ADRENERGIC ANTAGONISTS.ppt

ANRENERGIC ANTAGONISTS Prof. Dr. Aşkın TAŞ SYMPATHOLYTIC DRUGS • Adrenergic receptor blockers • Alpha adrenergic receptor blockers • Adrenergic neuron blockers: • Reserpine, Guanetidine, Debrisoquine, Betanidine – Beta adrenergic receptor blockers ALPHA ADRENERGIC RECEPTOR BLOCKERS 1-Phenoxyb...

ANRENERGIC ANTAGONISTS Prof. Dr. Aşkın TAŞ SYMPATHOLYTIC DRUGS • Adrenergic receptor blockers • Alpha adrenergic receptor blockers • Adrenergic neuron blockers: • Reserpine, Guanetidine, Debrisoquine, Betanidine – Beta adrenergic receptor blockers ALPHA ADRENERGIC RECEPTOR BLOCKERS 1-Phenoxybenzamine and other haloalkylamines • • • • 2-Ergot (rye spur) alkaloids 3-Phentolamine and tolazolin 4-Prazosine, Doxazosine, Terazosin, alfuzosin 5-Mixed-acting (α, β) blockers: Labetolol, Carvedilol • 6-Others PHARMACOLOGICAL EFFECTS • They remove sympathetic tone and vasodilate in vascular beds (reflex tachycardia) Postural hypotension is more significant in some cases •All drugs that reduce sympathetic tone on the vessels, affect the sympathetic system (α-receptor, adrenergic nerve ending, sympathetic ganglia or vasomotor centers in the CNS) They can generate postural hypotension – – 1-Hypovolemia 2-If the veins are physiologically enlarged (without exercise, hot) – 3-Vasodilator drugs – 4-Myocardial infarction – 5-Pheochromocytoma – – • They lower blood pressure and cause orthostatic (postural) type hypotension PHARMACOLOGICAL EFFECTS • They have no significant effect on the heart, with a reflex effect and by blocking nerve ending α2 receptors, they can increase sympathetic activity (tachycardia, increased flow rate) • They reverse the effect of adrenaline (α and β) • When they reduce blood pressure sufficiently, they reduce kidney blood flow and cause water and salt retention (the reason for the development of tolerance to their antihypertensive effects) • They cause myosis, do not affect accommodation • It blocks pilomotor contraction and the secretion of apocrine sweat glands. 1. PHENOXYBENZAMINE • Blocks alpha adrenergic receptors in an irreversible manner • Histamine also blocks serotonin and cholinergic receptors • Noradrenaline inhibits neuronal and extraneuronal re-uptake • α2 increases the release of noradrenaline from the nerve ending as a result of blockade. • It is not marketed in Turkey. 2. ERGOT ALKALOIDS • They are the alkaloids found in Ergot (rye spur) formed by the fungus Claviceps purpurea in the rye ear. • Amine alkaloid: Ergonovine (ergometrine, ergobazine) – Amino acids: Ergotoxin, Ergotamine – Dihydro derivatives: Dihydroergotoxin and Dihydroergotamine – Ergotoxin is a mixture of 3 alkaloids: Ergocriptine, Ergocristine, Ergokornin – Semi-synthetic derivatives: Bromocriptine, Lergotril, Lizuride, Metergolin, Cabergoline, Methisergid • The basic structure is lysergic acid 2. ERGOT ALKALOIDS • Pharmacological effects • Contracts smooth muscles (veins and uterus) • They perform vasoconstriction by performing both adrenergic blockade (vein) and serotonergic activation (artery, 5-HT1B / D) in the vessel and increase blood pressure. • Their effects on serotonin and alpha-adrenergic receptors is a partial agonist • Ergotoxin and dihydro derivatives have the the strongest α blocking effect • They activate central dopaminergic receptors (D2) (partial agonist). • This activity is significant in bromocriptine • They stimulate the chemoreceptor trigger zone, cause nausea and vomiting • They inhibit the secretion of prolactin and growth hormone from the anterior pituitary. 2. ERGOT ALKALOIDS • Pharmacological effects • Bradycardia (by stimulating the heart-related vagus nucleus and reducing sympathetic tone) • They reduce noradrenaline release by activating α2 receptors at the presynaptic end • They contract the uterine muscles, increase motility (oxytocic effect) • Ergonovine and methylergonovine are the ones with the most oxytocic effects and are preferred • They are used to hasten the expulsion of the placenta in the third period of labor and stop bleeding. 2. ERGOT ALKALOIDS ERGOTAMİN TARTRAT • Powerful vasoconstrictor • It is used in the treatment of migraine attacks (due to serotonergic effect) • Preparations combined with caffeine (Cafergot®, Avmigran®, Ergafein®) is also marketed • When the seizure begins, 2 tablets are taken without delay, and if there is no response, another 1 tablet is taken half an hour later • A total of no more than 4-6 tablets are taken in 24 hours • This application is not repeated before 4 days • No more than 10 tablets are taken per week 2. ERGOT ALKALOIDS DIHYDRERGOTAMIN MALEATE • It is used in the treatment of migraine that does not respond to analgesic drugs. • Only nasal spray is available in Turkey • At the beginning of a migraine attack, each nostril is sprayed once • If there is no response, it can be repeated after 15 minutes • A maximum of 4 squeezes are made and this squeezing sequence is not repeated before 8 hours • Dihydroergatamine is used together with heparin to constrict the veins of the lower extremities in deep vein thrombosis and associated pulmonary embolism SIDE EFFECTS AND CONTRAINDICATIONS • Nausea, vomiting, diarrhoea, abdominal pain • Cramps in the muscles • High doses can cause confusion and loss of consciousness • They cause cooling of the extremities, paresthesia and decrease in coronary blood flow due to diffuse vasoconstriction • Long-term use can cause chronic ergot poisoning (ergotism) • Ergotism: Symptoms of gangrene and CNS (headache, dizziness, confusion, myosis, paresthesia) • Sodium nitroprusside is used in the treatment of ergotism • It causes miscarriage in pregnant women • Contraindicated in liver failure, peripheral vascular disease, coronary heart disease, sepsis 3-PHENTOLAMINE AND TOLAZOLINE • Imidazoline derivatives are short-acting partial agonists on alpha-receptors. 4. PRAZOSİN AND İTS ANALOGUES • Prazosin • They are more selective on α 1A receptors in prostate tissue (other group members are not selective). • (Abnormal ejaculation causes intraoperative loose iris syndrome in patients undergoing cataract surgery) • Terazosin • Alfuzosin May increase the risk of QT prolongation • Silodosin more selective to α 1A (Retrograde ejaculation) • Doxsazosin • Tamsulosin PRAZOSIN • Selective α 1 blocker Causes hypotension of an orthostatic nature Tolerance occurs (water and salt retention) It can be used in hypertension (prazosin, doxazosin, indoramine), congestive heart failure, peripheral vascular diseases Does not impair the lipid profile, but improves it Prazosin and similar alpha blockers are also used in the treatment of benign prostatic hypertrophy (relaxing the smooth muscles of the prostate and reducing pressure on the urethra passing through it) They are useful in congestive heart failure and Raynaud's syndrome PRAZOSIN •Side effects •First dose syncope • If the first dose is high, blood pressure drops drastically, loss of consciousness, the elderly, low Na diet, those taking betablockers are more sensitive. Tachyphylaxis occurs over time • It is started with a low dose and the dose is increased at intervals of 3-7 days toreach the effective döşe. • It can cause drowsiness, weakness, nasal congestion, headache 5. LABETOLOL • It is both an alpha and beta blocker. • The beta-blocker effect is 4-8 times stronger than the alphablockade. • Due to the alpha-blocking effect, the antihypertensive effect begins immediately. • It is used in all mild-severe hypertension • IV can be applied in crisis treatment • During the treatment, periodic eye examination should be performed (collected in the choroidal layer) • Carvedilol is another hybrid blocker 6. OTHERS • Indoramine • Urapidil α 1 antagonist, weak α 2 agonist, 5-HT1A-agonist, weak β1 antagonist • Chlorpromazine is a 1 antagonist α haloperidol antipsychotics and an antagonist of dopamine • Trazodone is an antidepressant α 1 antagonist USE OF ALPHA BLOCKERS İN TREATMENT • Treatment of hypertension due to overdose of sympathomimetic drugs • Palliative treatment of benign prostatic hypertrophy (prazosin, doxazosin and the like) • Pheochromocytoma • Prevention of vasospasm (in open heart and kidney transplant surgeries) • Treatment of congestive heart failure (not preferred) • Peripheral vascular diseases (due to sympathetic activity, functional) ADRENERGIC NEURON BLOCKERS • They are used in the treatment of hypertension and vasospastic diseases: • Rezerpin and other Rauwolfia alkaloids(sirosingopin, metoserpidin, deserpidin (Enduronyl, Harmonyl) • Guanetidin • Guanadrel • Bethandin • Debrizokin • Resinamin INHIBITION OF ADRENERGIC MEDIATOR RELEASE • Methyrosine (α methyl-p-tyrosine) • Tyrosine hydroxylase • Reduces Noradrenaline, Dopamine and Serotonin synthesis • In the treatment of pheochromocytoma • or premedication before surgery • It is an enzyme inhibitor