PPT2 Flashcards
Outline some of the disorders of micturition
- Urgency urinary incontinence: associated with overactive bladder syndrome
- Stress urinary incontinence: due to urethral sphincter incompetence
- Mixed urinary incontinence: stress + urgency urinary incontinence
- Overflow incontnence: with continuous urine leakage, resulting from hypotonic bladder or bladder outlet obstruction producing urinary retention
Which group of patients are more prone to urge incontinence?
Older women
What is urge incontinence?
Sudeen , strong need to urinate AKA overactive bladder
Thought to occur due to detrusor overactivity leading to involuntary detrusor muscle contractions during bladder filling
Causes a strong urge to urinate and involuntary urination
What are the pharmacological options for urge incontinence?
- Muscarinic receptor antagonists: oxybutinin, tolterodine - inhibit actions of acetylcholine which functions via the parasympathetic nervous system to cause bladder contraction
- B3 adrenoceptor agonists: mirabegron
Discuss neurotransmitter release in the parasympathetic and sympathetic nervous systems
Parasympathetic nervous system: ACETYLCHOLINE pre and post ganglionic
Sympathetic nervous system: ACETYLCHOLINE pre ganglionic and NORADRENALINE post ganglionic
Which is the main muscarinic receptor subtype in the bladder?
M3 - acetylcholine binds to M3 receptors and causes contraction of the detrusor muscle
How does mirabegron work?
Stimulates B3 adrenoreceptors in the bladder trigone which flattens and lengthens the bladder base which facilitates urine storage
Adverse effects: increase in BP and HR - mirabegron is contraindicated in people with severe hypertension
What are the adverse effects of muscarinic blockade?
Dry mouth
Tachycardia
Constipation
Blurred vision
Urinary retention if there is bladde outflow obstruction
What type of incontinence occurrs when a person coughs or sneezes?
Stess incontinence
What is the cause of stress incontinence?
Urethral sphincter incompetence
What would be initially reccommended to a patient suffering with stress incontinence?
Pelvic floor muscle training for 8-12 weeks
When would drug therapy be recommended for stress incontinence?
If surgical treatment is not suitable
Drug therapy for stress incontinence is limited
Which surgical procedures are avalaible for stress incontinence?
- Surgical sling procedures: sling placed around the neck of the bladder to support it
- Colposuspension: stitches to vagina to hold it and support external sphincter when stress is placed upon it e.g. when sneezing
Which drugs are used to treat stress incontinence?
Duloxetine (SNRI)
- Reduces the frequency of incontinence episodes in 50% of those treated, recommended to those who are poor candidates for or averse to surgery
Enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphincter - allows for stronger external urethral sphincter contraction and therefore more pressure needed to overcome it
How can the severity of BPH be assessed?
International prostate severity score
Questions relating to: incomplete empyting, frequency, intermittency, urgency, weak stream and straining - rated 0-5
0-7 = mildly symptomatic
8-19 = moderately symptomatic
20-35 = severely symptomatic
What is the first therapeutic intervention for BPH?
Alpha blocker - tamsulosin
Alternatives: alfuzosin, doxazosin, terazosin
What is the mechanism of action of alpha blockers in BPH?
Most drugs in this class are highly selective for the a1 adrenoreceptor which are mainly found in the smooth muscle of blood vessels and the bladder (particularly the bladder neck and prostate)
Stimulation of the a1 adrenoreceptors causes smooth muscle contraction and blockade causes relaxation
Alpha1 blockers cause a reduced resistance to bladder outflow
They also cause vasodilation and thus a reduction in blood pressure
What can be offered in addition to alpha blockers for BPH?
5-alpha reductase inhibitor e.g. finasteride or dustasteride
What is the mechanism of action of 5-alpha reductase inhibitors?
Reduce the size of the prostate
5-alpha reductase usually converts testosterone to dihydrotestosterone which leads to prostate hypertrophy - blocking this leads to prostate shrinkage
Takes 6-12 months to provide symptomatic relief, more effective in men with larger prostates
What are the side effects of 5-alpha reductase inhibitors?
- Breast enlargement
- Breast tenderness
- Reduced libido
- Ejaculation disorders
- Impotence
Which drugs do 5-alpha reductase inhibitors interact with?
Verapamil and diltiazem - increase the concentrations of dultasteride (yellow alert)
What is an important consideration when prescribing 5-alpha reducatse inhibitors?
Pregnant women should not handle broken or damaged tablets and should not have unprotected sex with a man taking the tablets
Exposure of a male foetus to 5-a reductase inhibitors can cause abnormal development of the external genitals
What drugs can be used for prostate cancer?
Antiandrogens: flutamide
Gonadorelin analogues: leuprolide, goserelin, buserelin
Chronic administration of gonadorelin analogues results ina sustained suppression of pituitary gonatotropins, serum testosterone falls to levels comparable to surgical castration
What is the preferred initial approach for systemic therapy in patients with metastaic bladder cancer?
Platinum based chemotherapy
