Lesson 8: Adrenergic Transmission (Antagonists) - CEU 2024/25 PDF

Lesson 8 Adrenergic Transmission Adrenergic Antagonists 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  Peripheral Nervous System Parasympathetic Parasympathetic...

Lesson 8 Adrenergic Transmission Adrenergic Antagonists 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  Peripheral Nervous System Parasympathetic Parasympathetic Somatic Preganglionic neuron Ach Ach Ganglion Postganglionic neuron Nicotinic Receptor Nicotinic Receptor N.A. Ach Ach Adrenergic Receptor Muscarinic Receptor Nicotinic Receptor (Skeletal muscle) Effector organs Summary 1.Adrenergic antagonists 2.Noradrenergic transmission modulators. 3.Summary 3  Sympatholytic drugs ANTAGONIST: drugs that inhibit sympathetic activity either by binding to the receptor, or by modifying adrenergic transmission. They are divided into: α ANTAGONISTS β ANTAGONISTS MIXED  Sympatholytic drugs α- ADRENERGIC ANTAGONISTS. The main groups of α-adrenoceptor antagonists are: – non-selective between subtypes (e.g. phenoxybenzamine, phentolamine) - α1-selective (e.g. prazosin, doxazosin, terazosin) – α2-selective (e.g. yohimbine, idazoxan). – In addition, ergot derivatives (e.g. ergotamine, dihydroergotamine) block α receptors as well as having many other actions, notably on 5-HT receptors.  Sympatholytic drugs α- ADRENERGIC ANTAGONISTS. Main ADRs: - Orthostatic hypotension. - Impaired ejaculation (tamsulosin) - Ergotic derivatives: nausea, vomiting and anginal crises. Pharmacological actions: Vasodilation: Þ Hypotension and tachycardia. -Inhibition of contraction of the trigone, bladder sphincter and urethral smooth muscleÞ facilitates urination.  Sympatholytic drugs α- ADRENERGIC ANTAGONISTS. Clinical use: Severe hypertension: – α1-selective antagonists (e.g. doxazosin) in combination with other drugs. Benign prostatic hypertrophy – (e.g. tamsulosin, a selective α1A-receptor antagonist). Phaeochromocytoma: phenoxybenzamine – (irreversible antagonist)  Sympatholytic drugs α- ADRENERGIC ANTAGONISTS. Pheochromocytoma is a rare benign tumor that develops in the adrenal glands, leading to excessive production of catecholamines (adrenaline and norepinephrine). The main symptoms include episodes of hypertension, rapid heartbeat, profuse sweating, and anxiety. The primary treatment is surgical removal of the tumor after the use of phenoxybenzamine. 8  Sympatholytic drugs α- ADRENERGIC ANTAGONISTS. 9  Sympatholytic drugs β-ADRENERGIC ANTAGONISTS (β-Blockers). * Used in animal testing * 1ª Generation 2ª Generation 3ª Generation β- Selective β1- Selective Mixed α/β Classification based on drug selectivity *Antiarrhythmic: block calcium intake, slow the heart's atrioventricular conduction and increase the refractory period  Sympatholytic drugs β-ADRENERGIC ANTAGONISTS (β-Blockers). Non-selective between β1 and β2 adrenoceptors: – propranolol, alprenolol,oxprenolol. β1-selective: – atenolol, nebivolol. Alprenolol and oxprenolol have partial agonist activity. They binds to β- adrenergic receptors and activates them, but it does so less effectively than full agonists like noradrenaline. Important hazards: – bronchoconstriction, and bradycardia and cardiac failure (possibly less with partial agonists). *REMINDER* Partial agonists are drugs that bind to a receptor and activate it, but not to the same extent as full agonists. They can activate the receptor but produce a less-than-maximal response compared to a full agonist. 11  Sympatholytic drugs β-ADRENERGIC ANTAGONISTS Pharmacokinetics: (β-Blockers). They are administered orally or parenterally. They are metabolized in the liver and excreted in the urine. Pharmacological effects Cardiovascular effects ¯ Heart rate. ¯ Contractibility (inotropism-) ¯ Cardiac output. ¯ Decreased cardiac output and O2 consumption. ¯ BP ¯ intraocular pressure. ¯ glucose tolerance in diabetics. Inhibition of lipolysis. Bronchoconstriction (non-selective) Increased uterine contractions.  Sympatholytic drugs β-ADRENERGIC ANTAGONISTS (β-blockers). ADR: Heart failure, bradycardia, conduction blocks. Bronchoconstriction Raynaud's phenomenon: coldness in the extremities... Masking hypoglycemic symptoms in insulin-dependent diabetes. CNS: insomnia, depression, tiredness, dizziness, decreased libido. Contraindications: They should be administered with caution in patients with: Bradycardia, insulin-dependent diabetes, advanced heart failure, and peripheral vascular disease. ► Contraindicated in patients with: Asthma, AV block and indecompensated heart failure  Sympatholytic drugs β-ADRENERGIC ANTAGONISTS (β-blockers). Clinical use: Cardiovascular : – angina pectoris – myocardial infarction, and following infarction – Arrhythmia – heart failure (in well-compensated patients) – hypertension (no longer first choice;) β-blockers are antihypertensive drugs Other uses: – glaucoma (e.g. timolol eye drops) – anxiety , to control somatic symptoms (e.g. palpitations, tremor) – migraine prophylaxis (first phase) – benign essential tremor (a familial disorder). 13 15  Sympatholytic drugs β-ADRENERGIC ANTAGONISTS (Mixed) Use: 16 Summary 1.Adrenergic antagonists 2.Noradrenergic transmission modulators. 3.Summary 17  2. Noradrenergic transmission modulators. Drugs that affect noradrenaline synthesis, release or uptake 18  2. Noradrenergic transmission modulators. Drugs that affect noradrenaline synthesis, release or uptake 19  2. Noradrenergic transmission modulators. Drugs that affect noradrenaline synthesis, release or uptake (Last lesson) 20 INDEX 1. Adrenergic antagonists 1. Alfa 2. Beta 3. mixed 2. Noradrenergic transmission modulators. 3. Summary 21 4. Summary. 22 4. Summary. 23 4. Summary. 24 Questions?????