Basic Urological Sciences

Cover Half Title Title Page Copyright Page Contents Contributors Abbreviations Preface Foreword Section I: Basic Mechanisms 1. Cellular and Immunobiology Cell Structure Cell (Plasma) Membrane Cytoplasmic Organelles Nucleus Endoplasmic Reticulum (ER) Golgi Apparatus Mitochondria Intracellular Molecules Proteins Lipids Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) Others Cellular Processes Cell Cycle Cell Death Cell Metabolism Vesicle Trafficking Endocytosis Exocytosis Gene Regulation/Expression Transcription (Nucleus) Translation (Cytoplasm) Control of Gene Expression and Epigenetics Signal Transduction DNA Damage and Repair Nucleotide Excision Repair Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ) DNA Mismatch Repair (MMR) Migration/Movement Intracellular Connections/Cell Adhesion Cadherins Desmosomal Junctions Tight Junctions Gap Junctions Immunology Inflammation Innate Immunity Acquired/Adaptive Immunity Immune Checkpoints Recommended Reading 2. Genetics Chromosomes Chromosomes Abnormality Numerical Abnormality Chromosomal Rearrangements Gene Expression Patterns of Inheritance Autosomal Dominant Inheritance Autosomal Recessive Inheritance X-Linked Y-Linked Mitochondrial Inheritance Recommended Reading 3. Oncogenesis and Metastasis Oncogenesis Cancer Clinical Relevance of Cancer Cells Characteristics: Precursor Lesions Cell Populations and Stroma Invasion and Metastasis The Cell Cycle Cell Cycle Checkpoints Cyclins and Cyclin-Dependent Kinases (CDKs) Tumour Protein (TP53) Growth Factors and Signalling Pathways Signalling Immortality and Quiescence Retinoblastoma 1 (RB1) Telomerase and the Hayflick Limit Cell Death Apoptosis Autophagy (Autophagocytosis) Clinical Relevance of Triggering Cell Death Oncogenesis is a Step-Wise Process Cancer Genes Tumour Suppressor Genes (TSG) Clinical Relevance of Tumour Suppressor Gene Activation Oncogenes Hallmarks of Cancer Enabling Hallmarks Emerging Hallmarks Recommended Reading 4. Microbiology Classification of Bacteria Bacteria Structure Infection in the Catheterised Patients Appropriate Microbiology Tests Urine 'Dipstick' Testing Urine Cultures Polymerase Chain Reaction (PCR) Recommended Reading 5. Transplantation Self Versus Non-Self: The Relevance to Clinical Transplantation Blood Groups Major Histocompatibility Complex/Human Leucocyte Antigen Syngeneic Versus Allogeneic Clinical Transplantation (or Tissue-Typing) Laboratory Kidney Donor Types Living Donation Deceased Donation Donation after brain death Donation after circulatory death Ischaemic Reperfusion Injury (IRI) Basic Immunology Antigen Presentation T-Cell Activation Signal 1 Signal 2 Signal 3 Immunosuppression (IS) Steroids Calcineurin Inhibitors (CNI) Nucleotide Inhibitors mTOR Inhibitors Depleting Antibodies Kidney Transplant Surgery Vascular Anastomosis Ureteric Anastomosis Post-Operative Complications Medical Complications Rejection Recommended Reading 6. Haemostasis and Thrombosis Haemostasis Anticoagulant Mechanisms Fibrinolysis The Balance of Haemostasis Laboratory Measurement Thrombosis Specific Pathological States Recommended Reading 7. Systemic Response to Surgery and Shock Systemic Response to Surgery Activations of Stress Response Elements of Stress Response Metabolic Sequalae of Stress Response Unregulated Stress Response Strategies to Mitigate Stress Response Enhanced Recovery After Surgery Shock Cardiogenic Shock Hypovolaemic Shock Distributive Shock Compensatory Mechanisms Decompensatory Mechanisms Recommended Reading Section II: Embryology, Anatomy, and Physiology 8. Embryology, Anatomy, and Physiology of the Kidneys and Ureters Embryology of the Kidney and Ureters The Collecting System The Development of the Nephron Disorders of Renal Development Anatomy of the Kidney and Ureters Kidneys Gerota's Fascia Anatomical Relations Percutaneous Access Nephrectomy Sectional Anatomy Vascular Anatomy Key Points Venous Drainage Lymphatics Key Points Nerve Supply The Ureters Key Points Ureteric Function Ureteric Duplication Physiology of the Kidney Functions of the Kidney Assessment of Glomerular Filtration Tubular Function Proximal Convoluted Tubule Loop of Henle Distal Convoluted Tubule and Collecting Tubule Renin-Angiotensin-Aldosterone System Acid-Base Balance Erythropoiesis Calcium Regulation Vitamin D Parathyroid Hormone Recommended Reading 9. Embryology, Anatomy, and Physiology of the Adrenal Glands Embryology and Anatomy Physiology Recommended Reading 10. Embryology, Anatomy, and Physiology of the Bladder Embryology of the Bladder Bladder Histology Sphincter Bladder Trigone The Developing Bladder in Neonatal Life and Infancy Congenital Anomalies of the Urinary Bladder and its Outlet Urachal Anomalies Exstrophy of the Bladder Posterior Urethral Valves Anatomy of the Urinary Bladder Internal Structure of the Bladder Blood Supply Lymphatics Physiology of the Urinary Bladder Control of the Micturition and Storage Cycle Bladder Filling and the Guarding Reflex Bladder Voiding Bladder Compliance Acknowledgement Recommended Reading 11. Embryology, Anatomy, and Physiology of the Prostate Embryology of the Prostate Anatomy of the Prostate Surfaces and Relations Prostate Lobes Arrangement and Zones Arterial Supply Venous Supply Lymphatic Drainage Nerve Supply Internal Structures of the Urethra Urethral Sphincters Histology of the Prostate Physiology of the Prostate Endocrinology Continence Ejaculation Prostatic Secretions Recommended Reading 12. Embryology, Anatomy, and Physiology of the Male Reproductive System Introduction Embryology of the Testis Testis Development Testicular Descent Transabdominal Stage: Weeks 8-15 Inguinoscrotal Stage: Weeks 24-35 Scrotal Development Embryology of the Penis Anatomy of the Male Genitalia Penis Neurovascular Supply to the Penis (Table 12.3) Urethra Scrotum and Testis Physiology of the Testis Spermatogenesis Physiology of Ejaculation and Erection Neurophysiology () Ejaculation Erection Detumescence Central Neurotransmitters Involved in Erection Recommended Reading 13. Anatomical and Physiological Changes in Pregnancy Pregnancy Physiological Changes The Kidney Anatomy Glomerular Filtration Rate (GFR) Vasculature, Chemical Filtration, and Body Water Maintenance Cardiovascular Changes Renin-Angiotensin-Aldosterone (RAA) System The Ureter Renal Failure The Bladder Urinary Tract Infection (UTI) Renal Calculi Urethra Recommended Reading Section III: Benign Pathology 14. Pain Pain Pain Transmission and Drug Modulation Pain Expression Visceral Pain Neuropathic Pain Mechanisms of Neuropathic Pain Upper Urinary Tract Pain Lower Urinary Tract Pain Scrotal Pain Management of Pain Local Anaesthetics Metastatic Bone Pain Recommended Reading 15. Acute Kidney Injury and Chronic Kidney Disease Anatomy and Physiology (see Chapter 8) Functions of the Kidney Gross Kidney Structure Nephron Physiology Functional Anatomy of the Nephron The Glomerulus Proximal Tubules Loop of Henle Distal Convoluted Tubule Collecting Ducts Biomarkers for Renal Function - GFR Estimation Techniques Limitations to Using Creatinine as a Marker of Renal Function Acute Kidney Injury (AKI) Definition and Classification Risk Factors Creatinine and eGFR Transplant Acute Kidney Injury Pathophysiological Changes Pre-Renal: Aetiology and Pathophysiology Intrinsic or Renal: Aetiology and Pathophysiology Tubular Damage Glomerular Damage Interstitial Damage Vascular Damage Post-Renal: Aetiology and Pathophysiology Early Management in AKI Fluid Balance Optimisation of Intra-vascular Fluid Complications of AKI Electrolyte Complications Acid-Base Complications Fluid Balance Complications Waste Product Accumulation Indications for Acute Dialysis Chronic Kidney Disease Definition and Classification Pathophysiology Glomerulosclerosis Tubulointerstitial Fibrosis Complications of Progressive Disease Anaemia Mineral Bone Disease (CKD-MBD) Secondary Hyperparathyroidism and Osteitis Fibrosis Cystica Other Forms of Renal Osteodystrophy Renal Replacement Therapy (RRT) for CKD Haemodialysis Long-Term Vascular Access Peritoneal Dialysis CAPD (Continuous Ambulatory Peritoneal Dialysis) APD (Automated Peritoneal Dialysis) Transplantation (see Chapter 5) Recommended Reading 16. Inflammation and Infection Urinary Tract Infections (UTIs) Microbial Virulence Factors (Table 16.1) Lipoprotein α-Haemolysin (HlyA) Cytotoxic Necrotising Factor 1 (CNF1) Urease Host Defences Inflammatory Responses Neutrophil Recruitment: Cytokines Neutrophil Recruitment: Macrophages Mast Cells Asymptomatic Bacteriuria (ABU) Bacterial Detection Clinical Aspects of Urinary Tract Infections Complicated Versus Uncomplicated UTI Infective Cystitis Pyelonephritis Renal and Perirenal Abscess Genito-Urinary (GU) Tuberculosis Prostatitis Scrotal Infections Fournier's Gangrene Sepsis and Shock Recommended Reading 17. Urolithiasis Epidemiology Risk Factors for Urolithiasis Mechanism of Urolithiasis Urine Saturation Nucleation and Aggregation Inhibitors and Promoters Inhibitors Promoters Free-Flowing or Fixed Particle Urolithiasis Free Particle Growth Fixed Particle Theory Metabolic Syndrome, Urinary pH, and Urolithiasis Metabolic Syndrome Urinary pH Urinary Stone Composition Calcium Metabolism and Calcium-Based Calculi Oxalate Metabolism Serum Oxalate Hyperoxaluria Calcium Phosphate Uric Acid Calculi Cystine Calculi Infection-Related Stones Drug Metabolite Calculi Xanthine Calculi Anatominal Predispositions and Pregnancy Anatomical Predispositions Medullary Sponge Kidney (MSK) Pelvic-Ureteric Junction Obstruction (PUJO) Pregnancy Recommended Reading 18. Upper Urinary Tract Obstruction Upper Urinary Tract Obstruction (UUTO) Aetiology Antenatal Period Adults Clinical Presentation Antenatal Childhood Adults Diagnosis Anatomical Imaging Functional Imaging Pathological Features of UUTO Macroscopic Features Microscopic Features Physiological Pyeloureteric Peristalsis Obstructional Effects on Peristalsis Complete Obstruction Partial Obstruction Pathophysiology of UUTO Haemodynamic Changes in UUTO Complete UUO Complete BUO or UOSK Effects of UUTO on Tubular Function Post-Obstructional Renal Recovery Complete UUO Partial UUO Complete BUO Recommended Reading 19. Non-Neurogenic Lower Urinary Tract Dysfunction Introduction Failure to Store Dysfunctions 1. Stress Urinary Incontinence Stress Urinary Incontinence in Men Stress Urinary Incontinence in Women 2. Urgency Urinary Incontinence Interstitial Cystitis (IC)/Bladder Pain Syndrome Failure to Void Dysfunctions 1. Bladder Outlet Obstruction Benign Prostatic Hyperplasia Urethral Stricture Disease 2. Detrusor Underactivity 3. Fowler's Syndrome Urodynamic Aspects of LUTD Storage Voiding Urinary Retention Acute Urinary Retention (AUR) Chronic Urinary Retention Post obstructive diuresis (POD) Physiological POD Pathologic POD Recovery of Renal Function Occurs in Two Phases Recommended Reading 20. Neurogenic Lower Urinary Tract and Sexual Dysfunction Spinal Cord Neuroanatomy Descending Tracts Corticospinal (Pyramidal) Tract Corticobulbar (Pyramidal) Tract Extrapyramidal Tracts Ascending Tracts Dorsal Column-Medial Lemniscal (DCML) Tract Anterolateral System Spinocerebellar Tracts (Unconscious Sensation) The Lower Urinary Tract and Neuroanatomy (see Chapter 10) Spinal Cord Injury Phases of Spinal Cord Injury Shock Spinal Shock Neurogenic Shock Spinal Cord Syndromes (Figure 20.2) Central Cord Syndrome Brown-Séquard Syndrome Anterior Cord Syndrome Posterior Cord Syndrome Classification of Neuropathic Lesions Functional Outcome Clinical Features Botulinum Toxin Autonomic Dysreflexia (AD) Sexual Function Specific Neuropathologies Dementia Multiple Sclerosis Parkinson's Disease Multiple System Atrophy Spina Bifida Cauda Equina Syndrome Recommended Reading 21. Penoscrotal Pathology Penile Disorders Phimosis Zoon's Balanitis Lichen Planus Urethritis Crohns' Disease of the Penis Priapism Scrotal Pathology Classification Varicocele Hydrocele Epididymal Cyst Acute Scrotum Genital Lymphoedema Hidradenitis Suppurativa (HS) Recommended Reading 22. Male Sexual Dysfunction and Male Factor Infertility Erectile Dysfunction (ED) Erectile Dysfunction at a Cellular Level Pathophysiological Processes Neurological Erectile Dysfunction Post-Prostatectomy ED Vasculogenic Erectile Dysfunction Atherosclerosis - Early Pathophysiology Atherosclerosis - Late Pathophysiology Penile Doppler Ultrasound Hypertensive ED Metabolic Syndrome and ED Hyperlipidaemia, Smoking, and Obesity Endocrine Disease Diabetic ED Testosterone Psychogenic Erectile Dysfunction Performance-Related Anxiety Depression and ED Iatrogenic Erectile Dysfunction Other Causes of Erectile Dysfunction Peyronie's Disease Ejaculatory Dysfunction Premature Ejaculation (PE) Primary PE Secondary PE Retrograde Ejaculation (RE) Anejaculation Hypogonadism Age-Related Hypogonadism Male Factor Infertility Testicular Insufficiency Testicular Maldescent Varicocele Obstructive Azoospermia Ejaculatory Duct Obstruction Epididymal Obstruction Endocrine Disorders Kallmann Syndrome Anabolic Steroid Use (e.g., Bodybuilders) Genetic Infertility Klinefelter's Syndrome 47XXY Congenital Bilateral Absence of the Vas Deferens Y-Chromosomal Micro-Deletions Recommended Reading Section IV: Malignant Pathology 23. Renal Cancer Adult Malignant, Primary, Sporadic Renal Cancers Renal Cell Carcinoma Epidemiology Aetiology Non-Modifiable Risk Factors (Table 23.2) Modifiable Risk Factors (Table 23.2) Pathology Clear Cell RCC (ccRCC) Papillary RCC (pRCC) Chromophobe RCC (chRCC) Collecting Duct Carcinoma Renal Medullary Carcinoma MiT Family Translocation RCC Other RCC Subtypes (Table 23.1) Tumour Grading and Staging Grading Staging Pathophysiology of Signs and Symptoms Challenges in Pathology Small Renal Masses (SRM) Renal Biopsy Adult Primary, Hereditary Renal Cell Carcinoma (Table 23.3) Hereditary RCC Von Hippel Lindau Disease Hereditary Papillary RCC (HPRCC) Hereditary Leiomyomatosis and RCC (HLRCC) Succinate Dehydrogenase RCC (SDHRCC) Birt-Hogg-Dubé Syndrome Tuberous Sclerosis Other Hereditary Conditions Associated with RCC BAP1 Tumour Syndrome Cowden's Syndrome Cowden-Like Syndrome Familial Non-Syndromic RCC Other Adult Primary Malignant Renal Tumours Sarcoma of the Kidney Lymphoma of the Kidney Adult Secondary Renal Tumours Paediatric Tumours Wilms' Tumour Benign Renal Cysts and Tumours Renal Cysts Simple Renal Cysts Complex Renal Cysts Oncocytoma Angiomyolipoma (AML) Recommended Reading 24. Urothelial and Urethral Cancer Epidemiology of Urothelial Cancer Demographics Bladder Cancer (BC) Upper Urinary Tract Urothelial Carcinoma (UTUC) Aetiology and Risk Factors Genetic Risk Factors Inherited Gene Polymorphisms Inherited Cancer Syndromes Acquired Risk Factors Tobacco Smoking Occupational Exposures Environmental Factors Iatrogenic Factors Nutrition Factors Clinical Presentation of Urothelial Cancer Pathology Benign Lesions Epithelial Metaplasia Leukoplakia Malakoplakia Inverted Papilloma Papilloma Nephrogenic Adenoma Cystitis Cystica Cystitis Glandularis Bladder Cancer Upper Tract UCC Schistosomiasis (Bilharzia) Immunohistochemistry (IHC) Tumour Stage Carcinoma In Situ (CIS) Lamina Propria Invasion (pT1) Muscle Invasion Histological Grading Precursor Lesions Histological Variants Bladder Tumour Dissemination Multifocality and Tumour Recurrence Recurrence and Progression in NMIBC Risk Stratification of Non-Metastatic UTUC Molecular Biology of Bladder Cancer Low-Grade BC High-Grade BC Molecular Classification of MIBC Urine Cytology and Biomarkers in Urothelial Cancer Urine Cytology Urinary Biomarkers Urethral Cancer Epidemiology Aetiology Histopathology Staging and Grading Recommended Reading 25. Prostate Cancer Epidemiology of Prostate Cancer Demographics Aetiology and Risk Factors Genetics and Pathophysiology Genes and Pathways Epigenetic Events Pathophysiology Histopathology Histological Subtypes Malignant Pre-Malignant Immunohistochemistry (IHC) Diagnosis and Investigations Risk Calculators Tumour Staging Tumour Grading Tumour Risk Stratification D'amico PREDICT Tumour Dissemination Disease Progression Androgen Receptor Gene Mutation AR Splice Variants (ARV) Adrenal Androgens, Intraprostatic Testosterone, and Dihydrotestosterone (DHT) Androgen Receptor Bypass Signalling Molecular Markers Markers Recommended Reading 26. Testicular Cancer Epidemiology and Classification Risk Factors Cryptorchidism Personal or Family History Microlithiasis Testicular Dysgenesis Syndrome Pathogenesis GCNIS Different Tumours Have Different Origins Genetics Histological Types Seminoma Spermatocytic Seminoma (Spermatocytic Tumour) Embryonal Carcinoma Yolk Sac Tumour Choriocarcinoma Teratoma ('Monster Tumour' in Greek) Stromal Tumours Leydig Cell Tumours Sertoli Cell Tumours Granulosa Cell Tumours Gonadoblastoma Haematopoietic Tumours Tumour Markers Alpha-Feto Protein (AFP) Beta Human Chorionic Gonadotrophin (beta-hCG) Lactate Dehydrogenase (LDH) Staging Prognostic Factors Seminomas NSGCT Patterns of Lymphatic Spread Recommended Reading 27. Penile Cancer Epidemiology Risk Factors Histological Classification of Penile Cancer Immunohistochemistry (IHC) Clinical Manifestations of Pre-malignant Lesions Undifferentiated PeIN (HPV-related) Giant condylomata (Buschke-Löwenstein) Bowen's Disease (BD) and Erythroplasia of Queyrat (EQ) Bowenoid Papulosis Differentiated PeIN (non-HPV-related) Lichen Sclerosis (LS) Verrucous hyperplasia Penile Cutaneous Horn Molecular Pathways in the Pathogenesis of Penile Cancer HPV-dependent Pathways HPV-independent Pathways Tumour Progression and Metastatic Spread Tumour Grading and Staging Lymph Node Metastasis and Inguinal Lymph Node Anatomy Lymphatic Drainage Clinical assessment and management of lymph nodes Clinically normal inguinal lymph nodes (cN0) Dynamic Sentinel Lymph Node Biopsy (DSLNB) The modified inguinal lymphadenectomy (MILND) (Figure 27.4) Recommended Reading Section V: Therapeutics 28. Reconstruction Wound Healing Primary Healing (By First Intention) Secondary Healing (By Secondary Intention) Process of Wound Healing (Figure 28.1) Causes of Delayed Wound Healing Tissue Transfer Grafts Skin Grafts Oral Mucosa Grafts Graft Failure Flaps Biomaterials Urinary Tract Reconstruction Using Bowel (Table 28.3) Cutaneous Urinary Diversion Catheterisable Urinary Diversion Bowel Wall Structure and Function Principles of Bowel Urinary Reservoirs Metabolic and Functional Consequences Renal Deterioration Electrolyte and Acid-Base (More Common with Reservoirs Compared with Conduits) Bone Disease Urinary Tract Infection (UTI) Mucus Production Urolithiasis Spontaneous Perforation Bowel Function Abnormal Drug Kinetics Malignancy Recommended Reading 29. Pharmacology of the Lower Urinary Tract Introduction A) Muscarinic Receptors and Anti-Muscarinic Drugs Muscarinic Receptors Anti-Muscarinic Drugs (Anticholinergic Drugs) Molecular Characteristics: Route of Delivery Treatment Outcome B) Beta-3 Adrenoceptors and Beta-3 Agonist Beta-3 Adrenoceptors (β3-AR) β3-AR Agonists (Mirabegron) Antimuscarinics and β3 Agonists Combination C) Alpha-1A Adrenoceptors and Alpha-Blockers Alpha-Blockers Alpha-Blockers and Anti-Muscarinic Combination Alpha-Blockers and β3 Agonists Combination D) Intracellular Pathways Relevant to the Treatment of Lower Urinary Symptoms E) Plant Extracts: Phytotherapy Recommended Reading 30. Pharmacology of Male Sexual Function Erectile Dysfunction (see Chapters 12 and Chapters 22) Normal Physiology of Erection (Figure 30.1) Phases of Erection A) Pharmacology of Erectile Dysfunction (ED) Phosphodiesterase-5 Inhibitors (PDE5i) Pharmacodynamics Pharmacokinetics (Table 30.1) Practical Prescribing Contraindications Side Effects Apomorphine Side Effects Alprostadil Pharmacodynamics Pharmacokinetics Practical Prescribing Practical Prescribing Contraindications Side Effects B) Pharmacology of Premature Ejaculation Dapoxetine Pharmacodynamics Pharmacokinetics Practical Prescribing Contraindications Side Effects C) Pharmacology of Hypogonadism Testosterone Replacement Therapy (TRT) Pharmacodynamics Practical Prescribing Monitoring Contraindications Side Effects Testosterone Therapy and Cardiovascular (CV) Risk D) Pharmacology of Male Infertility Gonadotoxins Retrograde Ejaculation (RE) Sympathomimetics (e.g., Ephedrine/Pseudoephedrine) Pharmacodynamics Pharmacokinetics Practical Prescribing Contraindications Side Effects Monitoring Efficacy Alpha1 Agonist (e.g., Midodrine) Pharmacodynamics/Kinetics Practical Prescribing Contraindications Side Effects Monitoring Recommendation/Guidelines and Efficacy Tricyclic Antidepressants (e.g., Imipramine) Pharmacodynamics Pharmacokinetics Practical Prescribing Contraindications Side Effects Monitoring Recommendation/Guidelines and Efficacy Gonadotrophin Therapy (Including Oral Adjunctive Treatments) for Correcting Hypogonadism in Male Infertility Gonadotrophins Selective Oestrogen Receptor Modulators (e.g., Clomiphene) Aromatase Inhibitors (e.g., Anastrozole) E) Pharmacology of Penile Deformity (Peyronie's Disease) Oral Medication Vitamin E (Alpha-Tocopherol) Pharmacodynamics Pharmacokinetics Practical Prescribing Contraindications Side Effects Monitoring Potassium Para-Aminobenzoate (Potaba) Pharmacodynamics/Kinetics Practical Prescribing Contraindications Side effects Monitoring Tamoxifen Pharmacodynamics Pharmacokinetics Practical Prescribing Contraindications Side Effects Monitoring Colchicine Pharmacodynamics Pharmacokinetics Practical Prescribing Contraindications Side Effects Acetyl Esthers of Carnitine (Acetyl- and Propionyl-L-Carnitine) Pharmacodynamics Practical Prescribing Contraindications Side Effects Pentoxifylline Pharmacodynamics/Kinetics Practical Prescribing Contraindications Side Effects Monitoring Intralesional Treatment Steroids Verapamil Pharmacodynamics Practical Prescribing Contraindications Side Effects Interferon Alpha-2b Pharmacodynamics Practical Prescribing Side Effects Clostridium Collagenase Histolyticum (CCH, Xiapex®) Pharmacodynamics Practical Prescribing Contraindications Side effects Topical Therapy F) Pharmacology of Priapism Acute Priapism Phenylephrine Pharmacodynamics/Kinetics Practical Prescribing Contraindications Side Effects Monitoring Efficacy Alternative Treatment Options Stuttering Priapism Hormone Therapy Pharmacodynamics Practical Prescribing Contraindications Side Effects Monitoring PDE5 Inhibitors Pharmacodynamics Practical Prescribing Digoxin Pharmacodynamics/Kinetics: Practical Prescribing Contraindications Side Effects Monitoring Efficacy Recommended Reading 31. Antimicrobial Agents Introduction A) Antibiotics 1. Inhibitors of cell wall synthesis Beta-Lactam Antibiotics Mechanism of Action Metabolism General Adverse Effects Resistance Beta-Lactamase Inhibitors I. Penicillins II. Cephalosporins First Generation Second Generation Third Generation Fourth Generation III. Carbapenems IV. Monobactams Glycopeptides Mechanism of Action Key Features Adverse Effects 2. Inhibitors of nucleic acid synthesis Quinolones and Fluoroquinolones Mechanism of Action Key Features Adverse Effects Nitroimidazoles Mechanism of Action Resistance Key Features Adverse Effects 3. Inhibitors of protein synthesis Tetracyclines Mechanism of Action Metabolism Resistance Key Features Adverse Effects Macrolides Mechanism of Action Resistance Key Features Adverse Effects Aminoglycosides Mechanism of Action Resistance Key Features Adverse Effects 4. Others Nitrofurantoin Mechanism of Action Metabolism Resistance Key Features Adverse Effects Trimethoprim Mechanism of Action Resistance Key Features Adverse Effects Fosfomycin Mechanism of Action Resistance Key Features Adverse Effects Non-Antibiotic Treatments for Cystitis and Recurrent UTIs D-Mannose Methenamine Hippurate Oestrogens Intravesical Glycosaminoglycans (GAG) Cranberry Probiotics B) Anti-Fungals Polyenes Key Features Adverse Effects Azoles Mechanism of Action Imidazoles Key Features Triazoles Key Features C) Anti-Parasitics Anthelmintics I. Praziquantel Key Features Adverse Effects II. Albendazole Key Features Adverse Effects Anti-Protozoals Recommended Reading 32. Blood Products and Antithrombotic Agents Blood Products Pharmacology of Antithrombotic Agents Antiplatelet Agents (Table 32.2) Cyclooxygenase (COX) Inhibitor P2Y12 Receptor Antagonists Glycoprotein IIb/IIIa Antagonists Other Antiplatelet Agents Anticoagulants (Table 32.3) Vitamin K Antagonist (VKA) Non-VKA Oral Anticoagulants Parenteral Anticoagulants Anticoagulants Side Effects: Thromboprophylaxis Pre- and Post-Surgery Recommended Reading 33. Urological Anti-cancer Agents A) Cytostatic Agents Cell Cycle Classification of Cytostatic Agents Alkylating Agents (Ifosfamide, Cyclophosphamide, Estramustine) Platinum Analogues (Cisplatin, Carboplatin, Oxaliplatin) Antimetabolites (Gemcitabine, Methotrexate) Anti-Microtubule Agents (Paclitaxel, Vinblastine) Topoisomerase Inhibitors I (Topotecan) and II (Etoposide) DNA Intercalation (Anthracyclines: Doxorubicin, Adriamycin) Cytotoxic Antibiotics (Bleomycin, Mitomycin-C) Substance Profiles of Cytostatic Drugs Bleomycin Carboplatin Cisplatin Doxorubicin (Adriamycin) Docetaxel Etoposide Gemcitabine Methotrexate Paclitaxel Vinblastine Most Common Chemotherapy Regimens in Urological Cancer Urothelial Cancer Prostate Cancer Testicular Germ Cell Tumours Penile Cancer B) Intravesical Chemotherapy and Immunotherapy Intravesical Chemotherapy Instillation A Single, Immediate, Post-Operative Instillation Additional, Adjuvant Instillations Intravesical Mitomycin-C Intravesical Bacillus Calmette-Guérin (BCG) Immunotherapy C) Hormonal Therapies Androgen Synthesis (Testosterone and 5α-Dihydrotestosterone [DHT]) Testis Adrenal Glands Oestrogens Luteinising-Hormone-Releasing Hormone Agonists Luteinising-Hormone-Releasing Hormone Antagonists Steroidal Anti-Androgens Non-Steroidal Anti-Androgens D) Targeted Therapies Cellular Communication Development of Renal Cancer Tyrosine Kinase Inhibitors (TKI) Sunitinib, Pazopanib, Sorafenib, and Axitinib Cabozantinib and Lenvatinib Bevacizumab Mammalian Target of Rapamycin (mTOR) Inhibitors E) Cancer Immunotherapy Immunotherapy in Renal Cancer in the Pre-Targeted Therapy Era Immune Checkpoint Inhibition Most Common Immune Checkpoint Inhibitor Regimens Used in Urological Cancer Metastatic Urothelial Cancer Metastatic Renal Cell Carcinoma Recommended Reading 34. External Beam Radiotherapy and Brachytherapy Radiation Physics Therapeutic Ionising Radiation Basic Principles About External Beam Radiation Conformal Radiation Intensity Modulated Radiation Therapy (IMRT) Complications of Radiotherapy Relative Contraindications to Radiotherapy Basic Principles About Brachytherapy Radiation for Genito-Urinary Malignancies Prostate Cancer PSA Bounce Extreme Hypofractionation NICE Guidelines 2019: Radiation Options Adjuvant/Salvage Radiation Proton Beam Therapy Bladder Cancer Radiation Fields Radiation Dose NICE Guidelines 2015 Testicular Cancer Renal Cell Carcinoma (RCC) Penile Cancer Recommended Reading Index