Mens health Flashcards
Androgens
Produced by the testes, ovaries, and adrenal cortex
Testosterone is the principal endogenous androgen in both males & females
Noted most for their ability to promote expression of male sex characteristics but also influence sexuality in females
Significant physiologic and pharmacologic effects unrelated to sex
Primary clinical application is management of androgen deficiency in males
Principal adverse effects are virilization and hepatotoxicity
Testosterone
Effects on sex characteristics in females – moderate effect
Clitoral growth & maint of normal libido
Anabolic effects – from binding of androgens to same type of receptor that mediates androgen actions in other tissues
Skeletal muscle
in young males & females – effect can be significant (in adult males…extra dose only modest effect)*
Erythropoietic effects
↑ synthesis of erythropoietin
Men have greater hematocrit than women
with exogenous androgen, men only add 1gm/dL; with women it’s significant
Clinical Pharmacology of the Androgens-Therapeutic uses
Male hypogonadism – main indication; w/o androgens, puberty cannot happen (IM injections q2-4 wks for 3-4 yrs)
Replacement therapy – can do all androgenic efx but not fertility
Delayed puberty – best to wait
Replacement therapy in menopausal women – can alleviate sx; not approved in US but is in UK
Wasting in patients with AIDS – testos ↓ so risk for skeletal wasting ↑
Anemias – tx anemias refractory to other therapy (aplastic, renal failure, CA therapy, etc.)
stimulates synthesis of erythropoietin; may also ↑ WBC & plts
Clinical Pharmacology of the Androgens-Adverse Effects
Virilization (male enhancing) in women, girls & boys – in women can cause acne, deep voice, facial & body hair, male-pattern baldness, increased libido, clitoral enlargement* & menstrual irregularities.
Premature epiphyseal closure – need xray of hand & wrist q 6 mos to evaluate androgen effects on children.
Hepatotoxicity – (cholestatic hepatitis, hepatocellular carcinoma); need LFTs periodically
only with 17-alpha-alkylated androgens (should not be used long-term)
Effects on cholesterol levels (↓ HDL, ↑ LDL)
Use in pregnancy – Pregnancy Risk Category X***
Prostate cancer – don’t cause but does promote growth of prostate CA cells
Edema – androgen-induced retention of salt & water
Gynecomastia – in males receiving androgen replacement therapy (from conversion of certain androgens into estrogen)
Abuse potential (athletic performance) – SCHEDULE III CONTROLLED SUBSTANCE
Androgen preparations for male patients
For hypogonadism
Oral androgens (2 17-α-alkylated androgens)
Intramuscular testosterone ester
Transdermal testosterone patches (on upper arm, thigh, back or abd)
Transdermal testosterone gels – applied 1x/d work q24h
PROBLEM: 10% of dose is absorbed, the other 90% remains on skin
so transfer to partner/others (virilization/fetal harm) can easily occur
WASH HANDS AFTER HANDLING GEL EACH TIME
COVER GEL SITE WITH CLOTHING AFTER GEL DRIES
WASH GEL SITE BEFORE SKIN CONTACT WITH OTHERS
AVOID SKIN CONTACT WITH GEL SITE
IF COME IN CONTACT WITH GET SIT – WASH CONTAMINATED SKIN IMMEDIATELY
underarm liquid – on axilla only (others on shoulder, upper arm, abdomen)
Implantable testosterone pellets – subdermally in abd wall
Testosterone buccal tablets – in gum above incisor
Erectile Dysfunction
ED, also known as impotence Persistent inability to achieve or sustain an erection suitable for satisfactory sexual performance Affects up to 30 million men ED commonly associated with chronic illnesses: DM (35-75% men), HTN, depression Risk for ED increases with: advancing age use of other meds
Treatment for ED
1st-line: lifestyle changes (weight loss, ↑ exercise, stop smoking, etc.)
- Changing other drugs
- Drug therapy with:
Oral agents: PDE5 inhibitors - USE ONLY 1x/d
Sildenafil, vardenafil, and tadalafil
Nonoral agents: Papaverine plus phentolamine, and alprostadil - Psychotherapy
- Surgical implantation of penile prosthesis
Physiology of erection
- sexual arousal - ↑ parasympathetic nerve stim causing local nitric oxide increase
- nitric oxide activates enzyme making cGMP→ ↑ cGMP promotes relaxation of arterial smooth muscle & trabecular smooth muscle
- arterial dilation increases local blood flow & BP, and with relaxation of trabecular smooth muscle, allows expansion/engorgement of sinusoidal spaces in corpus cavernosum
- corpus cavernosum dilates which causes venous outflow occlusion
- both arterial engorgement & reduced venous outflow = erection
Sildenafil (Viagra)
Phosphodiesterase type 5 (PDE5) inhibitor 1
First oral agent for ED: introduced in 1998
Generally well tolerated
Can be dangerous if used concurrently with certain vasodilators Only enhances normal erectile response in the presence of stimuli
No significant impact on men who do not have ED*
Not approved for women – didn’t show much arousal enhancement
Sildenafil (Viagra)- AE’s
Hypotension
Priapism – painful erection > 6 hrs
for ALL PDE5 Is - by 4 hrs need to go to ED – can damage penile tissue causing permanent loss of potency
need to have blood aspirated from corpus cavernosum and irrigation with a vasoconstrictor
Headache, dyspepsia, flushing, nasal congestion, diarrhea, rash, dizziness, mild transient visual disturbances, intensification of obstructive sleep apnea
Rare side effects
Nonarteritic ischemic optic neuropathy (NAION) – irreversible blurring or loss of vision from blockage of blood to optic nerve
Sudden hearing loss, usually in 1 ear, w/ dizziness, vertigo, & tinnitus (complete w/ 2/3 that have the issue)
Sildenafil (Viagra)- drug interactions
Absorption slowed by high-fat meals
Nitrates (by ↑ cGmp, sildenafil by blocking cGMP breakdown)
Could cause life-threatening hypotension
ABSOLUTELY CONTRAINDICATED FOR MEN TAKING NITRATES
24 hours in between these medications for safety
& longer if using a CYP3A4 inhibitor or hepatic or renal pathology
Alpha blockers (dilate arterioles) Can cause symptomatic postural hypotension
Inhibitors of cytochrome P450 (CYP3A4) [Azole drugs, erythromycin, cimetidine, saquinavir, ritonavir, grapefruit juice…)
Can suppress metabolism of sildenafil
Vardenafil (Levitra)
PDE5 inhibitor II
Same MOA as sildenafil (relaxes arterial and trabecular smooth muscle in the penis)
Adverse effects:
virtually the same as sildenafil…except can prolong QT interval
Take 1 hr before sexual activity
Tadalafil (Cialis)
PDE5 inhibitor II
Relaxes penile and arterial and trabecular smooth muscle
Effects last up to 36 hours (longest of the three PDE5 inhibitors)
Also now approved for daily dosing if activity anticipated twice weekly
AEs & DIs the same as the other 2-
No alpha blockers (except tamsulosin [Flomax])
Take 1 hr before sexual activity
Benign Prostatic Hyperplasia
Nonmalignant prostate enlargement-
present in 50% by 60yo, 90% by 85yo
Caused by excessive growth of both:
epithelial (glandular) cells – causes mechanical obstruction of urethra
smooth muscle cells – causes dynamic obstruction of uretha
normal prostate is 4-20 gms – BPH prostate is 50-80 gms
Signs and symptoms – no correlation b/t sx and prostate size Urinary hesitancy Urinary urgency Increased frequency of urination Dysuria Nocturia Straining to void Post-void dribbling Decreased force and caliber of the urinary stream Sensation of incomplete bladder emptying
Finasteride (Proscar)
Inhibits 5-alpha-reductase: enzyme that converts testos to dihydrotestosterone (DHT) [active form of testos in prostate]
promotes regression of prostate epithelial tissue (↓ mechanical obstrux)
inhibits 5-alpha reductase found in ONLY reproductive tissues
Most effective with a very large prostate (mechanical obstruction)
Because ↓ levels of DHT, protects against low grade prostate CA (is FDA labelled as such)
but can increase high-grade tumor
Must treat for lifetime
