PHAR 100 Module 04: Common Prescription Drugs PDF

PHAR 100 INTRODUCTORY PHARMACOLOGY MODULE 04 COMMON PRESCRIPTION DRUGS Please note: This course was designed to be interacted and engaged with using the online modules. This Module Companion Guide is a resource created to compl...

PHAR 100 INTRODUCTORY PHARMACOLOGY MODULE 04 COMMON PRESCRIPTION DRUGS Please note: This course was designed to be interacted and engaged with using the online modules. This Module Companion Guide is a resource created to complement the online slides. If there is a discrepancy between this guide and the online module, please refer to the module. How can you help protect the integrity and quality of your Queen’s University course? Do not distribute this Module Companion Guide to any students who are not enrolled in PHAR 100 as it is a direct violation of the Academic Integrity Policy of Queen’s University. Students found in violation can face sanctions. For more information, please visit https://www.queensu.ca/academic- calendar/health-sciences/bhsc/. MODULE 04 COMPANION GUIDE PHAR 100 TABLE OF CONTENTS INTRODUCTION..................................................................................................................................................... 3 SECTION 01: Antibiotic, Antifungal, and Antiviral Agents................................................................................. 5 SECTION 02: Regulation of Fertility...................................................................................................................23 CONCLUSION.......................................................................................................................................................34 INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 2 MODULE 04 COMPANION GUIDE PHAR 100 INTRODUCTION Module 04 covers the mechanisms of action, therapeutic effects, and adverse effects of common prescription drugs such as antibiotics, antifungals, antivirals, and hormonal contraceptives. The information learned in this module will aid in the completion of Assessment 2. Watch the video for an introduction to Module 04 from Jeanne Mulder, P h D. Start of Video Transcript: In Module 04, you will cover common prescription drugs, such as antibiotics, antivirals, antifungals, and hormonal contraceptives. For each of these types of prescriptions drugs you will learn the mechanism of action, therapeutic effects, and adverse effects. Antibiotics, antivirals, and antifungals all eradicate infections through the concept of selective toxicity, which is when the drug harms the invading organism, but not the host. With antibiotics you will learn about penicillin, cephalosporins, fluoroquinolones, tetracyclines, macrolides, and antifolate drugs. You will learn about causes of antibiotic resistance and why it is important to work to prevent the emergence of resistant bacterial strains. In terms of antifungals, you will learn about two classes, the echinochandins and the imidazoles. And with antivirals you will learn about oseltamivir and acyclovir, as well as the difference between an antiviral and a vaccine. Next, you will learn about hormonal contraceptives, specifically oral contraceptives, depo-provera, I U Ds, and the transdermal patch. The module ends with a short discussion on research into potential male contraceptives. This is the shortest module in the course, but provides valuable information on prescription drugs that likely all of you have some first-hand knowledge of. End of Video Transcript. Module Learning Outcomes By the end of Module 04, you should be able to: 1. Explain how antibiotic, antifungal, and antiviral drugs utilize the concept of selective toxicity to eradicate infections. 2. Describe the different types of hormonal contraceptives, their mechanisms of action, and adverse effects. Module Assessments These assessment(s) are associated with Module 04. View the details of the assessment. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 3 MODULE 04 COMPANION GUIDE PHAR 100 Assessment 2: Individual Written Report The purpose of this assessment is to apply information learned in Modules 01-04 by answering the posed questions. For specific details about this assessment, visit the assessment page in your online learning environment. Activities Throughout the Module Note that text responses and interactions within the learning module will not be graded. However, your responses to these interactions are recorded in the module and viewable by your instructor(s). This includes the short quizzes at the end of each section. These questions are included to prepare you for the types of questions you will see on the midterm and final exam. Module Outline Section 01: Antibiotic, Antifungal, and Antiviral Agents Section 02: Regulation of Fertility Page Link: https://player.vimeo.com/video/630113584?h=313c8e7f6e End of Introduction INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 4 MODULE 04 COMPANION GUIDE PHAR 100 SECTION 01: ANTIBIOTIC, ANTIFUNGAL, AND ANTIVIRAL AGENTS Introduction to Antibiotic, Antifungal, and Antiviral Agents Drugs used to treat infections represent some of the most dramatic examples of the advances of modern medicine. Diseases that were associated with a high death rate in 1940 are now curable with the administration of a few tablets. The development of drugs to treat infections is based on the concept of selective toxicity, which is the use of drugs to harm an invading organism without harming the host. Antibiotics, antifungals, and antivirals all take advantage of differences between the invading organism and human cells. In this section, you will learn about antibiotic, antifungal, and antiviral agents. Many more antibiotics exist compared to antifungals and antivirals. For that reason, antibiotics will be discussed more thoroughly than antifungal and antiviral agents. What is an Antibiotic? An antibiotic is a chemical substance that suppresses the growth of bacteria, and may eventually destroy them. Recall from Module 01 that, technically, the term antibiotic refers specifically to chemical substances produced by microorganisms, and not synthetic compounds. In practice, however, antibiotics are commonly used to refer to both synthetic and non-synthetic compounds, and this is the way the term will be used in this course. The purpose of an antibiotic is to stop a bacterial infection. This can be accomplished through bacteriostatic or bactericidal effects. Structure of Bacterial Cells To understand how antibiotics are classified, you must first learn about the structure of bacterial cells. Unlike human cells, bacterial cells have a rigid outer layer called the cell wall, which completely surrounds the cytoplasmic membrane. The cell wall contains a peptidoglycan layer, which is a complex, cross-linked polymer of polysaccharides and polypeptides. These cross-links give the cell wall its structural rigidity and are responsible for maintaining the cell’s shape and integrity and preventing cell lysis from high osmotic pressure. Alt Text: A bacterial cell. Note the presence of both a cell wall and a cytoplasmic membrane. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 5 MODULE 04 COMPANION GUIDE PHAR 100 Gram-Positive vs Gram-Negative Bacteria Bacteria are classified as either Gram-negative or Gram-positive based on the composition of their cell wall. Learn the difference between Gram-positive and Gram-negative bacteria. Gram-Positive Gram-positive bacteria have a thick peptidoglycan layer and no outer membrane. Gram-Negative Gram-negative bacteria have a thin peptidoglycan layer and an outer membrane. Classification of Antibiotics by Spectrum Antibiotics are classified in two ways. One way to classify antibiotics is based on the spectrum of microorganisms affected. Compare narrow and broad spectrum antibiotics. Narrow Spectrum INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 6 MODULE 04 COMPANION GUIDE PHAR 100 Narrow spectrum antibiotics are only useful against particular species of microorganisms. For example, penicillin G is primarily effective against Gram-positive bacteria. Broad Spectrum Broad spectrum antibiotics are effective against a wider range of microorganisms, including both Gram-positive and Gram-negative bacteria. Tetracyclines are a common example. Classification of Antibiotics by Biochemical Pathway A second way to classify antibiotics is based on the biochemical pathway targeted in the bacterial cell. Antibiotics utilize the concept of selective toxicity by targeting and interfering with essential components of biochemical reactions in bacteria, killing the bacteria. Classifying antibiotics this way allows for the discussion of antibiotics with similar mechanisms of action. Read an introduction to the four groups of antibiotics. Cell Wall Synthesis Inhibitors Cell wall synthesis inhibitors function to stop the proper formation of the bacterial cell wall and/or membrane, influencing the structural integrity of the cell. In this section, you will learn about two classes of antibiotics that target bacterial cell wall synthesis: penicillins and cephalosporins. D N A Synthesis Inhibitors D N A synthesis inhibitors inhibit D N A replication in bacteria, preventing bacterial growth. You will learn about a class of antibiotics that inhibits bacterial D N A synthesis: fluoroquinolones. Protein Synthesis Inhibitors Protein synthesis inhibitors inhibit protein translation within bacteria and thereby protein synthesis. Two classes of antibiotics that inhibit bacterial protein synthesis will be discussed: tetracylines and macrolides. Metabolic Inhibitors Metabolic inhibitors block the formation of key bacterial metabolic substrates needed for bacteria to survive and reproduce. You will learn about one class of metabolic inhibitors: antifolate drugs. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 7 MODULE 04 COMPANION GUIDE PHAR 100 Cell Wall Synthesis Inhibitors: Penicillins The fact that Penicillium mould could produce and excrete an antibacterial substance was first discovered by Alexander Fleming in 1929, but penicillin wasn’t successfully isolated from the mould until the Second World War (1939-1945) by Florey and Chain. In general, two types of penicillins exist: natural (e.g., penicillin G) and semisynthetic (i.e., modified versions of penicillin G). Explore the natural and semisynthetic types of penicillins. Penicillin G Extracted and purified from Penicillium mould, penicillin G is a narrow spectrum antibiotic that destroys mainly Gram-positive bacteria. It is useful in the treatment of pneumonia, middle ear infections, skin infections, and meningitis. It is also very useful in the treatment of syphilis. Other natural penicillins exist, however, they are not used clinically. Methicillin Organisms can produce penicillinase (an enzyme that breaks down penicillin) and become resistant to penicillin G. Methicillin is an antibiotic resistant to attack by penicillinase. Ampicillin and Amoxicillin Ampicillin and amoxicillin are antibiotics that have a broader spectrum of antibacterial activity than penicillin G, and are useful against a range of infections caused by Gram-negative bacteria (e.g., urinary tract infections). Amoxicillin and Clavulanic Acid Amoxicillin and clavulanic acid is a combination of a semisynthetic penicillin plus an inhibitor of penicillinase that was introduced into therapy to combat penicillinase-producing strains of bacteria. Mechanism of Action of Penicillin Penicillin is closely related to D-alanyl-D-alanine, a chemical component necessary for the formation of new bacterial cell walls. As a result, penicillin interferes with new bacterial cell wall formation and the resulting cells are formed without cell walls. These cells are known as protoplasts and are fragile and can readily burst. Human cells do not have cell walls and are therefore unaffected by penicillin. Thus, penicillin is selectively toxic to bacteria. The diagram summarizes penicillin’s general action. The mechanism of action of penicillin will be discussed in greater detail in a few slides, at the same time as the mechanism of action of cephalosporins. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 8 MODULE 04 COMPANION GUIDE PHAR 100 Adverse Effects of Penicillin The most common adverse effect to penicillin is gastrointestinal distress (i.e., nausea and diarrhea) due to disturbance of healthy gut flora. Another adverse effect is penicillin allergy. Studies suggest that 1-10% of the population is allergic to penicillin. If an individual is allergic to one penicillin preparation, they may be allergic to other penicillin preparations. Common manifestations of penicillin allergy include rash, fever, face and tongue swelling, and itchy hives. In rare cases, individuals may experience severe difficulty breathing and a marked fall in blood pressure (i.e., anaphylactic shock). Alt Text: A severe rash resulting from penicillin use. Cell Wall Synthesis Inhibitors: Cephalosporins A second class of antibiotics that selectively inhibit cell wall synthesis is cephalosporins. These antibiotics are chemically similar to penicillins, but in general are more resistant to penicillinase than the penicillin group. Cephalosporins are divided into five generations, depending mainly on their spectrum of activity. The different classes of cephalosporins will not be covered in this course. You will learn about the mechanism of action of cephalosporins in a few slides. View the core structure of cephalosporin compared to penicillin. Note: Chemical structures are for your interest only and will not be tested. Cephalosporin Penicillin Note: Chemical structures are for your interest only and will not be tested. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 9 MODULE 04 COMPANION GUIDE PHAR 100 Adverse Effects of Cephalosporins The adverse effects of cephalosporins are similar to penicillins. Common adverse effects include gastrointestinal side effects such as nausea and diarrhea. There is potential for a person who is allergic to penicillin to also be allergic to cephalosporins, however, this is uncommon. Mechanism of Action of Penicillin and Cephalosporins You have now been introduced to two classes of antibiotics that inhibit cell wall synthesis, penicillin and cephalosporins. Watch the video to learn the mechanism of action of penicillin and cephalosporins (0:54). Start of Video Transcript: This figure shows the mechanism of action of the penicillins and the cephalosporins. In bacterial cell wall synthesis, two glycopeptide chains are connected by an enzyme called a transpeptidase. This reaction forms a strong, stable cell wall releasing D-alanine in the process. Penicillin and the cephalosporins resemble D-Alanine in structure and compete with D-Alanine for the binding spot on the transpeptidase, thus inhibiting the enzyme. Without this crosslinking, the cell wall is not functional. The intracellular pressure in bacteria is high and they need the rigid cell wall to protect against the high internal pressure. If the bacterial cell cannot form a proper cell wall, it will not be able to maintain its internal environment and will break open and die. Penicillin and cephalosporin are not toxic to human cells as human cells do not have cell walls, but rather have cell ranes. End of Video Transcript. D N A Synthesis Inhibitors: Fluoroquinolones Fluoroquinolones are a chemically distinct class of antibiotics that inhibit bacterial D N A synthesis. An example of this class of synthetic antibiotic is ciprofloxacin. It can be used for oral or intravenous therapy of infections caused by a wide variety of Gram- positive and Gram-negative microorganisms. Alt Text: Ciprofloxacin tablets and the chemical structure of ciprofloxacin. Note: Chemical structures are for your interest only and will not be tested. Protein Synthesis Inhibitors: Tetracyclines Tetracyclines were one of the first broad spectrum antibiotics developed. Because of widespread use for many years, many bacteria which were formerly susceptible to their action have become resistant. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 10 MODULE 04 COMPANION GUIDE PHAR 100 Learn more about tetracyclines. Mechanism of Action Tetracyclines bind to the 30S subunit of the m R N A-ribosome complex and prevent the addition of amino acids to the protein chain, inhibiting protein synthesis. Adverse Effects Adverse effects of tetracyclines include gastrointestinal effects such as nausea, vomiting, and diarrhea, as well as, discolouration of teeth and diminished bone growth. Use in Special Populations Tetracyclines have a strong affinity for calcium, therefore they are used very cautiously during pregnancy or in children under 12. Storage Tetracyclines can deteriorate into toxic degradation products if stored for long periods of time so it is important to discard outdated supplies. Protein Synthesis Inhibitors: Macrolides Macrolides are active against several bacterial infections caused by Gram-positive microorganisms. When an individual is allergic to penicillin, a macrolide may be an effective alternative. Erythromycin, a type of macrolide, is also effective in treating infections caused by some Gram-negative bacteria. Macrolides bind to the 50S ribosomal subunit on t R N A and block peptide bond formation. Adverse effects include nausea, vomiting, and diarrhea (most common cause of discontinuing treatment with erythromycin). Video: Mechanism of Action of Tetracycline and Macrolide As you just learned, tetracyclines and macrolides are two types of protein synthesis inhibitors that function using slightly different mechanisms. Watch the video to review the mechanisms of action for both tetracycline and macrolides (0:59). Start of Video Transcript: This figure shows the steps in bacterial protein synthesis and the site of action of the tetracycline and the macrolide antibiotics. In step 1, the charged transfer R N A carrying amino acid 6 binds to the acceptor site on the ribosome. In step 2, the peptidyl transfer R N A, with amino acids 1 through 5 then binds the amino acid chain to amino acid 6, increasing the peptide chain. In step 3, the uncharged transfer R N A is released. In step 4, the new 6 amino acid peptide moves into position with its new transfer R N A, and the process repeats. Tetracyclines bind to the 30S ribosomal subunit and prevent the binding of the charged transfer R N A, designated t6 in red, and stops protein synthesis. Macrolides bind to the 50S ribosomal subunit and block peptide bond formation, that is the addition of an amino acid to the peptide chain, preventing protein synthesis. End of Video Trancript. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 11 MODULE 04 COMPANION GUIDE PHAR 100 Metabolic Inhibitors Antifolates are inhibitors of folate metabolism in bacteria. Tetrahydrofolic acid, a folate, is essential for bacteria to synthesize D N A and protein. If tetrahydrofolic acid is not formed, bacterial growth will slow. Sulfonamides and trimethoprim are both classified as antifolate drugs. Learn about the two antifolate drugs. Sulfonamides Sulfamethoxazole, a member of the sulfonamide group of drugs, competitively inhibits an upstream step in the synthesis of tetrahydrofolic acid, by inhibiting para-aminobenzoic acid (P A B A) incorporation into dihydropteroic acid. Susceptible bacteria must synthesize tetrahydropfolic acid from P A B A, however, mammalian cells use preformed tetrahydrofolic acid from their surroundings. Thus, sulfonamides are selectively toxic to the bacteria. Trimethoprim Trimethoprim inhibits the enzyme dihydrofolic acid reductase, thus inhibiting tetrahydrofolic acid formation. While humans do possess this enzyme, trimethoprim is selectively toxic to bacteria because it has greater inhibitory actions on the bacterial enzyme than on the human enzyme. Combination Antifolates By inhibiting sequential steps in the metabolic pathway, a synergistic antibacterial effect is produced. As such, a combination product containing sulfamethoxazole and trimethoprim was developed. Sulfamethoxazole-trimethoprim, also known as co-trimoxazole, is useful in the treatment of urinary tract infections, respiratory tract infections, and gastrointestinal tract infections. Antibiotic Combinations On top of the antifolates you learned about on the previous slide, other antibiotics are sometimes used in combination. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 12 MODULE 04 COMPANION GUIDE PHAR 100 Learn when antibiotics should be used in combination and the disadvantages of using antibiotics in combination when not indicated. Use of Antibiotics in Combination Antibiotics should be used in combination for: Therapy of a severe infection where the microorganism responsible is not known or the infection is so dangerous that one cannot wait to determine by laboratory tests which microorganism is responsible. Treatment of a mixed bacterial infection where no single antibiotic could eliminate all the different bacteria responsible for the infection. Treating tuberculosis, where emergence of resistant mycobacterium is an important hazard. Therefore, treatment is always carried out with a combination of antitubercular drugs to decrease the chance of emergence of resistant tubercle bacilli. You will learn more about antibiotic resistance later in this section. Infections treated by two antibiotics that act synergistically. Disadvantages The disadvantages of using antibiotics in combination are: Unnecessary additional cost if a single antibiotic is effective. Increased chance of encountering toxicity. Enhanced opportunity for resistant bacteria to arise when the combination of antibiotics being used is not effective for the particular bacterial infection. Decreased number of normal populations of different bacteria, removing their inhibitory influence on potentially dangerous bacteria. Activity: Types of Antibiotics Review You have now explored antibiotics that inhibit cell wall, D N A, and protein synthesis. Select the correct term to match each class of antibiotic to its mechanism of action. Terms: Trimethoprim, Fluoroquinolones, Tetracycline, Macrolides, Penicillin/Cephalosporins, Sulfonamides Mechanism of Action Antibiotic Inhibit bacterial D N A synthesis Inhibit the formation of bacterial cell walls by inhibiting transpeptidase Inhibit protein synthesis by binding to the 30S ribosomal subunit and preventing the addition of amino acids to protein chains Inhibit protein synthesis by binding to the 50S ribosomal subunit and blocking peptide bond formation INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 13 MODULE 04 COMPANION GUIDE PHAR 100 Block folate metabolism by inhibiting PABA incorporation into dihydropteroic acid Block folate metabolism by inhibiting dihydrofolic acid reductase Feedback: Mechanism of Action Antibiotic Inhibit bacterial D N A synthesis Fluoroquinolones Inhibit the formation of bacterial cell walls by inhibiting transpeptidase Penicillin/Cephalosporins Inhibit protein synthesis by binding to the 30S ribosomal subunit Tetracycline and preventing the addition of amino acids to protein chains Inhibit protein synthesis by binding to the 50S ribosomal subunit Macrolides and blocking peptide bond formation Block folate metabolism by inhibiting PABA incorporation Sulfonamides into dihydropteroic acid Block folate metabolism by inhibiting dihydrofolic acid reductase Trimethropim Antimicrobial Resistance Emergence of resistant strains is a long standing problem with antimicrobials. During replication, bacteria can mutate and evolve to have different properties, and can therefore become resistant to antibiotics. The World Health Organization (W H O) issued a report outlining the seriousness of the development of resistant strains of organisms. Although rare, there are infections that are not treatable with currently available antibiotics. For your interest, read the W H O report. Antimicrobial resistance: global report on surveillance Switch between the images. World Map INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 14 MODULE 04 COMPANION GUIDE PHAR 100 World Map: Projected deaths due to antimicrobial resistance every year by 2050. This involves bacteria, viruses, and fungal infections, but you will focus on antibiotic resistance. Comparative Deaths Comparative Deaths: Deaths due to antimicrobial resistance every year now and by 2050 compared to other conditions. Factors Associated With Antibiotic Resistance Two major factors are associated with the development of antibiotic resistance: evolution of bacteria, and clinical and environmental factors (e.g., misuse of antibiotics both clinically and in the environment). How Antibiotic Resistance Develops Learn how bacterial evolution can result in antibiotic resistance. Start of Audio Transcript: When you have a bacterial infection, the initial bacterial population is composed of a diverse array of bacteria with different traits caused by mutations. Some bacteria may have traits making them resistant to certain antibiotics. When an antibiotic is taken, the subset of bacteria that are sensitive to its effects will die, INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 15 MODULE 04 COMPANION GUIDE PHAR 100 while bacteria resistant to its effects will not. Over time, these resistant bacteria will replicate forming a new population and the trait giving them antibiotic resistance will become common to the entire population. End of Audio Transcript. Causes of Antibiotic Resistance Steps to address the causes of antibiotic resistance and reduce its impact can be taken at all levels of society. Learn about causes of antibiotic resistance. Over-Prescription Physicians over-prescribe antibiotics for a number of reasons, such as lack of diagnostic equipment or pressure from drug companies and patients. Inappropriate Use Inappropriate use by individuals can contribute to antibiotic resistance. For example, premature discontinuation of treatment or using drugs prescribed to others. Additionally, some countries allow the sale of antibiotics over the counter, contributing to inappropriate use. Use in Agriculture The use of antibiotics in agriculture may expose the animals to an unnecessary antibiotic which increases the risk of drug-resistance development. Video: Antibiotics for the Flu A common misconception is that antibiotics will help fight colds and the flu. This is not the case. The flu and common cold are caused by viruses. Taking antibiotics for a cold or the flu only contributes to the emergence of resistant bacteria. Watch the video for an introduction to the idea that antibiotics are not always the answer (2:25). Start of Video Transcript: Antibiotics aren't always the answer. You have a cold or it could be the flu - whatever it is, you just want to feel better. You head to the doctor to get antibiotics so you can get back to normal life. Not so fast! Antibiotics save lives, but many times they are prescribed when they aren’t really needed, and that’s a problem. When you’re given antibiotics when they aren't needed, they won't help you, and the side effects could still hurt you. Those side effects can include a rash, dizziness, nausea, diarrhea, yeast infections, and an infection called Clostridium difficile (also called C. difficile or C. diff). Some antibiotics, called fluoroquinolones, have special warnings about severe side effects. These powerful antibiotics are often prescribed even when they aren’t the recommended treatment. Not only can antibiotics cause side effects, they also can lead to antibiotic resistance. Antibiotic resistance occurs when bacteria no longer respond to the drugs designed to kill them. This can make future infections harder to treat. At least two million Americans get infected with antibiotic-resistant bacteria each year. Antibiotics do not work on viruses such as those that cause colds and the flu, bronchitis, or runny noses. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 16 MODULE 04 COMPANION GUIDE PHAR 100 Antibiotics are only needed for treating certain infections caused by bacteria. Antibiotics also won't help some common bacterial infections, including many sinus infections, and some ear infections. When you have an infection caused by bacteria and your doctor prescribes antibiotics, take them exactly as prescribed. Talk with your healthcare professional if you have any questions about your antibiotics. Stay healthy and keep others healthy by cleaning hands, covering coughs, staying home when sick, and getting recommended vaccines, for flu, for example. Improving the way we take antibiotics will help keep us all healthy and will help fight antibiotic resistance so these critical drugs are available for years to come. To learn more about antibiotic prescribing and use, visit https://www.cdc.gov/antibiotic-use/index.html. End of Audio Transcript. Question: The New Superbug Read the article about antibiotic resistance in E. coli, then answer the question using the information in the article and what you have learned about why bacteria become resistant to antibiotics. The Superbug That Doctors Have Been Dreading Just Reached the U.S. What are some of the possible causes for this case of antibiotic resistance? Feedback: Since the m c r-1 gene was first identified in pigs, it is likely that this case of antibiotic resistance developed due to use of antibiotics in agriculture. How Organisms Become Resistant Bacteria have four basic mechanisms for how they acquire resistance to antibiotics. Learn the mechanisms by which organisms become resistant. Uptake Target Inactivation Efflux Pumps Small molecules A mutation in the Microorganisms Some microorganisms gain access to the target for the develop an enzyme will over express inside of the antibiotic can also that inactivates the transporters that microorganism by reduce the binding of antibiotic. For pump the drug out of moving through pores the drug to its target example, the the microorganism in the membranes. and be ineffective. formation of before the cell can be Mutation or lack of penicillinase, which injured. these pores makes the inactivates penicillin. organism resistant. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 17 MODULE 04 COMPANION GUIDE PHAR 100 Antifungal Drugs The incidence of serious fungal infections continues to increase, particularly in patients who are required to take immunosuppressive drugs. Unfortunately, only a few highly effective antifungal drugs are available. Learn how the two common classes of antifungals work. Echinocandins Echinocandins are a newer class of antifungals and are commonly used. They act by inhibiting the synthesis of a component of the cell wall, resulting in disruption of the cell wall and fungal death. Two examples are micafungin and caspofungin. Echinocandins are very well tolerated in patients and are only available for intravenous administration. Imidazoles (or Azoles) The imidazoles (e.g., ketoconazole, fluconazole, etc.) are effective when taken orally or intravenously for systemic fungal infections. These antifungals all inhibit a fungal cytochrome P450, thereby inhibiting ergosterol synthesis. Ergosterol is critical for fungal cell wall function and survival. The selective toxicity of the azoles lies in their higher affinity for the fungal P450 than the human P450s that are involved in drug metabolism. A number of these agents (e.g., miconazole) are available as over-the-counter drugs for the treatment of yeast infections. Question: P450 Pharmacokinetics Answer the question using what you recall from Module 01. Recall from Module 01 that P450s are also important to human pharmacokinetics. What step in pharmacokinetics are they involved in and why don't they interfere with this step when taken as an antifungal? Feedback: In humans, the P450 family of enzymes are responsible for the metabolism of the vast majority of clinically used drugs. Remember that many drugs rely on selective toxicity. The selective toxicity of the azoles lies in their higher affinity for the fungal P450 than the human P450s that are involved in drug metabolism. This selective toxicity is not perfect, however, and imidazoles can sometimes cause drug-drug interactions by interfering with metabolism. Viruses and Antiviral Drugs INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 18 MODULE 04 COMPANION GUIDE PHAR 100 A virus is a small, infectious agent that is only able to multiply within the living cells of other organisms, including animals, plants, and bacteria. Viruses can be deadly, and there is a great need for additional and more effective antiviral drugs. As such, efforts have been directed to synthesize and test new antiviral agents. Video: Viral Cycle The viral life cycle can serve as a means of identifying targets for drug therapy of viral disease. Watch the video for an introduction to the viral life cycle (2:28). As you watch: Focus on the steps of the viral cycle that are listed. Current antiviral drugs act by targeting one or more of these viral life cycle steps. Start of Video Transcript: You probably already know that viruses are responsible for causing a number of diseases, from AIDS to the flu. But did you ever wonder how a virus works? Viruses are basically infectious particles that take over the operation of a cell for the sole purpose of manufacturing new viruses. How exactly does a virus do this? In many ways it works in the same manner as a computer virus does – it has to first gain access and then convince the machinery within the device, in this case a cell, to make multiple new copies of the virus. There are many different types of viruses, but they do share some similar characteristics. First of all, viruses are usually specific in the types of cells that they infect. The specificity of the virus is dependent upon the types of receptors that are found on the surface of the target cell. Every cell in your body has a pattern of protein receptors on its surface. The virus uses these proteins to target specific cells for infection. In this example, the genetic material of the virus infecting the cell is D N A. However, unlike the complex D N A found in the nucleus of a cell, the D N A of a virus is relatively simple, and just contains the information needed to manufacture new virus parts. Once inside the cell, the instructions in the D N A are transcribed to R N A. The protein-building machinery of the host cell then translates these instructions into the components of a new virus. These parts are then assembled into new viruses within the host cell. These parts are then assembled into new viruses within the host cell. When ready, they emerge from the host cell, often killing it in the process. As they emerge, some viruses retain parts of the host cell membrane, forming an envelope around the virus. This envelope gives some protection to the virus from the immune system of the host organism. Each new virus is now capable of infecting another host cell and repeating the process of virus replication. By understanding how the life cycle of a virus works, scientists have been able to develop antiviral drugs that target specific points in the virus life cycle and thus prevent the virus from replicating. End of Video Transcript. Types of Antivirals Recent efforts have been focused on developing antiviral drugs that are more selective for their viral targets than initial therapies. Learn about two antivirals: oseltamivir (tamiflu) and acyclovir. Oseltamivir (Tamiflu) INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 19 MODULE 04 COMPANION GUIDE PHAR 100 Oseltamivir (brand name Tamiflu) is a neuraminidase inhibitor used to treat influenza. Neuraminidase is an enzyme that allows the spread of the virus from cell to cell. Drugs of this class prevent neighbouring cells from being infected with the virus. Acyclovir Acyclovir is taken up into infected cells, and the virus activates acyclovir to the active form. Active acyclovir then inhibits viral D N A replication. Thus, acyclovir is selective for cells that are infected with the virus. Acyclovir is the drug of choice for treatment of serious infections caused by herpes simplex virus (H S V). Long-term use of acyclovir will markedly decrease the frequency of recurrence of genital herpes. Acyclovir is also useful in combating infections due to varicella-zoster virus (V Z V), the virus that causes chickenpox and shingles. Question: Antivirals vs Vaccines As the search for more effective antiviral drugs to treat viral infections progresses, an alternative strategy used to control viruses in the community is through vaccines. Answer the question using what you have learned about antivirals and what you know about vaccines. 1 of 1: What do you think the major difference between vaccines and antivirals are? Feedback: The major difference between vaccines and antivirals are their general mechanism of action and when they are administered. Vaccines introduce non-functional fragments of the virus to the body prior to viral infections, such that the adaptive immune system is able to recognize and destroy the virus if it is introduced into the body. Vaccines are preventative, while antivirals treat infections already occurring in the body. Question: End of Section 01 Quiz (1 of 2) Answer the question based on what you have learned in this section. 1 of 2: Which one of the following penicillins is resistant to the action of penicillinase? a) Methicillin b) Penicillin G c) Ampicillin d) Amoxicillin Feedback: Correct response: a). Methicillin is resistant to the action of penicillinase. Question: End of Section 01 Quiz (2 of 2) Answer the question based on what you have learned in this section. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 20 MODULE 04 COMPANION GUIDE PHAR 100 2 of 2: Co-trimoxazole is a combination of trimethoprim and which other drug? a) Fluoroquinolones b) Penicillin V c) Sulfamethoxazole d) Cephalosporins Feedback: Correct response: c). Co-trimoxazole is a combination of trimethoprim and sulfamethoxazole. Section 01: Summary In this section you learned about drugs used to treat infections including antibiotics, antifungals, and antivirals. Antibiotics can be classified based on the spectrum of microbes they effect as well as the biochemical pathway they target. You explored classes of antibiotics that inhibit cell wall and cell membrane synthesis, D N A synthesis, and protein synthesis. You were then introduced to two common classes of antifungals and two types of antivirals. Finally, you examined the ongoing antimicrobial resistance problem, including how antimicrobial resistance occurs and how organisms become resistant to the effects of antimicrobials. Definitions: Bacteriostatic: Inhibits the growth and reproduction of bacteria. Bactericidal: Directly kills the bacteria. Cell Lysis: The cell membrane breaking down. Meningitis: Inflammation of the covering of the brain and spinal cord. Antimicrobials: An antimicrobial is an agent that kills or inhibits the growth of microbes. Antimicrobials include antibiotics, antifungals, antivirals and antiparasitics. Page Links: https://player.vimeo.com/video/183844400 https://player.vimeo.com/video/183844992 https://www.washingtonpost.com/news/to-your-health/wp/2016/05/26/the-superbug-that-doctors- have-been-dreading-just-reached-the-u-s/ https://www.youtube.com/embed/uIut0oVWCEg References: Adapted from Mcstrother, CC BY 3.0 , via Wikimedia Commons. Retrieved August 2021, from: https://commons.wikimedia.org/wiki/File:Penicillin_spheroplast_generation.svg INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 21 MODULE 04 COMPANION GUIDE PHAR 100 Image from VisualDx (www.visualdx.com). Retrieved August 2021, from: https://www-visualdx- com.proxy.queensu.ca/visualdx/diagnosis/drug-induced-hypersensitivity- syndrome?moduleId=100&contentModuleId=101&diagnosisId=51436&sex=F&age=7&imgSet=1&findin gId=25221,3725&reqFId=25221,3725&imgSet=1&ddxView=photos&ddxTab=drug#view=images&gid=1 &pid=19 Trivedi, H. K., Kshtri, N., & Patel, M. C. (2013). A Rapid, Validated RP-HPLC Method for the Simultaneous Determination of Cleaning Validation and Cross-Contamination of 12 Beta-Lactam Compounds. Scientia pharmaceutica, 81(1), 151–165. Retrieved August 2021, from: https://doi.org/10.3797/scipharm.1208-20 Review on Antimicrobial Resistance. (n.d.). Retrieved August 2021, from: https://amr- review.org/infographics.html End of Section 01 INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 22 MODULE 04 COMPANION GUIDE PHAR 100 SECTION 02: REGULATION OF FERTILITY Introduction to Regulation of Fertility and Contraception Medical science has contributed to allowing individuals to have more precise control of their reproduction by the development of various forms of contraception. While hormonal and non-hormonal types of contraception exist, you will only be learning about hormonal contraception in this section, including oral contraceptives, injectable contraceptives (i.e., Depo-Provera), intrauterine devices (I U Ds), and the transdermal patch. Video: The Monthly Ovarian Cycle The monthly ovarian cycle involves the intricate and coordinated interaction of a number of hormones and factors. The mechanism of action of hormonal contraceptives is associated with changes to the hormones in the ovarian cycle making it important to understand the ovarian cycle. Watch the video to review the monthly ovarian cycle (1:43). Start of Video Transcript: At the beginning of the menstrual cycle, the levels of both estradiol and progesterone in the blood are low and the endometrium is sloughed. This is known as menstruation. In response to the low levels of estrogen and progesterone, the hypothalamus begins to secrete gonadotropin releasing hormone, which stimulates the pituitary gland to release two gonadotrophins: follicle stimulating hormone and luteinizing hormone. In response to follicle stimulating hormone, a number of ovarian follicles, each containing one egg or ovum, begin to enlarge. After five or six days, one of these follicles develops rapidly, while the others regress. The maturing follicle begins to secrete estradiol, small amounts at first, then larger amounts, which causes the endometrium to thicken. Around day 14 of the cycle, levels of estrogen and follicle stimulating hormone peak. Luteinizing hormone secretion also peaks around day 14, stimulating the maturing ovarian follicle to grow more rapidly. The follicle swells and eventually bursts, releasing the ovum. This first stage is known as the follicular phase. The corpus luteum, which is the term for the ovarian follicle after it has burst and released the ovum, releases progesterone, which stimulates the endometrium to secrete nutrients that are needed to support the fertilized ovum when/if it arrives in the uterus. Progesterone is the hormone supporting the endometrium in this second half of the cycle. If there is no fertilized ovum, then after 10 or 12 days, the corpus luteum ceases to function, progesterone secretion diminishes, and the endometrium loses hormonal support, leading to sloughing of the endometrium. This second stage is known as the luteal phase. End of Video Transcript. Mechanism of Action of Hormonal Contraceptives The mechanism of action of all hormonal contraceptives is essentially the same. Learn the three main effects of hormonal contraceptives. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 23 MODULE 04 COMPANION GUIDE PHAR 100 Inhibit Hormone Release Hormonal contraceptives inhibit the release of gonadotropin-releasing hormone (G n R H) from the hypothalamus. As a result, the pituitary is not stimulated to release follicle-stimulating hormone (F S H) and luteinizing hormone (L H), resulting in no follicular maturation and the inhibition of ovulation. Inhibit Sperm Migration Hormonal contraceptives commonly include progestins, which alter the secretions of the endocervical gland to a scant, thick fluid not optimal for sperm migration. Inhibit Ovum Implantation Finally, hormonal contraceptives cause the endometrium to not fully develop making it unsuitable for implantation of a fertilized ovum. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 24 MODULE 04 COMPANION GUIDE PHAR 100 Hormonal Contraceptives Several types of hormonal contraceptives modify the ovarian cycle. In this section, you will focus on four main types: oral contraceptives, Depo-Provera, I U D, and transdermal patch. Learn how each type of hormonal contraceptive works and what their adverse effects are. Oral Contraceptives The term oral contraceptive usually refers to a product containing both an estrogen and a progestin. The preparations which contain both estrogen and a progestin are the most effective oral contraceptives developed to date, and are widely used. Types of Oral Contraceptives The oral contraceptives vary in the amount and type of hormones present in the pill, as well as how often the pill is taken. Compare and contrast the different types of oral contraceptives. Fixed Combination These pills have a fixed combination of estrogen and progestin. One preparation is intended to be taken for 21 days out of a 28 day cycle with menses occurring during the 7 day pill-free/placebo period. The first product, Enovid-E, became available in Canada in 1961. Some fixed combination pill regimens are taken for 28 days each cycle with no or very infrequent drug free periods. The advantage of this preparation is that menstruation is eliminated for the duration of therapy, which is particularly useful for individuals who have difficult or problematic menstruations. Multiphasic Multiphasic preparations usually contain a fixed amount of estrogen and variable amounts of progestin; the progestin increases from week to week. With this method of oral contraceptive, the hormone dose is kept to a minimum and adverse events are believed to be reduced as compared to the fixed-dose combination. Another advantage of a multiphasic approach is that the hormonal sequence more closely mimics the pattern of hormones released in the normal ovarian cycle. Progestin Only Pill Progestin only pills, also known at the mini-pill, contain a daily low dose of progestin is taken as long as the drug is needed. Patient acceptability is less than with the estrogen-progestin combinations, since breakthrough bleeding (bleeding between periods) is often a problem. Efficacy in preventing pregnancy is slightly less than with the combination products. Mild and Moderate Adverse Effects of Combination Oral Contraceptives Approximately 20 million females in North America are taking these preparations daily. As such, oral contraceptives are probably one of the most studied drug class in terms of toxicities. A large number of toxicities have been reported and range from mild to serious in severity. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 25 MODULE 04 COMPANION GUIDE PHAR 100 Learn the mild and moderate adverse effects of oral contraceptives. Mild Mild adverse effects include: Nausea, which is caused by the estrogen component and usually abates after one or two cycles. Edema, as the estrogen and progestin cause water retention. Headache (if severe, the drug must be stopped). Moderate Moderate adverse effects include breakthrough bleeding, weight gain, increased skin pigmentation (due to estrogen), acne and hirsutism (the progestin is believed to cause these two responses, as some of them have androgenic properties), and increased vaginal and uterine infections. Post-drug amenorrhea occurs in a few patients and may persist for months. Serious Adverse Effects of Combination Oral Contraceptives In addition to the mild and moderate adverse effects of combination oral contraceptives, serious adverse effects can occur with combination oral contraceptives. Learn about the serious adverse effects of combination oral contraceptives. Blood Clots Estrogens induce the production of some of the factors that are required for blood coagulation, increasing the death rate from blood clots from one per 100,000 individuals per year for non-users of the pill to three per 100,000 individuals per year for users. It can be argued that this is a very low incidence, but it is nonetheless increased. Heart Attack The estrogen-progestin oral contraceptives are associated with a small increased risk for heart attack. The risk is greater if the patient is obese, or if the patient smokes. This is believed to be associated with the progestin component. Some of the newer progestins may be free of this effect. Stroke Females taking oral contraceptives have an increased risk for cerebrovascular disease (stroke). The risk is greater if the patient is over 35 years of age, but all ages are affected. Hypertension Cardiovascular disease in users of oral contraceptives is more prevalent in females over 35 years of age. Cancer Many studies have investigated the effect of oral contraceptives on cancer risk. The current consensus is that endometrial and ovarian cancer risks are reduced and there is no apparent increased risk of developing breast cancer. No clear decision has been made with respect to cervical cancer, as it is complicated by human papillomavirus (H P V) infection. Due to these adverse effects, females should not be taking a combined estrogen-progestin oral contraceptive if they have: thromboembolic disease, cerebrovascular disease, impaired liver function INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 26 MODULE 04 COMPANION GUIDE PHAR 100 or overt liver disease, carcinoma of the breast or estrogen-dependent neoplasia, undiagnosed bleeding, migraines with auras, and/or pregnancy or suspected pregnancy. Oral contraceptives during pregnancy may be associated with congenital limb deformities, masculinization, and cryptorchidism. Non-Contraceptive Benefits of Oral Contraceptives Some of the non-contraceptive benefits of oral contraceptives include: Reduced risk of ovarian cysts. Reduced risk of ovarian and endometrial cancer. Reduced incidence of ectopic pregnancy. Less iron deficiency anemia, as menstrual flow is reduced. Less acne and hirsutism (for those containing newer progestins with less androgenic effects). Depot Depot is a slow-release formulation contraceptive injection. In this method, a progestin dose is injected intramuscularly every three months, and provides contraception for roughly the same timeframe. Adverse Effects Both Depot and the mini-pill are progestin-only hormonal contraceptives, resulting in similar adverse effects. Breakthrough bleeding between periods occurs frequently. Additionally, some progestins alter the profile of the plasma lipids, increasing low density lipoproteins and decreasing high density lipoproteins, which causes a small increase in the risk of coronary vascular disease. This effect does not occur with some of the newer agents. Intrauterine Devices Intrauterine devices (I U Ds) are implanted into the uterus by a medical professional. The most common type releases levonorgestrel and some are effective for up to 8 years. The I U D is a good choice for individuals who wish to have long term reversible contraception and where estrogen is contraindicated. Adverse Effects Associated with the I U D Common adverse effects associated with the IUD include heavy menstrual flow after insertion, pelvic discomfort, and increased uterine infections. Heavy menstrual flow usually resolves within a couple months. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 27 MODULE 04 COMPANION GUIDE PHAR 100 Transdermal Contraceptive Patch Transdermal contraceptive patches contain estrogen and progestin in a patch that is applied to the skin. The drug is delivered at a constant rate for seven days, requiring three patches per cycle. The mechanism of action is the same as for combined estrogen- progestin oral contraceptives. Activity: Hormone Preparations Select the hormone(s) included in the preparation of each type of birth control. Type of Birth Control Progestin Estrogen IUD Fixed, Multiphasic, and Continuous Oral Contraceptives Depo-Provera Mini Pill Transdermal Patch Feedback: Type of Birth Control Progestin Estrogen IUD ✔ Fixed, Multiphasic, and Continuous Oral Contraceptives ✔ ✔ Depo-Provera ✔ Mini Pill ✔ Transdermal Patch ✔ ✔ All types of hormonal birth control have progestin, but only fixed, multiphasic, and continuous oral preparations and the transdermal patch contain estrogen as well. Question: Pros and Cons of Hormonal Contraceptives Answer the question using your knowledge of common routes of drug administration from Module 01. What are some pros and cons to the various routes of administration used for hormonal birth control? Feedback: Pros and cons exist for each method of hormonal contraceptives. The best method will vary for each patient. Read through the table to learn the pros and cons associated with the common hormonal contraceptives. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 28 MODULE 04 COMPANION GUIDE PHAR 100 Pros Cons Most convenient and least Variable amount of absorption Enteral - expensive means of taking a drug, between patients due to differences Oral Contraceptives non-invasive, and self- in intestinal motility and subject to administered. the first pass effect. Patients do not control dosing, Volume of drug is limited Parenteral (Intramuscular) - delivers steady supply of drug for (intramuscular) and is a more The Shot set period, and avoids the first pass invasive procedure. effect. Convenient, delivers steady drug Expensive and can cause local Topical - The Patch supply for set period, and avoids irritation. the first pass effect. The I U D is considered a urogenital form of drug administration, which has not been otherwise discussed in the course. Efficacy of Hormonal Contraceptives This table lists the efficacy of various forms of contraception, expressed as percent effective. There are two measures: rate with perfect use and the rate with typical use. The exact percentages do not have to be memorized, rather the trends in effectiveness between the two columns, as well as which product is most effective, should be noted. Typical Perfect Method Rate Effectiveness Use Effectiveness (%) (%) Estrogen-Progestin O C 99.7 92 Transdermal Patch 99.7 92 Progestin Only Pill 98 92 Depo-Provera 99.7 97 I U D-Progestin 99.9 99.9 Male Contraceptives Historically, contraceptives have always been targeted towards female-bodied individuals. In recent years, research has begun on contraceptives for male-bodied individuals. Male contraceptives, which can be taken orally or injected, have not yet reached the Canadian market. Attempts to inhibit spermatogenesis have been largely unsuccessful, with most of the drugs and processes studied resulting in unacceptable rates of fertility. Review of Spermatogenesis INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 29 MODULE 04 COMPANION GUIDE PHAR 100 Before exploring the options for male contraceptives, it is important to be familiar with the process of spermatogenesis. Listen for a review of spermatogenesis. Start of Audio Transcript: The hypothalamus releases gonadotropin releasing hormone (G n R H), which stimulates the pituitary gland to release follicle stimulating hormone (F S H) and luteinizing hormone (L H). In males, follicle stimulating hormone stimulates the seminiferous tubules in the testes to produce sperm, while luteinizing hormone stimulates the Leydig cells to produce testosterone. Leydig cells are found adjacent to the seminiferous tubules in the testes. Testosterone is the hormone responsible for male secondary sex characteristics and the presence of testosterone in the body inhibits the hypothalamus from releasing more gonadotropin releasing hormone. This prevents overproduction of testosterone. Attempts to create male contraceptives by inhibiting the release of gonadotropin releasing hormone, and thus spermatogenesis, also decrease testosterone production, which leads to the adverse effect of a decrease in sex drive. End of Audio Transcript. Potential Male Contraceptives Four main compounds (or combinations of compounds) have been tested for use as male contraceptives. These contraceptives are primarily administered orally or via injection. Learn about the types of male contraceptives that have been tested. Androgen-Based Androgens can inhibit the release of G n R H and, thus, spermatogenesis. In the studies conducted to date, typically an injectable form of androgen was administered intramuscularly, and two major problems were encountered: o Only 80% of the subjects responded with a lowering of sperm count to less than four million/mL. o The excess androgen enhanced the secondary sex characteristics, including aggression. Estrogens Estrogens, when administered to men, suppress G n R H release and in turn spermatogenesis. When estrogens are given to men, however, testosterone production decreases, as does sex drive, and men develop feminine characteristics. Thus, the subjects were infertile, but they also lost interest in sex. To overcome the deleterious effects of estrogen on secondary sex characteristics, small amounts of androgens were added to the regimen. With this combined estrogen-androgen regimen, only 60% of the subjects became infertile, and adverse effects from the estrogen were too numerous. Progestin and Androgen In this combination, a synthetic progestin is used to inhibit the release of G n R H. This results in loss of spermatogenesis as well as testosterone production, decreasing male secondary sex characteristics. Androgen is added to the regimen to replace the lost testosterone and hence maintain the secondary sex characteristics. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 30 MODULE 04 COMPANION GUIDE PHAR 100 This method has shown more promise than other methods, but finding the appropriate dose of the exogenous androgen is a major challenge. Gossypol Gossypol is a compound obtained from cottonseed. It destroys elements of the seminiferous tubules, decreasing sperm production, but does not alter sex drive or other functions of testosterone. The drug has undergone extensive clinical trials in China; appropriate use led to infertile sperm counts in 99% of the subjects. Recovery of sperm count after discontinuing use of gossypol is not always guaranteed. However, it is more apt to occur if the sperm count does not fall too low and the duration of treatment does not exceed two years. Hypokalemia has been the major problem reported, resulting in transient paralysis. The drug was undergoing clinical trials in North America, but has now been abandoned. Question: Injectable Male Contraceptive A form of local injectable male contraceptive is currently undergoing preclinical trials. Read an article about Vasalgel, then answer the question. Male Contraceptive Gel 1 of 1: What benefits do you think a local, injectable, non-hormonal form of male contraceptive has over hormonal contraceptives? Feedback: A non-hormonal form of male contraceptive would avoid all of the side effects related to administering hormones, such as increased aggression, decreased libido, or the development of feminine characteristics. Additionally, an injectable form of contraceptive allows the patient to ensure contraceptive protection before engaging in sexual activity. Hormones in Transgender Individuals Hormone therapy and drugs that modulate the effects of the hormones you’ve learned about in this course are also used in transgender individuals. This topic is covered in upper year courses, such as PHAR370: Fundamentals of Pharmacology & Therapeutics. If you are interested in learning more about hormone therapy in transgender individuals, please visit: Rainbow Health Ontario. End of Section 02 Quiz Answer the question based on what you have learned in this section. 1 of 2: Which one of the following statements correctly applies to hormonal contraceptives? a) They are associated with few adverse effects. b) They can only be injected or applied as a patch. c) They make cervical gland secretions optimal for sperm migration. d) They are very effective when taken correctly. Feedback: INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 31 MODULE 04 COMPANION GUIDE PHAR 100 Correct response: d). Hormonal contraceptives are very effective when taken correctly, but are associated with multiple adverse effects. Oral and urogenital administration are also available methods in addition to injection and transdermal patch, and they make cervical gland secretions thick which is not optimal for sperm migration. 2 of 2: Which of the following statements correctly applies to gossypol? a) It decreased sperm count when taken orally in 99% of the subjects. b) It produces a contraceptive effect that is reversible following discontinuation of the drug after 5 years of use. c) It is derived from canola seed oil. d) It is widely used in Europe. Feedback: a). Gossypol was successful in decreasing sperm count when taken orally in 99% of subjects. Section 02: Summary In this section you learned about hormonal contraceptives. You learned that many different preparations of hormonal contraceptives exist, with different routes of administration, but in general, they all share a common mechanism of action. After comparing hormonal contraceptive methods that target the ovarian cycle, you explored contraceptives that target spermatogenesis. You learned that none of these methods have been approved for use in Canada and that the most promising new form of contraceptive is an injectable non-hormonal gel. Definitions: Contraception: The prevention of conception. Progestins: Progesterone-like compounds. Hirsutism: Abnormal growth of hair on a person’s face and body, especially on a female. Amenorrhea: The absence of menstruation. Thromboembolic disease: A blood clotting disease. Cryptorchidism: Udescended testes. Levonorgestrel: A progestin. Spermatogenesis: Sperm development. Less than Four Million/m L: This is the level considered to be infertile. Hypokalemia: Low potassium. Page Links: INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 32 MODULE 04 COMPANION GUIDE PHAR 100 https://player.vimeo.com/video/183845226 https://www.sciencedaily.com/releases/2017/02/170207191905.htm References: Adobe Stock Image. File #: 217994108. Direct link: https://stock.adobe.com/ca/images/contraception- day-control-pill-medication-oral-test-icons-set-flat-illustration-of-25-contraception-day-control-pill- medication-oral-test-vector-icons-for-web/217994108?prev_url=detail Stacey, D. (2020). Depo-Provera Contraception Injection. Your First Year of Depo-Provera Use. verywellhealth. Retrieved August 2021, from: https://www.verywellhealth.com/what-to-expect-before- your-first-dose-of-depo-provera-906873 Pentiumsoak, CC BY-SA 4.0 , via Wikimedia Commons. Retrieved August 2021, from: https://commons.wikimedia.org/wiki/File:Alat-kontrasepsi- IUD.webp End of Section 02 End of Module 04 INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 33 MODULE 04 COMPANION GUIDE PHAR 100 CONCLUSION You have now completed Module 04: Common Prescription Drugs. In this module, you learned about the mechanism of action, therapeutic effects, and adverse effects of common prescription drugs such as antibiotics, antifungals, antivirals, and hormonal contraceptives. The information you learned in this module will aid you in the completion of Assessment 2. All course content was originally authored and developed by Jeanne Mulder, P h D and William Racz, P h D, R P h. Revisions to course content were completed by Jeanne Mulder, P h D, Mandy Turner, P h D, and Nicole Nakatsu, R P h. This module was developed in collaboration with the Course Development Team within the Office of Professional Development and Educational Scholarship. Do not distribute this online learning module to any learners who are not affiliated with Queen’s University as it is a direct violation of the Queen’s Academic Integrity Policy. All materials in this module are protected by copyright and must not be distributed to third party sites. Learners found in violation can face sanctions. INTRODUCTORY PHARMACOLOGY | PHAR 100 MODULE 04 PAGE 34