repro (FEMALE & MALE HEALTH) Flashcards
1
Q
Amenorrhea
A
No menstrual bleeding in 90day period
2
Q
Amenorrhea etiology
A
1) Primary/ functional
- Absence of mensus by age 15
Female who never menstruated before
- Rare, <0.1% of pop
2) Secondary
- Absence of 3 cycles in previously menstruating female
- 3-4% of pop
- Freq in pop:
* <25 yo (young) w/ hx of menstrual irregularities
* Competitive athletics (low body fat)
* Massive weight loss (GnRH secretion decr, less FSH, LH)
3
Q
3 main cause of amenorrhea
A
1) Anatomical cause
○ Preg
- No shedding
○ Uterine struc abnormalities
- Prevent tissue from shedding
2) Endocrine disturbances
○ Lead to chronic anovulation
- No corpus luteum (no release of prog)
- No P,E withdrawal at end of cycle
3) Ovarian insuff/ failure
4
Q
tx for amenorrhea
A
1) Identify underlying cause
* Ovulation? Ovary? GnRH (FSH? LH?)
2) Non pharm
* Weight gain
* Reduction in exercise intensity
* Stress management
3) Pharm
* COC
* Estrogen only
○ If its low
* Progestin only
○ If its low
Can be top, suppl amt no need large amts
* Cooper IUD Incr menstrual bleeding
5
Q
Menorrhagia
A
Heavy menstrual bleed
* >80ml/ cycle
* Bleed for >7 days per cycle
As long as affects QOL
6
Q
Menorrhagia causes
A
1) Uterine-related factors
1. Growth outside/ inside uterus
a. Fibroids
b. Adenomyosis
c. Endometrial polyps
2. Gynecologic cancers
3. Alteration in hypothalamic-pituitary-ovarian (HPO) axis
a. GnRH, FSH, LH incr
2) Coagulopathy factors:
1. Cirrhosis (PLT, clotting factors)
2. Von willebrand disease (blood unable to clot properly)
3. Idiopathic thrombocytopenic purpura (decr PLT)
7
Q
tx for menorrhagia
A
Pharm
* Contraceptives
○ COC
○ Progestin IUD
○ POP
○ Progestin inj
* Non-contraceptives (help blood to clot)
○ NSAID during menses
○ Tranexamic acid during menses
○ Cyclic prog (14-21 days only)
Non-pharm
* Endometrial ablation
○ Polyps, cancer, fibroids
* Hysterectomy (remove uterus)
8
Q
dysmenorrhea
A
Crampy pelvic pain with/ just before menses
9
Q
dysmenorrhea causes
A
1) Primary
1. Release of prostaglandins, leukotrienes
2. Vasoconstriction
3. Cramp
2) Secondary
1. Endometriosis/ structural physiology
2. Tissue grows outside of uterus instead
10
Q
pharm for dysmenorrhea
A
- Pharm
- NSAID (inhibit PG)
- COC
- Progestin inj/ IUD
○ Make pt amenorrheic
- Non pharm
- Topical heat therapy
- Exercise
- Acupuncture
- Low-fat vege diet
11
Q
Premenstrual syndrome (PMS)
A
Cyclic pattern of symptoms occurring 5 days before menses
Resolves at onset of menses
MOST do not report impairment of daily activities
12
Q
PMS sx
A
Somatic symptoms (physical)
Affective symptoms (mood)
Severe mood symptoms: premenstrual dysphoric disorder (PMDD)
Psychiatric condition due to its debilitating effect
13
Q
Somatic symptoms (physical)
A
- Bloat
- Headache
- Weight gain
- Fatigue
- Dizzy/ N
- Appetite change
14
Q
Affective symptoms (mood)
A
- Anxiety/ depression
- Angry outburst
- Social withdrawal
- Forgetfulness
- Tearful
- Restlessness
15
Q
tx for PMS
A
Pharm
* Selective serotonin reuptake inhibitors (SSRIs) - Mood
○ Not for physical sx
* COC - Physical
○ Not for mood sx
Non pharm
* Exercise
* Reduce caffeine
* Reduce sugar intake
16
Q
Polycystic ovary syndrome (PCOS)
A
Irregular menses due to cysts
-Ovaries produce abnormal amt of androgens
- Small cysts (fluid-filled sacs) form in ovaries
17
Q
PCOS results in
A
- Menstrual irregularities
- Excess androgen
- Acne/ hirsutism/ Obesity
- Metabolic disease, insulin resistance
- DM, CVS disease
18
Q
PCOS tx
A
- COC
- Antiandrogenic progestin (4th gen)
○ Reduce acne, hirsutism
- Antiandrogenic progestin (4th gen)
- Metformin
- Not all PCOS need, but is commonly prescribed to reduce
- Insulin resistance, metabolic diseases
19
Q
Menopause
A
Permanent cessation of menses following the loss of ovarian follicular activity
- Retrospective diagnosis after 12mnths
20
Q
cause of menopause
A
- Natural
- Stages (perimenopause –> menopause –> post menopause)
- Induced
- Experienced anytime before natural menopause
- Removal of both ovaries
- Iatrogenic ablation of ovaries (treatment)
a. Chemotherapy
b. Pelvic radiation
21
Q
natural stages of menopause
A
1) Reproductive
2) Menopausal transition
a) Perimenopause (slight overlap into post)
○ Early stage:
- Varies
- Variable length, incr length of consecutive cycles (>7days)
□ Ovaries produce less and uneven amts of hormones
- Incr FSH
○ Late stage:
- 1-3 years
- Interval of amenorrhea > 60 days
- >25IU/L of FSH
- Vasomotor sx appear
3) Post-menopausal
* Stabilised high levels of FSH
* Incr sx of urogenital atrophy
22
Q
clinical presentation of menopause
A
1) Vasomotor sx
2) genitourinary sx
3) psychological/ cognitive
4) bone fragility
23
Q
Vasomotor sx
A
- (common sx, several times a day)
- Thermoregulatory dysfunction <– ESTROGEN WITHDRAWAL
○ Initiated at level of hypothalamus
1. Hot flush, night sweats
2. Heat on face
3. Rapid/ irregular HR
4. Flushing/ reddened face
5. Perspiration
6. Cold sweat
7. Sleep disturbances
8. Anxiety
24
Q
Genitourinary syndrome of menopause (GMS) sx
A
- Collection of sx due to change to labia, clitoris, vestibule, vagina, urethra, bladder
○ Decr estrogens, leads to less fat + dry
1. Genital dryness
2. Burning/ irritation/ pain
3. Sexual sx of lubrication difficulty
4. Impaired sexual function/ libido/ painful intercourse
5. Urinary urgency
6. dysuria
7. Recurrent UTI
25
Psychological/ cognitive sx
* Multi-factorial (stress/ hormonal fluctuations)
* Women of that age have a lot of anxiety
○ Stress (parents + kids)
○ Change in appearance, sexual
○ Hormones
1. Depression/ anxiety
2. Poor conc/ memory
3. Mood swings
26
Bone fragility
* Decr estrogen, more bone loss
1. Incr risk of osteoporosis & fractures
2. Incr joint pain
27
Non-pharm for menopause
If mild sx can try non-pharm
Mild vasomotor
○ Layered clothing removed when necessary
○ Lower room temp
○ Less spicy food/ caffeine/ hot drinks
○ More exercise
○ Dietary supplements
Mild vulvovaginal
○ Non hormonal vaginal lubricants
○Moisturizer
28
Isoflavones
□ Phytoestrogen (natural source of estrogen)
-Soybean pdts
- Legumes (lentils, chick pea)
29
Black cohosh
□ Herb native to North America
□ No sig DDI
□ Possible serotonergic activity at hypothalamus
- Vasomotor sx
30
Pharm, HRT --- estrogen should not be used to treat SOLELY
* Treatment of low libido
* CVD prevention
* Depression/ ANX/ cognitive/ memory issues
* Itchy skin/ hair loss
* Treatment of osteoporosis (only used for prevention)
31
pharm for menopause when
mod/severe vasomotor
mod/severe GMS sx
insuff resp to non pharm
32
pharm HRT 2 types
1) estrogen only
2) estrogen + progestin
33
Estrogen only if __
No intact uterus. Otherwise unopposed estrogen can cause endometrial cancer
PO tablets
□ Taken same time everyday. Start new pack after finishing
No pill-free interval, lower dose used
ADV:
- Relatively inexpensive
DISADV:
- Highest dose required --> higher risk of SE
-Potential for missed dose --> irregular bleeding, breakthrough
34
Uterus intact using estrogen-only (TOP)
Topicals (patch, gel)
□ Used twice a week (lower back, abdomen, thigh, buttocks --> rotate sites)
□ Ruler provided to measure dose of gel, applied on arms/ thigh
Let gel dry --> rotate sites
ADV:
- Lower systematic dose than PO
-Continuous estrogen release
DISADV:
- Expensive
-Skin irritation (rotate sites)
- Gel more variability in absorption
35
uterus intact using estrogen-only (LOCAL)
Local vaginal (pessary, creams)
□ Inserted x2/ week before bedtime, no reduce movement
ADV:
- Lower estrogen dose, no need concomitant progestin
- Continuous estrogen release
DISADV:
- Inconvenient/ uncomfortable
- Vagina discharge
-Only for localised urogenital atrophy (GMS)
36
Estrogen + progestin
a. Intact uterus, can use prog to protect endometrium from overgrowth (cancer risk)
1) Continuous cyclic
□ Prog added on either 1st/ 15th of mnth for 10-14days only
□ Withdrawal bleeding when prog stopped
- Regulate menses --> predictable bleeding
- Only if perimenopausal stage
2) Continuous-combined
□ Estrogen & progestin daily
□ No withdrawal bleeding, but may have breakthrough
□Amenorrhea take place after several mnths
37
Progestins role;
- Reduce risk of endometrial cancer associated with unopposed estrogen
- Data: improve VMS (but not monotherapy, not standard therapy)
Types:
Dyhydrogesterone, norethisterone, medroxyprogesterone, micronized progesterone, norgestrel, levonorgestrel, gestodene, desogestral, norgestimate
38
HRT considerations
* Takes 2-3mnths of use before seeing vast improvement of menopausal sx
* Continue HRT (systemic, local) if needed/ pt aware of risk vs benefits/ follow-up
Upon discontinue, 50% chance of sx returning
39
initiate HRT must monitor for
* Annual mammography
* Endometrial surveillance
○ Unopposed estrogen: any vag bleeding
○ Continuous cyclic (E/P off)
§ If bleed occur when P on
○ Continuous-combine (E/P)
§ If bleed prolonged
§ heavier than normal
§ freq
§ persists after treatment for > 10mnths
40
FOR VMS pharm
1) Antidepressants
* Serotonin and norepinephrine reuptake inhibitors (SNRIs)
○ venlafaxine
* Selective serotonin reuptake inhibitors (SSRIs)
○ Paroxetine
2) Gabapentin (cause pt to KO)
* Night sweat
* Sleep disturbances
41
SIMILAR TO HRT
Tribolone
* Synthetic steroid w/ estrogenic, progestogenic and androgenic effects
○ Improve mood, libido, menopause sx, vaginal atrophy
○ Protect against bone loss
* For postmenopausal women (12mnths since last natural period)
○ Not perimenopausal (risk irregular menses)
* Similar SE, risk factors
○ Risk of stroke, breast CA recurrence, endometrial cancer
42
BPH
Benign prostatic hyperplasia
* Progressive condition
* Lower urinary tract signs and sx (LUTS)
* Neg impact on QOL
* Non-malignant growth of some component of prostate
Transitional zone of prostate
43
pathogenesis of BPH
Etiology not well known (AGE, HORMONAL factors)
1) Static
a. Hormonal factors
b. Testosterone ---> DHT
c. Enlarge prostate tissue
2) Dynamic
a. Incr smooth muscle tissue & agonism of a1 receptors
b. Narrow urethra outlet
= urethral obstruction/ signs & sx
44
Physiology of prostate (normal)
Composed:
○ Epithelial (glandular) tissue
§ Androgens stimulate growth
○ Stromal (smooth muscle tissue)
§ Innerved by a1 adrenergic receptors
Testosterone --> DHT
○ By type II 5a-reductase (in prostate)
DHT for normal growth/ enlargement of prostate
45
LT pathophysiology of BPH = bladder response to obstruction
* Early: bladder musc force urine through narrowed urethra (contract FORCEFULLY)
* LT:
○ Bladder muscle hypertrophy
○ Muscle decompensates
=detrusor muscle irritable, sensitive
(overactive, instable)
* Contract abnormally in resp to small amt of urine in bladder
* Incr freq of urination
46
sx of BPH
Many pt
* Asymptomatic
* Symptomatic in 1/3 men >65yrs old
LUTS (obstructive // irritative)
* Weak stream
* Freq nocturia
* Intermittent stream
* Incomplete emptying
* Straining
* Urgency
*LUTS NOT specific to BPH, many other causes
- UTI, prostate/ bladder cancer, DM
47
Obstructive/ voiding sx (early)
Hesitancy
Weak stream
Sensation of incomplete emptying
Dribbling
Straining
Intermittent flow
48
Irritative/ storage sx (LT), musc decompensate, hyperactive
Dysuria
Freq
Nocturia
Urgency
Urinary incontinence
49
Assessment of BPH (7)
* Digital rectal exam
* Ultrasonography
* Max urinary flow rate (Qmax)
* Prostate size (<25g)
* Prostate specific antigen (PSA) > 1.5ng/mL
* post void residual >200mL
* AUA-SSI
50
prostate size
normal <25g
large > 40g
51
Prostate specific antigen (PSA)
* MIGHT be elevated in BPH
○ Correlated to prostate size, vol
* Predict progression of BPH
○ >1.5ng/mL
* Higher risk for prostate cancer
52
Post void residual (PVR)
after urinate, how much left in bladder
* <100ml = normal
* >200ml = inadequate emptying
○ Shows obstructive/ inactive bladder
○ Means no Anticholinergic drugs as bladder alr constricted
○ No anti-muscarinic if PVR >150-250mL
53
AUA-SSI (American urological assoc sx scoring index) 0-5 for each
Incomplete emptying
Freq
Intermittency
Urgency
Weak stream
Straining
Nocturia
Classification of sx: 3 grps based on bothersome sx, severity (affects treatment approach)
54
Mild
Score <7
Asymptomatic, mild sx
55
moderate
Score 8-19
All above sx
obstructive voiding sx
Irritative voiding sx
56
SEVERE BPH
Score >20
All sx + complications!
i. Recurrent UTI (trapped urine, bact grow)
ii. Bladder stone
iii. Acute urinary retention
iv. Urinary incontinence
v. Hematuria
(consider TURP, transurethral resection of prostate)
57
meds that affect BPH
* Anticholinergics
* Decr bladder musc contractibility
○ Antihist, tricyclic antidepressants (TCAs)
* A1 adrenergic AGONIST
* Contract prostate smooth muscles
* Decongestants (Pseudoepinephrine)
* Opioid analgesic
* Incr urinary retention
* Diuretic
* Incr urinary frew
* Testosterone
*Stimulate prostate growth
58
management before pharm
* Watchful waiting
* Mild sx (score <8)
* Moderate/ severe >8 but not BOTHERED by sx (not affect QOL)
* Reassess Sx with AUA SIS -- annually/ more freq
* Lifestyle change/ non pharm
59
non pharm for BPH
Limit fluid intake in evening
Minimise caffeine and alcohol intake
Educate pt to take time to empty bladder COMPLETELY, OFTEN
Avoid meds that exacerbate sx
weight loss
60
Pharm start when
~50% of sx BPH pt will eventually require clinical tx
○ Sx bother pt
○ Complications arise
* Choosing tx must consider:
○ LUTS severity: AUA SI
○ Prostate size
○ Concurrent comorbidities
§ HTN, ED
○ PSA value
○Presence of irritative/ storage sx
61
types of BPH tx
Alpha adrenergic antagonist
5-alpha reductase inhibitors
Phosphodiesterase 5 inhibitor
62
Alpha adrenergic antagonist TYPES
Non selective (peripheral vascular + urinary a1 adrenergic receptors)
Selective (selective urinary a1A receptors -- prostate, LUT)
63
Non selective a-adrenergic antagonist
need to titrate slowly to therapeutic dose (risk hypotension, syncope)
* Doxazosin
* Terazosin
* Prazosin (not recc for BPH)
64
Selective a-adrenergic antagonist
less risk for hypotension, dose titration not necessary
* Alfuzosin
* Tamsulosin
* Silodosin
65
benefits of alpha adrenergic antagonist
Effective in reducing LUTS (relax smooth muscle):
- mod, severe + small prostate <40g
* Does not reduce prostate size
○ no prevention for progression of BPH/ surgery
* Fast onset (days -- wks)
*s/s recur when discontinued
66
general SE of Alpha adrenergic antagonist
muscle weakness, fatigue, ejaculatory disturbance, headache (dilate vessel in brain, more blood flow)
- Bed time admin to decr orthostatic effects
67
Non selective ADR
○ Dizzy, first dose syncope, orthostatic hypotension
○ Could be beneficial in HTN pt that need further BP lowering
§ But not used as monotherapy for pt (HTN + BPH)
CI: pt history of syncope (BEERs list)
68
Uroselective ADR
○ Ejaculatory disturbances
§ Delayed retrograde ejaculation (no ejac after orgasm)
§ Silodosin > tamsulosin > alfuzosin
□ Less dysfunct < 5ARI
○ Intraoperative floppy iris syndrome
§ Complicates cataract surgery
§ MOA: block a1 receptors in iris dilator muscle
□ TAMSULOSIN
§ Only initiate after surgery/ hold off 2-3wks
○ May be used in pt that don’t need added BP lowering effect
○ Low to non-peripheral vascular dilatation
§ Less hypotension, syncope
69
5-alpha reductase inhibitors benefits
inhibit 5a reductase (type II), decr conversion from Testosterone --> DHT
* Reduce size of prostate
* Slow progression of disease, decr need for surgery
* Decr PSA lvls (add-on if initial PSA >1.5ng/mL) : high risk progression
70
indication for 5-alpha reductase inhibitors
* Mod-severe LUTS
* + large prostate >40g
* For pt that wants to avoid surgery/ cannot tolerate SE of a1 antagonist
71
consideration for 5-alpha reductase inhibitors
slow onset, 6-12mnths to decr prostate size
Need PSA lvl before initiate therapy (to monitor)
* Values harder to interpret after initiate
72
ADR of 5a reductase inhibitors
Ejaculatory disorders (reduced semen during ejaculation or delayed ejaculation)
○ Higher risk than a-antagonist
Decr testosterone:
○ Decr libido
○ ED
○ Gynecomastia, breast tenderness
Lesser risk of hypotension
73
CI of 5a i
TERATOGENIC: preg/ child bearing females not handle
74
PDE5i for PBH
BPH and ED share same pathophysiologic mechanism -- relax smooth muscle
- Does not affect prostate size
Tadalafil only (5mg PO daily)
75
indication for PDE5i --- BPH
* Usually as ADD-ON therapy
* Pt with concomitant ED
* Counter 5ARI SE
76
consideration for PDE5I --- BPH
* Onset: days -- wks
* Taken w/o regard to timing of sexual activity
* Duration of action: 36hrs
77
Monotherapy (?) for PDE5I -- BPH
* Controversial, but incr evidence viable (even w/o ED)
* Mono for pt with BPH-LUTS (w/ or w/o ED)
○ Younger age
○ Low BMI
○ Higher baseline sx
* Better effect of tx with PDE5i
78
PDE5i ADR
sig hypotension
79
COMBINATION THERAPY indicated
Combi > monotherapy
○ For pt with moderate sx
§ AUASI score 8-19
§ Prostate size > 25g
○ Benefit with mild ADR
80
5ARI + a1 antagonist
5ARI: mnths for optimal effect
A1 antagonist: relief sx rapid
§ For sx pt with enlarged prostate
§ Discontinue a1 antagonist after
81
5ARI + PDE5i
○ Mitigate sexual ADR, arise from 5ARI (ED)
○ But pt w/ BPH & ED usually have CARDIAC comorbidities
CI: Unstable angina, nitrates GTN -- no PDE5i
82
A1 antagonist + PDE5i
○ Not initial combi for 2 vasodilator
○ ADR: severe life threatening hypotension
§ **uro-selective a1 instead
§ ** optimise/ stabilise a1 antagonist dose first before + PDE5i
□ Use lowest dose of PDE5i
§ Both don’t address prostate enlargement
83
pharm for Irritative/ storage sx
Anti-muscarinic: Oxybutynin, tolterodine, solifenacin
- Add-on for pt with irritative voiding sx, mimics overactive bladder (OAB)
-PVR: <250mL ~ 150mL
□ Too much PVR, bladder cannot contract, bladder might BURST
b. MOA: blocks muscarinic receptors in detrusor muscle
i. Decr invol contraction of bladder
c. Was CI in BPH for urinary retention, but able to help OAB
84
considerations in BPH
1. Lifestyle changes are recommended at any stage for BPH --> 2* LUTS
2. Watchful waiting for mild sx, not bother by LUTS
3. Pharmacotherapy for mod-severe sx, bothersome
4. Surgery indicated when BPH complications present
85
Erectile dysfunction
* Persistent (at least 6mn) inability to achieve/ maintain an erection of suff duration and firmness to complete satisfactory intercourse
* Incidence:
* Low in men <40yo, incr as age incr
* 50% of men, >40yo
86
erection normal physiology
* Flaccid
○ Blood flow INTO penis = blood flow OUT of penis
* Erection
○ Arterial flow INTO penis > venous OUTflow
87
factors for normal erection
1) IN > OUT
2) activated parasympathetic system (Ach)
3) hormonal system
88
physiology of erection
1) Smooth muscle relax
2) Activated parasympathetic system --- Ach (acetylcholine)
3) hormonal
89
1) IN > OUT
* Smooth muscle relax
* Corpora cavernosa fills up with blood
= Incr Inflow
* Swelling causes compression of venules against tunica albuginea
= Dec OUTflow
90
2) Activated parasympathetic system --- Ach (acetylcholine)
* Ach incr NO
○ Incr activity of guanylate cyclase
○ Incr cGMP
* Ach & PGE
○ Incr adenyl cyclase
○ Incr cAMP
Smooth musc relax, vasodilation = incr INflow
91
3) Physiology of erection: hormonal
Functional hormonal system --- Testosterone
§ Encourage libido (sexual drive)
§ 300 - 1000ng/dL (10.4-38.2 mmol/L)
□ Lvl assessed based on pt sx
□ ED but normal lvl
□ No ED but low lvl
92
Physiology of detumescence:
1) Deactivate parasympathetic
i. cGMP deactivated --> by PDE5 (phosphodiesterase type5)
ii. Stops vasodilation (infow)
iii. Predominant enzyme found in penis
2) Activated sympathetic system
i. Induce smooth musc contract
ii. A2 adrenergic receptors of arterioles contract
iii. Reduce Inflow of blood
3) Serotonin
i. Inhibit effects of sexual arousal
ii. serotonin reuptake inhibitors
93
Etiology for ED
1) organic (80%) -- vascular, nervous, hormonal, meds
2) psychogenic
3) mixed (organic + psychogenic)
4) other
-Social habits:
○ smoking, excessive ethanol intake, illicit drug use
- Obesity
94
Vascular system
Insuff Inflow blood, narrow
○ Arteriosclerosis
○ Peripheral vascular disease (PVD)
○ HTN
○ DM
95
Nervous system
Central: lack sensation
§ spinal cord trauma/ disorders
§ Stroke
§ CNS tumor
Peripheral
§ DM
§ Neuropathy
§ Urethral surgery
96
Hormonal system
○ Hypogonadism
-Low testosterone
○ Hyperprolactinemia
- Prolactin supp testosterone
97
Medication induced
BP
anticholinergic
dopamine
serotonin selective reuptake inhibitors
5a reductase inhibitors
CNS depressants
98
BP
clonidine, methyldopa, BB (Xnevibolol), thiazide diuretic
○ MOA: Decr penile blood flow
○ Alt: nebivolol, ACEi, ARB, loop diuretic
99
Anticholinergics
TCA, 1st gen antihist, phenothiazines
○ MOA: decr Ach activity
○ Alt: bupropion, trazodone, 2nd gen antihistamine, atypical antipsychotics 2nd gen
100
dopamine
(metoclopramide)
○ MOA: decr ACh activity
○ Alt: PPI, erythromycin
101
SSRI
○ MOA: incr serotonin in brain, decr testosterone
○Alt: bupropion, trazodone
102
5a RI
(finasteride, dutasteride)
○ MOA: decr testosterone
○ Alt: (a-blockers) terazosin, alfuzosin
103
CNS depressants
(benzodiazepines, anticonvulsants)
○ MOA: suppress perception of psychic stimulus
○ Alt: anticonvulsant - valproic acid, gabapentin
104
PSYCHOGENIC
Thoughts, feelings (psycho) not physical
Malaise
Loss of attraction
Stress
Performance anxiety
Mental disorders
Sedation
105
signs and sx of ED
* Loss of interest in sexual activity
* Depression
* Performance anxiety
* Embarrassment
* Angry
* Low self esteem
* Disharmony in rs
106
Evaluation of ED
* Signs and sx
* Sexual health inventory for men (SHIM)
○ None--mild (17-21 pts)
○ Mod -- severe (<11 pts)
* Workup to identify UNDERLYING CAUSE of ED
○ Medical hist/ medications
○ Social hist
§ Drink, smoke, psychological
○ Surgical hist
○ Lab results
§ BGL, lipid, testosterone
107
CV evaluation
(in all pt with ED), closely linked
1) ED early sx of unidentified comorbid CVD
2) Sexual activity
a. Sympathetic activation
b. Incr BP, HR
c. Incr risk of MI
* Low risk of CV, can have sexual activity
* Unknown/ not low risk:
○ Exercise stress test to evaluate exercise capacity
○ HR high, see ST elevated, how much heart can tolerate
* Unstable/ severe sx CVD: defer until condition stabilised
○ Cardiac rehab and regular exercise to reduce risk of CV complications with sexual activity
108
Manage ED
1) Recognise. Reverse/ treat underlying cause
2) Non pharm
* Address modifiable risk factors
○ Stop smoking
○ Control weight/ lose weight
○ Control BGL/ BP/ Lipids
○ Exercise
○ Decr alcohol
* Psychotherapy (counselling)
* Device: vacuum erection devices (VEDs)
* Surgery (penile implant)
3) Pharm
* PDE5i
* Testosterone replacement
* Alprostadil
* Yohimbine
109
PDE5i in ED
* Inhibit PDE5enzyme, induce catabolism of cGMP
* Enhance cGMP activity (prevent breakdown by PDE5)
○ Induce smooth muscle relaxation, vasodilation
* Erection to form
110
benefits of PDE5I
* 1st line agents
* Cause and enhance erection only AFTER SEXUAL stimulation
* Failure rate 30-40%
○ Try 5-6 times
○ Try diff drugs in same class
SVTA
111
Sildenafil
* 50mg PO 1hr before intercourse
○ PRN, for sexual intercourse
* Onset: 15-60min
* Duration of action: 4h
* Consideration
○ Empty stomach
○ Hep, renal adj
112
Vardenafil
* 10mg PO 1hr before intercourse
○ PRN, for sexual intercourse
* Onset: 25-60min
* Duration of action: 4h
* Consideration
○ Empty stomach
○ Hep adj
QTc prolongation
113
Tadalafil
* 5mg PO 36hr before intercourse
○ Can be taken DAILY
* Onset: 15min-2hr
* Duration of action: 36h
* Consideration
○ Regardless of food
○ Hep, renal adj
Tadalafil with PDE11 affinity: muscle pain
114
Avanafil
* 100mg PO 30min before intercourse
○ PRN use
* Onset: 15- 30 min
* Duration of action: 6h
* Consideration
○ Regardless of food
115
initiate PDE5i
Low dose esp for:
○ Pt > 65yo
○ Alpha blockers
○ Renal failure pt
○ CYP3A4 inhibitors Incr serum conc of PDE5i
Erythromycin, cimetidine, ketoconazole, itraconazole, clarithromycin, grapefruit, ritonavir, saquinavir
116
ADR of PDE5I
* Headache
* Rhinitis
* Flushing
* Muscle and back pain
* Dizziness
* Hypotension
* Prolonged erections, priapism
○ Blood trapped inside)
○ Seek ED if >4hrs
* Sudden hearing loss
*Tinnitus and dizziness
117
Sildenafil, vardenafil (affinity with PDE6 retina)
○ reversible problem with colour discrimination (blue <--> green)
○ Light sensitivity
○ Nonarteritic anterior ischemic optic neuropathy (NAION)
§ Blood flow to optic nerve blocked
○ Risk factors
§ DM, smoke, HTN, CVD, dyslipidemia, age>50yo
○ Instruct pt with sudden decr vision/ vision loss to stop use and seek Medical attention
118
DDI with PDE5i
Nitrates (GTN)
○ Avoided for 12hrs after avanafil
○ 24hrs after sildenafil, vardenafil
○ 48hrs after tadalafil
Multiple antihypertensives
○ Risk of hypotension
Alcohol
○ Hypotension
CYP3A4i
○Incr conc of PDE5i
Erythromycin, cimetidine, ketoconazole, itraconazole, clarithromycin, grapefruit, ritonavir, saquinavir
119
Monitoring of PDE5i
Efficacy
○ Failure reported:
§ Admin w/ food
§ Time, freq of dosing
§ Sexual stimulation
§ Titration to max dose
Safety (BP, ADR, DDI)
Change in cardiac health status
120
Testosterone replacement
* Restore serum testosterone lvl to normal range (300-1100 ng/dL; 10.4-38.2 nmol/L)
* DF:
IM inj, buccal, patch, top gel, body spray, nasal spray, PO
121
indication for testosterone replacement
Symptomatic hypogonadism
○ Decr libido
○ Low serum testosterone conc
122
ADR of testosterone replacement
* Irritability
* Aggressive behaviour
* Undesirable hair growth
* Incr BP
* Hepatotoxicity
* Dyslipidemia
* Polycythemia
* Prostatic hyperplasia
123
monitor for testosterone replacement
1-3mnths
6/12mn interval
- Discontinue if no improvement after 3mn (high risk for SE)
-CI: prostate CANCER
124
Alprostadil MOA
* Prostaglandin E1 analog.
* MOA: stimulate adenyl cyclase
* Incr cAMP
* Induce smooth muscle relaxation
* Erection formed
125
considerations of alprostadil
* (unlike PDE5i): no need sexual stimulation to work
* Fast onset: 5-10mins
* DDI: not used with PDE5i
* DF:
1) Intraurethral
2) Intracavernosal
126
DF: Intraurethral alprostadil
Inserted into penis and release med
SE:
– Pain
– Warmth. Burning sensation in urethra
– Voiding difficulties
– Bleeding/ spotting
– Priapism
– Partner exp vaginal burn/ itch
127
DF: Intracavernosal
Preferred over intraurethral route, due to better efficacy, inj at side of penis
* Higher risk of SE:
– Priapism, bleeding, hematoma, fibrosis
* Disadv:
– Fear of needle, invasiveness, lack of spontaneity, complicated admin technique
128
yohimbine
* Derivative of African yohimbine tree
* a 2-antagonist
* MOA: decr sympathetic activation, remain dilated
* Efficacy controversial
Illegal, not HSA APPROVED
129
tx considerations for ED
1. PDE5i as 1st line agent
a. All have similar efficacy profile
b. Diff onset, duration of action, SE profile
2. Alprostadil
a. Avoided due to priapism & pain
3. Testosterone 1st line if
a. ED + symptomatic hypogonadism
b.Consider SE
