Sem 5

• Lower urinary tract


  Consists of the bladder and urethra, and in males also includes the prostate

  
• Micturition


  1. Spinal reflex facilitated and inhibited by higher brain centers

  2. Sensory fibers detect stretch in the bladder wall

  3. Stretch signals from the posterior urethra are mainly responsible for initiating the reflexes that cause bladder emptying

  4. Skeletal motor fibers transmitted through the pudendal nerve to the external bladder sphincter

  5. Parasympathetic - detrusor muscle contraction, trigone & external sphincter relaxation

  6. Sympathetic - detrusor muscle relaxation (β2), trigone & external sphincter contraction (α1)

  
• Prostate


  • Accessory gland and a muscle-driven mechanical switch between urination and ejaculation
  • Consists of lobes in gross anatomy and zones in microanatomy
  • Surrounded by an elastic, fibromuscular capsule and contains glandular tissue and connective tissue

  
• Prostate gland produces fluid that forms part of semen, which is slightly alkaline to help neutralize the acidity of the vaginal tract

  
• Disorders of the prostate


  • Enlargement (BPH)
  • Inflammation
  • Infection (prostatitis)
  • Carcinoma

  
• Clinical features of BPH


  • Frequent or urgent need to urinate (urgency)
  • Increased frequency of urination at night (nocturia)
  • Difficulty starting urination (hesitancy)
  • Weak urine stream or a stream that stops and starts
  • Dribbling at the end of urination
  • Inability to completely empty the bladder
  • UTI
  • Haematuria

  
• Drugs used in benign prostatic hyperplasia (BPH)


  • α1 blockers
  • 5α reductase inhibitors (dihydrotestosterone blockers)
  • Phosphodiesterase 5 inhibitors
  • Antimuscarinic drugs

  
• α1 adrenoreceptor blockers (α1 antagonists)

  Block α1B receptors causing relaxation of smooth muscle of bladder neck and prostate capsule
• Tamsulosin


  • Block α1A receptors in smooth muscle in prostate gland causing relaxation of bladder neck and prostate capsule
  • Reduces urethral resistance in patients with BPH
  • Mostly metabolized in the liver by cytochrome P450
  • 94%-99% protein bound
• Adverse effects of tamsulosin


  • Postural hypotension
  • Dizziness
  • Headache
  • Angioedema
• 5α reductase inhibitors (dihydrotestosterone blockers)


  • Have anti-androgen activity
  • Inhibit the formation of the male hormone dihydrotestosterone (DHT)
  • DHT is needed for the growth of the prostate

  
• Effects of DHT


  • Prostate enlargement
  • Prostate cancer
  • Hirsutism (excessive facial/body hair growth)
  • Pattern hair loss (androgenic alopecia or pattern baldness)

  
• Adverse effects of 5α reductase inhibitors


  • Erectile dysfunction
  • Loss of libido
  • Reduced ejaculated volume
  • Gynecomastia
  • Depression
  • Anxiety
• Phosphodiesterase (PDE) 5 inhibitors


  • Inhibition of PDE 5 enzyme
  • Reduces catabolism of cGMP
  • Causes relaxation of smooth muscle
• Tadalafil


  • Also used for BPH
  • Reduces symptoms like difficulty starting to urinate, weak urination stream, the urge to urinate frequently, incontinence

  
• Adverse effects of tadalafil


  • Headache
  • Backache
  • Flushing
  • Myalgia
  • Dyspepsia
  • Nasal stuffiness
• Antimuscarinic drugs


  • Inhibit muscarinic action of acetylcholine on smooth muscle
  • Reduce detrusor muscle activity, relaxing the bladder and preventing the urge to void
  • Reduce the strength of bladder contractions
• Adverse effects of antimuscarinic drugs


  • Dry mouth
  • Constipation
  • Dry eyes
  • Confusion
• Rationale for combination therapy in BPH
• Urinary symptoms


  • Urinary incontinence
  • Enuresis (urinary incontinence primarily in children, such as nocturnal enuresis)
  • Stress incontinence
  • Urge incontinence
  • Overflow incontinence

  
• Overactive bladder


  • Frequent feeling of needing to urinate due to premature bladder contractions
  • Need to exclude UTI and neurological causes
  • Characterized by urgency, urinary frequency, nocturia, and urge incontinence

  
• Drugs used in overactive bladder


  • Anticholinergic drugs (antimuscarinic)
  • Botulinum toxin injection
  • β3 adrenergic receptor agonists

  
• Botulinum toxin injection is used to treat overactive bladder
• β3 adrenergic receptor agonists


  • Relax smooth muscle of bladder
  • Mirabegron also decreases the frequency of non-voiding contractions
• Types of UTI


  • Lower UTI (bladder) - cystitis
  • Upper UTI (kidneys) - pyelonephritis
• Risk factors for UTI


  • Female gender (especially post-menopausal)
  • Age (increase in men, decrease in middle-aged women then increase after 65)
  • Sexual activity
  • Diabetes mellitus or immunosuppression
  • Dementia
  • Previous history of UTI
  • Indwelling urinary catheters or instrumentation
  • Urinary tract stones
  • Urinary tract stasis (incomplete bladder emptying)
• Principles of management of UTI


  • Hydration
  • Relieve obstruction
  • Remove foreign body
  • Antibiotics
• Antibiotics for uncomplicated UTI


  • Co-amoxiclav
  • Nitrofurantoin
  • Trimethoprim/co-trimoxazole
  • 1st generation cephalosporin

  
• Antibiotics for uncomplicated UTI are given as a 3-5 day course
• Urinary antiseptics


  • Oral agents
  • Antibiotics that are highly concentrated in the urine with little or no systemic antibacterial effect
  • Very effective at clearing bacteria from the urinary tract

  
• Nitrofurantoin


  • Bacteriostatic and bactericidal for many gram-positive and gram-negative bacteria
  • Mechanism of action is not known
  • Well absorbed after ingestion
  • Rapidly metabolized and excreted so no systemic antibacterial action is achieved
  • Excreted into the urine by both glomerular filtration and tubular secretion
• Adverse effects of nitrofurantoin


  • Nausea/vomiting
  • Hypersensitivity reactions involving the skin and the bone marrow (e.g. leukopenia)
  • Hepatotoxicity
  • Peripheral neuropathy

  
• Nitrofurantoin is contraindicated in significant renal insufficiency
• Nalidixic acid


  • Fluroquinolone
  • Bactericidal for UTI caused by susceptible gram-negative microorganisms including the majority of E. Coli, Enterobacter, Klebsiella, Proteus species
  • Pseudomonas species are resistant
  • Blocks bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase)
  • Rapidly absorbed and excreted through the kidneys