PST Level 6 Semester 1

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Genital Herpes Basic Pharmacotherapy • Source Session/Topic 17 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 17: Pharmacotherapy of Genital Herpes Learning Tasks By the end of this session students are expected to be able to: Define genital herpes Explain pathophysiology of genital herpes Explain the clinical presentation of genital herpes Outline diagnosis of genital herpes Describe pharmacological treatment of genital herpes Describe the monitoring of genital herpes therapy Activity: Buzzing • What is Genital Herpes? Definition of Genital Herpes Genital Herpes Genital herpes is a common sexually transmitted infection caused by the herpes simplex virus (HSV). Sexual contact is the primary way that the virus spreads. There are two types of Herpes Simplex viruses; herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). HSV-1 is associated most commonly with oropharyngeal disease, and HSV-2 is associated most closely with genital disease; However, each virus is capable of causing clinically indistinguishable infections in both anatomic areas. Definition of Genital Herpes Cont.…. Humans are the sole known reservoir for HSV. Infection is transmitted via inoculation of virus from infected secretions onto mucosal surfaces (e.g., urethra, oropharynx, cervix, and conjunctivae) or through abraded skin. The cycle of HSV infection occurs in five stages: primary muco-cutaneous infection, infection of the ganglia, establishment of latency, reactivation, and recurrent infection Pathophysiology Of Genital Herpes After viral inoculation, HSV infection is associated with cytoplasmic granulation(condensed areas of cellular material that may be bounded by a membrane), ballooning degeneration of cells (cells undergoing this form of death increase in size(balloon), and production of mononucleated giant cells ( cells formed by fusion of monocytes/macrophage) Initially, the cellular response is predominantly polymorph nuclear, followed by a lymphocytic response. Replication occurs with viral spread to contiguous cells and peripheral sensory nerves. Latency then is established in sensory or autonomic nerve root ganglia. Latency appears to be lifelong, interrupted only by reactivation of the viral infection. It is unclear what factors are important in maintaining latency, but immune responses and emotional and physical stresses appear important in reactivating latent virus. Clinical Presentation Of Genital Herpes The signs and symptoms of genital herpes infection are influenced by many factors, including previous exposure to HSV, viral type, and host factors such as age and site of infection. High percentage of initial and recurrent infections are asymptomatic, Viral shedding can occur in the absence of apparent lesions or symptoms A summary of the clinical presentation of genital herpes is provided in Table Diagnosis Of Genital Herpes A presumptive diagnosis of genital herpes commonly is made based on the presence of dark-field negative , vesicular, or ulcerative genital lesions. A prior history of similar lesions or recent sexual contact with an individual with similar lesions also is useful in making the diagnosis Viral culture. This test involves taking a tissue sample or scraping of the sores for examination in the laboratory . Diagnosis Of Genital Herpes Cont …. Polymerase chain reaction (PCR) test. PCR is used to copy patient DNA from a blood sample, tissue from a sore or spinal fluid. The DNA can then be tested to establish the presence of HSV and determine which type of HSV you have. Blood test. This test analyzes a sample of blood for the presence of HSV antibodies to detect a past herpes infection. Several serologic tests capable of distinguishing HSV-1 and HSV-2 antibodies are available. These tests detect antibodies to type-specific HSV-1 and HSV-2 proteins gG-1 and gG-2, respectively Activity : Small Group Discussion What is the treatment of Genital Herpes? Pharmacological Treatment of Genital Herpes The most achievable goals in the management of genital herpes are to relieve symptoms and to shorten the clinical course, to prevent complications and recurrences, and to decrease disease transmission. Although research has focused primarily on the treatment of active infection and suppression of recurrences, increasing emphasis is being placed on various approaches, including immunotherapy that might provide protection from disease transmission or possibly eliminate established latency. . Pharmacological Treatment of Genital Herpes Oral formulations of acyclovir, famciclovir , and valacyclovir have demonstrated efficacy in reducing viral shedding, duration of symptoms, and time to healing of first-episode genital herpes infections, with maximal benefits seen when therapy is initiated at the earliest stages of infection Pharmacological Treatment of Genital Herpes Monitoring of Genital Herpes Therapy Available antiviral compounds are of greatest benefit in patients experiencing first-episode primary infections, immunocompromised patients, and patients with frequent or severe recurrent infections. Antivirals, however, are palliative and not curative, and patients receiving these agents should be monitored closely for adverse drug effects. Discontinuation of suppressive therapy after 1 year should be considered to assess for possible changes in the patient’s intrinsic pattern of recurrence. In many patients, decreases in recurrence rates and the severity of symptoms occur over time. However, it is also preferred to continue suppressive therapy indefinitely because it significantly reduces asymptomatic viral shedding, a potential benefit in reducing the risk of disease transmission to uninfected sexual partners Key Points Genital herpes is a common sexually transmitted infection caused by the herpes simplex virus (HSV). Infection is transmitted via inoculation of virus from infected secretions onto mucosal surfaces (e.g., urethra, oropharynx, cervix, and conjunctivae) or through abraded skin The signs and symptoms of genital herpes infection are influencedby many factors, including previous exposure to HSV, viral type, and host factors such as age and site of infection Oral formulations of acyclovir, famciclovir , and valacyclovir have demonstrated efficacy in the treatment of genital herpes Evaluation What is genital herpes? What is the pathophysiology of genital herpes? What are the signs and symptoms of genital herpes? How is the treatment of genital herpes? References Wells BG, DiPiro J, Schwinghammer T (2013), Pharmacotherapy Handbook (6 th Ed). New York, NY: McGraw-Hill. DiPiro JT, Talbert RL, Yee GC,

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Urinary Tract Infections Basic Pharmacotherapy • Source Session/Topic 18 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 18: Pharmacotherapy of Urinary Tract Infections Learning Objectives By the end of this session students are expected to be able to : Define urinary tract infections Explain pathophysiology of urinary tract infections Explain the clinical presentation of urinary tract infections Outline diagnosis of urinary tract infections Describe pharmacological treatment of urinary tract infections Describe the monitoring of urinary tract infections therapy Activity: Buzzing What is Urinary Tract Infections? Definition of Urinary Tract Infections Urinary Tract Infections (UTI ) UTI is defined as the presence of microorganisms in the urinary tract that cannot be accounted for by contamination. The organisms present have the potential to invade the tissues of the urinary tract and adjacent structures. Infection may be limited to the growth of bacteria in the urine, which frequently may not produce symptoms. A UTI can present as several syndromes associated with an inflammatory response to microbial invasion and can range from asymptomatic bacteriuria to pyelonephritis with bacteremia or sepsis. Definition of Urinary Tract Infections Cont.…. UTIs are classified by lower and upper urinary tract infections. Upper tract infection include pyelonephritis (an infection involving the kidneys) represents Lower tract infections correspond to cystitis (bladder), Also, UTIs are designated as uncomplicated or complicated. Uncomplicated infections occur in individuals who lack structural or functional abnormalities of the urinary tract that interfere with the normal flow of urine or voiding mechanism. Definition of Urinary Tract Infections Cont.…. These infections occur in females of child-bearing age (15 to 45 years) who are otherwise normal healthy individuals. Complicated UTIs are the result of a predisposing lesion of the urinary tract, such as a congenital abnormality or distortion of the urinary tract, a stone, indwelling catheter, prostatic hypertrophy, obstruction, or neurologic deficit that interferes with the normal Classification of UTI Pathophysiology of Urinary Tract Infections The bacteria causing UTIs usually originate from bowel flora of the host. Although virtually every organism is associated with UTIs, certain organisms predominate as a result of specific virulence factors. The most common cause of UTIs is Escherichia coli , which accounts for 80% to 90% of community-acquired infections. Additional causative organisms in uncomplicated infections include Staphylococcus saprophyticus , Klebsiella pneumoniae, Proteus spp., Pseudomonas aeruginosa , and Enterococcus spp. Pathophysiology cont … Pathogenic organisms have differing degrees of pathogenicity (virulence), which play a role in the development and severity of infection. Bacteria that adhere to the epithelium of the urinary tract are associated with colonization and infection The mechanism of adhesion of gram-negative bacteria, particularly E. coli, is related to bacterial fimbriae that are rigid, hair-like appendages of the cell wall These fimbriae adhere to specific glycolipid components on epithelial cells The most common type of fimbriae is type 1, which binds to mannose residues present in glycoproteins Pathophysiology Cont. … Glycosaminoglycan and Tamm- Horsfall protein are rich in mannose residues that readily trap those organisms that contain type 1 fimbriae, which are then washed out of the bladder. Other fimbriae are mannose resistant and are associated more frequently with pyelonephritis, such as P fimbriae, which bind avidly to specific glycolipid receptors on uroepithelial cells These bacteria are resistant to washout or removal by glycosaminoglycan and are able to multiply and invade tissue, and causing infection Clinical Presentation of UTIs Signs and symptoms Lower UTI: dysuria, urgency, frequency, nocturia , suprapubic heaviness Gross hematuria Upper UTI: flank pain, fever, nausea, vomiting, malaise Physical examination Upper UTI: costovertebral tenderness Clinical Presentation of UTIs Cont … Laboratory tests Bacteriuria Pyuria (white blood cell count >10/mm 3 ) Nitrite-positive urine (with nitrite reducers) Leukocyte esterase-positive urine Antibody-coated bacteria (upper UTI ) Diagnosis of UTIs Symptoms alone are unreliable for the diagnosis of bacterial UTIs. The key to the diagnosis of UTI is the ability to demonstrate significant numbers of microorganisms in an appropriate urine specimen to distinguish contamination from infection. Diagnosis of UTIs Cont.… Urine testing The gold standard for a urine test is to perform a bacteriological urine culture, with identification of the pathogen, with quantification and sensitivity testing. To test whether the patient has a UTI at all, orientating indirect methods are often used in practice to detect the bacteria or inflammation (dip sticks). The bacterial count may be assessed by urine microscopy and immersion culture media. Midstream urine is normally collected Diagnosis of UTIs Cont.… Dip sticks Urine dip sticks are one of the most frequently used instruments for diagnostic testing if there is clinical evidence that a patient is suffering from UTI. Multistix are most often used, which may be able to detect nitrite (a metabolic product of typical pathogens of the urinary tract), leukocyte esterase, protein and blood (as a marker of inflammation ). Diagnosis of UTIs Cont.… Dip sticks…… If nitrite is detected, this increases the probability of a urinary tract infection, with a likelihood ratio [LR] of 2.6 to 10.6. However, the sensitivity is relatively low. In contrast, the detection of leukocyte esterase increases the probability to a lesser degree (LR 1.0 to 2.6). The detection of blood is admittedly highly sensitive, but the specificity is low. Activity : Small Group Discussion What is the treatment of UTI ? Pharmacological Treatment of UTIs The management of a patient with a UTI includes; Initial evaluation, Selection of an antibacterial agent and duration of therapy, and Follow-up evaluation. The initial selection of an antimicrobial agent for the treatment of UTI is based primarily on; The severity of the presenting signs and symptoms, The site of infection, and Whether the infection is determined to be uncomplicated or complicated. Other considerations include antibiotic susceptibility, side-effect potential, cost, and the comparative inconvenience of different therapies . Empirical Treatment of UTIs Treatment of UTI according to Pathogen Monitoring of UTI Therapy In

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Folliculitis, Furunculosis and Carbuncles Basic Pharmacotherapy • Source Session/Topic 19 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 19: Pharmacotherapy of Folliculitis, Furunculosis and Carbuncles Learning Objectives By the end of this session students are expected to be able to: Define folliculitis, furunculosis and carbuncles Explain pathophysiology of folliculitis, furunculosis and carbuncles Explain the clinical presentation of folliculitis, furunculosis and carbuncles Outline diagnosis of folliculitis, furunculosis and carbuncles Describe pharmacological treatment of folliculitis, furunculosis and carbuncles Describe the monitoring of folliculitis, furunculosis and carbuncles therapy Activity: Buzzing What are Folliculitis, Furunculosis and Carbuncles? Definition of Folliculitis, Furunculosis and Carbuncles Folliculitis , Furunculosis and Carbuncles Folliculitis is inflammation of the hair follicle and is caused by physical injury, chemical irritation, or infection. Infection occurring at the base of the eyelid is referred to as a stye. Folliculitis is a superficial infection with pus present only in the dermis , Furuncles and carbuncles occur when a follicular infection extends from around the hair shaft to involve deeper areas of the skin. A furuncle, commonly known as an abscess or boil, is a walled-off mass of purulent material arising from a hair follicle. Definition of Folliculitis, Furunculosis and Carbuncles The lesions are called carbuncles when they coalesce and extend to the subcutaneous tissue . This aggregate of infected hair follicles forms deep masses that generally open and drain through multiple sinus tracts. S. aureus is the most common cause of folliculitis, furuncles, and carbuncles. Inadequate chlorine levels in whirlpools, hot tubs, and swimming pools have been responsible for outbreaks of folliculitis caused by P. aeruginosa . Pathophysiology of Folliculitis, Furunculosis and Carbuncles The skin and subcutaneous tissues normally are extremely resistant to infection but may become susceptible under certain conditions. Even when high concentrations of bacteria are applied topically or injected into the soft tissue, resulting infections are rare. Several host factors act together to confer protection against skin infections. Because the surface of the skin is relatively dry and has a pH of approximately 5.6, it is not conducive to bacterial growth. Continuous renewal of the epidermal layer results in the shedding of keratocytes , as well as skin bacteria. In addition, sebaceous secretions are hydrolyzed to form free fatty acids that strongly inhibit the growth of many bacteria and fungi. Pathophysiology of Folliculitis, Furunculosis and Carbuncles Conditions that may predispose a patient to the development of skin infections include H igh concentrations of bacteria (>10 5 microorganisms), E xcessive moisture of the skin, I nadequate blood supply, A vailability of bacterial nutrients, and Damage to the corneal layer allowing for bacterial penetration. The majority of Skin and Soft Tissue Infections result from the disruption of normal host defenses by processes such as skin puncture, abrasion, or underlying diseases (e.g., diabetes). The nature and severity of the infection depend on both the type of microorganism present and the site of inoculation Clinical presentation and diagnosis of Folliculitis, Furunculosis and Carbuncles Folliculitis Pruritic, erythematous papules typically appear within 48 hours (range: 6 to 72 hours) of exposure to large numbers of organisms. Papules evolve into pustules that generally heal in several days. Systemic signs such as fever and malaise are uncommon, although they have been reported in cases caused by P. aeruginosa Clinical presentation and diagnosis of Folliculitis, Furunculosis and Carbuncles Cont.… Furuncles/ Furunculosis Furuncles can occur anywhere on hairy skin but generally develop in areas subject to friction and perspiration. Furuncles are discrete lesions, whether occurring as singular or multiple nodules. The lesion starts as a firm, tender, red nodule that becomes painful and fluctuant. Lesions often drain spontaneously. Lesions caused by CA-MRSA often have necrotic centers characteristic of “spider bites.” Culture of lesion for laboratory investigation to conform the presence and the type of the pathogen Clinical presentation and diagnosis of Folliculitis, Furunculosis and Carbuncles Cont.… Carbuncles Carbuncles are broad, swollen, erythematous, deep, and painful follicular masses. Carbuncles commonly develop on the back of the neck and are more likely to occur in patients with diabetes. Unlike folliculitis and furuncles, carbuncles are commonly associated with fever, chills, and malaise. Bacteremia with secondary spread to other tissues is common Culture of lesion for laboratory investigation to conform the prensence and the type of the pathogen Activity : Small Group Discussion What is the treatment of Folliculitis, Furunculosis and Carbuncles? Pharmacological treatment of Folliculitis, Furunculosis and Carbuncles Treatment of folliculitis generally requires only local measures, such as warm moist compresses or topical therapy (e.g., clindamycin, erythromycin, mupirocin , or benzoyl peroxide). Topical agents generally are applied two to four times daily for 7 days. Small furuncles generally can be treated with moist heat, which promotes localization and drainage of pus. Large and/or multiple furuncles and carbuncles require incision and drainage. Systemic antibiotics are usually not necessary unless accompanied by fever or extensive cellulitis. Treatment of more severe infections generally consists of a penicillinase-resistant penicillin (such as dicloxacillin ) or a first-generation cephalosporin (such as cephalexin) for 5 to 10 days Drug Treatment Monitoring of Folliculitis , Furuncles and Carbuncles Therapy Many follicular infections resolve spontaneously without medical or surgical intervention. Lesions should be incised if they do not respond to a few days of moist heat and nonprescription topical agents. Following drainage, most lesions begin to heal within several days without antimicrobial therapy. Any patient who is unresponsive to several days of therapy with a penicillinase-resistant penicillin or first-generation cephalosporin should have a culture and sensitivity Performed because of the increasing frequency of MRSA. Key Points Folliculitis is inflammation of the hair follicle and is caused by physical injury, chemical irritation, or infection Symptoms of Folliculitis include Pruritic, erythematous papules typically appear within 48 hours (range: 6 to 72 hours) of exposure to large numbers of organisms Treatment of folliculitis generally requires only local measures, such as warm

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Vulvovaginal Candidiasis Basic Pharmacotherapy • Source Session/Topic 20 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 20: Pharmacotherapy of Vulvovaginal Candidiasis Learning Objectives By the end of this session students are expected to be able to: Define vulvovaginal candidiasis Explain pathophysiology of vulvovaginal candidiasis Explain the clinical presentation of vulvovaginal candidiasis Outline diagnosis of vulvovaginal candidiasis Describe pharmacological treatment of vulvovaginal candidiasis Describe the monitoring of vulvovaginal candidiasis therapy Activity: Buzzing What is Vulvovaginal Candidiasis ? Definition of Vulvovaginal Candidiasis Vulvovaginal Candidiasis Vulvovaginal candidiasis (VVC) refers to infections in individuals with or without symptoms who have positive vaginal cultures for Candida species. Depending on episodic frequency, VVC can be classified as either; Sporadic or Recurrent. This classification is essential to understanding the pathophysiology, as well as the pharmacotherapy of VVC. Definition of Vulvovaginal Candidiasis Cont.… VVC may also be classified as; uncomplicated, which refers to sporadic infections that are susceptible to all forms of antifungal therapy regardless of the duration of treatment, or Complicated, in which consideration of factors affecting the host, microorganism, and pharmacotherapy all have an essential role in successful treatment. Complicated VVC includes recurrent VVC, severe disease, non– Candida albicans candidiasis, and host factors, including diabetes mellitus, immunosuppression, and pregnancy Pathophysiology of Vulvovaginal Candidiasis Candida albicans is the major pathogen responsible for VVC, accounting for 80% to 92% of symptomatic episodes. The remainders are caused by non– C. albicans species, with Candida glabrata dominating. The number of cases of non– C. albicans candidiasis appears to be increasing, possibly related to the use of nonprescription vaginal antifungal preparations and short-course therapy and/ or the increased use of long-term maintenance therapy in preventing recurrent infections. Candida species can act as commensal members of the vaginal flora. Asymptomatic colonization with Candida species has been found in 10% to 20% of women of reproductive age. Pathophysiology of Vulvovaginal Candidiasis Cont … Candida organisms are dimorphic; blastospores are believed to be responsible for colonization (transmission and spread), whereas Germinated Candida forms are associated with tissue invasion and symptomatic infections. To colonize the vagina, Candida species must be able to attach to the mucosa. The attachment process is complex. Not only are candidal surface structures important for attachment, but appropriate receptors for attachment must be present in the epithelial tissue. Pathophysiology of Vulvovaginal Candidiasis Cont.… Not all women have the same range of receptors, which may explain variation in colonization. Changes in the host’s vaginal environment or response are necessary to induce a symptomatic infection. Unfortunately, in most cases of symptomatic VVC, no precipitating factor can be identified C linical presentation of Vulvovaginal candidiasis General Often involves both the vulva and the vagina Symptoms Intense vulvar itching, soreness, irritation, burning on urination, and dyspareunia Signs Erythema, fissuring (crack), curdy “cheese”-like discharge, satellite lesions, edema Laboratory tests Vaginal pH—normal, saline and 10% KOH microscopy— blastospores or pseudohyphae Other diagnostic tests Candida cultures not recommended unless classic signs and symptoms with normal vaginal pH and microscopy are inconclusive or recurrence is suspected Activity : Small Group Discussion What is the treatment of Vulvovaginal Candidiasis ? Treatment of Uncomplicated Vulvovaginal candidiasis Pharmacological Treatment of Vulvovaginal Candidiasis Complicated Vulvovaginal Candidiasis Complicated VVC occurs in patients who are immunocompromised or have uncontrolled diabetes mellitus and pregnant. These individuals need a more aggressive treatment plan. Current recommendations are to lengthen therapy to 10 to 14 days regardless of the route of administration. Therapeutic options include those listed in Table however , regimens should be continued for 10 to 14 days. It is also recommended to repeat 150 mg dose of fluconazole 72 hours after the initial dose for better therapeutic outcomes Pharmacological Treatment of Vulvovaginal Candidiasis Cont.…. Antifungal-Resistant Vulvovaginal Candidiasis Resistance to azole antifungals should be considered in individuals who have persistently positive yeast cultures and fail to respond to therapy despite adherence to prescribed regimens. These infections can be treated with; Boric acid Boric acid administered as a 600 mg intravaginal capsule daily for 14 days of induction therapy, followed by a maintenance regimen of one capsule intravaginal twice weekly. Boric acid should not be administered orally, as it is toxic. OR 5-Flucytosine cream is administered vaginally, 1,000 mg inserted nightly for 7 days. Pharmacological Treatment of Vulvovaginal Candidiasis Cont.…. Monitoring of Vulvovaginal Candidiasis Therapy Efficacy of the antifungal agent is partly influenced by patient adherence to the medication regimen. Patients must be counseled on proper administration and dosing Safety end points include monitoring for occurrence of the relevant drug side effects and drug interactions It is still prudent to monitor for hypersensitivity reactions and side effects that might occur with any medication. Monitoring of Vulvovaginal Candidiasis Therapy Cont.….. GI intolerance is more associated with the oral azoles. Hepatotoxicity can occur when azole therapy is prolonged beyond 7 to 10 days or high doses are used. Periodic monitoring of liver enzymes (alanine transaminase and aspartate amino-transferase) should be considered, especially if prolonged therapy (longer than 21 days) is anticipated. Patients who are receiving IV amphotericin B require daily monitoring by the pharmacist. Key Points Vulvovaginal candidiasis (VVC) refers to infections in individuals with or without symptoms who have positive vaginal cultures for Candida species Symptoms include intense vulvar itching, soreness, irritation, burning on urination, and dyspareunia Azole antifungals and other topical antifungals are drug of choice for culvovaginal candidiasis Evaluation What is Vulvovaginal Candidiasis? What is the pathophysiology of Vulvovaginal Candidiasis? What are the signs and symptoms of Vulvovaginal Candidiasis? How is the treatment of Vulvovaginal Candidiasis? References Wells BG, DiPiro J, Schwinghammer T (2013), Pharmacotherapy Handbook (6 th Ed). New York, NY: McGraw-Hill. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML, (2008): Pharmacotherapy: A Pathophysiologic Approach (7 th ed ): New York, NY: McGraw-Hill. Katz M D., Matthias KR., Chisholm-Burns M A., Pharmacotherapy(2011) Principles & Practice Study Guide:

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Asthma Basic Pharmacotherapy • Source Session/Topic 21 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 21: Pharmacotherapy of Asthma Learning Objectives By the end of this session students are expected to be able to: Define asthma Explain pathophysiology of asthma Explain the clinical presentation of asthma Outline diagnosis asthma Describe pharmacological treatment of asthma Describe the monitoring of asthma Activity: Buzzing What is Asthma ? Definition of Asthma Asthma is a common, chronic respiratory disease of the airways of the lung characterized by either the intermittent or persistent presence of highly variable degrees of airflow obstruction from airway wall inflammation and bronchial smooth muscle constriction. People with asthma experience episodes of wheezing, breathlessness and chest tightness due to widespread narrowing of the airways. The cause of Asthma is unknown but the risk if associated with genetics and environmental factors. Genetic factors account for 60% to 80% of the susceptibility. Asthma represents a complex genetic disorder in that the asthma phenotype is likely a result of polygenic inheritance or different combinations of genes Definition of Asthma Cont.….. Environmental risk factors for the development of asthma include; S ocioeconomic status, F amily size, E xposure to secondhand tobacco smoke in infancy and in utero, A llergen exposure U rbanization , R espiratory syncytial virus infection, and E xposure to common childhood infectious agents List of agents and events Triggering Asthma Pathophysiology Of Asthma The major characteristics of asthma include a variable degree of airflow obstruction (related to bronchospasm, edema, and mucus hypersecretion) and airways inflammation To understand the pathogenetic mechanisms that underlies the many phenotypes of asthma, it is critical to identify factors that initiate, intensify, and modulate the inflammatory response of the airways and to determine how these processes produce the characteristic airway abnormalities . Pathophysiology Of Asthma Cont …. The immunohistopathologic features of asthma include inflammatory cell infiltration: Neutrophils (especially in sudden-onset, fatal asthma exacerbations; occupational asthma, and patients who smoke) Eosinophils Lymphocytes Mast cell activation Epithelial cell injury P athophysiology of Asthma cont. … Airway inflammation contributes to airway hyper responsiveness, airflow limitation, respiratory symptoms, and disease chronicity. In some patients, persistent changes in airway structure occur, including sub-basement fibrosis, mucus hypersecretion, injury to epithelial cells, smooth muscle hypertrophy, and angiogenesis. Gene-by-environment interactions are important to the expression of asthma. Atopy, the genetic predisposition for the development of an immunoglobulin E ( IgE )-mediated response to common aeroallergens, is the strongest identifiable predisposing factor for developing asthma . Viral respiratory infections are one of the most important causes of asthma exacerbation and may also contribute to the development of asthma Clinical Presentation And Diagnosis Of Asthma Clinical Presentation is divided into Acute Asthma Chronic asthma Acute asthma General An episode can progress over several days or hours (usual scenario) or progresses rapidly over 1 to 2 hours . Clinical Presentation And Diagnosis Of Asthma Acute asthma….. Symptoms The patient is anxious in acute distress and complains of severe dyspnea , shortness of breath, chest tightness, or burning and wheezing sound The patient is only able to say a few words with each breath. Symptoms are unresponsive to usual measures ( shortacting inhaled β 2 –agonist administration). Clinical Presentation And Diagnosis Of Asthma Cont … Acute asthma….. Signs Signs include expiratory and inspiratory wheezing on auscultation (breath sounds may be diminished with very severe obstruction), D ry hacking cough, T achypnea , T achycardia , P ale or cyanotic skin, Hyper inflated chest with intercostal and supraclavicular retractions, and Hypoxic seizures if very severe Clinical Presentation And Diagnosis Of Asthma Cont … Acute asthma…… Laboratory PEF(peak expiratory flow) and/or FEV(Forced expiratory volume 1) less than 40% of normal predicted values. Decreased arterial oxygen ( PaO 2 ), and O 2 saturations by pulse oximetry ( SaO 2 less than 90% on room air is severe). Increased arterial or capillary CO 2 if mild, but in the normal range or increased in moderate to severe obstruction . Clinical Presentation And Diagnosis Of Asthma Cont … Acute asthma… Other Diagnostic Tests Blood gases to assess metabolic acidosis (lactic acidosis) in severe obstruction. Complete blood count if there are signs of infection (fever and purulent sputum). Serum electrolytes as therapy with β 2 -agonist and corticosteroids can lower serum potassium, magnesium, and phosphate, and increase glucose. Chest radiograph if signs of consolidation on auscultation Clinical Presentation And Diagnosis Of Asthma Cont … Chronic Asthma General Asthma is a disease of exacerbation and remission, so the patient may not have any signs or symptoms at the time of exam. Symptoms The patient may complain of episodes of dyspnea, chest tightness, coughing (particularly at night), wheezing, or a whistling sound when breathing. These often occur in association with exercise, but also occur spontaneously or in association with known allergens . Clinical Presentation And Diagnosis Of Asthma Cont … Chronic Asthma…. Signs Expiratory wheezing on auscultation, dry hacking cough, or signs of atopy (allergic rhinitis and/or eczema) may occur. Laboratory Spirometry demonstrates obstruction (reduced FEV 1 /FVC(forced vital capacity) with reversibility following inhaled β 2 -agonist administration (at least a 12% improvement in FEV 1). Clinical Presentation And Diagnosis Of Asthma Cont … Chronic Asthma….. Other Diagnostic Tests A fall in FEV 1 of at least 15% following 6 minutes of near maximal exercise. Elevated eosinophil count and IgE concentration in blood. Positive methacholine challenge (PC 20 FEV 1 less than 12.5 mg/mL) or mannitol challenge (FEV 1 decrease of at least 15% from baseline after 635 mg or less ). Activity : Small Group Discussion What is the treatment of Asthma ? Pharmacological Treatment of Asthma Acute Severe Asthma The primary goal is prevention of life-threatening asthma by early recognition of signs of deterioration and early intervention. The principal goals of treatment include: Correction of significant hypoxemia ( A low

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Diabetes Mellitus Basic Pharmacotherapy • Source Session/Topic 22 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 22: Pharmacotherapy of Diabetes Mellitus Learning Objectives By the end of this session students are expected to be able to: Define diabetes mellitus Explain pathophysiology of diabetes mellitus Explain the clinical presentation of diabetes mellitus Outline diagnosis of diabetes mellitus Describe pharmacological treatment of diabetes mellitus Describe the monitoring of diabetes mellitus therapy Activity: Buzzing What is Diabetes Mellitus ? Definition of Diabetes Mellitus Diabetes mellitus (DM) is a group of metabolic disorders of fat, carbohydrate, and protein metabolism characterized by hyperglycemia that results from defects in insulin secretion, insulin action (sensitivity), or both. Or Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, or by the ineffectiveness of the insulin produced which results in increased concentrations of glucose in the blood, which in turn damage many of the body's systems, in particular the blood vessels and nerves. Definition of Diabetes Mellitus Cont.….. There are two types of DM Type 1 diabetes (formerly known as insulin-dependent) in which the pancreas fails to produce the insulin which is essential for survival. This form develops most frequently in children and adolescents, but is being increasingly noted later in life. Type 2 diabetes (formerly named non-insulin-dependent) which results from the body's inability to respond properly to the action of insulin produced by the pancreas. Definition of Diabetes Mellitus Cont.….. Type 2 diabetes is much more common and accounts for around 90% of all diabetes cases worldwide. It occurs most frequently in adults, but is being noted increasingly in adolescents as well. Certain genetic markers have been shown to increase the risk of developing Type 1 diabetes. Type 2 diabetes is strongly familial, but it is only recently that some genes have been consistently associated with increased risk for Type 2 diabetes in certain populations. Definition of Diabetes Mellitus Cont.….. Both types of diabetes are complex diseases caused by mutations in more than one gene, as well as by environmental factors. DM if not well managed can result into complications including; Microvascular complications such as retinopathy, neuropathy, and nephropathy Macrovascular complications such as coronary heart disease, stroke, and peripheral vascular disease. Definition of Diabetes Mellitus Cont.….. Gestational Diabetes It is a condition in which a woman without diabetes develops high blood sugar levels during pregnancy Diabetes in pregnancy may give rise to several adverse outcomes, including congenital malformations, increased birth weight and an elevated risk of perinatal mortality. Strict metabolic control may reduce these risks to the level of those of non-diabetic expectant mothers Pathophysiology Of Diabetes Mellitus Type 1 DM Type 1 DM is the result of a combination of genetic and environmental influences. Type 1 DM is characterized by an absolute deficiency of pancreatic β -cell function. Most often this is the result of an immune mediated destruction of pancreatic β cells, but rare unknown or idiopathic processes may contribute. It most commonly results from autoimmune destruction of insulin-producing β-cells in the pancreas. Pathophysiology Of Diabetes Mellitus Cont.…. One or more environmental factors, such as enteroviruses, dietary factors or toxins, might trigger the development of T-cell dependent autoimmunity in genetically susceptible individuals Autoimmunity is manifested by detectable antibodies to ICA512/IA-2, insulin autoantibody (IAA) and glutamic acid decarboxylase (GAD). Insulitis with gradual β-cell destruction leads to pre-diabetes and finally to overt DM. Pathophysiology Of Diabetes Mellitus Cont.…. Type 2 DM Type 2 diabetic individuals are characterized by defects in insulin secretion; and Insulin resistance involving muscle, liver, and the adipocyte. Impaired insulin secretion Impaired insulin secretion is a decrease in glucose responsiveness, which is observed before the clinical onset of disease. More specifically, impaired glucose tolerance (IGT) is induced by a decrease in glucose-responsive early-phase insulin secretion, and a decrease in additional insulin secretion after meals causes postprandial hyperglycaemia Pathophysiology Of Diabetes Mellitus Cont.…. In the type 2 diabetic patient, decreased postprandial insulin secretion is due to both impaired pancreatic beta cell function and a reduced stimulus for insulin secretion from gut hormones Normally there is an increased insulin secretion in response to an oral glucose stimulus and which is referred to as “the incretin effect” The incretin effect is the result that gut-derived hormones (,glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) when stimulated by glucose. In type 2 diabetic patients, this “incretin effect” is very minimal Pathophysiology Of Diabetes Mellitus Cont.…. The two gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulin tropic polypeptide (GIP), are responsible for over 90% of the increased insulin secretion seen in response to an oral glucose load. Patients with type 2 diabetes remain sensitive to GLP-1 while they are often resistant to GIP. Pathophysiology Of Diabetes Mellitus Cont.…. Insulin resistance Insulin resistance is a condition in which insulin in the body does not exert sufficient action proportional to its blood concentration. The impairment of insulin action in major target organs such as liver and muscles is a common pathophysiological feature of type 2 diabetes. Insulin resistance develops and expands prior to disease onset. Pathophysiology Of Diabetes Mellitus Cont.…. Insulin resistance is related to genetic factors and environmental factors (hyperglycaemia, free fatty acids, inflammatory mechanism, etc.). Known genetic factors, such as change in the shape of insulin receptors that directly affect insulin signalling mechanisms is associated with visceral obesity and promote insulin resistance. Glucolipotoxicity and inflammatory mediators are also important as the mechanisms for impaired insulin secretion and insulin signalling impairment Clinical Presentation Of Diabetes Mellitus The clinical presentations of type 1 DM and type 2 DM are very different. Autoimmune type 1 DM can occur at any age. Individuals with type 1 DM are often thin and are prone to develop diabetic ketoacidosis if insulin is withheld, or under conditions of severe stress;-

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Peptic Ulcer Disease Basic Pharmacotherapy • Source Session/Topic 23 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 23: Pharmacotherapy of Peptic Ulcers Disease Learning Objective By the end of this session students are expected to be able to: Define peptic ulcers disease Explain pathophysiology of peptic ulcers disease Explain the clinical presentation of peptic ulcers disease Outline diagnosis of peptic ulcers disease Describe pharmacological treatment of peptic ulcers disease Describe the monitoring of peptic ulcers disease therapy Activity: Buzzing What is Peptic ulcer Disease? Definition of Peptic Ulcers Disease Peptic ulcer disease refers to painful sores or ulcers in the lining of the stomach or first part of the small intestine, called the duodenum. Peptic ulcer disease (PUD), also known as a peptic ulcer or stomach ulcer, is a break in the lining of the stomach, first part of the small intestine, or occasionally the lower oesophagus An ulcer in the stomach is known as a gastric ulcer while that in the first part of the intestines is known as a duodenal ulcer . Most ulcers are caused by an infection with a type of bacteria called Helicobacter pylori (H. pylori). Definition of Peptic Ulcers Disease Cont.. Factors that can increase your risk for ulcers include: Use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as; Aspirin, even safety-coated aspirin and aspirin in powered form can frequently cause ulcers. naproxen, ibuprofen Definition of Peptic Ulcers Disease Cont.. Many other prescription drugs such; Concomitant use of oral bisphosphonates (e.g., alendronate) Concomitant use of corticosteroids Concomitant use of anticoagulant or coagulopathy Concomitant use of antiplatelet drugs (e.g., clopidogrel ) Concomitant use of selective serotonin reuptake inhibitor Definition of Peptic Ulcers Disease Cont.. Excess acid production from Zollinger -Ellison syndrome, (ZES) gastrinomas , tumors of the acid producing cells of the stomach that increases acid output Excessive drinking of alcohol Smoking or chewing tobacco Peptic ulcers are also associated with radiation, chemotherapy, vascular insufficiency, and other chronic diseases Pathophysiology of Peptic Ulcers Disease A physiologic imbalance between aggressive (gastric acid and pepsin) and protective factors (mucosal defense and repair) remain important issues in the pathophysiology of gastric and duodenal ulcers. Gastric acid is secreted by the parietal cells, which contain receptors for histamine, gastrin, and acetylcholine. Acid (as well as H. pylori infection and NSAID use) is an independent factor that contributes to the disruption of mucosal integrity. Increased acid secretion has been observed for patients with duodenal with Zollinger-Ellison syndrome (ZES) (described in the section Pathophysiology of Peptic Ulcers Disease Cont.. Zollinger-Ellison Syndrome) have profound gastric acid hypersecretion resulting from a gastrin-producing tumor H. pylori produce large amounts of urease, which hydrolyzes urea in the gastric juice and converts it to ammonia and carbon dioxide. The local buffering effect of ammonia creates a neutral microenvironment within and surrounding the bacterium, which protects it from the lethal effect of gastric acid . H. pylori also produces acid inhibitory proteins, which allows it to adapt to the low-pH environment of the stomach Pathophysiology of Peptic Ulcers Disease Cont.. Mucosal injury is produced by elaborating bacterial enzymes (urease, lipases, and proteases), Lipases and proteases degrade gastric mucus, ammonia produced by urease may be toxic to gastric epithelial cells, Adherence bacterial adherence enhances the uptake of toxins into gastric epithelial cells H. pylori virulence factors. H. pylori induces gastric inflammation by altering the host inflammatory response and damaging epithelial cells directly by cell-mediated immune mechanisms or indirectly by activated neutrophils or macrophages attempting to phagocytose bacteria or bacterial products Clinical presentation and Diagnosis of Peptic ulcers disease The clinical presentation of PUD varies depending on the severity of epigastric pain and the presence of complications Ulcer-related pain in duodenal ulcer often occurs 1 to 3 hours after meals and is usually relieved by food, but this is variable General Mild epigastric pain or acute life-threatening upper gastrointestinal complications Clinical presentation and Diagnosis of Peptic ulcers disease Cont …. Symptoms Abdominal pain that is often epigastric and described as burning but may present as vague discomfort, abdominal fullness, or cramping A typical nocturnal pain that awakens the patient from sleep (especially between 12 AM and 3 AM) The severity of ulcer pain varies from patient to patient and may be seasonal, episodes of discomfort usually occur in clusters, lasting up to a few weeks and followed by a pain-free period or remission lasting from weeks to years Clinical presentation and Diagnosis of Peptic ulcers disease Cont …. Symptoms….. Changes in the character of the pain may suggest the presence of complications Heartburn, belching, and bloating often accompany the pain Nausea, vomiting, and anorexia are more common for patients with gastric ulcer than with duodenal ulcer but may also be signs of an ulcer-related complication Clinical presentation and Diagnosis of Peptic ulcers disease Cont …. Signs Weight loss associated with nausea, vomiting, and anorexia Complications including ulcer bleeding, perforation, penetration, or obstruction Laboratory tests Gastric acid secretory studies The hematocrit and hemoglobin are low with bleeding, and stool hemoccult tests are positive. Tests for Helicobacter pylori . Clinical presentation and Diagnosis of Peptic ulcers disease Cont …. Diagnostic tests Fiberoptic upper endoscopy (esophagogastroduodenoscopy) detects more than 90% of peptic ulcers and permits direct inspection, biopsy, visualization of superficial erosions, and sites of active bleeding. Upper gastrointestinal radiography with barium and upper endoscopy are also the diagnostic procedures for suspected peptic ulcer. Tests for Detection of Helicobacter Pyroli Activity : Small Group Discussion What is the treatment of Peptic Ulcers Disease ? Pharmacological Treatment of Peptic Disease The treatment of chronic PUD varies depending on the etiology of the ulcer ( H. pylori or NSAID), whether the ulcer is initial or recurrent, and whether complications have occurred Overall treatment is aimed at relieving ulcer pain, healing the ulcer, preventing ulcer recurrence, and reducing ulcer-related complications. The

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Hypertension Basic Pharmacotherapy • Source Session/Topic 24 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 24: Pharmacotherapy of Hypertension Learning Objective By the end of this session students are expected to be able to: Define hypertension Explain pathophysiology of hypertension Explain the clinical presentation of hypertension Outline diagnosis of hypertension Describe pharmacological treatment of hypertension Describe the monitoring of hypertension therapy Activity: Buzzing What is Hypertension ? Definition of Hypertension Hypertension is defined as a systolic blood pressure (SBP) of higher than 140mmHg or a diastolic blood pressure (DPB) higher than 90mmHg The classification of BP is as been follows : Normal: Systolic lower than 120 mm Hg, diastolic lower than 80 mm Hg Prehypertension: Systolic 120-139 mm Hg, diastolic 80-89 mm Hg Stage 1: Systolic 140-159 mm Hg, diastolic 90-99 mm Hg Stage 2: Systolic 160 mm Hg or greater, diastolic 100 mm Hg or greater Definition of Hypertension Cont.….. Hypertension may be; Primary, which may develop as a result of environmental or genetic causes, or Secondary, which has multiple etiologies, including renal, vascular, and endocrine causes. Primary or essential hypertension accounts for 90-95% of adult cases, and secondary hypertension accounts for 2-10% of cases. Pathophysiology of Hypertension Multiple factors that control BP are potential contributing components in the development of essential hypertension. These include; Malfunctions in either humoral [i.e., the renin-angiotensin- aldosterone system (RAAS)] or vasodepressor mechanisms, Abnormal neuronal mechanisms, Defects in peripheral autoregulation, and Disturbances in sodium, calcium, and natriuretic hormone. Pathophysiology of Hypertension Cont … Many of these factors are cumulatively affected by the multifaceted RAAS, which ultimately regulates arterial BP. It is probable that no one factor is solely responsible for essential hypertension . Clinical Presentation and Diagnosis of Hypertension General: The patient may appear healthy or may have the presence of additional CV risk factors: Age (greater than or equal to 55 for men, greater than or equal to 65 for women) Diabetes mellitus Dyslipidemia (elevated cholesterol or fats in the blood) Microalbuminuria Family history of premature CV disease Obesity (body mass index greater than or equal to 30 kg/m2) Physical inactivity Tobacco use Clinical Presentation and Diagnosis of Hypertension Cont …. Symptoms: Usually none related to elevated BP. Signs: Previous BP values in either the prehypertension or the hypertension category. Laboratory Tests: BUN/serum creatinine, fasting lipid panel, fasting blood glucose , Clinical Presentation and Diagnosis of Hypertension Cont …. Laboratory Tests…. serum electrolytes (sodium, potassium), Spot urine albumin-to-creatinine ratio. The patient may have normal values and still have hypertension. However, some may have abnormal values that are consistent with either additional CV risk factors or hypertension-related damage. Other Diagnostic Tests: 12-lead electrocardiogram, Estimated glomerular filtration rate [using modification of diet in renal disease (MDRD) equation]. Clinical Presentation and Diagnosis of Hypertension Cont …. Hypertension-Related Target-Organ Damage: The patient may have a previous medical history or diagnostic findings that indicate the presence of hypertension-related target-organ damage: Brain (stroke, transient ischemic attack, dementia) Eyes (retinopathy) Heart (left ventricular hypertrophy, angina, prior MI, prior coronary revascularization, heart failure) Kidney (chronic kidney disease) Peripheral vasculature (peripheral arterial disease) Activity : Small Group Discussion What is the treatment of Hypertension ? Pharmacological Treatment Of Hypertension The overall goal of treating hypertension is to reduce hypertension- associated morbidity and mortality. This morbidity and mortality is related to hypertension-associated target-organ damage (e.g . CV events, cerebrovascular events, heart failure, and kidney disease). Reducing CV risk remains the primary purpose of hypertension therapy and the specific choice of drug therapy is significantly influenced by evidence demonstrating such CV risk reduction. Treating patients with hypertension to achieve a desired target BP value is simply a surrogate goal of therapy Pharmacological Treatment Of Hypertension Cont …. In most cases the target BP should be: systolic below 140 mmHg and diastolic below 90 mmHg. In diabetic patients and patients with cardiac or renal impairment, target BP should be below 130/80mmHg; The choice of initial drug therapy depends on the degree of BP elevation and presence of compelling indications ( e.g coexisting conditions such as diabetes and other cardiovascular conditions) Most patients with stage 1 hypertension should be initially treated with a first-line antihypertensive drug, or the combination of two agents. Combination drug therapy is recommended for patients with more severe BP elevation (stage 2 hypertension), using preferably two first-line antihypertensive drugs . Pharmacological Treatment Of Hypertension Cont …. Recommended Initial Medication Doses For Hypertension Treatment Thiazide diuretics Hydrochlothiazide 12.5mg/daily OR Bendroflumethiazide 5mg/daily OR Indapamide 5mg/daily preferred for patient with previous stroke/TIA Pharmacological Treatment Of Hypertension Cont …. Recommended Initial Medication Doses For Hypertension Treatment….. Loop diuretics Furosemide initial dose 40mg twice a day OR Torsemide 5mg/daily Dose can be up scaled depending on congestive status to maximum dose Pharmacological Treatment Of Hypertension Cont …. Recommended Initial Medication Doses For Hypertension Treatment…… Mineralocorticoid (Aldosterone) Receptor antagonist Spironolactone 25mg/daily OR Eplerenone 25mg/daily Angiotensin-Converting Enzyme Inhibitor (ACEI) Captopril 6.125mg, 12.5mg or 25mg three times daily OR Enalapril 10mg twice a day OR Perindopril 8mg/daily orally Pharmacological Treatment Of Hypertension Cont …. Angiotensin Receptor Blocker–ARB (*Don’t combine with ACEI contraindications, indicated in patient sensitive to ACEIs) Losartan 50mg/daily* Beta–blocker Atenolol 50mg/daily OR Metoprolol 50mg/daily Pharmacological Treatment Of Hypertension Cont …. Calcium Channel Blocker ( Dihydropyridines ): Nifedipine (Slow Release/Long Acting) 20mg/30mg/ 60mg/90mg/daily OR Amlodipine 5mg or 10mg/daily Non– dihydropyridine Verapamil 30mg twice–three times a daily OR Diltiazem 30mg twice–three times a day Monitoring of Hypertension Therapy Routine ongoing monitoring to assess disease progression, the desired effects of antihypertensive therapy The monitoring parameters include; Signs and symptoms of Disease Progression Efficacy of antihypertensive and BP goal attainment, and Undesired adverse side effects (toxicity) Monitoring of Hypertension Therapy Cont … Disease Progression Patients should be monitored for signs and symptoms of progressive hypertension-associated target-organ disease. A careful history for ischemic chest pain (or pressure), palpitations,

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Heart Failure Basic Pharmacotherapy • Source Session/Topic 25 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 25: Pharmacotherapy of Heart Failure Learning Objectives By the end of this session students are expected to be able to: Define heart failure Explain pathophysiology of heart failure Explain the clinical presentation of heart failure Outline diagnosis of heart failure Describe pharmacological treatment of heart failure Describe the monitoring of heart failure therapy Activity: Buzzing What is Heart Failure? Definition of Heart Failure Heart failure is a progressive clinical syndrome that can result from any abnormality in cardiac structure or function that impairs the ability of the ventricle to fill with or eject blood, thus rendering the heart unable to pump blood at a rate sufficient to meet the metabolic demands of the body. It is the final common pathway for numerous cardiac disorders, including those affecting the pericardium, heart valves, and myocardium. Diseases that adversely affect ventricular diastole (filling), ventricular systol(Contraction), or both can lead to heart failure Heart Failure is characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress Definition of Heart Failure Cont… Heart Failure is characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress Heart failure can result from any disorder that affects the ability of the heart to contract (systolic function) and/or relax (diastolic dysfunction) Therefore, Heart Failure can be; Systolic Heart Failure or/and Diastolic Heart Failure Definition of Heart Failure Cont… Heart failure with impaired systolic function (i.e., reduced LVEF) is the classic, more familiar form of the disorder LVEF (Left ventricular ejection fraction Common Cause Of Heart Failure Pathophysiology of Heart Failure Key components of the pathophysiology of cardiac remodeling are. Myocardial injury (e.g., myocardial infarction) results in the activation of a number of hemodynamic and neurohormonal compensatory responses in an attempt to maintain circulatory homeostasis. Chronic activation of the neurohormonal systems results in a cascade of events that affect the myocardium at the molecular and cellular levels. These events lead to the changes in ventricular size, shape, structure, and function known as ventricular remodeling. The alterations in ventricular function result in further deterioration in cardiac systolic and diastolic function, which further promotes the remodeling process. (LV left ventricular) Pathophysiology of Heart Failure Cont…. Clinical presentation and diagnosis of HF General Patient presentation may range from asymptomatic to cardiogenic shock. Symptoms Dyspnea, (Shortness of breath) Orthopnea (Discomfort when breathed) Paroxysmal nocturnal dyspnea (an attack of severe shortness of breath and coughing that generally occur at night) Exercise intolerance Tachypnea (Fast breathing) Clinical presentation and diagnosis of HF Cont….. Symptoms….. Cough Fatigue (feeling overtired) Nocturia (Frequent urination) Hemoptysis (Coughing up blood) Abdominal pain Anorexia Nausea Bloating (Build up of gas in the stomach and intestine) Poor appetite, early satiety Ascites (Abnominal swelling) Mental status changes Clinical presentation and diagnosis of HF Cont….. Signs Pulmonary rales (Abnormal lung sound) Pulmonary edema Cool extremities Pleural effusion (build up of fluids between the tissue that line the lungs and the chest) Tachycardia (Fast heart rate) Narrow pulse pressure Clinical presentation and diagnosis of HF Cont….. Signs……. Cardiomegaly Peripheral edema Hepatojugular reflux (test for measuring jugular venous pressure through the distention of the internal jugular vein) Hepatomegaly Clinical presentation and diagnosis of HF Cont….. Laboratory Tests Electrocardiogram may be normal, or it could show numerous abnormalities, including acute ST-T wave changes from myocardial ischemia, atrial fibrillation, bradycardia, and left ventricular hypertrophy. Serum creatinine may be increased due to hypo perfusion. Preexisting renal dysfunction can contribute to volume overload. Complete blood count (CBC) can be useful in determining if heart failure is due to a reduced oxygen-carrying capacity. Clinical presentation and diagnosis of HF Cont….. Laboratory Tests … Chest x-ray: useful for detecting cardiac enlargement, pulmonary edema, and pleural effusions Echocardiogram: used to assess the size of the left ventricle, valve function, pericardial effusion, wall motion abnormalities, and ejection fraction Hyponatremia: serum sodium <130 mEq/L is associated with reduced survival and may indicate worsening volume overload and/or disease progression Activity: Small Group Discussion What is the treatment of Heart Failure?? Pharmacological Treatment of Heart Failure Treatment of Heart Failure of depends on the stage of the Disease There are four identified stages of heart failure, and their treatment recommendations Unless contraindicated, all patients with HF-REF(reduced ejection fraction) should be started on an ACE inhibitor and a beta blocker (and a diuretic, in most cases). No patient should receive three drugs which block the renin-angiotensin-aldosterone system as hyperkalaemia and renal dysfunction will be common. The safety and efficacy of combining an ACE inhibitor, an ARB and MRA is uncertain and the use of these three drugs together is not recommended Functional Classification of Heart Failure Treatment allogarism of Heart failure according to functional stage of Heart Failure Pharmacological Treatment of Heart Failure Cont…. Beta Blockers A meta-analysis confirms that beta blockers also reduce mortality in patients with diabetes and HF All patients with heart failure with reduced ejection fraction,class II-IV, should be started on beta blocker therapy as soon as their condition is stable. Bisoprolol, carvedilol or nebivolol should be the first choice of beta blocker for the treatment of patients with heart failure with reduced ejection fraction. If beta blockers are contraindicated consider using ivabradine Pharmacological Treatment of Heart Failure Cont…. Angiotensin-Converting Enzyme Inhibitors Patients with heart failure with reduced ejection fraction of all NYHA functional classes, should

NTA Level 6 • Semester 1 • PST06106 Pharmacotherapy of Schizophrenia Basic Pharmacotherapy • Source Session/Topic 26 Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability. PST 06106 Basic Pharmacotherapy Session 26: Pharmacotherapy of Schizophrenia Learning Objectives By the end of this session students are expected to be able to: Define schizophrenia Explain pathophysiology of schizophrenia Explain the clinical presentation of schizophrenia Outline diagnosis of schizophrenia Describe pharmacological treatment of schizophrenia Describe the monitoring of schizophrenia therapy Activity: Buzzing What is Schizophrenia ? Definition of Schizophrenia Schizophrenia Schizophrenia is a chronic and severe mental disorder characterised by disorganized and bizarre thoughts, delusions, hallucinations, inappropriate affect, and impaired psychosocial functioning Pathophysiology of Schizophrenia The pathophysiology of schizophrenia is complex. A number of theories attempt to explain the link between altered brain function and schizophrenia, including; T he Dopamine hypothesis The Glutamate hypothesis Neurodevelopmental model Pathophysiology of Schizophrenia Cont… The Dopamine Hypothesis The first formulations of the dopamine hypothesis of schizophrenia came from post-mortem studies finding increased striatal availability of D 2 /D 3 receptors in the striatum, as well as studies finding elevated CSF levels of dopamine metabolites. Psychotic symptoms are related to dopaminergic hyperactivity in the brain. Hyperactivity of dopaminergic systems during schizophrenia is result of increased sensitivity and density of dopamine D2 receptors in the different parts of the brain. Pathophysiology of Schizophrenia Cont… The glutamate hypothesis In humans, NMDA receptor antagonists such as phencyclidine, ketamine and dizocilpine can produce both positive and negative psychotic symptoms-in contrast to amphetamine which produces only positive symptoms. It has therefore been postulated that schizophrenia may result from disruption of glutamatergic neurotransmission, evident as a reduction in the function of NMDA receptors Pathophysiology of Schizophrenia Cont ….. Neurodevelopmental model Neurodevelopmental model supposes in schizophrenia the presence of “silent lesion” in the brain, mostly in the parts, important for the development of integration (frontal, parietal and temporal), which is caused by different factors (genetic, inborn, infection, trauma) during very early development of the brain in prenatal or early postnatal period of life. It does not interfere too much with the basic brain functioning in early years, but expresses itself in the time, when the subject is stressed by demands of growing needs for integration, during formative years in adolescence and young adulthood Clinical presentation of schizophrenia The symptoms of schizophrenia fall into three categories: P ositive , Negative, Cognitive. Clinical presentation of schizophrenia Cont.… Positive symptoms: “ Positive” symptoms are psychotic behaviors not generally seen in healthy people. People with positive symptoms may “lose touch” with some aspects of reality. Symptoms include: Hallucinations Delusions Thought disorders (unusual or dysfunctional ways of thinking) Movement disorders (agitated body movements) Clinical presentation of schizophrenia Cont.… Negative symptoms: “ Negative” symptoms are associated with disruptions to normal emotions and behaviors. Symptoms include: “Flat affect” (reduced expression of emotions via facial expression or voice tone) Reduced feelings of pleasure in everyday life Difficulty beginning and sustaining activities Reduced speaking Clinical presentation of schizophrenia Cont.… Cognitive symptoms: For some patients, the cognitive symptoms of schizophrenia are subtle, but for others, they are more severe and patients may notice changes in their memory or other aspects of thinking. Symptoms include: Poor “executive functioning” (the ability to understand information and use it to make decisions) Trouble focusing or paying attention Problems with “working memory” (the ability to use information immediately after learning it) Diagnosis of Schizophrenia The Diagnostic and Statistical Manual of the American Psychiatric Association, text revision (DSM-IV-TR), is the guide for diagnosing and classifying schizophrenia and other psychiatric disorders Diagnosis of Schizophrenia Cont… Many patients demonstrate both positive and negative symptoms. Patients with negative symptoms frequently have more antecedent cognitive dysfunction, poor premorbid adjustment, low level of educational achievement, and a poorer overall prognosis. Differential diagnosis has to be made in order to exclude other psychiatric conditions that resembles schizophrenia as indicated in the table below ; Differential Diagnosis Of Schizophrenia Activity : Small Group Discussion What is the treatment of Schizophrenia ? Pharmacological Treatment Of Schizophrenia The treatment falls under Acute Phase and Maintenance Phase Acute Phase Haloperidol 5 mg (IM) repeat in 30–60 minutes, if required. (Max dose: 20 mg within 24 hours) AND Diazepam 10 mg (IV), stat. Repeat after 30–60 minutes if needed. OR Promethazine 25–50 mg (deep IM). Repeat after 30–60 minutes if needed. OR Lorazepam 4 mg (IM), stat. Repeat after 30–60 minutes if needed Pharmacological Treatment Of Schizophrenia Cont…. If haloperidol is unavailable give; Chlorpromazine 25–50 mg (deep IM). May be repeated as necessary 4 times in 24 hours. If patient is known to suffer from schizophrenia and is not neuroleptic naïve give: Zuclopenthixol acetate 50–150 mg (IM) Repeat after 2–3 days, if necessary If patient develops acute dystonia give: Promethazine deep IM 25–50 mg. In the elderly 25 mg. OR Anticholinergic agent, e.g . Biperiden , IM/IV, 2 mg. Repeat as necessary . Pharmacological Treatment Of Schizophrenia Cont…. For maintenance: Haloperidol 3-4.5 mg (PO) 12hourly OR Chlorpromazine 100–600 mg (PO) daily in divided doses OR Olanzepine 5–10mg (PO). Maximum dose 25mg/day OR Risperidone 1mg (PO) 12 hourly then increase by 1mg every 2–3 days to 2–3mg 12 hourly. Maximum dose 16mg/day 7 Monitoring of Schizophrenia Therapy Monitoring parameters for patients with Schizophrenia focuses on three general areas: Improvement of four positive symptoms which are suspiciousness, hallucinations, unusual thought contents and conceptual disorganization Improvement of negative symptoms such as prolonged time to respond, emotion including unchanging facial expression, blank, expressionless face, reduced social drive, poor grooming and hygiene Cognition Monitoring of Schizophrenia Therapy Cont.. Pharmacotherapeutic plan should include specific monitoring parameters for side effects. Given the risk of weight gain, diabetes, and lipid abnormalities associated with many of the Antipsychotics, baseline parameters should be taken before beginning antipsychotics: F amily history, W eight , H eight , B ody mass index , Monitoring of Schizophrenia Therapy Cont.. Waist circumference, Blood pressure, Fasting plasma glucose,