demonstrate the presence of CMV, suggests that CMV retinitis is a likely diagnosis. You begin administration of an intravenous medication that acts to inhibit viral DNA polymerase after activation by a viral kinase. Ganciclovir Similar Valganciclovir. Drugs Mechanism Ganciclovir is an analogue of guanosine. After of Action phosphorylation by a viral kinase into the nucleotide analogue, ganciclovir acts to preferentially inhibit CMV DNA polymerase, thereby leading to the inhibition of DNA synthesis. Clinical Ganciclovir is used to treat CMV infections, especially CMV Uses retinitis (often seen in AIDS patients).  Side Pancytopenia; nephrotoxicity; seizures. Effects Other Foscarnet is a pyrophosphate analogue that acts to inhibit viral DNA polymerase without requiring activation by a viral kinase. It is used as a second-line treatment of CMV retinitis and other CMV infections as well as in the treatment of acyclovir- resistant HSV and VZV infections. The major side effect is nephrotoxicity. Cidofovir is a phosphate nucleotide analogue of cytosine that inhibits viral DNA polymerase. Similar to foscarnet, it also does not require activation with a viral kinase, and thus can be used against acyclovir-resistant HSV. It is also indicated for the treatment of CMV retinitis. It too carries a risk of nephrotoxicity. A 68-year-old woman with a past medical history of COPD presents to the hospital in January with progressive dyspnea despite a recent increase in her home oxygen administration. She says that she has not received any vaccines in the last year. On physical exam, she has a fever of 102.4°F and her oxygen saturation is 85% on room air. Her breathing is somewhat labored and she is using accessory muscles of respiration. Diffuse crackles are heard during the lung exam. When antibody testing confirms the presence of influenza, you decide to give her an agent that inhibits neuraminidase and thereby prevents virus release from infected cells. Oseltamivir Similar Zanamivir. Drugs Mechanism Oseltamivir is a prodrug that is activated intracellularly to of Action inhibit the viral enzyme, neuraminidase. Neuraminidase acts to cleave the sialic acid moiety on glycosylated hemagglutinin, which subsequently allows budding viral particles to be released  from the host cell. By inhibiting the action of neuraminidase, oseltamivir prevents intercellular viral spread. Clinical Oseltamivir can be used for either prophylaxis or treatment of Uses influenza A and B infections. It is especially recommended for those patients at risk for severe complications from influenza infections, such as young children, the elderly, patients with COPD, and immunosuppressed patients. Side Headache, vomiting. Effects Other A 62-year-old man with no significant past medical history presents to your clinic in December, complaining of malaise, headache, congestion, and weakness that began about 24 hours ago. While interacting with your patient, he tells you that his grandson visited him several days ago, but, unfortunately, his grandson has since come down with the flu. The patient was unable to get a flu vaccine this year due to a vaccination shortage. Physical examination is significant for cervical lymphadenopathy and a fever of 101.7°F. You begin the patient on a course of medication that will reduce the duration of illness and you ask the patient to return to the clinic immediately if he experiences any slurred speech, dizziness, or problems with gait or coordination. Amantadine Similar Rimantadine. Drugs Mechanism Amantadine binds to the M2 surface protein proton channel on of Action influenza A viral particles, thereby blocking the uncoating of the viral RNA within the host cells and thus inhibiting intracellular viral replication. Amantadine has also been shown to stimulate the release of dopamine from neurons of the nigra striatum.  Clinical Amantadine is used to reduce the duration of influenza A Uses symptoms as well as for influenza A prophylaxis in elderly and immunocompromised patients. It is also used in the treatment of Parkinson’s disease. Side CNS symptoms (ataxia, slurred speech, dizziness); GI upset. Effects Other A 6-month-old previously healthy infant presents to the emergency room with a 3-day history of rhinitis, non-productive cough, tachypnea, and fever. On physical examination, his respiratory rate is 42 breaths/min and his oxygen saturation is 90% on room air. Further examination reveals subcostal retractions and coarse breath sounds bilaterally with wheezes. When laboratory studies reveal a positive RSV test, you begin treatment with a first-line agent and you admit the infant to the hospital. Ribavirin Similar Drugs Mechanism Ribavirin is a guanosine analogue that acts to inhibit guanine of Action nucleotide synthesis and to inhibit viral RNA polymerase, thereby resulting in the inhibition of viral replication. Clinical Ribavirin is used to treat RSV bronchiolitis and other RSV Uses infections, influenza A and B infections, and chronic hepatitis C infection. Side Hemolytic anemia; elevated bilirubin levels; teratogenic Effects compound. Other Ribavirin is contraindicated in pregnancy and in patients with renal insufficiency. Entecavir is a guanosine nucleoside analogue that acts to  preferentially inhibit hepatitis B viral polymerase. It is used to treat hepatitis B infection. A 40-year-old man with a history of chronic hepatitis C arrives for his appointment at the hepatology clinic. He reports that he has been feeling more fatigued than usual. Laboratory studies demonstrate a detectable HCV viral load as well as elevated ALT and AST levels. The patient states that he has been taking his ribavirin as instructed. After confirming the patient’s viral genotype, you decide to prescribe a medication that is often given as part of combination therapy with ribavirin for the treatment of chronic HCV, and that can allow patients to avoid medications with more severe side effect profiles. Sofosbuvir Similar Drugs Mechanism Sofosbuvir is an HCV RNA-dependent RNA polymerase of Action inhibitor, thereby causing chain termination and inhibition of viral replication. Clinical Sofosbuvir is used to treat chronic HCV for genotypes 1, 2, 3, Uses and 4. It is often used in concert with ribavirin with or without pegylated interferon. Side Fatigue; headache; insomnia; GI distress. Effects Other Simeprevir is a hepatitis C NS3/4A protease inhibitor, which acts to prevent effective viral replication. It is used often as part of combination therapy with either interferon and ribavirin or sofosbuvir. Side effects include photosensitivity, headache, and fatigue. Simeprevir may also be used in combination with ledipasvir, which inhibits the hepatitis C NS5 protein, thereby further blocking viral replication. Side effects include headache and fatigue. A 38-year-old man with advanced AIDS presents to the emergency department with a 6-day history of fever, hemoptysis, pleuritic chest pain, and difficulty breathing. On physical examination, he is in respiratory distress and a lung examination reveals bilateral rales. A CT scan of the chest demonstrates a multifocal pneumonia with a cavitary lesion containing a fungus ball. You immediately begin the patient on an anti-fungal agent, which acts by altering the permeability of the fungal cell membrane, to treat his severe lung infection. Amphotericin B Similar Drugs Mechanism Amphotericin B binds to ergosterol, a sterol found only in the of Action fungal cell membrane, and alters permeability of the fungal cell membrane, eventually leading to cell death. Clinical Amphotericin B is a broad-spectrum anti-fungal agent used to Uses treat systemic mycotic infections caused by Cryptococcus, Coccidioides, Aspergillus, Blastomyces, Candida, Histoplasma, and Mucor. Side Infusion-related reaction (fever, chills, muscle spasms, Effects headache); nephrotoxicity (including renal tubular acidosis and renal insufficiency); hypotension; anemia; arrhythmias (potentially related to concurrent electrolyte abnormalities); abnormal LFTs. Other Amphotericin B must be given intrathecally when used to treat fungal meningitis since it does not cross the blood-brain barrier. Due to the extensive side effect profile of amphotericin B, it is sometimes given in a liposomal formulations to reduce side effects. Nystatin has a similar mode of action as amphotericin B, altering fungal cell membrane permeability, thereby leading to  cell death. It is more toxic than amphotericin B and thus is not used systemically. It is used topically to treat oral and cutaneous candidiasis. A 32-year-old immigrant from southern Africa presents to the emergency room, complaining of progressive dyspnea and fever. He is currently being treated for tuberculosis. He was previously doing well; however, he admits that he has forgotten to take several doses of his antibiotic regimen. Physical examination reveals a cachectic gentleman with labored breathing and rales heard on auscultation. Imaging demonstrates multifocal lesions in both lobes. He is admitted to the intensive care unit. Bronchoalveolar lavage demonstrates Aspergillus. You decide to start treating the patient for invasive aspergillosis with voriconazole as well as an agent that inhibits the formation of a component of the fungal cell wall. Micafungin Similar Other echinocandins include caspofungin and anidulafungin. Drugs Mechanism Micafungin competitively inhibits the beta-1,3-D-glucan of Action synthase enzyme. This enzyme is required for production of beta-glucan, an essential component of the fungal cell wall. Depletion of beta-glucan leads to cell lysis through osmotic forces. Clinical Used for the treatment of invasive candidiasis or aspergillosis. Uses Side Hepatotoxicity; infusion-related allergic reactions; GI upset. Effects Other Note that micafungin is typically tolerated better than other systemic antifungal agents. A 52-year-old lymphoma patient has been undergoing several rounds of chemotherapy over the course of the last several weeks. He is admitted to your service due to signs and symptoms consistent with meningitis. Cerebrospinal fluid cultures grow out Cryptococcus and you start him on amphotericin B. His condition continues to deteriorate and you are concerned that the intrathecal infusion of amphotericin B may not be enough to counteract the fungal meningitis. You decide to add a second anti-fungal agent that is commonly used in combination with amphotericin B to combat fungal meningitis. Flucytosine Similar Drugs Mechanism Within the fungal cell, flucytosine is converted into nucleotide of Action analogues (5-FdUMP and FUTP), which then acts to inhibit thymidylate synthetase, thereby inhibiting fungal DNA and RNA synthesis. Note that its mechanism of action is analogous to the chemotherapeutic agent, 5-fluorouracil, which inhibits the same enzyme. Clinical Flucytosine is used in combination with other anti-fungal Uses agents (often amphotericin B) for treatment of systemic mycotic infections and fungal meningitis caused by Cryptococcus and Candida species. Side Bone marrow suppression; hepatotoxicity. Effects Other A 43-year-old diabetic woman presents to your clinic complaining of a white, itchy vaginal discharge. On physical examination, you observe a cottage cheese- like discharge in the vaginal vault. You believe that the patient’s diabetes has predisposed the patient to this infection, and you suggest that the patient obtain an anti-fungal vaginal suppository to cure the infection. Ketoconazole Similar Miconazole; clotrimazole. Drugs Mechanism Ketoconazole acts to inhibit the formation of ergosterol, an of Action essential component of the fungal cell membrane, by inhibiting fungal cytochrome P-450 enzymes. Ketoconazole also inhibits mammalian cytochrome P-450 enzymes, thereby disrupting gonadal and adrenal steroid synthesis. Clinical Ketoconazole is used as a broad-spectrum anti-fungal agent in Uses the treatment of Blastomycosis, Coccidioides, Histoplasmosis, Aspergillus, Mucor, and Candida infections. It is also used to treat patients with Cushing syndrome and prostate cancer. Side Hormone synthesis inhibition (which leads to decreased libido, Effects gynecomastia, and menstrual irregularities—this is especially seen in ketoconazole); mild GI upset; abnormal liver enzymes. Other Ketoconazole inhibits cytochrome P-450, thereby leading to increased serum levels of several drugs (e.g., cyclosporine, warfarin, phenytoin, histamine antagonists). Miconazole and clotrimazole possess the same mechanism of action as ketoconazole. Since they have high levels of toxicity, they are only used topically to treat cutaneous fungal infections (e.g., vulvovaginal candidiasis, tinea pedis, and tinea cruris). A 43-year-old woman with AIDS presents to the emergency room complaining of fever and chills. Her vital signs upon presentation reveal a temperature of 103°F and a blood pressure of 88/66 mm Hg. Physical examination is significant for the presence of creamy plaques on her tongue and upper palate. You draw blood cultures, which eventually reveal the presence of Candida albicans. You immediately begin the proper anti-microbial treatment with a drug that inhibits both fungal and mammalian cytochrome P-450 enzymes, but does not have much effect on gonadal and adrenal steroid synthesis. Fluconazole Similar Itraconazole; voriconazole. Drugs Mechanism Fluconazole acts to inhibit the formation of ergosterol, an of Action essential component of the fungal cell membrane, by inhibiting fungal cytochrome P-450 enzymes. Fluconazole also inhibits mammalian cytochrome P-450 enzymes similar to ketoconazole, but its effects on gonadal and adrenal steroid synthesis are minimal. Clinical Fluconazole is used to treat systemic fungal infections Uses (especially cryptococcal meningitis and sepsis from Candida). It is also used to treat blastomycosis, coccidiomycosis, and histoplasmosis. Side Mild GI upset; abnormal liver enzymes; fevers and chills. Effects Other Fluconazole inhibits cytochrome P-450, thereby leading to increased serum levels of several drugs (e.g., cyclosporine, warfarin, phenytoin, histamine antagonists). A 6-year-old girl is brought to the pediatric clinic by her mother, who states that the child has been experiencing hair loss over the last week. The child has no systemic symptoms. On physical examination, you find several ring-shaped lesions with raised papules along its rim and notable alopecia near the lesions. There is no sign of inflammation at the lesions and the child denies pruritus. You believe that the child is suffering from a dermatophytic infection and you begin the patient on oral treatment with a medication that interferes with microtubule function. You also suggest that the mother wash all sheets and clothing and disinfect combs and brushes to prevent reinfection with the offending organism in the future. Griseofulvin  Similar Drugs Mechanism Griseofulvin interferes with microtubule function in fungal of Action cells in keratin-rich tissues (e.g., skin, nails, and hair), thereby inhibiting mitosis and fungal cell replication. Clinical Griseofulvin is an oral anti-fungal agent used in the treatment Uses of topical dermatophytic infections caused by Epidermophyton, Microsporum, and Trichophyton. Side Headaches; confusion; GI upset; allergic reaction; hepatitis. Effects Other Terbinafine acts to inhibit squalene epoxidase, a fungal enzyme involved in ergosterol synthesis. It is also used to treat topical dermatophytic infections (e.g., onychomycosis). A 32-year-old male physician is planning to participate in a medical mission to sub-Saharan Africa. In addition to a hepatitis vaccine, he wishes to take prophylactic medications for other serious illnesses that he may encounter. You prescribe a single medication that will serve as chemoprophylaxis for malaria. When asked what side effects he may encounter, you explain that the medication may cause pruritus, GI distress, and blurry vision, and you advise him to contact you or a nearby clinic if any of these side effects occur. Chloroquine Similar Other anti-malarial drugs include mefloquine and quinine. Drugs Mechanism Chloroquine: Concentrates in parasite food vacuoles and of Action prevents heme metabolism, thereby causing toxicity and cell death due to the buildup of soluble heme. Quinine and mefloquine: Mechanisms of action are unknown. Clinical Chloroquine: Treatment of P. falciparum malaria;  Uses chemoprophylaxis for malaria; treatment of erythrocytic form of P. vivax and Plasmodium ovale. Quinine: Treatment of drug-resistant P. falciparum malaria; also used to treat Babesia microti infection. Mefloquine: Treatment of drug-resistant P. falciparum malaria; also used for chemoprophylaxis for P. falciparum malaria. Side Chloroquine: GI upset; pruritus; visual disturbances; ECG Effects changes. Quinine: Cinchonism (tinnitus, headache, dizziness, nausea); Coombs positive hemolytic anemia; fetal toxicity. Mefloquine: GI upset; mental status changes; cardiac abnormalities. Other Pyrimethamine inhibits dihydrofolate reductase, thereby inhibiting folic acid synthesis and interfering with DNA and RNA synthesis. It is commonly used in the treatment and prophylaxis of P. falciparum as well as in the treatment of Toxoplasma gondii (when given in combination with sulfadiazine). Significant side effects include bone marrow suppression. A 36-year-old man presents with a 10-day history of episodic chills and fever. He states that the fever bouts will occur every 2 to 3 days and last for several hours at a time. His history is significant for malaria, which he contracted during a trip to Southeast Asia 2 months ago. His malaria was believed to be successfully treated with a full course of chloroquine and mefloquine. On physical examination, the patient looks pale with marked hepatomegaly and splenomegaly. You believe that the patient has dormant liver malaria and you prescribe a medication that will eradicate this infection. Primaquine Similar  Drugs Mechanism While the mechanism of action of primaquine is not completely of Action understood, researchers have speculated that metabolites of primaquine act as oxidants, which cause parasitic and host cell damage and death. Clinical Primaquine is used to treat the hepatic forms of P. vivax and Uses P. ovale malaria. Side Hemolytic anemia in G6PD patients; abdominal pain. Effects Other Primaquine is contraindicated in pregnancy, since it may cause a hemolytic anemia in the fetus. A 46-year-old man with AIDS presents to your clinic for a follow-up appointment. His last CD4 count was 150. Although you have advised him that he ought to take antibiotic prophylaxis for P. carinii pneumonia, he has refused for the past year, stating that he cannot tolerate any medications used for P. carinii pneumonia prophylaxis, including TMP-SMX and dapsone, due to violent allergic reactions to both medications. You suggest that he try an alternative medication to protect him against opportunistic pneumonias that is believed to act by inhibiting parasitic RNA synthesis. Other Anti-Protozoan Agents Pentamidine Mechanism: Unknown, although it is believed to inhibit parasitic RNA synthesis. Clinical use: Alternative treatment of T. brucei infection (African trypanosomiasis) and leishmaniasis; alternative treatment and prophylaxis for P. carinii pneumonia. Side effects: Nephrotoxicity; leukopenia; hypotension. Nifurtimox Mechanism: Breakdown of the drug generates oxygen radicals, which damage the parasite. Clinical use: Treatment of T. cruzi infections (Chagas  disease). Side effects: Neuropathy; seizures. Suramin Mechanism: It is believed to inhibit parasitic enzymes involved in energy metabolism. Clinical use: Treatment of early T. brucei infections (i.e., before CNS involvement); also used to treat Onchocerca volvulus infections. Side effects: Neurologic disturbances; renal abnormalities. Melarsoprol Mechanism: Unknown, although it is believed to inhibit multiple parasitic enzymes. Clinical use: Treatment of late T. brucei infections (i.e., after CNS involvement). Side effects: Encephalopathy; hypersensitivity reactions; myocarditis. Sodium Mechanism: Unknown, although it is believed to inhibit Stibogluconate parasitic glycolysis. Clinical use: Treatment of leishmaniasis. Side effects: Myopathy; cardiotoxicity. A 19-year-old college student presents to the university health services clinic complaining of an intensely itchy rash over the last 5 days. She states that her two roommates are suffering from similar symptoms. On physical examination, you observe a pimple-like rash that is most prominent between the fingers, on the wrists, and on the waist. You perform a skin scraping to confirm your diagnosis. In the meantime, you prescribe the patient a topical lotion, which acts to block sodium flow in parasitic neuronal cells, and you recommend that she and her roommates wash all bedding, towels, and clothing in their dorm room in hot water. Permethrin Similar  Drugs Mechanism Permethrin acts to block the movement of sodium ions of Action through neurons in parasites, ultimately leading to parasitic paralysis and death. Clinical Permethrin is used topically for the treatment of head lice Uses (Pediculus; Pthirus) as well as scabies (Sarcoptes scabiei). Side Pruritus; skin irritation; erythema. Effects Other Malathion is an acetylcholinesterase inhibitor that can be used topically to treat head lice. Because it is an organophosphate, it is not administered systemically. Topical lindane is used also for the treatment of lice and scabies. It acts by blocking GABA chloride channels on the neuron, thereby leading to neuronal hyperactivity and resulting cell death. Due to the risk of neurologic and hepatic sequelae, as well as a risk of aplastic anemia, lindane is considered a second-line treatment. While on a medical mission in central Africa, you come across a group of villagers camped by a river, all of whom are suffering from the same ailment. Several young teenagers report larvae appearing near sites where they were bitten by black flies. Some of these children have infections in the areas of their eyes and they tell you that they feel extremely itchy. You note that all of these children exhibit disfiguring skin nodules over the surfaces of their body. Fortunately, you have a large supply of a drug on hand that can cure this nematode infection, and you immediately give the medication to these children in hopes of preventing blindness. Anti-Helminthic Agents Ivermectin Mechanism: Activates GABA receptors, thereby leading to worm paralysis and death. Clinical use: Treatment of river blindness  (Onchocerca volvulus) and strongyloidiasis. Side effects: Mazotti reaction (fever, rash, hypotension, arthralgias, vertigo). Mebendazole, Mechanism: Inhibits microtubule synthesis and albendazole, and function. thiabendazole Clinical use: Mebendazole and albendazole are used to treat whipworm (Trichuris), hookworm (Necator/Ancylostoma), roundworm (Ascaris), and pinworm (Enterobius). Albendazole is also used to treat strongyloidiasis, neurocysticercosis, hydatid disease, and cutaneous larva migrans. Thiabendazole is used to treat strongyloidiasis, cutaneous larva migrans, and trichinosis. Side effects: All cause GI upset and allergic reactions. Pyrantel pamoate Mechanism: Activates parasitic nicotinic receptors, thereby causing worm paralysis. Clinical use: Treatment of hookworm, roundworm, and pinworm infections. Side effects: GI upset. Praziquantel Mechanism: Increases cell Ca2+ uptake, thereby causing parasite contraction and paralysis. Clinical use: Treatment of schistosomiasis, neurocysticercosis, hydatid disease, and infections caused by Taenia species, D. latum, and Clonorchis species. Side effects: GI upset; elevated LFTs. Diethylcarbamazine Mechanism: Exact mechanism is not known, but diethylcarbamazine is believed to inhibit arachidonic acid metabolism, thereby increasing phagocytosis of the microbe. Clinical use: Treatment of lymphatic filariasis (due to Wuchereria bancrofti or Brugia) or subcutaneous filariasis (due to Loa loa or Onchocerca volvulus). Side effects: Mazotti reaction (fever, rash, hypotension, arthralgias, vertigo).  2 ADRENERGIC RECEPTORS Receptor Mechanism of Location Action Preferred Type Activation Substrate α1 PLC activated → Vascular smooth Promotes Epi ≥ NE >> increased IP3 → and muscle vasoconstriction