Drugs Acting on Sympathetic & Parasympathetic Nervous System PDF

DRUGS ACTING ON Sympathetic & Parasympathetic Nervous System ANNE CELIS – SOTTO R.N; LPT Divisions of human nervous system Central Nervous Human System Nervous system Peripheral Autonomic Nervous Nervous System System...

DRUGS ACTING ON Sympathetic & Parasympathetic Nervous System ANNE CELIS – SOTTO R.N; LPT Divisions of human nervous system Central Nervous Human System Nervous system Peripheral Autonomic Nervous Nervous System System Nervous system Includes neurons and Peripheral ganglia outside of the Nervous brain and spinal cord System *Either “fight and Somatic *Autonomic Nervous flight” mode or “rest Nervous System System and digest” (involuntary) (voluntary) With Parasympathetic neurotransmitters Sympathetic Nervous System Nervous System norepinephrine and (adrenergic) (cholinergic) acetylcholine DEFINITION OF TERMS Central Nervous System (CNS) Components: Comprises the brain and spinal cord. Function: Acts as the control center of the body, processing information and directing responses. Brain: Responsible for higher-level functions such as thought, memory, emotion, reasoning, and voluntary movement. Spinal cord: Carries signals between the brain and the rest of the body, and controls some reflexes independently of the brain. Main Roles: Sensory integration: Processes sensory information received from the PNS. Motor control: Coordinates voluntary and involuntary motor functions. Cognition: Responsible for reasoning, memory, and learning. DEFINITION OF TERMS Peripheral Nervous System (PNS) Components: Includes all nerves outside the CNS, subdivided into the Somatic and Autonomic Nervous Systems. Function: Connects the CNS to the limbs and organs, relaying information between the body and the CNS. Somatic Nervous System: Controls voluntary muscle movements and relays sensory information to the CNS. Autonomic Nervous System (ANS): Regulates involuntary functions (like heartbeat and digestion), further divided into: Sympathetic nervous system: Prepares the body for "fight or flight" responses. Parasympathetic nervous system: Promotes "rest and digest" functions to conserve energy. Enteric nervous system: Regulates gastrointestinal function. CNS processes information and issues commands, while the PNS transmits sensory data to the CNS and executes motor commands in response to the CNS's directions. DEFINITION OF TERMS Neurons are the fundamental units of the brain and nervous system, responsible for transmitting information throughout the body. They communicate via electrical impulses and chemical signals. Function: Sensory neurons: Transmit sensory information from the body to the CNS. Motor neurons: Carry instructions from the CNS to muscles and glands. Interneurons: Connect neurons within the CNS and facilitate communication between sensory and motor neurons. DEFINITION OF TERMS Ganglia are clusters of neuron cell bodies located outside the Central Nervous System (CNS) in the Peripheral Nervous System (PNS). Function: Ganglia act as relay points, processing and transmitting signals between different parts of the body and the CNS. Sensory ganglia: Receive sensory signals and send them to the CNS. Autonomic ganglia: Part of the autonomic nervous system, controlling involuntary functions like heart rate, digestion, and respiratory rate. They mediate signals between the CNS and peripheral organs. Types of Ganglia: Dorsal Root Ganglia: Contain the cell bodies of sensory neurons that transmit sensory information to the spinal cord. Autonomic Ganglia: Include sympathetic and parasympathetic ganglia, which are involved in regulating involuntary functions in organs and glands. DEFINITION OF TERMS Neurotransmitters are chemical messengers that neurons use to communicate with each other or with muscles and glands. They transmit signals across a synapse (the gap between neurons) to trigger a response in another neuron, muscle, or gland. Synapse A synapse is the tiny gap between two neurons or between a neuron and a target cell (like a muscle or gland). It allows the transmission of chemical or electrical signals. Presynaptic Neuron: The neuron sending the signal. Postsynaptic Neuron: The neuron receiving the signal. Neurotransmitters are released from the presynaptic neuron into the synapse, where they bind to receptors on the postsynaptic neuron to trigger a response. DEFINITION OF TERMS Neurotransmitters are chemical messengers that neurons use to communicate with each other or with muscles and glands. They transmit signals across a synapse (the gap between neurons) to trigger a response in another neuron, muscle, or gland. Synapse A synapse is the tiny gap between two neurons or between a neuron and a target cell (like a muscle or gland). It allows the transmission of chemical or electrical signals. Presynaptic Neuron: The neuron sending the signal. Postsynaptic Neuron: The neuron receiving the signal. Neurotransmitters are released from the presynaptic neuron into the synapse, where they bind to receptors on the postsynaptic neuron to trigger a response. DEFINITION OF TERMS Preganglionic neurons are the nerve fibers that extend from the Central Nervous System (CNS) to a ganglion (a cluster of neuron cell bodies) in the Peripheral Nervous System (PNS). Postganglionic neurons are nerve fibers that extend from the ganglion to the target organ (like a muscle, heart, or gland).Function: They carry the signal from the ganglion to the target tissue or organ, where a response is triggered, such as muscle contraction or secretion of hormones. DEFINITION OF TERMS Receptor sites in the nervous system are specialized proteins located on the surface of neurons (nerve cells) and other cells that respond to neurotransmitters, hormones, or other signaling molecules. These receptors play a crucial role in transmitting signals across the nervous system, allowing it to function effectively. Here are some key receptor types in the nervous system: 1. Cholinergic Receptors Nicotinic Receptors: These are found in both the central nervous system (CNS) and peripheral nervous system (PNS), including skeletal muscles and autonomic ganglia. Nicotinic receptors respond to the neurotransmitter acetylcholine (ACh) and are ionotropic, meaning they directly open ion channels to depolarize the cell. Muscarinic Receptors: Located primarily in the parasympathetic nervous system and various organs. They respond to acetylcholine but work through G-protein-coupled mechanisms (metabotropic receptors), affecting processes like heart rate, digestion, and glandular secretion. DEFINITION OF TERMS 2. Adrenergic Receptors These receptors bind to norepinephrine (noradrenaline) and epinephrine (adrenaline) and are primarily found in the sympathetic nervous system. Alpha (α) Receptors: α1: Mostly located on smooth muscle cells and blood vessels, causing vasoconstriction. α2: Found in presynaptic nerve terminals, where they inhibit the release of norepinephrine. Beta (β) Receptors: β1: Primarily in the heart, increasing heart rate and contractility. β2: Located in smooth muscles of the lungs and other organs, causing bronchodilation and vasodilation. β3: Found in fat cells, involved in lipolysis (fat breakdown). SYMPATHETIC Fight or Flight PARASYMPATHETIC Rest and Digest SYMPATHETIC NERVOUS SYSTEM WHAT ARE THE FUNCTIONS OF SYMPATHETIC NERVOUS SYSTEM? - The sympathetic nacreous system is normally active even at rest; however, it assumes a dominant role when the body becomes stressed in some way. MAJOR RECEPTORS IN THE SYMPATHETIC NERVOUS SYSTEM (ADRENOCEPTORS) - Adrenergic receptors: - Alpha1 (a1) - Alpha2 (a2) - Beta 1 - Beta2 Alpha 1 adrenergic receptors – are present on vascular smooth muscle and myocardial tissue, therefore the stimulation causes vasoconstriction and positive inotropic effect. Alpha 2 adrenergic receptors – the stimulation of this receptors is responsible for sedation, analgecia and sympatholytic effect. Found on vascular smooth muscle and mediate vasopressor effect. Beta 1 – are located in the heart. When it is stimulate it increases the heart rate and contraction (contractility) Beta 2 – are located in the lungs. It causes relaxation of bronchial smooth muscle, leading to widened airways. This is crucial in conditions like asthma, where inhaled β2 agonists (e.g., albuterol) are used to relieve bronchoconstriction. Drugs that act on the sympathetic nervous system are known as adrenergic drugs sympathomimetics. These drugs either mimic the action of the sympathetic neurotransmitters (norepinephrine and epinephrine) or inhibit their action. They can target adrenergic receptors, which include alpha (α) and beta (β) receptors, producing a range of effects. 1. Sympathomimetics (Adrenergic Agonists) These drugs mimic the action of norepinephrine or epinephrine and activate adrenergic receptors. Sympathomimetics can be either direct-acting, indirect-acting, or mixed-acting depending on their mechanism.  Key Receptor Agonists Alpha-1 Agonists: Vasoconstriction, increased blood pressure, pupil dilation (e.g., Phenylephrine). Alpha-2 Agonists: Decrease sympathetic outflow (inhibit norepinephrine release), used in hypertension (e.g., Clonidine). Beta-1 Agonists: Increase heart rate and force of contraction (e.g., Dobutamine for heart failure). Beta-2 Agonists: Bronchodilation and relaxation of smooth muscles (e.g., Albuterol for asthma). Other Names: Adrenergic agonists, catecholamines (for endogenous substances like epinephrine), sympathomimetic amines. 2. Sympatholytics (Adrenergic Antagonists or Adrenergic Blockers) Sympatholytics are drugs that block the effects of the sympathetic nervous system. They bind to adrenergic receptors without activating them, thus preventing norepinephrine or epinephrine from exerting their effects.  Key Receptor Antagonists Alpha-1 Blockers: Cause vasodilation by blocking vasoconstriction, lowering blood pressure (e.g., Prazosin). Alpha-2 Blockers: Rarely used because of their role in inhibiting norepinephrine release. Beta-1 Blockers: Reduce heart rate and force of contraction, used in heart conditions (e.g., Atenolol). Beta-2 Blockers: Can cause bronchoconstriction, so non-selective beta blockers like Propranolol are used with caution in asthma patients. Other Names: Adrenergic blockers, antiadrenergics, sympatholytic agents.  3. Alpha-Adrenergic Drugs Drugs that specifically target alpha receptors (α1 or α2) and affect vascular smooth muscles and other areas. Alpha-1 Agonists Phenylephrine: A potent vasoconstrictor used to increase blood pressure during hypotensive states and as a decongestant. Midodrine: Used for orthostatic hypotension (low blood pressure when standing). Alpha-2 Agonists Clonidine: Works by decreasing sympathetic outflow, often used in the treatment of hypertension and withdrawal symptoms. Methyldopa: Another alpha-2 agonist used for hypertension, especially in pregnancy. Alpha Blockers (Antagonists) Prazosin, Doxazosin: Block α1 receptors, causing vasodilation and used for hypertension. Phentolamine: A non-selective alpha antagonist used in pheochromocytoma (tumor of the adrenal gland).  4. Beta-Adrenergic Drugs Drugs that specifically target beta receptors (β1, β2, or β3) and primarily affect heart, lungs, and metabolic functions. Beta-1 Agonists Dobutamine: Increases cardiac output by stimulating β1 receptors in the heart, used in heart failure. Beta-2 Agonists Albuterol, Salmeterol: Used as bronchodilators in asthma and chronic obstructive pulmonary disease (COPD) by stimulating β2 receptors in the lungs. Beta Blockers (Antagonists) Propranolol: A non-selective beta blocker that affects both β1 (heart) and β2 (lungs). Used in hypertension, angina, and anxiety. Atenolol, Metoprolol: Cardioselective beta blockers (β1 selective) used in the treatment of hypertension, arrhythmias, and heart disease. SUMMARY PARASYMPATHETIC NERVOUS SYSTEM  What are the actions of parasympathetic nervous system? - The parasympathetic nervous system is predominant under tranquil condition. It slows heart rate, lowers blood pressure, increases intestinal motility, constricts pupils, empties the urinary. ✔ Also known as the REST and DIGEST SYSTEM WHAT RECEPTORS DOES THE PARASYMPATHETIC NERVOUS SYSTEM ACTS ON? - CHOLINERGIC RECEPTORS - Muscarinic and nicotinic Muscarinic receptors – are receptors involved in peristalsis, micturition, bronchoconstriction and several parasympathetic reactions. - Are acetylcholine receptors are activated when they bind to acetylcholine. - Muscarinic receptors are involved in the transduction of cholinergic signals in the central nervous system, autonomic ganglia, smooth muscles, and other parasympathetic end organs. 5 main subtypes of MUSCARINIC RECEPTORS M1 M2 M3 M4 M5 THEY ARE ENCLOSED WITH SEPRATE GENES AND LOCALIZED TO DIFFERENT SUB-TYPES M1 – is found in the cerebral cortex, gastric and salivary glands M2- is found in smooth muscles and cardiac tissue M3 - found also ins smooth muscles, gastric and salivary glands M4 and M5 – hypocampus and substantia nigra WHAT ARE NICOTINIC RECEPTORS? - Nicotinic acetylcholine receptors (nACHRs) – are receptor polypeptides that responds to the NT acetylcholine - Nicotinic receptors also respond to drugs such as agonist nicotine. They are found in the central and peripheral nervous system and other body tissues. - The key functions of nicotinic receptors is to trigger rapid neutral and neuromuscular transmission. TYPES OF NICOTINIC RECEPTORS N1 – MUSCLE NICOTINIC RECEPTOR is at the neuromuscular junction on muscle cells generating voluntary movement which causes contraction of skeletal muscles. N2 – NEURAL NICOTINIC RECEPTOR – responsive to acetylcholine, the key function is to trigger rapid neural and neuromuscular transmission. THE ACETYLCHOLINE What are the physiological functions of acetylcholine? - Affects almost every system of the body What are the clinical indications of acetylcholine? - Used to achieve miosis during ophthalmic surgery. In general, it is rarely used because it has a widespread effect and is rapidly hydrolyzed by acetylcholinesterase. Drugs that act on Parasympathetic System OTHER NAME Cholinergic drugs Parasympathomimetics. These drugs either mimic the action of the neurotransmitter acetylcholine (ACh) or block its action, depending on the desired effect. The parasympathetic nervous system is primarily responsible for the "rest and digest" functions, and drugs that act on this system target cholinergic receptors: muscarinic and nicotinic receptors. 1. Parasympathomimetics (Cholinergic Agonists) These drugs mimic the action of acetylcholine and stimulate cholinergic receptors, resulting in parasympathetic effects such as reduced heart rate, increased glandular secretion, and smooth muscle contraction. DIRECT ACTING AGONISTS SIX EXAMPLES OF DIRECT ACTING AGONISTS 1. Acetylcholine (prototype) 2. Bethanecol 3. Carbachol 4. Pilocarpine 5. Methacholine 6. Nicotine BETHANICOL What type of chemical compound is bethanicol? - A carbamic acid ester What receptor does it work on? - Bethanicol works primarily in muscarinic receptors, but it has some mild nicotinic properties What are the therapeutic uses of BETHANICOL? - Bethanicol increases intestinal motility, especially after surgery. - This drug stimulates detrusor muscle of the bladder - It is also used to treat urinary retention. BBB – BETHANICOL stimulates BLADDER and BOWEL What are the adverse effects of bethanecol administration? The adverse effects are those result form generalized cholinergic stimulation (DUMBELS) CARBACHOL What type of compound is carbachol? - A carbamic ester similar to bethanecol What is its clinical use? - The drug rarely used today - Used for glaucoma and to stimulate miosis during ophthalmic surgery What receptors that carbachol work on? - Both muscarinic and nicotinic receptors What are the adverse effects of carbachol? - Those result from excessive cholinergic stimulation PILOCARPINE What type of compound is pilocarpine? - An alkaloid What are pilocarpine’s physiological functions? - Causes of miosis and contraction of the ciliary muscle (accommodation) - Decreases heart rate - Causes bronchial smooth muscle contraction - Increases secretions from salivary, lacrimal and sweat glands The state of clinical use of pilocarpine: - Good for stimulating miosis and opening the trabecular meshwork around the canal of schlemn. Used to treat glaucoma How it is administered? - Usually given topically What is the adverse effect of pilocarpine? - Able to enter the brain and cause CNS disturbances such as hallucinations and convulsions, along with generalized cholinergic stimulation METHACOLINE What is methacholine used for? - Used in the diagnosis of asthma and bronchial hyper-activity what receptor doe it stimulates? - Muscarinic receptors What are the adverse effects? - Generalized cholinergic stimulation  6 examples of indirect-acting cholinergic agonists 1. Isoflurophate 2. Echothiophate 3. Parathion 4. Edrophomium 5. Physostigmine 6. Neostigmine How do they work? - Inhibit the enzyme acetylcholinesterase, which is responsible for hydrolysis of acetylcholine. Which receptors do the act on? - Because they increase the synaptic concentration of acetylcholine, stimulate both nicotinic and muscarinic receptors ISOFLUROPHATE, ECHOTHIOPHATE and PARATHION - ORGANOPHOSPHATE bind covalently to acetylcholinesterase and can permanently inactivate the enzyme. The effects can last long What are these drugs used for the past? - Organophasphates were used in wars as nerve gases. They produce immense stimulation at cholinoreceptors through the body, causing respiratory muscle paralysis and convulsions. What are these drugs used for today? - Isoflurophate and echothiophate are used occasionally for accommodate esotropia What drug is used to treat organophosphate poisoning? - ATROPINE IS USED ALONG WITH gastric lavage and charcoal What are the toxicities of organophosphates? - Excessive cholinergic stimulation PHYSOSTIGMINE WHEN PHYSOSTIGMINE ADMINISTERED? - For glaucoma - Overdose of atropine, phenothiazines, tricyclic anti-depressants - Intestinal bowel atony - Accommodative estropia What are the adverse effects of physostigmine? - Convulsions - Muscle paralysis secondary to over stimulation - Cataracts - Excessive cholinergic stimulation NEOSTIGMINE (PROSTIGMINE) Does this drug enter the CNS? - No, because it is polar quaternary carbamate WHAT ARE THE THERAPEUTIC USES? - Treatment of myasthenia gravis - Treatment of urinary retention and paralytic ileus What are the adverse effects of NEOSTIGMINE? Excessive cholinergic stimulation. CHOLINERGIC ANTAGONISTS WHAT ARE CHOLINERGIC ANTAGONISTS? - Drugs that bind to cholinergic receptors (muscarinic and nicotinic) but do not trigger the usual intracellular response. 2. Parasympatholytics (Anticholinergics) Also known as cholinergic antagonists, these drugs block the effects of acetylcholine at muscarinic receptors, inhibiting the parasympathetic system. The result is an increase in heart rate, bronchodilation, reduced secretion of glands, and relaxation of smooth muscles. Muscarinic Antagonists Atropine: Used in emergency settings to treat bradycardia (slow heart rate) and as an antidote for organophosphate poisoning. Ipratropium and Tiotropium: Used for bronchodilation in the treatment of COPD and asthma. Scopolamine: Used to treat motion sickness by reducing nausea and vomiting. Oxybutynin and Tolterodine: Used to treat overactive bladder by relaxing the bladder muscles and reducing urinary frequency. Nicotinic Antagonists Neuromuscular blockers: Drugs like Pancuronium, Rocuronium, and Vecuronium block nicotinic receptors at the neuromuscular junction, causing muscle relaxation during surgery or intubation. Ganglionic blockers: Drugs like Mecamylamine block nicotinic receptors in the autonomic ganglia, though these are rarely used today due to severe side effects. Other Names: Anticholinergic drugs, muscarinic blockers, parasympatholytics, cholinergic antagonists. 3. Reversible vs. Irreversible Anticholinesterases Reversible Anticholinesterases: These drugs, such as Neostigmine, Pyridostigmine, and Donepezil, bind temporarily to acetylcholinesterase, allowing them to be used for chronic conditions like myasthenia gravis and Alzheimer's disease. Irreversible Anticholinesterases: These drugs form permanent bonds with acetylcholinesterase, leading to long-lasting effects. They include organophosphates and nerve gases like Sarin. Atropine is often used as an antidote for poisoning by these agents. 1. Sympathetic Nervous System (Fight or Flight) – "A Bee Pounces Dangerously, Be Cautious" This mnemonic helps remember the adrenergic receptors and the drugs acting on them. A: Alpha-1 (Vasoconstriction) – Example: Phenylephrine B: Beta-1 (Heart) – Example: Dobutamine P: Phenylephrine (Alpha-1 Agonist) D: Dopamine (Beta-1 & Alpha-1 Agonist) B: Beta-2 (Bronchodilation) – Example: Albuterol C: Clonidine (Alpha-2 Agonist) Parasympathetic Nervous System (Rest and Digest) – "SLUDGEM" This mnemonic helps recall the effects of parasympathetic stimulation or cholinergic drugs. S: Salivation L: Lacrimation (tears) U: Urination D: Defecation G: Gastrointestinal upset E: Emesis (vomiting) M: Miosis (pupil constriction Parasympathetic Nervous System (Rest and Digest) – "SLUDGEM" This mnemonic helps recall the effects of parasympathetic stimulation or cholinergic drugs. S: Salivation L: Lacrimation (tears) U: Urination D: Defecation G: Gastrointestinal upset E: Emesis (vomiting) M: Miosis (pupil constriction 3. Anticholinergic Side Effects – "Can't See, Can't Pee, Can't Spit, Can't Sh*t" This common mnemonic helps remember the effects of anticholinergic drugs: Can't See: Blurred vision (due to pupil dilation) Can't Pee: Urinary retention Can't Spit: Dry mouth Can't Sh*t: Constipation 3. Anticholinergic Side Effects – "Can't See, Can't Pee, Can't Spit, Can't Sh*t" This common mnemonic helps remember the effects of anticholinergic drugs: Can't See: Blurred vision (due to pupil dilation) Can't Pee: Urinary retention Can't Spit: Dry mouth Can't Sh*t: Constipation 4. Beta-Blocker Types – "BABY AIM" This mnemonic helps differentiate between cardioselective and non-selective beta-blockers: B: Bisoprolol (Cardioselective β1 blocker) A: Atenolol (Cardioselective β1 blocker) B: Betaxolol (Cardioselective β1 blocker) Y: (Yes) – Indicates cardioselectivity A: Acebutolol (Non-selective β blocker) I: Inderal (Propranolol) (Non-selective β blocker) M: Metoprolol (Cardioselective β1 blocker) 5. Cholinergic Drugs (Direct-Acting) – "BP" This helps remember two important direct-acting cholinergic drugs: B: Bethanechol (used for urinary retention) P: Pilocarpine (used for glaucoma and dry mouth) 6. Anticholinergic Drugs – "ATROPINE" This mnemonic helps recall the most common anticholinergic drug effects: A: Atropine (main drug) T: Tachycardia R: Reduced secretions (dry mouth, reduced sweating) O: Obstruction of the bladder P: Pupil dilation (Mydriasis) I: Increased heart rate N: No sweating E: Excitability or confusion (especially in elderly patients) ATROPINE as cholinergic antagonist What family of compounds does atropine belong? - Atropine comes from the plant Atropa belladonna and is known as belladonna alkaloid What is the significance of plant’s name? - Belladonna in latin meaning “pretty lady”. During the Roman Era, the plant was used to dilate women’s pupil which was considered to be attractive. What is atropine mechanism of action? - It causes reversible, nonselective blockage of muscarinic receptors. What agent can be used to counteract the effects of atropine? - High concentrations of acetylcholine or an equivalent muscarinic agent. What are the pharmacologic actions of atropine? 1. CNS – toxic doses can cause restlessness hallucinations and delusions 2. CARDIOVASUCLAR SYSTEM – atropine blocks muscarinic receptors of the heart and thus induces tachycardia 3. GASTROINTESTINAL – reduces salivary glands secretion and GI motility 4. PULMONARY SYSTEM – reduces bronchial secretions and stimulates bronchodilation 5. URINARY SYSTEM – blocks muscarinic receptors in the bladder wall, relaxes bladder wall 6. EYE – causes the paralysis of the sphincter muscle of the iris and ciliary muscles of the lens resulting mydriasis (dilation) 7. SWEAT GLANDS – SUPRESES SWEATING. REMEMBER THAT THE ACTIONS OF ATROPINE THAT BLOCKED CHOLONERGIC RECEPTORS RESULT IN AN UNOPPOSED SYMPATHETIC RESPONSE TOXIC EFFECTS OF ATROPINE: 1. DRY MOUTH 2. INHIBITION OF SWEATING 3. TACHYCARDIA 4. BLURRING OF VISISON 5. HALLUCINATIONS AND DELIRIUM 7. Beta-Blocker Side Effects – "5 B's" These are key side effects of beta-blockers: Bradycardia (slow heart rate) Blood pressure reduction (hypotension) Bronchoconstriction (caution in asthma) Blood sugar masking (hypoglycemia unawareness in diabetics) Block AV node (can cause heart block)