Men' Health Dr. Bossaer Flashcards
Dr. Bossaer
What are the causes of erectile dysfunction?
-blood supply to the penis -> Vascular diseases
>Peripheral vascular disease
>Arteriosclerosis
>Hypertension, BP meds
>Coronary artery disease
>Smoking, Obesity
-nerve signals for stimulation -> Neurologic
>Diabetic -> peripheral neuropathy
>Alcohol use, CNS depressants, depression (psychological)
>Trauma (prostatectomy)
-Hormonal
>Aging
>Hypogonadism (low Testosterone)
Drugs that can cause ED
-Anticholinergics: Antihistamines, TCAs, SSRIs (fluoxetine, sertraline, fluvoxamine), Benztropine (anti-parkinsonian drugs)
-Dopamine antagonist: Phenothiazines (metoclopramide, promethazine > prochlorperazine)
-Estrogens, antiandrogens: Digoxin, spironolactone, ketocanozole
-CNS depressants: EtOH, barbituates, anticonvulsants, opioids
-decreasing penile blood flow: diuretics, ß-blockers, central sympatholytics (clonidine)
-Others: 5-alpha reductase, MAOIs, Lithium, Gemfibrozil
Which testosterone level is considered Hypogonadism?
< 300 ng/dl
normal: 300 -1100 ng/dl
symptoms: malaise, depression, decreased libido
treat with testosterone replacement ONLY when testosterone is low and symptomatic
Which formulation for testosterone replacement is preferred?
Parenteral - preferred IM injection of Testosterone
-oral is hepatoxic
-transdermal products are often messy/oily
products should mimic circadian rhythms (AM peak/PM troughs)
normal testosterone metabolites (estrogen and DHT)
should be inexpensive and easy to use
Considerations with Testosterone
-Na retention -> higher BP
-increased hemoglobin (polycythemia) - makes the blood thick and harder for things to move around
-increased risk for VTE and CV events
-increased risk for liver cancer and hepatic complications with ORAL formulations
-gynecomastia -> due to the metabolite estradiol
-high risk of fractures?
What is the peak time for most phosphodiesterase inhibitors (PDEs)?
30-90 min
should be taken 30 - 60 min prior
Sildenafil
Avanafil
Vardenafil
Which PDE has the greatest time to peak?
Tadalafil with 2hrs
should be taken 60-120 min prior
-it also has the longest half-life and duration (24-36h)
-it has a daily dose available: 2.5 - 5 mg
Which PDEs absorption rate is not affected by a fatty meal?
Tadalafil
for Avanafil: the delay in Cmax is not clinically significant, can be taken with meal
Which PDEs have a pre-intercourse dose of 5-20 mg?
Tadalafil
Vardenafil
For Sildenafil: 25-100 mg
For Avanafil: 100-200 mg
start with low dose in patients with hepatic impairment
Which enzyme affects the metabolism of PDEs?
CYP 3A4
for Sildenafil: CYP 3A4 and 2C9
for Vardenafil: CYP 3A4, 2C9, and 3A5
Cross-reactivity of Sildenafil (PDE)?
inhibits PDE-6 (eyes)
-visual disturbance, blurry vision, color changes
to some degree PDE-11 (muscles)
Cross-reactivity of tadalafil (PDE)?
inhibits PDE-11 (muscles)
-myalgia (lower back, arms, legs)
-flushing -> they cause vasodilation
-headache
to some degree with PDE-6
Counseling points
-it takes time to work (~ 1 hour)
-erection after 4hr -> ER due to ischemia (blood is trapped, no perfused blood entering)
-Hypotension: Sildenafil/vardenafil drop SBP 8 to 10 mm Hg
-caution with alpha antagonist - (vasodilate smooth muscle cells of blood vessels) (IR formulations)
-vision loss? -> ER
Nonarteritic anterior ischemic optic neuropathy (NAION), potentially irreversible
contraindicated with nitrates!!!
Benefits of Tadalafil daily use
-reserved for on-demand failure
-can be more spontaneous with sex life
-better efficacy over on demand-use
-less toxic
-also effective for BPH symptoms
A patient with ED who takes nitroglycerin, which is the best PDE?
Sildenafil on-demand, may be used even though it has a contraindication
it has a short half-life so it will interfere the least with nitrate
Flibanserin (Addyi): drug profile
mixed (serotonin) 5HT agonist/ 5HT antagonist originally studied for depression
indication: Hypoactive sexual desire disorder
100 mg nightly - to avoid syncope and accidental injury from falling
ADE of Flibanserin
-hypotension, syncope, CNS depression
.-Contraindication:
Relative: EtOH use within 2 hours
Absolute CI: strong or moderate 3A4 inhibitors
-> Flucanozole (strong 2C19 inhibitor)
Absolute CI: hepatic impairment
Female Sexual dysfunction - menopause
-in menopausal women suffer from vaginal dryness and atrophy, pain during intercourse
-> topical estrogen
What are the 3 tissues of the prostate?
-Epithelial: prostatic secretion
-Stromal: stimulation -> muscle contraction -> urethra compression through abundant alpha receptors
2:1 stromal to epithelial, in BPH 5:1 -> so alpha 1 receptor is a drug target
-Capsule: on the outside, mostly connective tissue, alpha1-receptors
What causes prostate growth?
-aging: more testosterone converted to DHT by 5-alpha-reductase, DHT has a greater affinity to intraprostatic androgen receptors
-2 types of 5-alpha-reductase
Type 1: hair follicles and sebaceous glands
Type 2: prostate, genital tissue, scalp
Pathophysiology of BPH
Static (structural): obstruction due to enlarged prostate
Dynamic: increased muscle tone within the prostatic bladder neck
environmental (fight or flight)
drugs: alpha-adrenergic agonists:
-pseudoephedrine
-anticholinergics (TCA, antihistamines, phenothiazines - dopamine antagonists)
-EtOH, caffeine, diuretics
Which drug classes are used for moderate cases of BPH?
small prostate: alpha-antagonist -> reduce muscle contraction
large prostate: alpha-antagonist PLUS 5-alpha reductase -> to also slow down the growth of the prostate (it took years to grow, so it may take months to shrink)
concomitant Erectile dysfunction: alpha-antagonist and/or tadalafil
Alpha-antagonists MOA
-inhibit alpha-1-receptors in prostate/bladder neck
-relaxes smooth muscle of prostate/bladder neck
-relieves dynamic symptoms
-work after 2-4 weeks
-First-line (start with alpha-1-blocker to treat BPH)
What are the Alpha-1-receptor subtypes
alpha-1A: prostate, bladder neck (target)
alpha-1B: vascular smooth muscle (we do not want to target those)
alpha-1D: prostate (target)
ADE Alpha-1-antagonists
with older generations:
Hypotension and Orthostasis (dizziness when standing up)
-nasal congestion
-sexual (ejaculation) dysfunction: since alpha-1-receptors are blocked the penis cant push out the semen
-floppy iris syndrome: with tamsulosin and other alpha-blockers (caution in case of eye surgery)
What are the early generation alpha-1-antagonists
-Prazosin
-Doxazosin
-Terazosin
not often used anymore
caution for Hypotension and Orthostasis
3rd gens alpha antagonists
-Tamsulosin (Flomax): targets alpha-1A and 1D
0.4 - 0.8 mg QD
-Silodosin (Rapaflo): targets alpha-1A
8 mg QD
-Alfuzosin: technically 2nd gen, but clinically uroselective
ADE 5-alpha reductase
anti-androgenic effects: lower the number of DHT (androgenic)
-sexual dysfunction: impotence, decreased libido, erectile dysfunction
-Gynecomastia
-Hair growth (finasteride -> target type 1 and type 2 5-alpha reductase)
Precaution:
hepatic disease
reduces PSA (prostate screening marker) by 50% due to reducing the size of the prostate
increased risk of AGGRESSIVE prostate cancer
5-alpha reductase options
Finasteride for BPH (Proscar): 5 mg QD
Finasteride for Alopecia (Propecia): 1 mg QD
Dutasteride: 0.5 mg QD
anti-androgenic effects: decreased libido, impotence (Erectile dysfunction), gynecomastia, increased risk for AGGRESSIVE prostate cancer
-slow onset: 3-6 months
-no CV side effects
What is the most effective way to treat symptoms of BPH?
combination of alpha-1-blockers and 5-alpha reductase
alpha-1-blocker: short-term improvement but the improvement doesn’t get greater with time
5-alpha-reductase: it takes longer to work, but the condition improves more with time, since the size of the prostate gets smaller
-consider for men with enlarged prostate and moderate to severe symptoms
How does Tadafil (PDE inhibitor) work for BPH?
Because there are PDE-5 receptors in the bladder and around the prostate -> can cause muscle relaxation and easier urine outflow from the bladder
MOA Vibegron & Mirabegron
ß3 agonist
-relaxation of the detrusor muscle during the storage phase of urination
-allowing the bladder to store more urine, so to not go to the bathroom so frequently, but doesn’t make it easier to urinate
-used when alpha-blockers don’t work
-dose: 25 mg daily, up to 50 mg
