men's health Flashcards
component of prostate
1) epithelial (glandular) tissue
- androgen stimulate growth
2) stromal (smooth muscle tissue)
- innervated by alpha 1 adrenergic receptor
effect of noradrenaline
- prostate smooth muscle maintained by noradrenaline released from adrenergic nerves & stimulating post-junctional alpha-1 adrenoreceptors
- brain receive stimulation -> release noradrenaline -> stimulate vein & arteries to constrict -> contraction of internal sphincter in bladder -> X pee
testosterone and DHT
testosterone converted by Type II 5alpha-reducrtase in prostate to DHT -> normal growth/enlargement of prostate
pathophysiology of BPH - components
1) static component
- hormonal factor -> enlarge prostate tissue -> press onto organ -> irritative symptoms
2) dynamic component
- increase smooth muscle tissue & agonism of alpha 1 receptor -> vasoconstriction of prostate -> narrowing of urethra outlet
long term bladder response to obstruction (BPH)
1) early phase
- bladder force urine through narrowed urethra by contracting more forcefully
2) over time
- bladder hypertrophy -> decompensate when detrusor muscle achieve highest state of hypertrophy -> need to urinate more frequently (overactivity)
- detrusor irritable and overly sensitive
- contract abnormally in response to small amt of urine
- X full & strong contraction
when does BPH clinical presentation start to show
> 65 yo
obstructive/voiding symptoms for BPH
- hesitancy, weak stream, sensation of incomplete emptying, dribbling, straining, intermittent flow
- happen in early stages
irritative/storage symptoms of BPH
- several years of untreated BPH
- dysuria, frequency, nocturia, urgency, urinary incontinence
assessment components for BPH
1) digital rectal exam (DRE)
- yearly after age of 40
- feel abnormalities (nodules)
2) ultrasonography
- volume/size
3) max urinary flow rate
4) postvoid residual (PVR)
- normal < 100ml, > 200ml inadequate
5) prostate specific antigen (PSA)
6) medication history
medications vs BPH
1) anticholinergic
- decrease bladder muscle contractility
- 1st gen antihist, tricyclic antidepressant
2) alpha 1 adrenergic agonist
- contract prostate smooth muscle
- decongestant
3) opioid analgesic: increase urinary retention
4) diuretics: increase frequency
5) testosterone: Stimulate prostate growth
classifications of BPH
1) stage I
- X bothered, QoL < 3
- X significant outflow obstruction/complications, residual urine < 100ml
- j observe
2) Stage II
- bothered, QoL ≥ 3
- X significant outflow obstruction/complication, residual urine < 100ml
- pharmacotherapy
3) Stage III
- irrespective symptoms
- significant outflow obstruction/complication, uroflow < 10 ml/s, residual urine > 100ml
- surgery
4) stage IV
- irrespective symptoms
- retention of urine, bladder calculi, recurrent UTI, persistent macroscopic haematuria
- surgery (TURP)
nonpharmaco BPH
1) limit fluid intake in evening
2) minimise caffeine & alcohol intake
3) education
4) avoid meds that exacerbate symptoms
treatment algorithm for BPH (QoL ≥ 3)
1) prostate ≤ 2 fingerbreadth
- w ED: PDE5i
- wo ED: alpha 1 antagonist
2) voiding diary
- overactive bladder (anti-muscarinic)
3) prostate ≥ 2 fingerbreadth
- QoL 3-4: alpha 1 antagonist
- QoL 5 - 6: combination(alpha 1 + 5ARI)
alpha adrenergic antagonist for BPH - MOA
- competitive reversible antagonist
- block adrenoreceptor on smooth muscle of prostate -> reduce vasoconstriction induced by noradrenaline -> relax muscle tone -> relieve obstruction -> increase urine flow -> reduce enlarged bladder -> reduce pain & discomfort
alpha adrenergic antagonist - non selective
- good if need BP lowering effect
- Doxazosin
- titrate slowly to prevent hypotension & syncope
alpha adrenergic antagonist for BPH - selective
1) alfuzosin, silodosin
2) tamsulosin
- well absorbed orally, 0.4mg OD
- highly plasma protein bound
- metabolised by CYP (food drug interaction)
- excreted unchanged in urine
SE of alpha adrenergic antagonist for BPH
1) general
- muscle weakness, fatigue, headache
2) non selective
- dizziness
- first dose syncope & orthostatic hypotension (prevent w bedtime admin)
3) uroselective
- ejaculatory disturbance (S > T > A)
4) intraoperative floppy iris syndrome - only tamsulosin
- complicate cataract surgery
- block alpha 1 receptor in iris dilator muscle
- avoid initiation until cataract surgery completed or hold at least 14 days before surgery
alpha adrenergic antagonist for BPH - CI
use alpha1 adrenoreceptor antagonist (prazosin)
5 alpha reductase inhibitor (5ARIs) for BPH - MOA
- competitively inhibit 5 alpha reductase
- reduce conversion of testosterone to DHT
- reduce prostate size (improve urine flow, reduce frequency of urinary retention, reduce need for surgical procedure for transurethral resection & prostatectomy
5 alpha reductase inhibitor (5ARIs) for BPH - benefit
1) slow progression of disease
2) decrease need for surgery
3) decrease size of prostate
4) reduce PSA levels
5 alpha reductase inhibitor (5ARIs) - disadvantages
slow onset (6-12 months)
5 alpha reductase inhibitor (5ARIs) for BPH - PK
1) absorption
- well absorbed orally
- 5mg OD
- X dose adjustment even if renal/hepatic impair or old
2) distribution
- highly plasma protein bound
3) metabolism
- liver, t1/2 6h
4) elimination
- 50% unchanged faeces
- metabolites urine & faeces
5 alpha reductase inhibitor (5ARIs) for BPH - AE
1) ejaculatory disorder (reduce semen, delayed)
2) decreased libido & sexual potency
3) ED, gynaecomastia, breast tenderness
5 alpha reductase inhibitor (5ARIs) for BPH - CI
pregnant, women, child
phosphodiesterase 5 inhibitor (PDE5i) for BPH
- smooth muscle relaxation
- tadalafil
- take wo regards to timing of sex
- significant hypotension
combination therapy for BPH
1) alpha 1 antagonist + 5ARI
- 1st line
- alpha blocker onset wks, 5ARI months
- finasteride + doxazosin
2) 5ARI + PDE5i
- mitigate sexual AE
- X initiate PDE5i if unstable angina
3) alpha 1 antagonist + PDE5i
- high risk hypotension
anti-muscarinic for irritative/storage BPH
- block muscarinic receptor in detrusor muscle = decrease involuntary contraction of bladder
- oxybutynin
definition of ED
- persistent (at least 6 month) inability to achieve/maintain erection of sufficient duration & firmness to complete satisfactory intercourse
what happens during erection
1) Activated parasympathetic system (Ach)
** activated processes
- increase NO production -> increase activity of guanylate cyclase -> increase cGMP production
- Ach + prostaglandin -> increase adenyl cyclase -> increase cAMP
** process outcome
- smooth muscle relax (more space for blood to flow in) + vasodilation -> corpora cavernosa fill up w blood -> swelling -> compression of venules against tunica albuginea (decrease venous outflow)
2) functional hormonal system
- testosterone: encourage libido
detumescence
- subsiding of erection
- process:
1) deactivate parasympathetic (cGMP deactivated by PDE-5 -> stop vasodilation)
2) activate sympathetic system
** induce smooth muscle contraction via aplha2 adrenergic receptor of arterioles -> reduce blood flow - possible inhibitory effect be serotonin
aetiology of organic ED
1) vascular
- atherosclerosis, peripheral vascular disease (PVD), HTN, DM
2) hormonal
- hypogonadism
- hyperprolactinemia (suppress testosterone production)
3) nervous
- central: spinal cord trauma/disorder, stroke, CNS tumour
- peripheral: DM, neuropathy, urethral surgery
4) medication induced
medication induced for organic ED
1) clonidine, methyldopa, BB (except nevibolol), thiazide diuretics
- decrease penile flow
- alternative: Nevibolol, ACEi, ARBs, loop diuretic
2) anticholinergic
- TCAs, 1st gen antihistamine, phenothiazine
- decrease ACh activity
- alternatives: bupropion, trazodone, 2nd gen antihistamine, atypical antipsychotic (2nd gen)
3) dopamine antagonist (metoclopramide)
- dopamine cause sexual arousal/stimulation
- alternatives: PPis, erythromycin
4) serotonin selective reuptake inhibitor (SSRIs)
- increased serotonin in brain
- decrease testosterone
- alternatives: bupropion, trazodone
5) finasteride, dutasteride
- decrease testosterone
- alternative: terazosin, alfuzosin
6) CNS depressant (benzodiazepine, anticonvulsant)
- suppress perception of psychic stimulus
- alternative: gabapentin
psychogenic ED
- thought/feeling
- malaise, loss of attraction, stress, performance anxiety, mental disorder, sedation
other aetiology ED
smoking, excessive alcohol, illicit drug use, obesity
Sexual health inventory for men (SHIM)
- mild to no ED: 17 - 21 points
- moderate to severe: < 11 points
evaluation of cardiovascular disease for ED
- ED potential early symptom of comorbid CVD
- sex = sympathetic activation = increase HR & BP = increase MI risk
- generally:
1) low risk: ok
2) unknown, X low risk: exercise stress test
3) unstable/severe symptomatic CVD: defer until stabilised - cardiac rehab & regular exercise until reduce risk of CV complications w sexual activity
nonpharmaco for ED
1) modifiable risk factors
- smoking, control weight, control glucose/BP/fluid, exercise, decrease alcohol
2) psychotherapy
3) vacuum erection device (VED)
4) surgery: penile implant
types of pharmacotherapy for ED
1) PDE5i
2) testosterone replacement
3) alprostadil
PDE5i for ED - MOA
inhibit PDE5 -> inhibit catabolism of cGPM -> enhance cGMP activity -> induce smooth muscle relaxation -> increase blood flow -> erection
PDE5i for ED - general
cause & enhance erection after sexual stimulation
PDE5i for ED - types
1) tadalafil
- long enough t1/2 for OD dose
- taken regardless of food
- hepatic & renal adjustment
2) sildenafil
- 5mg OD
- onset 30-60 mins
- taken before sex
- empty stomach (2 hrs after food)
- X adjustment if hepatic/renal impair or old
- metabolised by liver (CYP3A4 major, CYP2C9 minor)
3) vardenafil
- taken before sex
- empty stomach (2 hrs after food)
- hepatic dose adjustment
PDE5i for ED - lower initial dose for
1) ≥ 65 yo
2) on alpha blockers
3) renal failure
4) CYP3A4 inhibitor
PDE5i for ED - SE
1) headache, rhinitis, flushing, muscle & back pain, dizziness, hypotension
2) prolonged erection & priapism (seek treatment if > 4 hrs)
3) sudden hearing loss
4) QTc prolongation (Vardenafil)
5) muscle pain (esp tadalafil)
6) ocular problem
- sildenafil, vardenafil
- irreversible problem w colour discrimination (blue -> green)
- light sensitivity
- nonarteritic anterior ischaemic optic neuropathy (NAION)
** hyperperfusion, seek immediate help
PDE5i for ED - drug interactions
1) nitrates
- avoid 24 hrs after sildenafil vardenafil, 28 hrs after tadalafil
2) anti-HTN, alcohol
3) CYP3A4
testosterone replacement for ED - normal ranges
300 - 1100 ng/dL or 10.4 - 38.2 nmol/L
testosterone replacement for ED - Indication
symptomatic hypogonadism confirmed by
1) decreased libido
2) low serum testosterone concentration
testosterone replacement for ED - SE
irritability, aggressive behaviour, undesirable hair growth, increase BP, dyslipidemia, polycythaemia (increase clot & stroke risk), prostatic hyperplasia
testosterone replacement for ED - monitoring
testosterone
- 1 - 3 months
- 6 - 12 month interval
- discontinue if X improve after 3 month
alprostadil for ED - general
X require sexual stimulation, fast onset, super invasive
alprostadil for ED - MOA
stimulate adenyl cyclase -> increase cAMP -> induce smooth muscle relaxation -> erection
alprostadil for ED - DDi
X PDE5i concurrent
alprostadil for ED - dosage form
1) intraurethral pellet
- duration: 30 - 60 mins
- SE: pain, warmth/burning sensation in urethra, voiding difficulties, bleed, priapism, partner vaginal burn/itch
2) intracavernosal
- better efficacy
- higher risk of priapism, bleeding, haematoma, fibrosis
- :( : fear of needle, invasiveness, complicated
- X more than 3x per wk
