• Sexual arousal activates release of neurotransmitters (ACh, NO) from nerve terminals in the wee wee
• The NTs activate endothelial cells of the small arteries and arterioles
• The activates endothelial cells produce more NO
• NO enters nearby smooth muscle cells and causes elevation of intracellular cGMP
• The vascular smooth muscle cells relax
• The dilation causes filling of the sinusoids in the corpora cavernosa
• Filling of the corpora cavernosa compresses veins which helps to maintain an erection

• Agonist (ACh, Bradykinin) binds to receptor on endothelial cell
• Ca2+ channels in the cytoplasmic membrane and sarcoplasmic reticulum membrane are opened causing increase in [Ca2+]i
• Ca2+ binds and activates calmodulin and the Ca2+-calmodulin complex activates endothelial nitric oxide synthase (eNOS)
• eNOS synthesizes NO from L-Arg
• NO diffuses into nearby smooth muscle cells where guanylyl cyclase is activated and cGMP is subsequently produced -- NO also opens K+ channels on the SMC membrane
• The rise in [cGMP]i (and opening of K+ channels) causes SMC relaxation and widening of the vessel lumen thus decreasing resistance to blood flow in arterial vessels thereby filling the sinusoids

Sildenafil, Vardenafil, Tadalafil

MOA

• Increases SMC cGMP
• Activates protein kinase G (PKG)

SE

• Priapism rare
• Visual disturbances -- due to inhibition of ocular  PDE-6

PD-Interactions

Vasodilators (especially alpha adrenergic blockers and nitrates)

• Testosterone enters cell
• Testosterone is converted to DHT by 5alpha-reductase type 2
• DHT promotes transcription of genes that code for growth factors
• Growth factors act in an autocrine and paracrine fashion by binding to receptors on the stromal cell and epithelial cells

• Testosterone enters cell
• Testosterone is converted to DHT by 5alpha-reductase type 2
• Testosterone and DHT from stromal cells promote transcription of genes that code for growth factors
• Growth factors act in an autocrine and paracrine fashion by binding to receptors on the epithelial cell and stromal cells

Terazosin, Doxazosin, Tamsulosin, Alfuzosin, Silodosin

MOA

Relaxation of prostatic and urethral smooth muscle

SE

• Postural hypotension
• QT prolongation concern

Dutasteride, Finasteride

MOA

Blocks androgen dependent growth

SE

• Sexual dysfunction
• Teratogenic

Finasteride: type II

Dutasteride: type I and type II

• Kinefelter's syndrome (XXY syndrome)
• Uncorrected cryptorchidism
• Chronic disease (HIV, COPD, end stage renal disease)
• Hyperprolactinemia
• Medications (opiates, anabolic steroids)
• Aging
• Alcoholism

• Fluoxymesterone
• Methyltestosterone
• Testosterone esters amd preparations

Benefits

• May elevate mood
• Help maintain bone mass, RBC count and muscle mass
• May help with erectile dysfunction and increase libido
• May also improve cognitive ability

Adverse Effects

• Potentiates BPH and prostate cancer
• Abnormally high RBC production (erythrocytosis)
• Hepatic dysfunction (increase bilirubin and hepatic enzymes)
• Hepatic malignancy
• Oily skin and acne
• Edema, sodium retention
• Teratogenic
• May lower LDL and increase LDL
• Worsens sleep apnea