You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information.
What is Tadalafil should NOT be used in and explain in detail?
(B) Patient on Nitrates therapy[?]Sildenafil, Tadalfil, Vardenafil & Avanafil are the only approved & effective oral agents for the treatment of Erectile Dysfunction.oThese 4 drugs markedly improved the management of erectile dysfunction, because they are effective for the treatment of a broad range of causes, including psychogenic, diabetic, vasculogenic, post-radical prostatectomy (nerve-sparing procedures), & spinal cord injury.oThese are Selective & Potent Inhibitors of PDE-5, the predominant phosphodiesterase isoform found in the penis.DrugOnset of ActionHalf-lifeDoseAdverse EffectsContraindicationsTadalafilTmax,30-60 min Duration, 12-36 h Plasma concentration Not affected by food or ETOH17.5 h10 mg, 20 mg; 2.5 or 5 mg or daily doseHeadache,dyspepsia,back pain,nasalcongestion,myalgiaNitratesHypotensionCardiovascular risk factorsRetinitis pigmentosaChange dose with some antiretroviralsShould be on stable dose of alpha blockers[?]Significant Drug Interactions & Contraindications:oPhosphodiesterase 5 (PDE5) inhibitors include Sildenafil (Viagra), Vardenafil (Levitra), & Tadalafil (Cialis).-The administration of any of these drugs with doses of any Nitrate is contraindicated.-The combination can cause dangerously low blood pressure.[?]Contraindications of Tadalafil Black 80 mg:oThe consumption of this drug is chiefly avoided due to some medical issues in men like:-Abnormal conditions or deformity of genitals-Hypersensitivity problem to any ingredient of this drug.-Heart related problems-Severe renal insufficiency-History of stroke & heart attack-Severe pulmonary disorders.-Patients with history of AMI/stroke/fatal arrhythmias <6 month Nitrates - total contraindication/PDEIs in small dose + spacing at least 24 hrs (48 hrs with Tadalafil) for fear of developing IHD/AMI due to severe hypotension.oPrecautions for Tadalafil:-With alpha blockers (except Tamsulosin) - orthostatic hypotension.-With hepato/renal insufficiency.-With Pyronie's disease-With bleeding tendencies (leukemia's, hemophilia, Vitamink K deficiency, Antiphospholipid syndrome... etc).-With quinidine, procainamide, amiodarone (class I & III antiarhtmics) (Vardenafil).-Dose adjustment; when using drugs that have interaction on hepatic livery microsomal enzymes i.e., inhibitors or inducers.-Retinitis pigmentosa.OTHER OPTIONS[?]Nitrates are vasodilators acts by producing vascular smooth muscle relaxation through cGMP pathway.-Cyclic GMP is hydrolyzed to 5 GMP by PDE5-Tadalafil is a Phosphodiesterase 5 (PDE5) inhibitors-Inhibition of PDE5 prolongs and accentuates the cGMP in smooth muscle causes relaxation.-Taking tadalafil with vasodilator drug like nitrate can cause sudden & serious decrease in blood pressure.oTadalafil in treatment of Pulmonary Arterial Hypertension is used to improve haemodynamics & excercise ability oTadalafil in treatment of Sexual dysfunction like Erectile dysfunction is treated by5-20 mg taken 1-2 h before sex, is now the standard treatment for maintaining erections.oRemember1-Combination with vasodilators results in sudden changes of blood pressure values:-Tadalafil relaxes muscles of the blood vessels and increases blood flow to particular areas of the body.-Used to treat erectile dysfunction, and symptoms of benign prostatic hypertrophy-Also in treatment of Pulmonary Arterial Hypertension is used to improve haemodynamics & excercise ability.oWhen given alone to men with severe coronary artery disease, these drugs have modest effects on blood pressure, producing >10% fall in systolic, diastolic & mean systemic pressures & in pulmonary artery systolic & mean pressures.oSildenafil, tadalafil & vardenafil all have a significant & potentially dangerous interaction with organic nitrates, the therapeutic actions of which are mediated via their conversion to NO with resulting increases in cyclic GMP.oIn the presence of a PDE5 inhibitor, nitrates cause profound increases in cyclic GMP and can produce dramatic reductions in blood pressure.