Genitourinary Module Flashcards
Name the main antimuscarinics used to treat urinary incontinence
Oxybutynin, propantheline, darifenacin, solifenacin, tolterodine
What is the MOA of urinary antimuscarinics?
Non-selective muscarinic receptor antagonists
Reduce bladder muscle contractility and increase bladder capacity
What is the indication/s for urinary antimuscarinics?
Urinary urge incontinence
Name some ADRs for urinary antimuscarinics
Drowsiness & seizures (H1 block)
hallucinations and agitation (wrong dosage)
Blurry vision, dry mouth, constipation (M-receptor block)
Palpitation and cardiac arrhythmias
Which urinary antimuscarinics are more selective? (Uroselectivity)
Darifenacin, solifenacin, tolterodine
Which antimuscarinics has the highest incidence of dry mouth?
Oxybutynin
Which urinary antimuscarinics will increase QT interval and constipation?
Solifenacin
True or False
Oxybutynin has an increased likelihood of CNS effects?
TRUE
What are the four concepts of uroselectivity?
Receptor-selective, tissue selective, clinically uroselective, functionally selective
Explain the following type of uroselectivity:
Receptor-selectivity
Difference in potency for one receptor compared to another
(E.g. selectivity for alpha 1A subtype that regulate smooth muscle contraction compared to vascular smooth muscle contraction alpha 1B)
Explain the following type of uroselectivity:
Tissue selective
Primarily distributed in the target tissues of the urinary tracts versus other tissues and organs
Explain the following type of uroselectivity:
Clinically uroselective
The drug is able to produce the desired pharmacological effect with few side effects
(E.g. improves urinary flow rate and BPH symptoms with few ADR such as dizzy, orthostatic hypotension)
Explain the following type of uroselectivity:
Functional selectivity
The drug is able to act on the physical function of the organ, changing its function from normal
(E.g. preferentially dec urethral pressure versus arterial BP)
Name the urinary selective alpha blockers
Alfuzosin, prazosin, silodosin, tamsulosin, terazosin
What is the MOA of urinary alpha-1 selective blockers?
Blocks alpha 1 receptor > decreasing circulating Ca2+ > relax smooth muscle (SM) in bladder neck and prostate > dec resistance to urine outflow
E.g. MOA of alpha-agonist = Noreadrenaline
Binding noreadrenaline to alpha1 receptor > mobilization of intracellular Ca2+ stores > smooth muscle contraction (SM)
Which alpha 1 blockers show equal selectivity to all receptor subtypes?
Terazosin, doxazosin, alfuzosin
Makes them non-selective =)
Which urinary alpha 1 blockers show receptor selectivity?
Tamsulosin (Alpha1a = alpha1 d > Alpha1 B)
Silodosin (Alpha1a > alpha1 d > Alpha1 B)
What is the indication for genitourinary selective alpha-1 blockers?
Symptomatic relief of benign prostatic hyperplasia (BPH)
Name some ADRs of Prazosin
(just know some/be able to explain some)
Depression, nervousness
Headache, drowsiness = blood vessel changes due to alpha1-Ab inhibition
Palpitations, tachycardia = physiological reflex reaction to alpha 1Ab block
Orthostatic hypotension = alpha 1Ab block > decrease PVR > decrease BP
Priapism, impotence, gynaecomastia
Nasal congestion, nosebleeds = alpha1 antagonism > vasodilation
Name some Tamsulosin ADRs
Constipation, Diarrhoea
Blurry vision, floppy iris syndrome
Postural hypotension
Priapism, abnormal ejaculation (retrograde ejaculation)
What is the MOA of 5-alpha-reducatse inhibitors
block 5-alpha reductase > prevent conversion of testosterone to dihydrotestosterone (DHT, stimulate prostatic growth) > reduce prostate size and improve urinary output
Name the two relevant 5-alpha-reducatse inhibitors
Dutasteride, finasteride
What are the indications for genitourinary 5-alpha-reducatse inhibitors (Dutasteride, finasteride)
Benign prostatic hyperplasia (BPH)
Male pattern baldness
Name some notable side effects for genitourinary 5-alpha-reducatse inhibitors
Impotence, ejaculation disorders, decreased libido
breast tenderness/enlargement = less testosterone
Which is more potent, dutasteride or finasteride?
Dutasteride
What are the genitourinary indications for desmopressin?
nocturnal enuresis
What drug class is desmopressin?
Vasopressin analogue
What are the notable ADR of desmopressin?
Headache, nausea, vomiting
Weight gain (water gain)
Seizures = due to decrease Na+ concentration in blood
hyponatraemia = due to decrease Na+ concentration in blood
What is the mechanism of action for desmopressin?
Agonist of V2 receptor in the renal collecting duct > increasing water re-absorption and decreasing urine output
What is the class of imipramine?
Tricyclic antidepressant
What is the indication for imipramine?
nocturnal enuresis
What is the MOA of Imipramine?
inhibit reuptake of noradrenaline and serotonin into presynaptic terminals
Unrelated to therapeutic effects, they also block:
- histaminergic receptor
- cholinergic receptor
- alpha-1 adrenergic receptor
- serotonergic receptor
Name the notable ADRs for Imipramine
Anticholinergic effects: blurred vision, dry mouth, constipation, difficulty urinating
Drowsiness, sedation = H1 block
Name the three notable phosphodiesterase 5 inhibitors used to treat sexual dysfunction
Sildenafil, Tadalafil, Vardenafil
Name the drugs used to treat sexual dysfunction and their class
Phosphodiesterase 5 inhibitors = sildenafil, tadalafil, vardenafil
Alprostadil = prostaglandin E1 agonist (analogue) —> vasodilation, can cause necrosis and damage
Dapoxetine = SSRI
Papaverine = cholinergic agonist –> work in absence of sexual arousal
True or False
Sildenafil, Tadalafil, and Vadenafil can work in the absence of sexual stimulation
FALSE
They are phosphodiesterase inhibitors used to treat sexual dysfunction but all require sexual stimulation to work.
What are the indications for Sildenafil, Tadalafil, and Vardenafil (phosphodiesterase inhibitors)
Erectile dysfunction
Pulmonary arteriolar hypertension
Sildenafil, Tadalafil, and Vardenafil contraindications and precautions
Migraines = vasodilation will aggravate them
History of non-arteritic anterior ischaemic optic neuropathy (NAION)
- 2-fold inc risk of developing
- sildenafil is most likely to cause
Cardiovascular
- Use of nitrates –> mass vasodilation and mass drop in BP –> death
- Unstable angina = dilation of blood vessels will worsen heart’s ability to get nutrients
Name some ADRs for Phosphodiesterase inhibitors (Sildenafil, Tadalafil, and Vardenafil)
Transient amnesia, headache, hearing loss, vision loss, migraine, flushing, seizure
Priapism
Nasal congestion/rhinitis, diarrhoea, dyspepsia
How can medicines affect urinary incontinence?
Increase urine production, act directly lower urinary tract, impairing cognitive function, causing constipation
What is the primary drug target of Dutasteride?
5-alpha-reductase inhibitors sub types I and II
What is the primary drug target of Finasteride?
5-alpha-reductase inhibitors sub type II
How do alpha-1 adrenergic agents cause urinary incontinence?
Alpha-1 Agonists = contract the neck of bladder causing overflow incontinence (e.g. pseudoephedrine, phenylephedrine)
Alpha-1 antagonists = relax bladder neck/sphincter causing stress incontinence (e.g. prazosin, tamsulosin, terazosin, etc.)
How do cholinergic agents cause urinary incontinence?
Anticholinergic agents (cholinergic antagonist) = reduce detrusor activity causing overflow incontinence (e.g. Oxybutynin, propantheline, etc)
Cholinergic agonist = increase detrusor activity causing urge incontinence (e.g. bethanechol)
Cholinesterase inhibitors = increase detrusor activity causing urge incontinence (e.g. donepezil, rivastigmine, etc.)
How do antihypertensive agents cause urinary incontinence?
ACE inhibitors = stress incontinence due to sphincter weakness
Diuretics = cause polyuria and constipation causing urge incontinence (e.g. frusemide, hydrochlorothiazide, indapamide)
Calcium channel blockers = cause constipation and reduce detrusor activity causing overflow incontinence (e.g. dilitiazem, verapamil)
How do psychotropic agents cause urinary incontinence?
Antipsychotics = cause sedation and confusion due to H1-R block and anticholinergic actions causing overflow, functional, and stress incontinence (e.g. clozapine, olanzapine, risperidone, amisulpride, etc.)
Antidepressants = increase detrusor activity and cause sedation/impaired mobility causing urge and functional incontinence (e.g. SSRI, moclibemide, venlafaxine)
Antidepressants (TCA’s, mirtazepine, reboxetine) = anticholinergic effects and sedation/impaired mobility causing overflow and functional incontinence
Benzodiazepines = cause sedation and impaired mobility resulting in functional incontinence
Lithium = cause polydipsis, nocturia, and frequency causing functional incontinence
How do opioids cause urinary incontinence?
Through inhibition of voiding reflex and reduction of detrusor muscle activity
Causes overflow and functional incontinence
How do systemic hormone replacement therepy agents cause urinary incontinence?
Cause ineffective urethral closure
Causing stress and urge incontinence
