ED Flashcards
Phosphodiesterase Inhibitors
Alpha-2 Antagonists
Prostaglandin-E1 Analogs
ED Drug classes
what does phosphodiesterase do?
it forms phosphate bonds
ED has many physical and psychological causes, including what?
vascular disease, diabetes, medications, depression, and sequelae to prostatic surgery
Erectile dysfunction (ED) is the inability to maintain what?
maintain penile erection for the successful performance of sexual activity
first line therapy for men with ED?
Because of the efficacy, ease of use, and safety of oral phosphodiesterase (PDE) inhibitors, these drugs are now considered to be first-line therapy for men with ED
-afil suffix
ED therapy
INDICATION Erectile Dysfunction (Viagra®) Pulmonary Arterial Hypertension (Revatio®) DOSING [25, 50, 100 mg] 1 tab qd prn
SILDENAFIL CITRATE
INDICATION
CLINICAL PHARMACOLOGY
Vasodilator
Mechanism of Action
PDE-5 Inhibitor; sustains the vasodilatory effects of nitric oxide-dependent synthesis of cGMP
sildenafil citrate moa
nitric oxide is what?
free radical –> binds to anything –> causes damage
key mechanism of attack used by white blood cells
free radicals –> will kill invading organism
what does NO do?
stimulates vasodilation inhibits platelet aggergation inhibits monocyte adhesion inhibits ldl oxidation inhibits superoxide radical elaboration (in low doses antiinflammatory)
what are 6 things NO do?
stimulates vasodilation
inhibits platelet aggergation
inhibits LDL oxidation
inhibits superoxide radical elaboration (in low doses antiinflammatory)
inhibits smooth muscle cell proliferation (seen in artherosclerosis)
inhibits monocyte adhesion (adhesion of monocytes to vessel wall –> first step of it leaving blood stream and entering tissue=antiinflammatory)
what cell makes no?
endothelial cell
larginine + no –> NO (lipid soluble) –> enters muscle cell –> GC is stimulated (has heme moiety) –> converts GTP into cyclicGMP –> energy of cleavage produces GMP
no induced vasodilation mechanism
cyclic GMP –> activates kinases that activate ion channels that lead to closure of ion channels and muscle relaxation
how does cyclic gmp work?
pde5 does what?
breaks cgmp and turns it into GMP
IF WE inhibit cgmp, what happens?
continues to stimulate kinase causing relaxation
where else is pde5 found?
lungs; therefore is also used in pulmonary hypotension
if pde5 is not selected, and pde3 is what will happen?
inhibit contraction of heart muscle
why is pde6 special?
its selectivity is only 10 percent less than pde5; and its responsible for color vision and retinal phototransduction
why is pde6 special?
its selectivity is only 10 percent less than pde5; and its responsible for color vision and retinal phototransduction
disc of rod is important because?
contains rhodopsin, which in the presence of light takes trans configuration; in absence of light takes cis
light –> rhodopsin –> isomerization –> activates transducin –> pde6 activation –> degrade cGMP –> ion channels will close –> (in light, less sodium is entering the cell) –> hyperpolarization
rod phototrandsuction and pde mechanism
viagra depends on what molecule to initiate vasodilation?
NO
lack of selectivity of viagra, will inhibit activity in what?
possibly phototransduction –> impacting vision
ADVERSE EFFECTS
Common: headache, abnormal vision, dizziness, nasal congestion
SERIOUS ADVERSE EFFECTS
CV: MI, stroke, ventricular tachycardia, hypotension/shock
Hematology: anemia, leukopenia
OCULAR ADVERSE EFFECTS
Ocular: Retinal heme, NAION, vision loss, elevated IOP, cyanopsia
sildenafil citrate (adverse effects)
ADVERSE EFFECTS
Common: headache, abnormal vision, dizziness, nasal congestion
SERIOUS ADVERSE EFFECTS
CV: MI, stroke, ventricular tachycardia, hypotension/shock
Hematology: anemia, leukopenia
OCULAR ADVERSE EFFECTS
Ocular: Retinal heme, NAION, vision loss, elevated IOP, cyanopsia
sildenafil citrate (adverse effects)
SILDENAFIL CITRATE
DRUG INTERACTIONS
Azole Antifungals, Erythromycins, Cyclosporine (Reduced metabolism)
Alpha-Blockers, Beta-Blockers (Additive)
SILDENAFIL CITRATE
DRUG INTERACTIONS
SILDENAFIL CITRATE
DRUG INTERACTIONS
Azole Antifungals, Erythromycins, Cyclosporine (Reduced metabolism)
Alpha-Blockers, Beta-Blockers (Additive)
SILDENAFIL CITRATE
DRUG INTERACTIONS
pde5 and seratonin do what to blood?
pde5 is found in platelets; seratonin helps form platelets
pde5 and seratonin do what to blood?
pde5 is found in platelets; seratonin helps form platelets
pde5 and seratonin do what to blood?
pde5 is found in platelets; seratonin helps form platelets
how is viagra eliminated?
hepatic metabolism involving p450-3a4 enzyme
retinitis pigmentosa is partly a genetic disorder of what?
retinal phosphodiesterases
what is released during sexual arousal?
NO
what do PDE’s promote?
cyclic GMP (cGMP) degradation
PDE5 is found where?
arterial wall smooth muscle of the penis and lung vasculature
PDE3’s selectivity is what?
> 700 (cardiac contractility)
PDE6’s selectivity is what?
10 less (retinal phototransduction; color vision)
PDE6’s selectivity is what?
10 less (retinal phototransduction; color vision)
what is PDE5?
in platelets, thus, its inhibition poses a potential risk of hemorrhage
PDE5 is found where?
skeletal muscle
what does pde5 do?
arterial venous dilation
