• physical and mental health
• hormonal status, mood, attitude, circumstances
• psychological conditioning and expectation
• therapeutic and nontherapeutic use of drugs

• alter sex drive
• alter sensation (rare)
• alter performance
  • male
    • ability to achieve or maintain erection
    • ability to achieve orgasm and/or ejaculation
  • female
    • ability to achieve adequate lubrication
    • ability to achieve orgasm

• increasing DA (DA R agonists)
• increase NE (alpha 2 block)
• nicotinic receptor agonist??
• decrease serotonin (serotonin antagonists)

• depleting DA (DA R antagonists)
• beta receptor antagonists and alpha agonists (decreased NE)
• muscarinic cholinergic antagonists
• increasing serotonin (serotonin R agonists) 

• male
  • engorgement and erection of penis
  • complete closure of bladder neck
• female
  • erection of clitoris
  • vaginal lubrication

• males
  • partial closure of bladder neck
  • seminal emission
  • ejaculation
  • detumescence
• female
  • contraction of uterus
  • contraction of fallopian tubes
  • contraction of vagina

• males- participation in ejaculation and orgasm
• females- orgasm

• hormonal
  • increase PRL secretion
  • anti androgenic (decrease testosterone)
• CNS effects
  • block DA, NE, ACh (muscarinic) R's
  • enhanced serotonin
  • sedation drugs

• peripheral anti muscarinic actions
• decreased blood flow

• alpha 1 blockade
• local anesthetic
• sedation

• antihypertensives
• antidepressants
• BZ's
• fenfluramine/siburtramine
• antiseizure drugs
• cimetidine
• opioids
• levodopa

• ganglionic blockers (complete ANS block)- complete failure of erection and orgasm
• beta blockers- mainly erectile problems with some loss of libido
• alpha 1 blockers- ejaculatory failure
• alpha 2 agonists (sympatholytic)- interfere with orgasm and can cause impotence
• thiazide diuretics- impotence (mech unclear)
• spironolactone- increase PRL leads to decreased testosterone, so decrease libido
• calcium channel blockers (FEW PROBLEMS)
• ACE inhibitors (FEW PROBLEMS)

• DA receptor blockade (both neuronal and endocrinological components)
  • more common in males, some female report increase
• CNS anticholinergic effects
• CNS sedative effects

• erection- due to peripheral anticholinergic effects
• orgasm- peripheral alpha 1 blockade

• peripheral effects
  • impotence
  • decreased lubrication (anticholinergic)
  • impaired orgasm (alpha 1 block)
• CNS effects
  • sedative
  • enhances serotonin (decrease libido)

• decrease libido
• difficulty achieving orgasm

• most common difficulty is orgasm
• ejaculatory failure in men, esp. with phenelzine

• bupropion (mild stimulant, and may enhance libido via DA effect)
• mirtazapine (alpha 2 block, may enhance libido, but highly sedating)
• nefazadone (sedating)
• trazodone (mixed reports of enhanced libido with anorgasmia)
  • also very sedating
  • rare reports of priapism

• sedating
• delayed orgasm
• ejaculatory failure

• decreased libido (enhance serotonin)

• causes increase in PRL and E2
• this causes decreased libido

• acute
  • small dose- disinhibits, increased libido and activity
  • higher doses (higher than 0.04% BAC)- impotence, delayed and/or less intense orgasm (male, female)
• chronic
  • neuropathy can cause impotence
  • decrease testosterone lowers libido
    • promotes loss of secondary sex characteristics in men

Other CNS depressants have similar effects

• acute
  • lower doses- enhancement of sensory effects, disinhibition, increased empathy
  • higher doses- impotence, anxiety
• chronic
  • decrease spermatogenesis
  • decrease plasma testosterone
    • lower libido
    • impotence
  • women- irregular menstrual cycles, anovulation

• acute
  • lower doses
    • enhanced libido (increase DA)
    • delayed orgasm (specific to cocaine)
    • general stimulant effects can also interfere with sexual activity
  • higher doses or IV
    • direct stimulation of erection, ejaculation
    • anxiety
• chronic
  • loss of libido
  • depression
  • ejaculatory failure

• acute- can be associated with increased sexual activity, possibly from disinhibition
• chronic
  • overall decrease in sexual activity (pt due to PRL levels)
    • most report lowered libido and ejaculatory delay
    • half report erectile dysfunction

• can enhance sensory experiences
• little association with altered sexual activity

• used to enhanced sexual feelings and empathy

• non associated with sexual activity, but can inhibit sensation
• chronic use associated with depression and psychosis

• lack of desire
• arousal difficulties
• difficulty achieving erection
• difficulty achieving orgasm
• perfomance anxiety
• premature ejaculation
• painful intercourse
• lack of pleasure in sex

• local anesthetics
• agents to delay orgasm
  • clomipramine (TCA)
  • thioridazine (neuroleptic antipsychotic)
  • MAOI's
  • benzodiazepines

• testosterone
  • replacement therapy for decreased gonadal function in males
  • libido response in both males, females
  • adverse effects: accelerate prostate cancer, atherosclerosis
• dopamine agonist
  • L DOPA
  • bromocriptine (used in prolactinemia)
  • apomorphine (currently in clinical trials)
  • methylphenidate
  • bupropion

• papaverine
• phentolamine (used as adjunct with papaverine but can interfere with orgasm)
• PGE1 (alprostadil)

• for dx and tx of ED
• adverse effects (limit its use)
  • bradycardia
  • hypotension
  • priapism
  • if chronic use: hepatotoxicity, penile fibrosis

• use- ED (used before viagra)
• routes of administration- injectable and urethral suppository
• side effects
  • hypotension
  • mild penile pain
  • occasional priapism

Seen mainly in folk medicine but is available as a prescription

• mechanism- potential CNS alpha 2 antagonist
• effects on sexuality
  • possible increase libido (use w/SSRI)
  • some effects in pateints with erectile dysfunction
  • overall efficacy uncertain
• adverse effects- sympathomimetic (many side effects)
  • palpitations
  • sweating
  • tremor
  • increase bp
  • increase HR
  • anxiety
  • irritability

• sidenafil
• vardenfafil (Levitra)
• tadafalil (Cialis)

Work on erection, not libido

1. inhibition of PDE5
2. leads to increase of cGMP in smooth muscle of corpus cavernosa
3. relaxation of smooth muscle
4. erection

• sildenafil- peak plasma conc. in one hour
  • you have to take it one hour prior to anticipated intercourse
  • have to wait longer after long meal
  • half life-4 hrs (effective duration similar)
• newer drugs have longer kinetcs
  • vardenafil (peak 1/2-2 hrs) w/half life of 4-5 hrs
    • high protein binding
    • high volume of distribution
    • plus active metabolites, so allows for longer DOA
  • tadalafil (peak in 1-6 hrs w/mean of 2 hrs) w/ half life of 18 hrs
    • effective DOA=36 hrs
    • marketed now as once daily pill

• vascular smooth muscle relaxation leads to hypotension (drop 9/6)
• common: headache, flushing, indigestion
• less common
  • visual disturbances (colors and light sensitivity) (unclear cause and effect)
    • nonarteritic ischemic optic neuropathy (NAION)
    • progressive, usually after continual use
    • partial vision loss, but perminant
    • higher risk with artheroschlerosis, small optic cup to disk ratio
  • nasal congestion
  • diarrhea
  • rash
• reports of sudden hearing loss

• caution: patients with CV disease
• should never be given with nitrates
  • large decrease in bp, syncope, lower cardiac perfusion, MI
  • nitrates include: nitroglycerine, isosorbide, nitroprusside, pentaethrytritol tetranitrate
  • includes recreational drugs like amyl nitrate, butyl nitrite

None approved by FDA

• hormones
  • estrogen (for menopause)
  • testosterone patches (for libido, especially post menopausal)
• viagra
• PGE1 inhibitors via cream increase blood flow and arousal
• phentolamine
• bupropion (useful with SSRI patients)
• DA agonists for libido