Exam 2 Flashcards
1
Q
Estradiol brand name and therapeutic class
A
Vivelle-Dot, Alora, Climara, Femring, Estring, Vagifem, Divigel, Estrace
Hormone/Estrogen
2
Q
Estrogens (conjugated) brand name and therapeutic class
A
Premarin
Hormone/estrogen
3
Q
Medroxyprogesterone acetate brand name and therapeutic class
A
Provera
Hormone replacement
4
Q
Progesterone brand name and therapeutic class
A
Prometrium
Hormone replacement
5
Q
Venlafaxine HCL brand name and therapeutic class
A
Effexor XR
Antidepressant (SNRI)
6
Q
Desvenlafaxine
A
Pristiq
Antidepressant (SNRI)
7
Q
Paroxetine HCl brand name and therapeutic class
A
Paxil XR, Pexeva
Antidepressant (SSRI)
8
Q
Fluoxetine HCl brand name and therapeutic class
A
Prozac, Sarafem
Antidepressant (SSRI)
9
Q
Perimenopause
A
Start of menstrual cycle irregularity until 12 months after last menstrual cycle
10
Q
Menopause
A
12 months after last menstrual cycle
11
Q
Early menopause
A
Menopause at age 40-45
12
Q
Estrogens
A
refers to estradiol, estrone, estriol, and synthetic estrogens
13
Q
Progestogen
A
Refers to progesterone and synthetic progestins
14
Q
ET
A
estrogen therapy
15
Q
EPT
A
estrogen plus progesterone therapy
16
Q
Menopause etiology
A
Occurs at average of age 51
Loss of ovarian function leads to hormonal deficiencies
Due to: natural aging, ovarian surgery, meds, pelvic irradiation
<25% of women experience menopause without symptoms
Symptoms may last months to years
17
Q
Hormonal changes in menopause
A
Increase in FSH and LH
Decrease in estrone and estradiol
18
Q
Symptoms of menopause
A
Vasomotor symptoms (hot flushes, night sweats)
Sleep disturbances
Mood changes
Decreased libido
Problems with concentration and memory
Arthralgia
Genitourinary symptoms- vaginal dryness and dyspareunia
19
Q
Lab tests in menopause
A
Perimenopause: FSH on day 2 and 3 of the menstrual cycle greater than 10-12 IU/L
Menopause: FSH greater than 40IU/L
20
Q
Nonpharm therapy for menopause
A
Hot flushes- layered clothing, lowering room temperature, decreasing spicy foods, caffeine, hot beverages, exercise
Vaginal symptoms: vaginal lubricants, moisturizers
Efficacy- little evidence, most women need additional therapy
21
Q
Indications for treatment of menopause
A
Symptomatic women age <60 OR <10 years since menopause
Vasomotor symptoms +/- vaginal symptoms= systemic treatment
Vaginal symptoms only- topical treatment
Prevention of post-menopausal osteoporosis (in <60 year old postmenopausal women)
22
Q
Treatment goals of menopause
A
Menopause is NOT a disease
Decrease symptoms
Improve QOL
Minimize AE
23
Q
When should you avoid MHT?
A
Unexplained vaginal bleeding, stroke, TIA, MI, PE, VTE, breast or endometrial cancer, active liver disease
24
Q
When should you use caution in MHT?
A
Diabetes, hypertriglyceridemia, active gallbladder disease, increased risk of breast cancer or CVD, migraine with aura
25
What do you need to evaluate before starting MHT?
CV and breast cancer risk
26
Benefits of MHT
```
Decreased vasomotor symptoms
Decreased vaginal atrophy
Osteoporosis prevention and treatment
Potential colon cancer risk reduction
Increased QOL, mood, cognition
Decreased dementia
Decreased DM
Less weight gain
```
27
Risks of MHT
```
Breast cancer
CV disease
Endometrial cancer
Ovarian cancer
Lung cancer
VTE
Gallbladder disease
```
28
Treatment of menopause with intact uterus
Must have estrogen AND progesterone due to risk of endometrial hyperplasia
29
Duration of MHT
Based on patient symptom duration and risk factors
Should not be life-long, assess yearly
Generally accepted duration is 5 years or less
Taper slowly over several months to prevent rebound symptoms
Low dose intravaginal therapy can continue indefinitely
30
Estrogen therapy AE
Nausea, HA, breast tenderness, heavy bleeding
31
Route of administration of estrogen therapy
oral, transdermal, topical, IM, implanted pellets
32
Oral estrogens for menopause
Estradiol is most potent, but only 10% reaches circulation as free estradiol
Formulations: conjugated equine estrogens, micronized 17beta-estradiol, estradiol acetate, esterified estrogens, synthetic conjugated estrogens, estropipate
33
Other (non oral) estrogen formulations
```
Forgoes first pass metabolism and thus increased estradiol concentrations
Transdermal patch (Vivelle-dot, Alora, Climara)- continuous delivery of estradiol, causes skin reactions so much rotate site
Topical sprays, gels, emulsions- vary in drug absorption
Estradiol pellets- insert subcutaneously, difficult to remove, can have increased estradiol levels for months after removal
```
34
Intravaginal estrogens
```
Used in genitourinary symptoms
Can have systemic absorption
Creams (premarin, estrace)
Tablet (vagifem)
Ring (Estring)
```
35
Progestogens AE
Irritability, weight gain, bloating, headache
36
Progestogens agents
```
Should be used in combo with estrogens in anyone with an intact uterus
Medroxyprogesterone acetate (Provera)
Micronized progesterone (Prometrium)
Norethindrone acetate (Aygestin)
```
37
Combo therapy of MHT`
Continuous EPT- estrogen daily and progestogen concomitantly for 12-14 days/month
Continuous combined EPT
Continuous long-cycle EPT- estrogen daily and progestogen concomitantly for 12-14 days every OTHER month
Intermittent combined EPT- 3 days estrogen alone, 3 days estrogen-progestogen
38
Why can't you use COC in menopause?
The dosing is very different. You need more estradiol in menopause than in COC
39
Other hormonal therapies for menopause (bazedoxifene)
Conjugated estrogens/bazedoxifene
MOA- bazedoxifene is a selective estrogen receptor modulator (SERM)
Indicated in patients WITH a uterus and have vasomotor symptoms or for osteporosis prevention
40
BBW for MHT
Estrogen- endometrial cancer, probable dementia
Progestogen- Breast cancer
Both- Should not be used for prevention of CV disorders
41
Contraindications of MHT
Known, suspected, or history of breast cancer or other estrogen or progesterone positive neoplasia
Active deep vein thrombosis
Active or recent coronary thromboembolic disease (stroke, MI)
Active liver dysfunction or disease
42
Relative contraindications to MHT
HTN, hypertriglyceridemia, hypothyroidism, fluid retention, severe hypocalcemia, ovarian cancer
43
Alternatives to hormonal therapy for hot flushes
Antidepressants using similar doses to depression
-Venlafaxine, desvenlafaxine, paroxetine (Brisdelle is only one approved for this indication)
Megestrol acetate-antineoplastic progestin
Clonidine
Gabapentin
44
Selective estrogen receptor modulators (SERMs)
Estrogen agonists in bone tissue
Estrogen antagonists in breast and uterus tissues
Tamoxifen, raloxifene (reduces risk or osteoporosis and breast cancer), ospemifene (used for dyspareunia)
AE- hot flushes, leg cramps
45
Sexual differentiation
Genetic sex- XY or XX
Gonadal sex- Testes or ovaries
Phenotypic sex- male/female genital tract and external genitalia
Psychological sex
46
Male sex differentiation
XY chromosomes- presence of SRY gene (on Y chromosome). This is the sex-determining region of the Y and encodes TDF (testis determining factor)
Primordial gonads differentiate into fetal testes- sertoli and leydig cells
47
Sertoli cells
Make mullerian-inhibiting substance (MIS)/ Anti- mullerian hormone
This causes regression in the mullerian ducts
48
Leydig cells
Make testosterone which leads to the wolffian ducts transforming into epididymis, vas deferens, seminal vesicles, ejaculatory duct
Testosterone can turn into dihydrotestosterone which leads to the development of the penis, scrotum, and prostate
49
Sperm production temperature
Sperm production requires temperatures several degrees below normal body temperature, thus the function of the scrotum. Thus, a warmer or colder scrotum can impact fertility
50
Semen fluids
Epididymis H secretion decreases pH of luminal fluid
Seminal vesicle- secretion and storage of fructose- rich product, PG, ascorbic acid, fibrinogen and thrombin-like proteins
Prostate- secretion and storage of fluid rich in acid phosphate and protease (prostate specific antigen: PSA)
Cowper glands- mucus upon arousal
51
What happens during prostate removal?
Removal of the ductal connection thus all of the proximal fluid components of the ejaculate. The prostatic urethra is left intact.
52
Composition of semen
1. ) Testis- sperm (5%)
2. ) Seminal vesicle- mucoid material: fructose, ascorbic acid, inositol, and other compounds (60%)
3. ) Bulobourethral/ Cowpers gland- mucus secretions (15%)
4. ) Prostate- think, milky alkaline fluid: citric acid, calcium, phosphatases, and other (20%)
53
Gonadotropin secretion
1. ) Fetal to 1st year- GnRH, gonadotropins, sex hormones secreted at relatively high levels
2. ) Infancy to puberty- secretion rates very low, reproductive function quiescent
3. ) At puberty- secretion rates increase markedly, large cyclical swings in female, starts period of active reproduction
4. ) Later in life- gonads become less responsive to gonadotropins, reproductive function diminishes, ceases entirely in females
54
Testosterone is at the highest level in the
morning
55
Effects of estradiol in the male
```
17beta estradiol (aromatase activity)
Epiphyseal closure, prevention of osteoporosis, feedback regulation of GnRH secretion
```
56
Pathologies of androgens in males in fetal development
Defect in 5alpha reductase- does not allow for DHT production. Male genitalia will not fully develop, high levels of testosterone during puberty lead to development of genitalia, but urethra does not extend through penile shaft
Androgen insensitivity- defect in androgen receptor- partial or complete. Complete insensitivity results in female appearance (Y chromosome, testes present)
57
Pathologies of androgens in males during postnatal life
Hyposecretion before puberty- eunuchs. Bones keep growing; patient grows tall but has feminine characteristics
Hyposecretion after puberty- may not change many secondary characteristics
Normally, testosterone is secreted throughout life, but is reduced with advancing age
Early excess secretion of testosterone leads to precocious puberty- early development of sex characteristics, lack of growth
Treat with GnRH analogs (histrelin, nafarelin, leuprorelin)
58
LH and FSH receptors
Closely related to TSH receptor
Coupled via G alpha s
McCune albright syndrome- precocious puberty
Activating mutations of LH receptor- male limited familial precocious puberty
Loss of function in FSH receptor- infertility in males and females. Females primarily amenorrhea
59
Exogenously administered androgens
Can achieve normal systemic levels of testosterone but not normal seminiferous tubule levels. Normalize secondary sexual characteristics but not spermatogenesis.
Exogenous testosterone will inhibit LH and FSH secretion (impaired spermatogenesis)
Anabolic steroids (modified androgens) may lead to decreased fertility and erectile dysfunction (via decrease androgernic activity)
Long term use leads to irreversible CV disease (cardiomyopathy, atherosclerosis)
60
During erection, what happens to the penis?
Corpora cavernosa becomes rigid
| Corpus spongiosum remains pliable
61
Reflex pathways for erection
Descending CNS pathways triggered and either stimulatory or inhibitory
-Increase activity of neurons that release nitric oxide
-Decrease activity of sympathetic neurons
Input from penis mechanoreceptors
-spinal reflex system
62
Masters and Johnson sexual response cycle
Desire (libido)
Arousal (excitement)
Orgasm
Resolution
63
Physiology of penile erection
Sexual stimulation causes endothelial cell derived nitric oxide secretion.
This increases GTP, cGMP, and GMP
64
Erectile dysfunction
Failure to achieve a penile erection suitable for satisfactory sexual intercourse
65
ED causes
Organic-
hormonal: hypogonadism, hyperprolactinemia, hyperthyroidism
Neurovascular: spinal cord injury, neurologic conditions (PD), neuropathy (DM)
Anatomical: penile abnormalities
Psychogenic- relationship stress, performance anxiety, depression
66
Hormonal physiology of penile erection
Testosterone principally produced by testes- free 2%, majority bound to sex hormone-binding globulin
Highest levels in morning, lowest in evening (10pm)
Testosterone stimulates libido and increases muscle mass
Testosterone is activated to DHT which stimulates prostate gland growth, increases facial/body hair, induces baldness, and causes acne
Testosterone naturally decreases after age 40
Normal physiologic serum total testosterone 3,000-1,100 ng/dL
67
Common risk factors for ED
Same as CVD. There is a common pathway linking CVD and ED (endothelial dysfunction and atherosclerosis)
Age, smoking, diabetes, HTN, dyslipidemia, depression, obesity, sedentary lifestyle
68
Screening tools for ED
IIEF-5- can be used to monitor response
69
Medication causes of ED
Alcohol, nicotine, illicit drugs (amphetamines, barbiturates, cocaine, opiates, marijuana)
Analgesics (opiates)
Anticonvulsants (phenobarbital, phenytoin)
Antidepressants (SNRI, TCA, SSRI, MAOI, lithium)
Antihistamines
Antihypertensives (alpha blockers, beta blockers, CCBs, clonidine. methydopa, resserpine)
Antiparkinson agents (bromocriptine, levodopa, trihexyphenidyl)
Antipsychotics (chlorpromazine, haloperidol, pimozide, thioridazine, thiothixene)
CV agents (digoxin, disopyramide, gemfibrozil)
Cytotoxic agents (diuretics, spironolactone, thiazides)
Hormones and hormone active agents
Immunomodulators- interferon alfa
Tranquilizers- benzodiazepines
70
First line therapies for ED
lifestyle modifications
Medication changes if needed
Oral phosphodiesterase-5 inhibitor if not contraindicated
71
2nd line therapy for ED
Intraurethral or intracavernosal alprostadil (Caverject)
| Vacuum device
72
PDE-5 inhibitors and CV risk
Low risk- patient can be started
Intermediate risk- pt should undergo complete CV workup and treadmill stress test to determine tolerance to increased myocardial energy. Reclassify as low or high risk
High risk- contraindicated, recommend against sexual intercourse
73
PDE isoenzymes
Isoenzyme type 1- vasculature
Isoenzyme type 5- corpus cavernosum of penis and vasculature of the lung
Isoenzyme type 6- rods and cones of eyes
Isoenzyme type 11- striated muscle
74
PDE-5 inhibitor MOA
Competitive, reversible inhibition of PDE-5 found in genital tissues
Requires sexual stimulation for effect
Efficacy around 60-80%
75
PDE-5 inhibitor agents
Avanafil (Stendra), Sildenafil (Viagra), Tadalafil (cialis), Vardenafil (Levitra, Staxyn)
76
Sildenafil
PDE-5 inhibitor
25 to 1000 mg orally 30 to 60 minutes before sexual activity
Lower dose in pts taking 3A4 inhibitors, hepatic/renal impairment, age >65 years
Onset of action: 30 minutes
Duration of action: 4-12 h
77
Vardenafil
```
PDE-5 inhibitor
5 to 20mg 1 hour before sexual actibity
Lower dose in patients take 3A4 inhibitors, hepatic impairment, age >65
Onset of action- 30-60 minutes
Duration of action- 4-6 h
```
78
Avanafil
PDE-5 inhibitor
50-200 orally 15 to 30 minutes before sexual activity
Lower dose in patients taking 3A4 inhibitors and hepatic impairment
Onset of action- 25-40 minutes
Duration of action- 6+ hours
79
Tadalafil
PDE-5 inhibitor
5 to 20 mg 30 min to 36 hours before activity. Consider 2.5-5mg QD for men who take >2times/week
Lower dose in patients taking 3A4 inhibitors, hepatic/renal impairment
Onset of action- 45 min
Duration of action- 24-36 h
80
Which PDE-5 inhibitors do fatty meals decrease absorption?
Sildenafil, vardenafil
81
Which PDE-5 inhibitors are affected by alcohol?
Avanafil- >3 drinks increases risk of hypotension
| Tadalafil- >5 drinks increases risk of hypotension, dizziness, HA, tachycardia
82
Which PDE-5 inhibitors work on isoenzyme type 1?
Sildenafil, vardenafil
83
Which PDE-5 inhibitors work on isoenzyme type 6?
Sildenafil
Vardenafil
Moderate avanafil
84
Which PDE-5 inhibitor works on isoenzyme type 11?
Tadalafil
85
50mg sildenafil=
10mg vardenafil, 10mg tadalafil, 100mg avanafil
86
Contraindications of PDE-5 inhibitors
Concomitant use of any type of nitrate (withhold for 24-48 hours after PDE-5 inhibitor)
87
Precautions with PDE-5 inhibitors
Concomitant alpha 1 antagonists therapy (use uroselective)
QT prolongation with vardenafil
Use caution with CVD, hypotension, HTN, MI, stroke within 6 months, life-threatening arrhythmias, penile deformities, renal or stroke hepatic dysfunction, and degenerative retinal disorders
88
AE of PDE-5 inhibitors
HA, nasal stuffiness, nausea, dizziness
Flushing (lowest with tadalafil)
Dyspepsia (lowest with avanafil)
Myalgias (lowest with vardenafil and avanafil)
Visual impairment (blurred vision, impaired color perception, color tinge to vision) (highest with sildenafil)
89
Patient education for PDE-5 inhibitors
Patients must engage in sexual stimulation for response
Sildenafil and vardenafil should be taken on an empty stomach
Continue for 5-8 doses before dose failure is declared
Dose titration may be required
Avoid excessive EtOH use
Smoking cessation, weight loss
Involve sexual partner
Staxyn- take w/o liquids
90
Alprostadil
Used for ED
MOA: Prostaglandin E1 increases cAMP
Intracavernosal injection more effective than intraurethral pellets
Some experts recommend a combo of alprostadil with papaverine and phentolamine- improves efficacy and decreases ADR
91
Hypogonadism
Primary- Leydig cells of the testes slowly and progressively decrease testosterone production
Symptoms: decreased libido, erectile dysfunction, gynecomastia, small testes, reduced growth of body hair and beard, decreased muscle mass, increased body fat
If left untreated may lead to anemia and osteoporosis
92
Evaluation of testosterone deficiency algorithm
Measure TT, If less than 300, repeat TT, measure LH, and measure Hct
If Hct >50% and second TT <300 withhold testosterone therapy and refer
If LH low or normal and second TT <300, test prolactin. If prolactin is normal than testosterone deficiency is confirmed
If Hct <50%, high/normal LH, and second TT <300, testosterone deficiency confirmed
PSA testing in pts >40
93
Treatment algorithm of hypogonadism
Patient meets criteria for testosterone deficiency and is a candidate for therapy
Need to do CV risk assessment before initiating therapy
Exogenous testosterone- gels/creams, patch, buccal, IM, SQ pellet, nasal spray
Alternative- SERM, hCG, AI
94
Monitoring testosterone therapy/ dosing changes
If the patient is achieving therapeutic levels without symptom improvement, consider testosterone cessation 3-6 months after starting treatment.
Lab testing every 6-12 months
Dose adjust or change modalities if not effective. Consider changing to exogenous testosterone.
95
Testosterone replacement therapy controlled
CIII
96
Advantages of testosterone injections (testosterone cypionate, testosterone enanthate)
No daily administration (IM every 2-4 weeks)
Inexpensive
Flexible dosing
Sometimes injected at home in the US
97
Disadvantages of testosterone injections (testosterone cypionate and testosterone enanthate)
Injection site pain, fluctuations in testosterone levels may lead to variations in symptoms (mood, libido) that may increase with longer intervals, may causemore increases in hematocrit and hemoglobin than topical
Rare cough after injection
98
Advantages of gel testosterone (Androgel)
Less skin irritation than patches
99
Disadvantages of gel testosterone (Androgel)
skin irritation and odor
Risk of skin to skin transfer to another person (need to wash hands after application and wear clothes over application site)
Pumps must be primed prior to first use
100
Application of gel testosterone (Androgel)
Do not apply to genitals
Do not apply to abdomen (exception is Androgel 1%)
Do not swim or wash for 2 hours after applying (5 hours for Androgel 1%)
101
Testosterone therapy AE
Erythrocytosis
Acne/oily skin
Detection of subclinical prostate cancer
Growth of prostate cancer
Reduced sperm production and fertility
Formulation specific
IM- fluctuation in mood/libido, injection site pain, coughing
Gel- potential risk of transfer, skin irritation
Buccal- alterations to taste, irritation of gums
Pellet implants- infection, expulsion of pellets
102
Contraindications of testosterone therapy
Contraindicated in men with breast or prostate cancer
103
Monitoring of testosterone therapy
Topical, oral/buccal- within 4 weeks
IM- after cycle 4
Pellets- 2 and 12 weeks after each insertion
Goal- mid-normal range (450-600 ng/dL)
Monitor every 6-122 months once stabilized
104
Labs for testosterone therapy
Hg/HCT- measure every 6-12 months or sooner to maintain HCT levels below 54%
PSA- in men without a h/o prostate cancer may need monitoring. Need to monitor in men with prostate cancer
105
Other treatments for SD
Vacuum erection device
| Penile prostheses
106
Hypoactive sexual desire disorder (HSDD)
In females, most common sexual dysfunction
Recommend a 3-6 month trial of testosterone
Alternative therapy is flibanserin or bremelanotide
107
Flibanserin BBW
Use with moderate/strong 3A4 inhibitors
Hepatic impairment
Alcohol use
108
Two major functions of the prostate
Secrete fluids that make up a portion of the ejaculate volume
Provide secretions with antibacterial effect
109
Three types of tissues in the prostate
1.) Epithelial
2.) Stromal (smooth muscle tissue)- embedded with predominantly alpha 1a adrenergic receptors
#.) Capsule
110
Diagnosis of BPH
Histological diagnosis based on proliferation of glandular epithelial tissue, smooth muscle, and connective tissue
111
Epidemiology of BPH
Most common prostate problem for men >50
| Increases exponentially after age 40
112
Pathophysiology of BPH
Exact etiology is unknown, however, it is thought to be multifactorial and related to testosterone
5a reductase type 1 and 2
Imbalance between growth and apoptosis leads to increases in cellular mass
113
BPH leads to
BPE, BPO, and LUTS
114
Static vs dynamic factors of BPH
Static- anatomic enlargement, produces physical block at bladder neck and obstructs urinary outflow
Dynamic- excessive alpha adrenergic tone results in contraction of the prostate around urethra
115
Clinical presentatio of BPH
LUTS
Obstructive- unable to empty all of bladder
Irritative- storage issues, post void residual, frequent urination
116
Medication related symptoms of BPH
Testosterone- gets converted to DVT and increases prostate mass
a-adrenergic agonists- phenylephrine vasoconstricts around urethra
b-adrenergic agonists
Anticholinergics
Diuretics
Avoid CCBs and Benzos
117
Disease progression of BPH
Symptoms vary over time
Majority of patients will have stable symptoms when evaluated 4 years after initial BPH diagnosis
Most men with mild disease improve without treatment in 2-5 years
Markers of worsening symptoms and complications- prostate gland size 30-40 g, PSA >1.4 ng/mL
118
Complications of BPH
Acute, painful urinary retention can lead to renal failure
Persistent or intermittent gross hematuria when tissue growth exceeds blood supply
Overflow urinary incontinence or unstable bladder
Recurrent urinary tract infection that results from urinary stasis
Bladder diverticula
Bladder stones
Chronic renal failure from long-standing bladder outlet obstruction
119
Goals of treatment for BPH
Control symptoms
Reduce risk of complications
Delay need for surgical intervention
120
IPSS
Ranks BPS symptoms
| Lower points= less symptoms
121
BPH mild disease treatment
Watchful waiting
Reassess every 6-12 months by looking at IPSS, urinary flow rate, PVR urine volume, prostate size
Educate patient about disease and behavior modification
122
Behavior modification for BPH
Restrict fluids before bedtime or going somewhere with limited bathroom access
Limit caffeine, alcohol, and spicy food
Do bladder training or pelvic floor exercises
Treat and prevent constipation
Increase activity; avoid sitting for long periods of time
Avoid drugs that could exacerbate voiding symptoms
123
Treatment algorithm for BPH
Alpha blockers are DOC, if pt also has ED he can start with PED5 as initial therapy
Lack or incomplete response to alpha blocker- consider trial of PDE5 or add on 5ARI if prostate is >30cc
124
2nd generation alpha 1 receptor antagonist
```
Used for BPH
Prazosin (not recommended dur to short T1/2)
Terazosin
Doxazosin
Alfuzosin (clinically uroselective)
```
125
3rd generation alpha 1 receptor antagonist
Used for BPH
Selective for alpha 1 A subtype
Choose because they decrease risks of AE
Tamsulosin, silodosin
126
alpha 1 receptor antagonist MOA
Relaxes smooth muscle in the prostate and bladder neck
Improve AUA symptom score within 2-6 weeks
Increase urinary flow rate
Reduce PVR urine volume
Durable clinical benefit
Effectiveness is dose dependent (start low and titrate)
No effect on prostate volume, does not reduce PSA levels. Just decreases the effects associated with increases in alpha receptors
127
Alpha 1 receptor antagonists AE
All- HA, malaise, fatigue, URI/nasal congestion
Doxazosin, terazosin- first dose syncope, orthostasis, dizziness
Tamsulosin- Floppy iris syndrome, decreased libido
Terazosin- impotence
Ejaculatory dysfunction- tamsulosin and silodosin
128
When should you avoid tamsulosin?
In severe sulfa allergy
129
Floppy iris syndrome
Alpha blockers block alpha-1 receptors in the iris
This prevents the iris from fully dilating during eye cataract surgery
Pupillary constriction occurs despite use of mydriatic agents and iris billows out
Cannot be on alpha blockers before cataract surgery
130
Uroselective alpha 1 receptor antagonists
Tamsulosin, Rapaflo, Uroxatral
131
Onset of alpha 1 receptor blockers
Days-weeks
132
5 alpha reductase inhibitors MOA
block 5-alpha reductase II which inhibits the conversion of testosterone to DHT
133
5-alpha reductase inhibitors indication
Indicated for management of LUTS/BPH with prostatic enlargement as judged by prostate volume of >30cc on imaging, a prostate specific antigen >1.5 ng/dL, or palpable prostate enlargement on DRE
Reduce prostate size by 15-25%
Increases peak urinary flow rate
Improves voiding symptoms
Durable clinical benefit, it does not become less effective over time
134
5 alpha reductase inhibitor agents
Finasteride (type II only)
Dutasteride (type I and II)
Onset is 3-6 months
135
5-alpha reductase inhibitors AE
```
Decreased libido, ejaculatory disorder, ED
Breast changes can also occur
Decrease PSA (need to get baseline)
Prostate cancer
"post finasteride syndrome"
Pregnancy category X
```
136
PDE-5 inhibitors in BPH
Tadalafil is only one FDA approved
Relaxes smooth muscle in the prostate and bladder neck (increases cGMP)
Good to use if patient has ED and BPH
Leads to significant improvement in voiding symptoms, but little improvement in urinary flow rate or reduction in PVR urine volume.
Takes 4 weeks to work
137
Anticholinergic agents in BPH
Add on therapy for irritative voiding symptoms
Caution in acute urinary retention
Agents- tolteridone, oxybutynin, trospium, solifenacin, darifenacin, fesoterodine
138
Mirabegron
B3-adrenergic agonist used in BPH
Increases urinary bladder capacity and interval between voiding
AE- HTN, URI
139
Finasteride/Tadalafil combo
For patients with a significantly enlarged prostate
D/C alpha-blockers at least 1 day prior to initiation
Provides a small benefit over finasteride alone for symptom relief in men with prostate volume >30 cc
Only studied for 26 weeks
140
Which BPH treatments relax prostatic smooth muscle?
Alpha 1 antagonists
| PDE5-inhibitors
141
Which BPH treatments decrease prostate size
5ARI
142
Which BPH treatment halts disease progression?
5ARI
143
Which BPH treatment has CV AE
A1-antagonist, PDE5-i, Anticholinergics, beta 3 agonist
144
Which BPH therapy causes efficacy in relieving BOO
A-1antagonists
5ARI
PDE5-i
145
Which BPH therapy decreases PSA?
5ARI
146
F/U of BPH
Evaluate 4-12 weeks after initiating treatment
| Wait 3-6 months for longer onset drugs (5ARIs)
147
M3 receptor of the bladder
parasympathetic stimulation of the M3 receptor by ACh causes contraction and the ability to urinate
148
B3 receptors in the bladder
Inhibitory
| Causes relaxation and sodium release
149
Physiology of urinary incontinence
Any disruption in the integration of musculoskeletal and neurologic function can lead to loss of normal bladder control
1. ) bladder fills- detrusor muscle relaxes, beta receptor mediated (bladder fills), pelvic floor and urethral sphincter contracts (alpha receptor mediated)
2. ) first sensation to void- bladder half full, urination voluntarily inhibited until appropriate time
3. ) Normal desire to void- bladder full)
4. ) Micturition- cholinergic mediated, detrusor muscle contracts and pelvic floor relaxes
150
Epidemiology of urinary incontinence `
Highly prevalent, more common in women
Substantial impact
Associated with decreased QoL, decreased personal/social activities, increased psychological stress
151
Stress incontinence
F>M
| Risk factors: weak pelvic floor muscles (childbirth, pregnancy, menopause); post-urologic surgery in men
152
Urge incontience
Risk factors: increased age, neurologic disease (stroke, PD, MS, spinal cord injury, chronic bladder outlet obstruction
153
Functional incontinence
Common causes: musculoskeletal limitations (OA, RA, PD, stroke) or cognitive impairment
154
Overflow incontinence
Common causes: bladder outlet obstruction, diabetic neuropathy, spinal cord injuries, MS
155
Overactive bladder
Detrusor muscle contracts before bladder is full
156
Clinical presentation of urinary incontinence
lower abdominal fullness, hesitancy, straining, decreased force of stream, incomplete bladder emptying, frequency, urgency, abdominal pain, increase PVR
Urgency, frequency (>8 times/day), nocturia (>1 void/night), enuresis
157
Clinical evaluation of incontinence
Symptoms, history, physical exam, urinalysis
Bladder diary- liquid intake, number of trips to bathroom, activities during leakage, strength of urge to void, accidental leaks
158
Reversible causes of urinary incontinence
```
Delirium
Infection
Atrophic vaginitis/urethritis
Psychiatric disorders
Pharmacologic agents
Excessive urine output
Restricted mobility
Stool impaction
```
159
Meds than decrease bladder contractility (cause retention and overflow UI)
```
ACE
Antidepressants
Antihistamines
Antimuscarinics
Antiparkinsonian agents
Antipsychotics
beta agonists
CCBs
Opioids
Sedatives, hypnotics
Skeletal muscle relaxants
```
160
Meds that increase detrusor irritability or CrCl (cause urge UI)
Alcohol, caffeine, diuretics, acetylcholinesterase inhibitors
161
Meds that increase urethral sphincter tone (cause retention and overflow UI)
Alpha agonists
Amphetamines
TCAs
162
Meds that decrease urethral sphincter tone (cause stress UI)
Alpha 2 antagonists
163
Diagnostic tests for UI
Stress incontinence- cough stress test
OAB- urodynamic; urinalysis should be negative
Overflow- assessment of PVR; renal function tests to rule out renal failure due to chronic urinary retention
164
Goals of treatment for UI
Reduce or eliminate symptoms
Increase QOL
Prevent negative consequences associated with incontinence
Clinical- rashes, pressure sores, skin and UTIs, falls
Psychological/social- embarrassment, isolation, depression, anxiety, dependency
165
Nonpharm for UI
1st line to all patients
Toilet proximity, safe path to bathroom, raised toilet seats, grab bars, toilet substitutes, weight loss if overweight, smoking cessation
166
Bladder training
Retrain pelvic mechanisms and the CNS to inhibit urge sensation between voids
Used in patients with urge incontinence in patients without cognitive impairment
167
Habit training
Individualized toileting scheduled to preempt involuntary voiding
Used in patients with urge incontinence WITH cognitive impairment
168
Pelvic floor muscle exercises
Muscle contraction and relaxation to reduce incontinence by producing urethral closure and decreasing central nervous system stimulation of detrusor muscle
Used for urge and/or stress incontinence in patients without cognitive impairment
169
Prompted and scheduled voiding
Indicated for urge incontinence for patients WITH cognitive impairment
170
Red flags for UI
If present, refer to specialist
Associated pain, persistent hematuria or proteinuria, significant pelvic organ prolapse, previous pelvic surgery or radiation, suspected fistula, elevated postvoid residual
171
Guideline for treatments of UI
Behavioral modifications 1st line
Oral antimuscarinics or beta 3 adrenergic agonists as second line
Prefer ER forms due to lower rates of dry mouth
Transdermal oxybutynin may be offered
172
UI clinical principles
Inadequate symptom control and/or AE- dose modification or switch drugs
Should not use antimuscarinics in pts with narrow angle glaucoma
Use caution in patients with impaired gastric emptying or history of urinary retention
Manage constipation and dry mouth before abandoning an effective antimuscarinic therapy
Use caution in frail patients
173
Stress UI treatment options
Duloxetine, antimuscarinics, topical. estrogen
174
Overflow UI treatment options
alpha antagonists (tamsulosin in women), 5ARI (men)
175
Urge incontinence treatment options
Antimuscarinics
Beta 3 agonists
Intravaginal estrogen for women
176
Antimuscarinic agents for UI
Inhibits muscarinic receptors resulting in decreased urinary bladder contraction, increased residual urine volume, and decreased detrusor muscle pressure
Reduces UI frequency by 50%
Agents have similar efficacy
Oxybytynin, tolteridone, fesoterodine, trospium, solifenacin, darifenacin
177
Which antimuscarinic causes QT prolongation?
Solifenacin
| Tolterodine
178
Which antimuscarinics are nonselective?
Oxybutynin, tolterodinee, fesoterodine
179
Which antimuscarinics are selective?
Trospium, Solifenacin, Darifenacin
180
Which antimuscarinic is a prodrug?
Fesoterodine
181
Which antimuscarinic is impacted by food?
Trospium
| Take 1 h before or 2 h after meals
182
Antimuscarinic AE
Dry mouth, dry eyes, constipation, urinary retention, cognitive impairment, dizziness, visual changes, HA, thirst
183
Oxybutynin AE
IR- orthostatic hypotension, sedation, weight gain
| transdermal- pruritis, erythema, application site
184
Which anticholinergics cause the most dry mouth, visual disturbances, dizziness, and constipation?
Oxybutynin
185
Contraindications and precautions of antimuscarinics
```
Urinary retention
Gastric retention
Severely decreased GI motility
Angioedema
Myasthenia gravis
Uncontrolled narrow angle glaucoma
Worsening hepatic/renal condition or concomitant drug therapy
Mental status change or risk for falls
```
186
Beta 3 agonists
Modestly effective in reducing urinary frequency and incontinence
Relaxation of detrusor smooth muscle during storing phase increases bladder capacity
Mirabegron and Vibegron
Both increase digoxin levels
187
B3 agonists AE
Mirabegron- HTN, nasopharyngitis, UTI, HA
| Vibegron- GI (constipation, D, N, xerostomia), nasopharyngitis, HA, PVR, urinary retention
188
Precautions with beta 3 agonists
Mirabegron- urinary retention, severe uncontrolled HTN (>180/110), increased effect of narrow therapeutic index drugs that are 2D6 substrates, QT prolongation, angioedema
Vibegron- urinary retention
189
Duloxetine
Used for stress incontinence, but not FDA approved
190
Topical/vaginal estrogens for UI
Topical for stress incontinence
Intravaginal for urge incontinence
Increases urethral tone
Mild benefit
191
Bethanechol
Cholinergic stimulation of detrusor
Used for overflow incontinence but only FDA approved for urinary retention
Take on an empty stomach
AE- flushing, abdominal cramps, diarrhea, acute exacerbation of asthma
192
Onabotulinumtoxin A
Botox
FDA approved for UI
Can only be used if pt will self-catheterize
Repeat doses no sooner than 12 weeks
