Module 2 - Autonomic & Somatic Nervous System Flashcards
What drugs should people with glaucoma be careful with?
- The side effects of many drugs (e.g., anticholinergics, hypotensive effects, sedatives) are often more dangerous in the elderly and may exacerbate glaucoma
- Anticholinergics cause paralysis of the iris sphincter which causes increased intraocular pressure, thus are contraindicated in glaucoma
What is the MOA of anticholinergic drugs?
- These drugs competitively antagonize the effects of ACh (acetylcholine) and other muscarinic agonists at cholinergic postganglionic (muscarinic) sites found in the heart, salivary glands & smooth muscle of the GI and GU tract
- They simply bind to and block the receptor site.
- The main actions of all members of this class of drug are qualitatively similar to atropine
What are the systemic effects of anticholinergic drugs (sympathetic)?
(Ex: CNS, Eyes, Heart, Lungs, GI, GU)
- CNS:Scopolamine has marked CNS depressant effects. Elderly patients may be particularly sensitive. In contrast, toxic doses of atropine cause central stimulation.
- Eye: Atropinic drugs block the response of the sphincter muscle of the iris and ciliary muscle of the lens to cholinergic stimulation, resulting in mydriasis (dilation of the pupil) and cycloplegia (loss of focus). Consequently, patients may complain of photophobia and blurring of near objects.
- Heart: The atria of the heart are richly innervated by parasympathetic nerve fibers, and the SA node is very sensitive to muscarinic receptor blockade. The average clinical dose of atropine (0.4 mg) may transiently decrease heart rate due to a central vagal stimulation prior to onset of the peripheral block. Large doses cause progressively increasing tachycardia by blocking vagal effect at the SA node pacemaker (average increase in heart rate: 35-40 beats/minute). Atropine may fail to accelerate the heart in infants and elderly.
- GI: It inhibits salivary secretion. However, gastric secretion is not greatly altered by conventional doses of antimuscarinics. Effective doses invariably cause dry mouth & can cause constipation
- Sweat glands: Small doses of atropine inhibit the activity of sweat glands.
- Lungs: Atropine decreases secretions in the nose, mouth, pharynx, and bronchi. It also blocks vagal-induced bronchoconstriction.
- GU: Muscarinic antagonists decrease normal tone and amplitude of contraction of the ureter and bladder.
What are the indications and uses for anticholinergic drugs?
- Preoperative medication: Atropine or scopolamine is administered prior to induction of anesthesia to protect heart from vagal reflexes and prevent excessive respiratory secretions. Patients with glaucoma require special consideration
- Sedation: Scopolamine is 100 times more sedative than atropine in depressing the ascending reticuloarousal system (ARAS). Scopolamine can also cause amnesia. Occasionally scopolamine may cause restlessness or somnolence, particularly in the elderly.
- Antisialagogue (antisaliva) effect: Scopolamine is 3 times more potent as atropine. In equivalent antisialagogue doses, scopolamine is less likely than atropine to produce heart rate changes. Glycopyrrolate is twice as potent as atropine in antisialagogue effect and has a longer duration of action.
- Bradycardia: Atropine is used to reverse severe sinus bradycardia in adults and neonates (0.01-0.03 mg/kg IV), especially when due to parasympathetic influence (e.g., digoxin, beta blockers).
- Bronchoconstriction: Anticholinergic drugs can relax bronchial smooth muscles by blocking the constrictor effects of the vagus nerves. The anticholinergic drugs are more effective bronchodilators when administered by aerosol inhalation (e.g., ipratropium [Atrovent], a quaternary ammonium compound). In spite of their bronchodilatory effect, systemic anticholinergics are usually contraindicated in asthmatic patients because of drying of secretions and increased risk of mucus plugs
- Biliary & Ureteral Smooth Muscle Spasm: Atropine decreases the tone of the smooth muscle of the biliary tract & ureter and produces relaxation.
- Overactive Bladder: Oxybutynin is useful in treating incontinence & bladder spasms
- Produce Mydriasis & Cycloplegia: tropicamide is useful in dilating eyes for eye examinations. This will increase IOP in patient’s (careful w/ glaucoma)
- Prevention of motion-induced sickness:
What are the adverse effects of anticholinergic drugs?
Adverse effects can be predicted from knowledge of parasympathetic innervation of various organs such as tachycardia (usually not clinically important and possibly transient bradycardia), decreased gland secretions & GI motility, urinary retention (benign prostatic hyperplasia is a contraindication), mydriasis, cycloplegia, and increased intraocular pressure. Hallucinations and coma may occur with tertiary amines, such as atropine or scopolamine, which are lipid soluble and cross the blood-brain barrier. Quaternary amines (e.g., glycopyrrolate) have a positive charge and do not cross plasma membranes or the blood-brain barrier and have more peripheral effects.
What is the MOA of cholinergic drugs?
Muscarinic agonists act directly on postganglionic parasympathetic receptors (including those cells that have receptors but do not receive parasympathetic innervation, such as some blood vessels)
What are the systemic effects of cholinergic drugs (parasympathetic)?
(Ex: CNS, Eyes, Heart, Lungs, GI, GU)
- Heart: A decrease in heart rate and force of contractility is due to the cholinergic innervation of the SA and AV nodes and atrial muscle.
- GI: Increased tone and amplitude of contraction, peristaltic activity, and secretory action. This may cause nausea, vomiting, diarrhea, belching, salivation, and intestinal cramps.
- GU: Increase in ureteral peristalsis and contraction of the detrusor muscle.
- Other: Stimulates secretions in the tracheobronchial tree, produces bronchoconstriction and miosis.
What happens when the Sympathetic nervous system (adrenergic) is stimulated?
Sympathetic stimulation produces:
- Increase in heart rate
- Increase in blood pressure
- RBCs pour into circulation from spleen
- Blood flow shifts from skin & splanchnic region to skeletal muscle (causes pallor)
- Blood glucose increases (glycogen in the liver is broken down into glucose, but insulin is also released)
- Bronchiolar smooth muscles relax and pupils dilate
- Intestinal smooth muscle relaxes but sphincters contract.
- Activation of the renin-angiotensin-aldosterone system –> Decreased urine output
What happens when the Parasympathetic nervous system (cholinergic) is stimulated?
Parasympathetic stimulation produces:
- Decrease in heart rate
- Decrease in blood pressure
- Blood flow shifts from skin & splanchnic region to skeletal muscle (causes pallor)
- Blood glucose decreases
- Bronchiolar smooth muscles contract and pupils constrict
- Intestinal smooth muscle constrict but sphincters relax.
What is acetylcholinesterase and what is its effect?
- It is an esterase (enzyme) whose principle site of action is within the synapse of both ganglionic and postganglionic parasympathetic nerve endings and the neuromuscular junction.
- It functions to rapidly destroy acetylcholine.
- Inhibition of AChE will result in a buildup of endogenous acetylcholine at all sites, leading to diffuse cholinergic effects (parasympathetic).
What type of drug is neostigmine and what is its MOA?
- It is an acetylcholinesterase inhibitor
- It produces reversible inhibition of AChE by the formation of a carbamyl-ester complex which dissociates slowly, hence provides longer action. Neostigmine and pyridostigmine are quaternary ammonium compounds that are ionized hence do not cross the blood-brain barrier.
What is neostigmine used for?
- It used in the treatment of myasthenia gravis (characterized by weakness and fatigue caused by the production of antibodies that decrease the number of functional nicotinic receptors on the postjunctional endplates in the somatic nervous system).
- They act preferentially at the neuromuscular junction (NMJ) and restore skeletal muscle strength by increasing the availability of acetylcholine.
- Pyridostigmine is generally preferred in myasthenia because of its longer duration of action (6 hr vs. 2 hr for neostigmine).
What are some examples of adrenergic agonists (sympathomimetics)?
- epinephrine
- dopamine
- Isoproterenol
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What are the systemic effects of adrenergic drugs (sympathetic)?
(Ex: CNS, Eyes, Heart, Lungs, GI, GU)
- Peripheral excitatory action on certain smooth muscle, e.g., constricts blood vessels of the skin and mucous membrane (α1).
- Peripheral inhibition action in certain smooth muscles, e.g., large blood vessels, the wall of the gut and bronchial tree (β2).
- Cardiac excitation (β1). –> Increased HR
- Metabolic actions, e.g., increased rate of glycogenolysis in liver and muscle (beta receptors).
- Endocrine actions, as modulation of secretion of insulin, renin & pituitary hormones. Insulin secretion is inhibited by alpha-2 receptors and enhanced by beta-2 receptors. The beta is the predominant effect.
- CNS actions, as respiratory stimulation and increased wakefulness.
What happens when Alpha-1 receptors (postsynaptic) are stimulated?
- Vasoconstriction
- Mydriasis
- Contraction of GI sphincters
- Contraction of bladder sphincter
What happens when Alpha-2 receptors (presynaptic) are stimulated?
- Inhibition of NE release.
- (Centrally, α2 receptors have an inhibitory effect on sympathetic activity).
What happens when Beta-1 receptors (postsynaptic receptors) are stimulated?
- Increased conduction velocity
- Increased automaticity
- Increased contractility
- Tachycardia
- Increased lipolysis
What happens when Beta-2 receptors (postsynaptic receptors) are stimulated?
- Vasodilation (response to low concentrations of epinephrine)
- Bronchodilation
- GI relaxation
- Uterine relaxation
- Glycogenolysis (=hyperglycemia)
- Release of glucagon
- Skeletal muscle tremor
- Decreases plasma potassium (increase uptake by cells)
What is the MOA of Epinephrine?
It regulates myocardial contractility, heart rate, vascular & bronchial smooth muscle tone, glandular secretions, & metabolic processes such as glycogenolysis and lipolysis. It acts on all adrenergic receptors (A1,A2,B1,B2 receptors)
What is the MOA of Norepinephrine?
- NE is a potent alpha agonist (but less so than epi). It produces intense arterial & venous vasoconstriction. It is equal to epi for stimulation of beta 1, but has little or no effect on beta 2 receptors.
- It is indicated for blood pressure control in acute hypotensive states.
What is the MOA of Dopamine?
Dopamine has dose-dependent receptor specificity. Depending on dose, dopamine stimulates dopamine receptors in renal vasculature producing renal vasodilation, beta-1 receptors in the heart in larger doses, and alpha receptors in eripheral vasculature in still larger doses. Extravasation produces intense local vasoconstriction (treat by local infiltration of phentolamine). Dopamine does not cross the blood brain barrier
What is dopamine used for?
It is used to increase cardiac output in patients with low blood pressure, atrial filling pressures, and low urine output. It is useful in cardiogenic and bacteremic shock. Dopamine simultaneously increases myocardial contractility, renal blood flow, glomerular filtration rate, excretion of sodium, and urine output.
What are some adverse effects of dopamine?
The most common adverse effects of dopamine are tachycardia, dysrhythmias, and angina pain; the result from activation of beta-1 receptors in the heart.
What are some alpha-2 receptor agonists?
- clonidine [Catapres]
- methyldopa [Aldomet]
What is the MOA of methyldopa and what is it used for?
- MOA: Stimulates alpha-2 adrenergic receptors in the hypothalamus (centrally). These fibers are inhibitory and inhibit sympathetic nervous outflow from the vasomotor center to the periphery. As a result, decreases in peripheral vascular resistance, heart rate, & blood pressure occur; however, compensatory sympathetic reflexes remain intact.
- Uses: It is an effective antihypertensive. Pregnancy Category B, it is often listed as a drug of choice for treating hypertension in pregnant women.
- CV effects: Produces significant reductions in BP and PVR while CO and renal, cerebral & myocardial blood flows are maintained.
What are some side effects associated with methyldopa?
Sedation, hepatic dysfunction (elevations of transaminase enzymes; fever, malaise & jaundice may occur), development of a positive Coomb’s test (in 10-20% of patients taking 1 g daily for > 6 mo; hemolytic anemia does not occur), flu-like symptoms, and rebound hypertension (on sudden withdrawal of the drug). Retention of sodium and weight gain may occur during treatment.
What is the MOA of Clonidine and what is it used for?
- MOA: Clonidine is also a centrally acting alpha-2 agonist that acts as an antihypertensive drug. It is well absorbed from the GI tract with a tmax of 1-3 h, a half-life of 12 h, and is eliminated 50% unchanged in the urine.
- Uses: Clonidine is indicated for the treatment of hypertension and attention deficit hyperactivity disorder (ADHD). Clonidine has been used (off label) to aid in the diagnosis of pheochromocytoma, in suppressing signs and symptoms of withdrawal from opioids, to enhance analgesic effect of opioids, & intrathecally as an analgesic.
What are the side effects of clonidine?
Sedation and xerostomia occur but these usually decrease after several weeks of therapy. Sodium and water retention may occur. Skin rashes, dry mouth and constipation are frequent and impotence occurs occasionally. Abrupt discontinuation of clonidine can result in rebound hypertension as soon as 8 and as late as 36 hours after the last dose.
What are alpha-1 adrenergic blockers & what some precautions to take with them?
- Alpha antagonists bind selectively to (and block) alpha receptors and interfere with the ability of catecholamines or other sympathomimetics to provoke alpha responses. The effects of sympathomimetics on the smooth muscle and peripheral vasculature and the inhibitory action of epinephrine on insulin secretion are blocked by alpha receptor antagonists
- Orthostatic hypotension, baroreceptor-mediated reflex tachycardia, & impotence are invariable side effects of alpha blockade. Further, the absence of beta blockade permits maximum expression of cardiac stimulation from NE.
What is the MOA of Propranolol and what is it used for?
- MOA: Propranolol is a nonselective beta blocker that lacks ISA. It blocks beta 1 and 2 receptors equally.
- It decreases HR and cardiac output, especially during exercise or in the presence of increased sympathetic activity.
- Concomitant block of β2 receptors results in increased peripheral vascular resistance including coronary vascular resistance, but decreased heart rate & myocardial contractility predominate, thus propranolol may relieve myocardial ischemia even though drug-induced increases in coronary vascular resistance decrease coronary blood flow.
- It is used to treat Hypertension, angina pectoris, SVT, ST, MI’s,
What are some side effects of propranolol?
Bradycardia, bronchospasm, & fatigue are the most frequently reported. Hypoglycemia may occur in diabetic patients. Reduced cardiac output, precipitation of heart failure, and AV heart block may occur. Contraindicated in patients with asthma
What is pindolol and what is it used for?
Pindolol [Visken]: is a nonselective blocker with ISA (Intrinsic Sympathomimetic Activity). Because of its ISA, pindolol produces less resting bradycardia. It is well absorbed but plasma concentrations vary greatly. 50% of a dose is recovered unchanged in urine.
What are some adverse effects of beta blockers?
Adverse effects of beta-1 blockade include bradycardia, reduced cardiac output, precipitation of heart failure, AV heart block and rebound cardiac excitation (however they are 1st line drugs in certain types of heart failure). Side effects of beta-2 blockade include bronchoconstriction and hypoglycemia from inhibition of glycogenolysis. Dizziness, lethargy & fatigue are listed as common side effects.
What type of drug is Succinylcholine and what is its MOA?
- It is a depolarizing (binds competitively to ACh-n receptors but cause a persistent depolarization with subsequent block due to receptor desensitization) Neuromuscular blocking agent that causes complete skeletal muscle relaxation, including paralysis of respiratory muscles. They are highly polar and not effective when given by mouth, nor do they cross the blood-brain barrier or placenta.
- Unless given an anesthetic, patients are awake and can hear but cannot move or speak
What are the adverse effects of Succinylcholine?
- Paralysis of respiratory muscle. Block of sympathetic ganglia causes a drop in blood pressure.
- Drug-induced histamine release may cause bronchoconstriction and hypotension.
- Hyperkalemia is a problem with succinylcholine, especially in children and adolescents.
What type of drug is ipratropium (atrovent) and what is its MOA?
- It is an Anticholinergic (muscarinic antagonist) drug that relaxes bronchial smooth muscles by blocking the muscarinic cholinergic receptors in the bronchi.
- Therapeutic effects of this drug begin within 30in, reach 50% of their maximum for 6 minutes and persist for 6hrs.
What type of drug is Levodopa and what is its MOA?
- It is a dopamine precursor
- Levodopa increases dopamine synthesis. When passes through the blood-brain barrier, it is converted to dopamine.
What type of drug is Tolterodine (Detrol) and what is it used for?
- It is a muscarinic antagonist (anticholinergic)
- It is used for the treatment of an overactive bladder
What type of drug is Methyldopa (Aldomet) and what is its MOA?
- It is an Alpha 2 Agonist
- Methyldopa stimulates alpha-2 adrenergic receptors in the hypothalamus (centrally). These fibers are inhibitory and inhibit sympathetic nervous outflow from the vasomotor center to the periphery. As a result, decreases in peripheral vascular resistance, heart rate, & blood pressure occur; however, compensatory sympathetic reflexes remain intact.
What is Glycopyrrolate (Robinul) used for?
- It is used as an Antisialagogue (antisaliva) medication
- Is twice as potent as atropine in antisialagogue effect and has a longer duration of action.
What type of drug is Atenolol (Tenormin) and what is its MOA?
- is a selective beta-1 antagonist considered intermediate in lipid:water solubility.
