Muscarinic-receptor antagonists produce cycloplegia by blocking parasympathetic tone, leading to paralysis of the ciliary muscle and loss of accommodation. These drugs produce mydriasis by blocking parasympathetic tone to the iris circular constrictor muscle. Unopposed sympathetic stimulation of the radial muscle results in dilation of the pupil. Cardiovascular system a.
Muscarinic-receptor antagonists increase heart rate due to cholinergic blockade at the SA node. These drugs dilate blood vessels in facial blush area atropine flush , which is not related to the antagonist action.
GI tract a. Muscarinic-receptor antagonists decrease salivation. These drugs reduce peristalsis, resulting in prolonged gastric emptying and intestinal transit.
They also reduce gastric acid secretion. Other effects a. Muscarinic-receptor antagonists produce some bronchodilation and decrease mucus secretion. These drugs relax the ureters and bladder in the urinary tract and constrict the uri- nary sphincter. Tertiary amines can produce restlessness, headache, excitement, hallucinations, and delirium. These drugs produce anhidrosis and dry skin because of the inhibition of sympathetic cholinergic innervation of the sweat glands. Pharmacologic properties 1.
Atropine and scopolamine have relatively long durations of action. Therapeutic uses Table 2. Eye a. Shorter-acting muscarinic-receptor antagonists e. Longer-acting muscarinic-receptor antagonists such as homatropine are generally preferred as adjuncts to phenylephrine to prevent synechia formation in anterior uve- itis and iritis.
Cardiovascular system uses are limited and include the administration of these drugs as a treatment for acute myocardial infarction with accompanying bradycardia and hypoten- sion or arrhythmias e. Urinary tract uses of atropine and other muscarinic-receptor antagonists include the administration of these drugs for symptomatic treatment of urinary urgency in inflam- matory bladder disorder.
Oxybutynin Ditropan and trospium SpasMex , and the more selective M3-receptor antagonists darifenecin Enablex , solifenacin Vesicare , tolterodine Detrol , and fesoterodine Toviaz , are additional agents in this class used to treat certain urinary tract disorders. Central nervous system a.
Antimuscarinic drugs, benztropine, biperiden, trihexyphenidyl, and others, are used as adjunct to levodopa therapy for some patients with Parkinson disease see Chapter 5. Scopolamine used orally, intravenously, or transdermally prevents motion sick- ness by blocking muscarinic receptors in the vestibular system and in the CNS see Chapter 8.
Scopolamine also has additional amnestic and sedative properties. Respiratory system a. Atropine and scopolamine can be used to suppress bronchiolar secretions during sur- gical and spinal anesthesia and to prevent the muscarinic effects of AChE inhibitors used to reverse muscle paralysis at the end of surgery.
Ipratropium Atrovent and tiotropium Spiriva are used as an inhalant to treat reac- tive airway disease such as asthma and chronic obstructive pulmonary disease COPD. Other uses: Tertiary agents such as atropine are used to block peripheral and CNS effects due to cholinergic excess, especially those caused by poisoning with AChE inhibitor- containing insecticides and muscarine-containing mushrooms. Adverse effects and contraindications 1. Symptomatic treatment rather than use of physostigmine is recommended.
Neostigmine is used to treat poisoning with quaternary muscarinic-receptor antagonists. Contraindications relative are glaucoma, particularly angle-closure glaucoma, GI and urinary tract obstruction e. Drug interactions of muscarinic-receptor antagonists include the production of additive effects when administered with other drugs with muscarinic-receptor antagonist activity certain antidepressants, antipsychotics, and antihistamines.
Mechanism and therapeutic uses see Table 2. Ganglion-blocking drugs a. Trimethaphan Arfonad and mecamylamine Inversine inhibit the effect of ACh at nicotinic receptors by acting competitively nondepolarizing blockade at both sym- pathetic and parasympathetic autonomic ganglia.
Because of a lack of selectivity and numerous adverse effects, they are used rarely in the clinical setting hypertensive emergencies. Classification and structure 1. Neuromuscular junction-blocking drugs see Table 2.
Classified as either nondepolarizing or depolarizing types, neuromuscular junction- blocking drugs cause neuromuscular paralysis.
They are structurally similar to ACh. These drugs contain one or two quaternary nitrogens that limit their entry into the CNS. Spasmolytic drugs act to reduce abnormal muscle tone without paralysis. These drugs increase or mimic the activity of f-aminobutyric acid GABA in the spinal cord and brain or interfere with the release of calcium in skeletal muscle. Nondepolarizing agents 1. Mechanism a. Nondepolarizing agents competitively inhibit the effect of ACh at the postjunctional membrane nicotinic receptor of the neuromuscular junction.
There is some prejunc- tional inhibition of ACh release. These agents prevent depolarization of the muscle and propagation of the action potential. Pharmacologic properties a. Nondepolarizing agents are administered parenterally and are generally used for long-term motor paralysis. Paralysis and muscle relaxation occur within 1—5 minutes.
Nondepolarizing agents have durations of action that range from 20 to 90 minutes. Most nondepolarizing agents are metabolized by the liver or are excreted unchanged. The duration of action may be prolonged by hepatic or renal disease. Intermediate-acting steroid muscle relaxing agents e. Specific drugs Table 2. Tubocurarine prototype is seldom used clinically at this time.
Metocurine Metubine is a derivative of tubocurarine. It has the same properties, but with less histamine release and thus less hypotension and bronchoconstriction. Atracurium Tracrium and Cisatracurium Nimbex 1 Atracurium causes some histamine release. It is inactivated spontaneously in plasma by nonenzymatic hydrolysis that is delayed by acidosis. Its duration of action is reduced by hyperventilation-induced respiratory alkalosis. Laudanosine, a breakdown product of atracurium, may accumulate to cause seizures.
It has replaced atracurium use in clinical practice. Mivacurium Mivacron is a short-acting 10—20 min , which is rapidly hydrolyzed by plasma cholinesterase, has a slow onset of action relative to succinylcholine, and produces moderate histamine release at high doses. Vecuronium Norcuron , Rocuronium Zemuron , and Pancuronium Pavulon 1 All are steroid derivatives with little, histaminic or ganglion-blocking activity.
They are metabolized primarily by the liver. It is excreted by the kidney with only minimal hepatic metabolism. Nondepolarizing agents are used during surgery as adjuncts to general anesthetics to induce muscle paralysis and muscle relaxation. The order of muscle paralysis is small, rapidly contracting muscles e. Recovery of muscle function is in reverse order, and respiration often must be assisted. These agents are also used for muscle paralysis in patients when it is critical to control ventilation, e.
Reversal of nondepolarizing drug blockade: AChE inhibitors, such as neostigmine, are administered for pharmacologic antagonism to reverse residual postsurgical muscarinic receptor blockade and avoid inadvertent hypoxia or apnea.
Adverse effects and contraindications Table 2. Cardiovascular system. Tubocurarine, atacurium, mivacurium, pancuronium, and metocurine may produce cardiovascular effects such as hypotension or increased heart rate due to histamine release, ganglionic-blocking activity, or vagolytic activity. Respiratory system: Some nondepolarizing agents can produce bronchospasm in sen- sitive individuals due to histamine release.
Agents that release histamine are contra- indicated for asthmatic patients and patients with a history of anaphylactic reactions. Drug interactions a. General inhalation anesthetics, particularly isoflurane, increase the neuromuscular blocking action of nondepolarizing agents.
The dose of the neuromuscular junction- blocking drug may have to be reduced. Aminoglycoside antibiotics, among others, inhibit prejunctional ACh release and potentiate the effect of nondepolarizing and depolarizing neuromuscular junction- blocking drugs. Depolarizing agents Table 2. Mechanism of action a. Succinylcholine is a nicotinic receptor agonist that acts at the motor endplate of the neuromuscular junction to produce persistent stimulation and depolarization of the muscle, thus preventing stimulation of contraction by ACh.
After a single IV injection and depolarization of the muscle, there are initial muscle contractions or fasciculations in the first 30—60 s that may be masked by general anes- thetics. Because succinylcholine is metabolized more slowly than ACh at the neuro- muscular junction, the muscle cells remain depolarized depolarizing or phase I block and unresponsive to further stimulation, resulting in a flaccid paralysis 5—10 min.
With continuous long-term exposure 45—60 min , the muscle cells repolarize. However, they cannot depolarize again while succinylcholine is present and, there- fore, remain unresponsive to ACh desensitizing or phase II block.
AChE inhibition will enhance the initial phase I block by succinylcholine but can reverse phase II block. Succinylcholine has a rapid onset and short duration of action. Action is rapidly ter- minated 5—10 min by hydrolysis by plasma and liver cholinesterase. Reduced plasma cholinesterase synthesis in end-stage hepatic disease or reduced activity following the use of irreversible AChE inhibitors may increase the duration of action.
Therapeutic uses of succinylcholine include the administration of the drug as an adjunct in surgical anesthesia to obtain muscle relaxation while using lower levels of general anes- thetic, to induce brief paralysis in short surgical procedures, and to facilitate intubation. Adverse effects a. Postoperative muscle pain at higher doses.
Hyperkalemia 1 Hyperkalemia results from loss of tissue potassium during depolarization. Malignant hyperthermia 1 Malignant hyperthermia is a rare but often fatal complication in susceptible patients that results from a rapid increase in muscle metabolism.
Mechanical ventilation is necessary. Bradycardia from direct muscarinic cholinoceptor stimulation is prevented by atropine. Increased intraocular pressure may result from extraocular muscle contractions; use of succinylcholine may be contraindicated for penetrating eye injuries. Succinylcholine produces increased intragastric pressure, which may result in fas- ciculations of abdominal muscles and a danger of aspiration.
Spasmolytic drugs 1. These muscle relaxants reduce increased muscle tone associated with a variety of nervous system disorders e. Selected drugs a. Dantrolene Dantrium 1 Dantrolene acts directly on muscle to reduce skeletal muscle contractions. Long-term use can result in hepatotoxicity that may be fatal.
Hepatic function should be monitored during treatment. It is a GABAB-receptor agonist that hyperpolarizes neurons to inhibit synaptic transmission in the spinal cord. Tizandine Zanaflex 1 Tizandine is an alpha2 adrenoceptor agonist analog of clonidine that reduces muscle spasm with less muscle weakness than baclofen, dantrolene, and diazepam. Botulinum toxin Botox 1 Botulinum toxin acts by inhibiting the release of ACh from motor nerve terminals.
It is also used for cosmetic reduction of facial wrinkles. Action and chemical structure 1. These drugs act either directly or indirectly to activate postjunctional and prejunctional adrenoceptors to mimic the effects of endogenous catecholamines such as norepinephrine and epinephrine. Their actions can generally be predicted from the type and location of the receptors with which they interact and whether or not they cross the blood—brain barrier to enter the CNS.
Indirectly acting agents act within nerve endings to increase the release of stored catecholamines, act at the prejunctional membrane to block the reuptake of catechol- amines that have been released from nerve endings, or act enzymatically to prevent their biotransformation.
In normotensive patients less effect in those with hypoten- sion , the increased blood pressure may invoke a reflex baroreceptor vagal discharge and a slowing of the heart, with or without an accompanying change in cardiac output.
Eye see Table 2. These drugs also increase the outflow of aqueous humor from the eye. Respiratory system effects include a2-receptor agonist-induced relaxation of bronchial smooth muscle and decreased airway resistance. Metabolic and endocrine effects a. Specific sympathomimetic drugs are selected for use depending on the duration of action, route of administration, and also the specific effect on a particular tissue, which in turn depends on the tissue population of adrenoceptor subtypes.
Epinephrine and norepinephrine a. Epinephrine and norepinephrine are poorly absorbed from the GI tract and do not enter the CNS to any appreciable extent. Absorption of epinephrine from subcutane- ous sites is slow because of local vasoconstriction.
Nebulized and inhaled solutions and topical preparations of epinephrine are available. Epinephrine and norepineph- rine are most often administered IV with caution to avoid cardiac arrhythmias or local tissue necrosis. Metabolites are excreted by the kidney.
Epinephrine and norepinephrine actions at neuroeffector junctions are terminated primarily by simple diffusion away from the receptor site and by active uptake into sympathetic nerve terminals and subsequent active transport into storage vesicles.
The mean arterial pressure may increase slightly, decrease, or remain unchanged, depending on the balance of effects on systolic and diastolic pressure. Dopamine Intropin a. Dopamine activates peripheral a 1-adrenoceptors to increase heart rate and contractility.
Dopamine activates prejunctional and postjunctional dopamine D1-receptors in the renal, coronary, and splanchnic vessels to reduce arterial resistance and increase blood flow. Prejunctionally, dopamine inhibits norepinephrine release. At low doses, dopamine has a positive inotropic effect and increases systolic pressure, with little effect on diastolic pressure or mean blood pressure.
Terbutaline Brethine, Bricanyl , albuterol Proventil, Ventolin , metaproterenol Alupent , pirbuterol Maxair , salmeterol Serevent , and formoterol Foradil are examples of drugs with more selective a2-receptor agonists that relax bronchial smooth muscle with fewer cardiac effects and longer duration of action than epinephrine.
Selectivity is lost at high concentrations. It dilates bronchial smooth muscle. Metaraminol also has indirect activity; it is taken up and released at sympathetic nerve endings, where it acts as a false neurotransmitter. It also releases epinephrine. It lowers blood pressure by reducing peripheral vascular resistance. Other adrenoceptor agonists a. Ephedrine 1 Ephedrine acts indirectly to release norepinephrine from nerve terminals and has some direct action on adrenoceptors.
Amphetamine, dextroamphetamine Dexedrine , methamphetamine Desoxyn , modafinil Provigil , methylphenidate Ritalin , and hydroxyamphetamine Paremyd see Chapter 5 1 These drugs produce effects similar to those of ephedrine, with indirect and some direct activity. The use of sympathomimetic agents in most forms of shock is controversial and should be avoided.
Further vasoconstriction may be harmful. Dobutamine is used to treat congestive heart failure. Methyldopa is used to treat hypertension. Fenoldopam Corlopam is a selective dopamine D1-receptor agonist used to treat severe hypertension. Isoproterenol and epinephrine have been used for temporary emergency treatment of cardiac arrest and heart block because they increase ventricular automaticity and rate and increase AV conduction.
Epinephrine is commonly used in combination with local anesthetics , dur- ing infiltration block to reduce blood flow. Phenylephrine has also been used. Epinephrine is used during spinal anesthesia to maintain blood pressure, as is phenyl- ephrine, and topically to reduce superficial bleeding.
Long-term use may result in ischemia and rebound hyperemia, with develop- ment of chronic rhinitis and congestion. They are also used for treatment of COPD. For chronic asthma, these drugs, including sal- meterol and formoterol with long durations of action, should be used in combination with steroids.
Epinephrine is administered IM to treat acute bronchospasm and also bronchospasm, congestion, angioedema, and cardiovascular collapse of anaphylaxis. Phenylephrine facilitates examination of the retina because of its mydriatic effect. It is also used for minor allergic hyperemia of the conjunctiva.
CNS a. Amphetamine and related analogs e. Hydroxyamphetamine and phenylephrine are used for the diagnosis of Horner syndrome. Other uses include tizaididine Zanaflex as a muscle relaxant. Adverse effects and toxicity 1. The adverse effects of sympathomimetic drugs are generally extensions of their pharma- cologic activity. Overdose with epinephrine or other pressor agents may result in severe hypertension, with possible cerebral hemorrhage, pulmonary edema, and cardiac arrhythmia.
Milder effects include headache, dizziness, and tremor. Increased cardiac workload may result in angina or myocardial infarction in patients with coronary insufficiency. Phenylephrine should not be used to treat closed-angle glaucoma before iridectomy as it may cause increased intraocular pressure. Drug abuse may occur with amphetamine and amphetamine-like drugs.
Tricyclic antidepressants block catecholamine reuptake and may potentiate the effects of norepinephrine and epinephrine. Pharmacologic effects a.
Drug Receptor Features Major Uses. It reduces peripheral resistance and decreas- es blood pressure. Others include terazosin Hytrin , doxazosin Cardura , tamsulosin Flomax , silo- dosin Rapaflo , and alfuzosin Uroxatral. Pheochromocytoma 1 Pheochromocytoma is a tumor of the adrenal medulla that secretes excessive amounts of catecholamines.
Symptoms include hypertension, tachycardia, and arrhythmias. Prazosin and others in its class, and labetalol, are used with other drugs to treat essen- tial hypertension.
Major adverse effects of phentolamine and phenoxybenxamine include postural hypo- tension and tachycardia. Prazosin, terazosin, and doxazosin produce postural hypotension and bradycardia on initial administration; these drugs produce no significant tachycardia. Adverse effects of labetalol include postural hypotension and GI disturbances. Bradycardia occurs with overdose. However, long-term adminis- tration results in decreased peripheral resistance in patients with hypertension.
Timolol Blocadren , levobunolol Betagan , nadolol Corgard , and sotalol Betapace 1 These drugs are nonselective a-receptor antagonists. Metipranolol OptiPranolol is also used to treat glaucoma. BRS Pharmacology 6th Edition Pdf Free Download is designed for medical students, dental students, and other students preparing to enter the health care professions. It is intended primarily to help students prepare for licensing examinations, such as the USMLE, but can be used for course review or as a supplementary text.
This book presents succint descriptions of how drugs act on the major body systems, providing readers with vital information without overloading them with extraneous details. Please bear in mind that we do not own copyrights to these books. We highly encourage our visitors to purchase original books from the respected publishers. If someone with copyrights wants us to remove this content, please contact us immediately. If you feel that we have violated your copyrights, then please contact us immediately.
Excretion of Drugs 15 VII. Pharmacokinetics 16 Review Test Parasympathomimetic Drugs 32 III. Muscarinic-Receptor Antagonists 37 IV.
Ganglion-Blocking Drugs 39 V. Skeletal Muscle Relaxants 39 VI. Sympathomimetic Drugs 43 VII. Adrenergic Receptor Antagonists 48 Review Test Drugs Acting on the Renal System 61 I. Diuretics 61 II. Drugs Acting on the Cardiovasc ular System 73 I. Antiarrhythmic Drugs 79 III. Antianginal Agents 85 IV.
Antihypertensive Drugs 87 V. Sedative—Hypnotic Drugs II. Antidepressant Drugs IV. Drugs Acting on Myeloid Cells Ill. Antiemetics II. Drugs Used to Manage Obesity Ill. Introduction to Pulmonary Disorders II. Hormone Receptors II. Tue Hypothalamus Ill.
Tue Anterior Pituitary IV. Tue Posterior Pituitary V. Tue Calcium Homeostatic System X. Retinoic Acid and Derivatives Review Test Infectious Disease Therapy II.
Antimycobacterial Agents VII. Antiparasitic Drugs IX.
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