ANS Medications PDF

ANS Medications Adrenergic Drugs Drugs that mimic or block neurotransmitters like norepinephrine and epinephrine Adrenergic Agonists Adrenergic agonists are drugs that stimulate adrenergic receptors (either α or β receptors), mimicking the effects of sympathetic neurotransmitter...

ANS Medications Adrenergic Drugs Drugs that mimic or block neurotransmitters like norepinephrine and epinephrine Adrenergic Agonists Adrenergic agonists are drugs that stimulate adrenergic receptors (either α or β receptors), mimicking the effects of sympathetic neurotransmitters (norepinephrine and epinephrine). They can act on specific receptor subtypes, and their effects vary depending on which receptors they stimulate. Alpha-1 (α₁) Agonists: Alpha-1 receptors are primarily found in smooth muscles, including blood vessels, the eye, and the urinary tract. When stimulated, they cause vasoconstriction, leading to increased blood pressure, pupil dilation (mydriasis), and smooth muscle contraction Phenylephrine treats hypotension Alpha-2 (α₂) Agonists: Alpha-2 receptors are primarily located in the brainstem. When stimulated, they inhibit the release of norepinephrine and reduce sympathetic outflow, leading to a decrease in blood pressure and sedation. Clonidine treats hypertension and withdrawal symptoms Beta-1 (β₁) Agonists:  Beta-1 receptors are located primarily in the heart. When stimulated, they increase heart rate (chronotropy), contractility (inotropy), and conductivity (dromotropy), improving cardiac output. Dobutamine: Used in acute heart failure or cardiogenic shock to increase cardiac output. Beta-2 (β₂) Agonists: Beta-2 receptors are found in smooth muscles of the lungs, uterus, and vasculature. Stimulation causes bronchodilation, vasodilation, and relaxation of uterine smooth muscle. Albuterol: A short-acting bronchodilator used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Terbutaline: Used to treat bronchospasm and premature labor. Beta-3 (β₃) Agonists: Beta-3 receptors are found in adipose tissue and the bladder. Activation leads to lipolysis(fat breakdown) and relaxation of the bladder muscle. Mirabegron: Used to treat overactive bladder. Adrenergic-Blocking Drugs Adrenergic antagonists, or adrenergic blockers, inhibit the effects of endogenous catecholamines (norepinephrine and epinephrine) by blocking the adrenergic receptors. These drugs can be selective (acting on specific receptor subtypes) or non-selective. Alpha-1 (α₁) Antagonists:  Alpha-1 blockers work by blocking the alpha-1 receptors on smooth muscle, resulting in vasodilation, reduced blood pressure, and relaxation of the bladder and prostate smooth muscle. Prazosin: Used to treat hypertension and symptoms of benign prostatic hyperplasia (BPH). Tamsulosin: Primarily used for BPH treatment. Alpha-2 (α₂) Antagonists: Alpha-2 blockers increase norepinephrine release by blocking the inhibitory action of alpha-2 receptors. This leads to increased sympathetic tone and potentially increased blood pressure. Yohimbine: Used to treat erectile dysfunction and orthostatic hypotension. Beta-1 (β₁) Antagonists (Beta Blockers): Beta-1 blockers primarily affect the heart, reducing heart rate, contractility, and cardiac output. This makes beta blockers useful in treating hypertension, arrhythmias, and heart failure. Metoprolol, Atenolol: Selective beta-1 blockers used to treat hypertension, arrhythmias, and heart failure. Beta-2 (β₂) Antagonists: Beta-2 blockers are rarely used therapeutically, as their blockade can lead to bronchoconstriction, which is contraindicated in asthma and COPD patients. However, non-selective beta blockers (which block both beta-1 and beta-2 receptors) can have such effects.  Propranolol: Non-selective beta blocker that can cause bronchoconstriction in susceptible individuals. Non-selective Beta Blockers (Beta-1 and Beta-2 Blockers): These drugs block both beta-1 and beta-2 receptors, affecting the heart, lungs, and vasculature. Propranolol, Carvedilol: Used for hypertension, heart failure, and anxiety. Indirect-Acting Adrenergic Drugs These drugs do not directly stimulate adrenergic receptors but instead increase the availability of norepinephrine or epinephrine in the synaptic cleft, thus indirectly enhancing adrenergic signaling. Amphetamines: Increase the release of norepinephrine and dopamine, leading to central nervous system stimulation. Cocaine: Inhibits the reuptake of norepinephrine, dopamine, and serotonin, enhancing their effects. Cholinergic drugs Cholinergic drugs are medications that interact with the cholinergic system, which uses acetylcholine (ACh) as its primary neurotransmitter. These drugs influence cholinergic receptors located throughout the body, primarily the muscarinic receptors (M1, M2, M3, M4, and M5) and nicotinic receptors (Nn and Nm). The primary effects of cholinergic drugs are related to their stimulation of the parasympathetic nervous system, leading to a "rest-and-digest" response in various organs. 1. Direct-Acting Cholinergic Drugs Direct-acting cholinergic drugs are those that directly stimulate cholinergic receptors, either muscarinic or nicotinic receptors. Muscarinic Receptor Agonists (Parasympathomimetics) Muscarinic agonists specifically stimulate muscarinic receptors, which are G protein-coupled receptors found in various tissues such as the heart, smooth muscles, and glands. These receptors mediate the typical effects of the parasympathetic nervous system (e.g., bradycardia, increased secretion, smooth muscle contraction). Mechanism of Action: Muscarinic receptor agonists mimic the action of acetylcholine, leading to a range of effects depending on the receptor subtype activated: ○ M1: Found mainly in the central nervous system (CNS) and gastric parietal cells, modulates cognition and gastric acid secretion. ○ M2: Found primarily in the heart, mediates negative chronotropy (slows heart rate) and negative inotropy(reduces heart muscle contractility). ○ M3: Found in smooth muscles and glands, mediates smooth muscle contraction (e.g., bronchoconstriction, miosis) and increased glandular secretions (e.g., salivation, sweating). Examples: ○ Pilocarpine: Used to treat glaucoma (reduces intraocular pressure) and xerostomia (dry mouth). ○ Bethanechol: Used to treat urinary retention by stimulating bladder contraction. Nicotinic Receptor Agonists Nicotinic agonists stimulate nicotinic receptors, which are ion channels found at the neuromuscular junction (Nm receptors) and in autonomic ganglia (Nn receptors). Activation of nicotinic receptors leads to depolarization and stimulation of target tissues. Mechanism of Action: ○ Nn receptors: Found in autonomic ganglia, stimulation of Nn receptors increases sympathetic and parasympathetic tone, depending on the organ system. ○ Nm receptors: Found at the neuromuscular junction, activation causes muscle contraction. Example: ○ Nicotine: Stimulates both Nn and Nm receptors, leading to a variety of effects including CNS stimulation, increased heart rate, and increased blood pressure. 2. Indirect-Acting Cholinergic Drugs Indirect-acting cholinergic drugs work by increasing the concentration of acetylcholine (ACh) at cholinergic synapses. This is typically achieved by inhibiting the enzyme acetylcholinesterase, which breaks down ACh. Acetylcholinesterase Inhibitors These drugs inhibit the enzyme acetylcholinesterase (AChE), which is responsible for the hydrolysis of acetylcholine. By preventing acetylcholine breakdown, these drugs increase the duration and intensity of ACh action at both muscarinic and nicotinic receptors. There are two main categories of acetylcholinesterase inhibitors:  1. Reversible Inhibitors: These drugs temporarily inhibit acetylcholinesterase. ○ Mechanism of Action: By inhibiting AChE, reversible inhibitors allow acetylcholine to accumulate at cholinergic synapses, enhancing both muscarinic and nicotinic neurotransmission. ○ Examples: Neostigmine: Used to treat myasthenia gravis (by improving neuromuscular transmission) and to reverse neuromuscular blockade during surgery. Physostigmine: Used to treat anticholinergic toxicity (e.g., from atropine overdose) and glaucoma. Donepezil, Rivastigmine: Used to treat Alzheimer's disease by increasing ACh levels in the brain. 2. Irreversible Inhibitors: These drugs form a covalent bond with acetylcholinesterase, leading to prolonged inhibition. ○ Mechanism of Action: These agents permanently inactivate acetylcholinesterase, leading to prolonged accumulation of acetylcholine, but this effect can only be reversed by the synthesis of new enzyme molecules. ○ Examples: Organophosphates (e.g., malathion, sarin): Used in pesticides and chemical warfare agents, they cause prolonged ACh accumulation, leading to toxic effects such as muscle paralysis and respiratory failure. Treatment involves pralidoxime and atropine. Cholinesterase Reactivators Some drugs (e.g., pralidoxime) can reactivate acetylcholinesterase that has been inhibited by organophosphates, reversing the toxic effects. 3. Clinical Applications of Cholinergic Drugs Cholinergic drugs have various therapeutic applications based on their mechanism of action: Direct-Acting Muscarinic Agonists: Pilocarpine: Used to treat glaucoma by reducing intraocular pressure and xerostomia (dry mouth) caused by Sjögren’s syndrome or radiation therapy. Bethanechol: Used to treat urinary retention or gastric atony by stimulating smooth muscle contraction. Indirect-Acting Acetylcholinesterase Inhibitors: Neostigmine: Used for myasthenia gravis, postoperative ileus, and to reverse neuromuscular blockade after surgery. Donepezil, Rivastigmine: Used to treat Alzheimer's disease by increasing ACh availability in the brain. Physostigmine: Used for the treatment of anticholinergic toxicity (e.g., atropine overdose). Toxicology (Cholinergic Poisoning): Organophosphates (e.g., sarin gas, pesticides): Cause severe poisoning by irreversibly inhibiting acetylcholinesterase, leading to muscle paralysis, seizures, and respiratory failure. Treatment includes atropine(to block excessive muscarinic stimulation) and pralidoxime (to reactivate acetylcholinesterase). 4. Side Effects and Toxicity While cholinergic drugs can be beneficial, they may also lead to unwanted effects due to overstimulation of the parasympathetic system (excessive muscarinic or nicotinic effects). Muscarinic Effects: ○ Bradycardia, hypotension, bronchoconstriction, salivation, sweating, diarrhea, miosis (pupil constriction). ○ Toxicity: SLUDGE syndrome (Salivation, Lacrimation, Urination, Defecation, Gastrointestinal distress, Emesis). Nicotinic Effects: ○ Muscle weakness, fasciculations, and paralysis (due to overstimulation of neuromuscular junctions). In cases of toxicity or overdose, atropine (a muscarinic antagonist) is used to counteract muscarinic effects, and pralidoxime is used for organophosphate poisoning to regenerate acetylcholinesterase. Cholinergic blocking drugs known as anticholinergics or antimuscarinic drugs, are substances that block the action of acetylcholine (ACh) at cholinergic receptors, primarily the muscarinic receptors. These drugs interfere with the normal parasympathetic nervous system (PNS) functions, as acetylcholine is the primary neurotransmitter for the parasympathetic system. The main effect of cholinergic blockers is to produce sympathomimetic effects (i.e., mimicking the effects of the sympathetic nervous system), leading to a "fight or flight" response. This results in a range of physiological changes, such as increased heart rate, bronchodilation, dilated pupils, reduced gastrointestinal motility, and drying of secretions (saliva, mucus, etc.). Muscarinic Antagonists (Antimuscarinics) These are the most commonly used cholinergic blocking drugs, and they block muscarinic receptors selectively, often without affecting nicotinic receptors. Atropine: One of the most well-known antimuscarinic drugs. It is used for a variety of purposes: ○ Bradycardia: Increases heart rate by blocking the parasympathetic influence on the heart (useful in cases of sinus bradycardia or AV block). ○ Antidote for cholinergic poisoning: Used to counteract the effects of organophosphate poisoning (e.g., nerve agents, pesticides). ○ Pupil dilation: Used in ophthalmology for mydriasis (dilation of the pupil) for eye exams and treatment of iritis or uveitis. ○ Pre-anesthetic medication: To reduce salivation and bronchial secretions during surgery. Scopolamine: A potent muscarinic antagonist used for: ○ Motion sickness: Used as a transdermal patch or oral form to prevent nausea and vomiting caused by motion sickness. ○ Pupil dilation and cycloplegia in eye exams. Ipratropium and Tiotropium: Antimuscarinic bronchodilators used to treat:  ○ Chronic obstructive pulmonary disease (COPD) and asthma. These drugs block muscarinic receptors in the airways to cause bronchodilation. Glycopyrrolate: Used in perioperative settings to reduce salivation and secretions during anesthesia and to treat peptic ulcers by reducing gastric acid secretion. Oxybutynin, Tolterodine, Solifenacin: These drugs are used to treat overactive bladder by relaxing the bladder smooth muscle (antispasmodic effect). 2. Ganglionic Blockers Ganglionic blockers inhibit the transmission of nerve impulses through autonomic ganglia by blocking nicotinic receptors (Nn) on the cell bodies of sympathetic and parasympathetic neurons. These drugs are rarely used today due to significant side effects, as they affect both the sympathetic and parasympathetic systems. Hexamethonium and Trimethaphan: Once used to treat hypertension in emergency situations, but largely replaced by other agents due to their widespread and unpredictable effects on both sympathetic and parasympathetic systems. 3. Centrally Acting Muscarinic Antagonists These drugs exert their effects on the CNS and are used in specific conditions, particularly those related to motion sickness or Parkinson's disease. Benztropine and Trihexyphenidyl: Used in the treatment of Parkinson's disease to reduce tremors and rigidity. They block  muscarinic receptors in the CNS, particularly the striatum, to restore balance between dopamine and acetylcholine. Procyclidine: Another drug used to treat the extrapyramidal symptoms of Parkinson's disease or antipsychotic-induced movement disorders. Physiological Effects of Cholinergic Blockers The effects of cholinergic blockers are largely a result of reduced parasympathetic activity. Some of the key effects include: 1. Cardiovascular Effects: ○ Increased heart rate (tachycardia): By blocking M2 receptors in the heart, cholinergic blockers reduce vagal tone, leading to increased heart rate. ○ Decreased cardiac output and blood pressure: In some cases, due to reduced parasympathetic control of the vasculature. 2. Respiratory Effects: ○ Bronchodilation: Blocking M3 receptors in the lungs reduces bronchoconstriction and can be useful in conditions like asthma or COPD. ○ Dry mouth and throat: Blockage of salivary gland activity reduces secretions. 3. Gastrointestinal Effects: ○ Decreased gastrointestinal motility: By blocking M3 receptors in the GI tract, cholinergic blockers can reduce peristalsis, leading to constipation. ○ Reduced gastric acid secretion: Drugs like scopolamine can reduce the secretion of gastric acid. 4. Urinary System Effects:  ○ Urinary retention: Blockage of muscarinic receptors in the bladder smooth muscle can result in difficulty emptying the bladder, leading to urinary retention. 5. Pupil Dilation (Mydriasis): ○ Cholinergic blockers cause pupil dilation by blocking the M3 receptors in the iris, leading to mydriasis and cycloplegia (paralysis of the ciliary muscle). 6. CNS Effects: ○ Cognitive effects: Central muscarinic blockade can cause confusion, memory disturbances, and even hallucinations, particularly in elderly patients. ○ Sedation or drowsiness: Some anticholinergics, like scopolamine, have sedative effects and are used in motion sickness. Clinical Uses of Cholinergic Blocking Drugs Cholinergic blockers are used in a variety of clinical situations: Pre-anesthesia medication (e.g., atropine, scopolamine) Treatment of motion sickness (e.g., scopolamine) Management of COPD and asthma (e.g., ipratropium, tiotropium) Treatment of overactive bladder (e.g., oxybutynin, tolterodine) Management of Parkinson's disease (e.g., benztropine, trihexyphenidyl) Eye exams (e.g., atropine, scopolamine for mydriasis and cycloplegia) Management of bradycardia (e.g., atropine) Side Effects and Toxicity While cholinergic blockers are useful therapeutically, they can have unwanted side effects, especially when used excessively or in the elderly. Common side effects: ○ Dry mouth, blurred vision, photophobia, urinary retention, constipation, and tachycardia. ○ Cognitive impairment and delirium (especially in elderly patients). Toxicity: ○ Symptoms of anticholinergic toxicity include "hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter": Hyperthermia (due to sweating inhibition), blurred vision (due to pupil dilation), dry mouth, flushed skin, and agitation or confusion. Treatment of Toxicity Physostigmine (an acetylcholinesterase inhibitor) can be used to reverse anticholinergic toxicity by increasing acetylcholine levels at the receptor site.