ED Flashcards
What does a loss of libido indicate
An Androgen deficiency
What does a loss of erection indicate
Arterial, venous, neurogenic, hormonal, or psychogenic cause
What are some RF for ED
HTN 2/2 Diuretics HLD (arteriosclerosis) DM Metabolic syndrome Smoking Chronic ethanol abuse Psychological etiologies
What Antichlinergics can cause ED
Antihistamines Antiparkinson's TCA Phenothiazines SSRI- Paroxetine, Sertraline, Fluvoxamine, Fluoxetine
What Dopamine antagonists can cause ED
Metoclopramide
Phenothiazines
How do Dopamine antagonists cause ED
Inhibit PRL inhibitory factor= increased PRL= Inhibit testicular testosterone production
What estrogens and antiandrogens cause ED
LHRH Digoxin Spironalactone Ketoconazole Cimetidine
What CNS Depressants cause ED
Barbituates, narcotics, benzos
They suppress preception of psychogenic stimuli
What agents decrease penile arterial blood flow to corpora
Diuretics
peripheral Beta antagonists
Central sympatholytics (methyldopa, clonidine)
Other meds that can cause ED include
Gemfibrozil, Finasteride, dutasteride, Clofibrate, MAOI
OPIATES!
What are the types of sexual dysfunction in men
Decreased or Increased libido Impotence Delayed ejaculation Retrograde ejaculation Infertility
What nervous systems innervate the penis
Point and Shoot
PNS= erection (arterial flow increases, venous outflow decreases)
SNS= Ejaculation
What is the order of Tx for ED from least to most invasive
Vacuum erection devices
Oral PDE inhibitors (first line!)
Intracavernosal injections or Intraurethral inserts
Surgery for penile prosthetic
Who is VED best for
Couples in a stable relationship
They are very obvious and take about 30 min to work- Lasting for about one hour (goal)
Can use constriction band or tension ring to prolong erection
What is the normal job of alpha 1
Vasoconstrict in the periphery
What oral meds can be used in the treatment of ED
Yohimbine Trazodone PDE Inhibitors (Sildenafil, Tadalafil, Vardenafil, Avanafil)
How does Yohimbine work and what are it’s ADE
Reduce Alpha adrenergic tone= vasodilation
ADE: Tachy, insomnia, anxiety, HTN
What is Trazodone
a poor antidepressant, decent sleep agent
Peripheral alpha adrenergic antagonist
What are key concepts of PDE inhibitors
Effective regardless of etiology of ED
Effective in 60-70%
CI in ANYONE taking Nitrates
What is the MOA of PDE inhibitors
Sexual stimulation= NO release= increased cGMP= erection
PDE catabolizes cGMP= lose erection
PDE inhibitors= PDE can NOT catabolize cGMP= maintained erection
What is specific about PDE 5
Found in genital tissues (also extragenital- peripheral vascular tissue, trachea smooth muscle, and platelets)
Decreases catabolism of cGMP
What is specific about PDE 6
Local to rods and cones of eyes
ADE: blurred vision, Cyanopsia (MC with viagra)
What is specific to PDE 11
Local to striated muscle
ADE: Myalgia, muscle pain (MC tadalafil)
What PDE-inhibitors need to be titrated
Sildenafil (viagra)
Vardenafil (levitra)
Tadalafil (Cialis)
What PDE-inhibitors have delayed absorption when taken with food
Sildenafil (viagra)
Verdenafil (levitra)
Staxyn
What PDE-inhibitors can be taken with food
Tadalafil (Cialis)
Avanafil (stendra)
What is Staxyn
a PDE inhibitor that is dissolved on the tongue 1 hour prior to sex
Why is Tadalafil special
It can be taken at a higher dose (5-10mg) 30 min prior to sex, OR, at a low dose (2.5-5mg) daily
BUT* contraindicated in those with severe hepatic impairment
What PDE-inhibitors are not to be taken with alcohol
Tadalafil (cialis)
avanafil (stendra)
–Can cause orthostatic hypotension
How does Tadalafil work
Blocks PDE 5 and 11 (not 6- so no vision ADE)
Takes 45 minutes to onset, and 2 hours to peak (longer onset)- but lasts 24-36 hours
has NO active metabolite
What drug interaction is important with Sildenafil (viagra)
Decrease viagra dose with CYP45- 3A4 inhibitors (Ketoconazole, Ritonavir, Cimetidine, Erythromycin, Clarithromycin, Itraconazole, Squinavir)- must know all those
When must you reduce Tadalafil’s dose
Only with the most potent CYP450 3A4 inhibitors (Ketoconazole, Itraconazole)
What are the MC ADE of PDE inhibitors
HA Facial flushing Dyspepsia Nasal congestion Dizziness (all 2/2 vasodilation or smooth muscle relaxation from PDE5 in extragenital tissues)
What is the worst ADE of PDE inhibitors
NAION- nonarteritic anterior ischemic optic neuropathy (AKA decreased blood flow to optic nerve)
Sudden, unilateral, painless blindness, irreversible
What patients are high risk for NAION
Glaucoma macular degeneration diabetic retinopathy HTN s/p eye surgery/eye trauma 50+ y/o smokers (alters platelets)
What ADE is specific to Tadalafil (Cialis)
low back pain– linked to PDE 11 inhibition (striated muscle)
What ADE is specific to Vardenafil
QT prolongation (can cause torsades- Tx with mag!)
What can cause a priapism
Sildenafil and Vardenafil (shorter half life)
Excess PDE-Inhibitor dose
Concomitant therapy with other erectogenic drugs
How do you treat a priapism
- Icepack to perineum and penis
- Walk upstairs to get blood flowing (arterial steal phenomenon)
- External perineal compression
- If these fail, HOSPITAL
What is medical treatment of a priapism
oral pseudoephedrine 60-120 mg (alpha-agonist= constriction)
Phenylephrine, epinephrine, methylene blue into corpus cavernosa
What drugs can interact with PDE inhibitors
Organic nitrates (severe hypotension)
CCB
adrenergic antagonist
morphine
How do Nitrates interact with PDE-inhibitors
They produce hypotension on their own, so combined it’s even stronger
NO can increase tissue levels of cGMP
Who should and should not take PDE inhibitors based on cardiovascular risk
Low risk: Can be started on PDE-I
Intermediate: need cardio workup and treadmill stress test to assess tolerance to increased myocardial energy consumption
High risk: PDE-I contraindicated
What is “low risk”
- Asx w/ <3 CVD RF
- HTN well controlled
- mild CHF (NYHA I or II)
- mild valvular disease
- MI >8 weeks ago
What is “intermediate risk”
- 3+ CVD RF
- mild/mod stable angina
- MI/stroke w/in 2-8 weeks
- mod CHF (NYHA class III)
- Hx of CVA/TIA/PAD
What is “high risk”
- Unstable/refractory angina
- HTN uncontrolled
- Severe CHF (NYHA IV)
- MI/stroke w/in 2 weeks
- Mod/severe valve disease
- High risk cardiac arrhythmias
- Obstructive HCM
Who can be treated with testosterone
Sx patients;
-Hypogonadism + Decreased libido and low serum testosterone
What is “male menopause”
When testosterone starts declining (age 40) by 10% per decade
What are symptoms of low testosterone
decreased libido ED gynecomastia small testes less body hair/beard less muscle mass more body fat **If untreated, anemia and osteoporosis
When should you measure testosterone
Early morning (8AM)
Normal is 300-1100
*Measure with LH
Why do we measure LH with testosterone
To determine the type of hypogonadism
Primary: elevated LH
Secondary: decreased LH
What does testosterone replacement actually do
-Improves libido secondarily correcting ED
BUT, testosterone does not directly correct ED
-Corrects Sx of hypogonadism: malaise, low strength, depression
Who should never receive testosterone
Men w/ normal testosterone levels
ASx patient with hypogonadism
Pt with ED as only sign of hypogonadism
What does testosterone replacement stimulate
-Directly stimulates androgen receptors in CNS
+/- stimulates NO synthase= more NO in cavernosa= enhanced PDE5 effects
What are oral testosterone supplements
- Methyltestosterone (not recommended, hepatotoxic)
- Fluoxymesterone (not recommended, hepatotoxic- alkylated androgen)
What is the testosterone buccal system
Place just above incisor, remove before every morning and night tooth brush
DO NOT chew or swallow
ADE: gum irritation, bitter taste
What are parenteral testosterone options (IM)
- Cypionate (ADE mood swings 2/2 supraphysiologic serum concentrations- CI in severe hepatic or renal dz)
- Enanthate (ADE mood swings- steer clear if w/ severe hepatic or renal dz)
- *the above have ADE of mood swings, gynecomastia, polycythemia, HLD
- Undecanoate (need REMS program to Rx- single dose)
What is significant about the testosterone patch (androderm)
Admin at bedtime to testosterone is produced in circadian pattern
Apply to upper arm, back, abd, or thigh- rotate q7 days
Dont swim, shower, or wash w/in 3 hours of application
ADE: Dermatitis
What are the testosterone gel options
Androgel/Testim 1% (apple in AM to shoulder, up arms, or abd- Titrate @ 14d interval- cover and wash hands with soap and water after placement- kids and women avoid touching)
Androgel 1.6% (apply in AM to shoulder and up arms- Titrate after 14-28 d)
How do you use Testosterone spray
4 sprays to front and inner thighs Cover after application avoid contacting women and children wash hands w/ soap and water Titrate at 14-35 day intervals
How do you use testosterone solution
Apply to axilla only (deoderant can be used prior to Axiron)
Dont swim or shower for 2 hours after applying
Titrate at 14-35 day intervals
How do you use a testosterone pellet
Forearm incision and subQ implant under local anesthesia
1 pellet= 75mg testosterone (use 2-6)
Results NOT immediate (3-4 months)
Needs to be placed by trained health professional
ADE: can be extruded accidentally
What is significant about oral testosterone
It really should not be used- causes HLD and sodium retention
Oral alkylated (Fluoxymesterone) will achieve normal testosterome srum level, but it is very hepatotoxic
So just steer clear of oral testosterone
What do we need to know about testosterone admin time and monitoring
Gel and patch are more circadian
What is Alprostadil
intracavernosal injection or intraurethral pellet to Tx ED
(MUSE efficacy is 43-65%)
(Caverject and Edex efficacy is 70-90%)
With training, pt can self administer
What is the Intraurethral pellet
Alprostadil (MUSE)
What are the Intracavernosal injection options
Alprostadil (Caverject or Edex)
Papaverine (PDE5 inhibitor)
Phentolamine (nonselective a-adrenergic blocker= dilation)
How do Caverject and Edex work (injection)
stimulate adenyl cyclase= more cAMP= less intracell calcium= smooth muscle relaxation= more blood flow in corpora
(NO independent, good for DM pt, s/p radical prostatectomy, and PDE failure pt)
-Acts w/in 5-15 min, should last no more than 1 hour (half life 5-10 min)- duration related to dose
*Can use with VED
How does MUSE work (pellet)
Admin 5-10 min before sex, no more than 2x day
Void completely before placing
Most is removed by first pass through LUNGS- so minimal systemic absorption!
Use with constriction band to improve, or with VED
What is penile prosthesis
Surgical insertion to treat ED for pt who dont respond to or are not candidates for any other Tx
What can you do for “non-responders”
Switch from one PDE5 inhibitor to another
-No response to viagra= give Vardenafil
Switch to as needed daily Tadalafil
May combine PDE5 inhibitor with Alprostadil in some patients
