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Details Title: pharma tx for sex dysfunction Description: 4.27.07 Total Flash Cards: 38 Created: 04/29/2007 14:51:08	To study from this set of flash cards, or to create your own your own study flash cards, register HERE. If you are already a registered user, CLICK HERE.
Cards Term what are the 3 major disturbances associated with male dysfunction? Definition Loss of libido Impotence Ejaculatory failure Term Control of sexual function is complex Definition Neural control derives in the forebrain limbic system to generate sexual drive that in turn is chronically stimulated by the effects of circulating androgens Term what is impotence? Definition Failure to attain an erection of sufficient strength to carry out sexual intercourse – 25% of the time; Impotence is common. It increases with age; Will affect approx 50% of the population over 50 yrs at some point; 25% of males > 70 yrs have impotence due to aging alone; 10% no satisfactory explanation can be found Term what are drug abuse causes of impotence? Definition ETOH ; Nicotine; Narcotics; Stimulants; Androgens Term what are prescribed drugs causes of impotence? Definition Antihypertensive drugs: (b blockers, ACEIs, which are ACE inhibitors, for hypertension); Anticholinergics; Antihistamines; Disulfuram; Psychotropic drugs; Estrogens Term what are other common causes of impotence? Definition Prostatectomy and other pelvic surgeries; Diabetes, Hypothyroidism; Vascular disease (CVD Stroke); Chemotherapy and radiotherapy; Neurological disease (MS) and Trauma; Liver + renal failure Term How Dx impotence? Definition Of exclusion Routine labs; Nerve supply Bulbocavernosus reflex test ; NPT testing – nerve and blood flow Tumescence correlates with REM sleep If normal ------- psychogenic If abnormal ------- organic; Intracorporeal injection of vasodilators – vascular cause Term what is the sequence of events for normal erectile functioning? Definition 1. Central (Brain) - Initiating events involve a combination of tactile, visual, auditory and imaginative stimuli 2. Increase in parasympathetic outflow and Inhibition of sympathetic outflow 3. Local parasympathetic reflex arc local tactile stimuli “penis – spinal cord – penis” 4. INCREASE BLOOD FLOW: Result is relaxation of helicine arteries in corpora cavernosa – increase blood flow Relaxation of smooth muscle of trabeculae of the corpus cavernosa – increase blood flow 5. maintain an erection: Venous drainage is impeded as a result of compression by the engorged corpora cavernosa - the erection is maintained 6. The sacral efferents are also responsible for ejaculation Term how are the changes in blood flow mediated? Definition The changes in blood flow are mediated by the release of nitrous oxide from the post synaptic parasympathetic neurons and endothelial cells Term what does NO do? Definition The readily diffusible NO stimulates guanylate cyclase in the trabecular and arterial smooth muscle cells increasing their content of cyclic GMP which in turn relaxes the cells Term what are conceptual approaches for TX? Definition 1. Mechanical approaches: Vacuum device In men who achieve a partial erectile response, Cumbersome 2. Vasodilators Direct injection or Intrameatal suppository of alprostadil Within 15 min of application Not user friendly 3. Agents that would increase the formation of cGMP or delay the breakdown of cGMP More specific target Oral drugs - more user friendly 4. Surgical therapy Penile Implants Term what is the problem with the cGMP approach? Definition lack of specificity of effect: cGMP is involved in several other signaling pathways Sperm motility, testosterone synthesis Vaginal smooth muscle Esophageal motility Color vision in the retina Inhibition of platelet aggregation Vasodilatation in other vascular beds renovascular, cardiovascular, pulmonary vascular Term tx approaches to male sexual dysfunction: Definition 1. Treat the cause Counseling if psychogenic Surgery if local genital abnormality Adjust drug regimen – if drug induced Testosterone – if androgen deficient 2. Specific treatment Penile Prosthesis Intracorporeal injection of vasodilators – papaverine side effect is priapism Intracavernosal injection alprostadil - PGE1 Intraurethral application of PGE1 Oral PDE 5 inhibitors Term what is PGEi? Definition a type of prostaglandin that works to dialate smooth muscle Term what are examples of PDE5 inhibitors? Definition Sildenafil is the prototype (Viagra) Vardenafil (Levitra) and Tadalafil (Cialis) Term how do cGMP PDE 5 inhibitors work? Definition cGMP phosphodiesterase inhibitors act by inhibiting the breakdown of cGMP by a specific cGMP phosphodiesterase - PDE 5 Work by maintaining the vasodilatory response Term what are the Pks? Definition They work quickly. Rapidly absorbed. 40% bioavailability. Peak plasma concentration 30 to 90 mins after oral dosing in the fasting state. Term what are they metabolized by? Definition Metabolized by hepatic microsomal enzyme system - CYP3A4- to an active metabolite. The metabolite accounts for 20% of sildenafil’s activity Term are they widely distributed? Definition yes: Distribution: Tightly bound to plasma proteins and half-lives of both the parent drug and the metabolite is approx 4 hours. Volume of distribution is 105L which means it is widely distributed into body tissues Term how are they excreted? Definition Excretion: 80% feces and 13% urine. Term why might plasma levels increase Definition Plasma levels increased by 40% in the elderly(>65) be careful with dosing 80% in patients with hepatic dysfunction 100% in those with severe renal impairment (so diabetic pts who are impotent are in trouble) 100% in patients on specific inhibitors of CYP3A4 Term what are some specific inhibitors of CYP3A4? Definition Macrolide antibiotics – erythromycin, clarithromycin Antifungal agents – ketoconazole, itraconazole Protease inhibitors – indinavir, ritonavir (Tx of HIV) Cimetidine (Tagamet) Term what are the pharmadynamics? Definition Think vasodilation! Primary indication – erectile response Term what are low doses used for? Definition Pulmonary hypertension, in males and in females Term What are the 4 major groups of Adverse effects? Definition Vasodilation headache - 16% flushing - 10% rhinitis - 4% Cardiovascular Hypotension and tachycardia Platelet inhibition Gastrointestinal Dyspepsia due to relaxation of lower esophageal sphincter (LOS) pressure Visual abnormalities blue green color tinged vision, increased light perception and blurred vision sildenafil and vardenafil are weak inhibitors of PDE6 Not seen with tadalafil Term what drug drug interactions are produced with nitrate? Definition The vasodilator actions of nitrates are profoundly amplified with concomitant use of all PDE 5 inhibitors resulting in hypotension and potentially fatal events It is not known how much time must elapse between taking a PDE 5 inhibitor and taking prescribed nitrates – 24 hours recommended for sildenafil Tadalafil has a longer half life Recreational use of amyl nitrate (poppers) and PDE5 inhibitors is ill advised Term as a result of the coinidcation with nitrate, how should we advise common comorbidity of impotence and CVD? Definition Common co-morbidities Approximately 5.5 million men take nitrates on a regular basis for angina Another 500,000 will experience an MI each year and will become potential candidates for nitrates Therefore PDE 5 inhibitors are potentially contraindicated in 6 million men in the US Term what are the caveats with PDE5 inhibitors? Definition The initial stimulatory response is necessary for clinical response to be seen PDE 5 inhibitors inhibit cGMP catabolism and thereby maintain the erectile response Generation of cGMP, however, requires activation of the parasympathetic nervous system de novo Their effects are not limited to the penile vascular tissue and as noted previously cGMP is involved in other significant signaling pathways The availability and extensive advertising of PDE5 inhibitors for the treatment of erectile dysfunction means that many more people will seek help for this condition Term do pde5 inhibitors create erections? Definition no, they maintain them Term are PDE5 inhibitors limited to penile tissue? Definition no Term what are 5 types of female sexual dysfunction? Definition Loss of sexual drive or arousal (arousal) Discomfort during intercourse (pain) Diminished blood flow to vagina Trauma-related aversion to sex Inability to achieve orgasm (anorgasmia) Term what are 3 current theories on why? Definition The Vascular Theory The Hormone Theory The Dissatisfaction Theory Term what are big dog causes of FSD? Definition Alcohol Anxiety Depression Stress Term dx? Definition Psychological Hyopactive Sexual disorder (arousal) Sexual Aversion disorder (desire) Female Orgasmic disorder (orgasm) Sexual Pain disorder (dyspareunia,vaginismus) Term what tests might be done? Definition physiological test Rarely done (vaginal pH, photoplethysmography, biothesiometer) Term what are medical reasons for sexual dysfunction in FEMALES! Definition Medical Diabetes, pituitary, thyroid disease Neurological – MS, trauma Term what horomones are involved in horomone replacement surgery? Definition E2, sometimes T Term what are vascular tx? Definition Vascular Treatment: 1. PDE5 inhibitors (SSRI induced dysfunction) 2. Eros Therapy FDA approved handheld device increases clitoral blood flow 3. L-arginine topical treatment (Viagel, Sensua) Substrate for NO synthesis Under evaluation