Al al-Bayt University
PART 3: Drugs Affecting the Autonomic Nervous System
✓ I: Introduction to ANS.
✓ II: Adrenergic drugs.
✓ III: Adrenergic antagonists.
✓ IV: Cholinergic drugs.
✓ V: Cholinergic antagonists.
I: introduction to autonomic nervous system
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- Over view:
The autonomic nervous system (ANS), along with the endocrine system, coordinates the regulation and integration of bodily functions. The endocrine system sends signals to target tissues by varying the levels of blood-borne hormones. In contrast, the nervous system exerts its influence by the rapid transmission of electrical impulses over nerve fibers that terminate at effector cells, which specifically respond to the release of neuromediator substances.
The ANS works to regulate blood pressure, heart rate, respiration, body temperature, water balance, urinary excretion, and digestive functions, among other things. This system exerts minute-to-minute control of body responses, which is balanced by the two divisions of the ANS.
- Divisions:
The ANS is divided into two branches: the sympathetic nervous system and the parasympathetic nervous system.
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Neurotransmitters in ANS
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Receptors in ANS
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Synthesis and storage of acetylcholine
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Synthesis and storage of epinephrine.
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: Adrenergic Drugs:
Overview:
Adrenergic compounds include several exogenous and endogenous substances. They have a wide variety of therapeutic uses depending on their site of action and their effect on different types of adrenergic receptors.
Adrenergic drugs stimulate the sympathetic nervous system (SNS) and are also called adrenergic agonists. They are also known as sympathomimetics, because they mimic the effects of the SNS neurotransmitters norepinephrine, epinephrine, and dopamine. These three neurotransmitters are chemically classified as catecholamines.
Adrenergic receptors: these are the sites at which adrenergic drugs bind and produce their effects. Adrenergic receptors are located in many anatomic sites. Many physiologic responses are produced when they are stimulated or blocked. Adrenergic receptors are further divided into alpha-adrenergic receptors and beta-adrenergic receptors, depending on the specific physiologic responses caused by their stimulation. Both types of adrenergic receptors have subtypes, designated 1 and 2.
The alpha1-and-alpha2- adrenergic receptors are differentiated by their location relative to nerves. The alpha1-adrengic receptors are located on postsynaptic effector cells (the tissue, muscle, or organ that the nerve stimulates). The alpha2-adrenergic receptors are located on the presynaptic nerve terminals. They control the release of neurotransmitters. The predominant alpha-adrenergic agonist response is vasoconstriction and central nervous system stimulation.
The beta-adrenergic receptors are all located on postsynaptic effector cells. The beta1-adrenergic receptors are primarily located in the heart, whereas the beta2-adrenergic receptors are located in the smooth muscle fibers of the bronchioles, arterioles, and visceral organs. A beta-adrenergic agonist response results in bronchial, gastrointestinal (GI), and uterine smooth muscle relaxation; glycogenolysis; and cardiac stimulation.
Another type of adrenergic receptor is the dopaminergic receptor. When stimulated by dopamine, these receptors cause the vessels of the renal, mesenteric, coronary, and cerebral arteries to dilate, which increases blood flow to these tissues. Dopamine is the only substance that can stimulate these receptors.
Location Receptor Response
Cardiovascular
Blood vessels alpha1 Constriction
beta2 Dilation
Cardiac muscle beta1 Increased contractility
AV Node beta1 Increased heart rate
SA Node beta1 Increased heart rate
Gastrointestinal
Muscle beta2 and alpha Decreased motility
Genitourinary
Bladder alpha1 Constriction sphincter
Uterus alpha1 Contraction
beta2 Relaxation
Respiratory
Bronchial beta2 Dilation muscles
Pupils alpha1 Dilation
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Pharmacology overview:
ADRENERGIC DRUGS:
A. Catecholamines produce a sympathomimitic response and are either
- Endogenous substances such as epinephrine, norepinephrine, and dopamine.
- Synthetic substances such as isoproterenol and dobutamine.
- These three endogenous catecholamines, (epinephrine, norepinephrine, and dopamine) are also available in synthetic drug form.
B. Noncatecholamines
Compounds lacking the catechol hydroxyl groups have longer half lives, because they are not inactivated by COMT. These include phenylephrine, ephedrine, and amphetamine.
When any of the adrenergic drugs is given, it bathes the synaptic cleft. Once there, the drug has the opportunity to induce the response. This can accomplish in one of three ways: by direct stimulation, by indirect stimulation, or by a combination of the two (mixed acting).
✓ Mechanism of action:
1- A direct-acting sympathomimetics binds directly to the receptor and causes physiologic response. Epinephrine is an example of such a drug.
2- An indirect-acting sympathomimetic is an adrenergic drug that, when given, causes the release of the catecholamine from storage sites (vesicles) in the nerve endings; it then binds to the receptors and causes a physiologic response.
Amphetamine and other related anorexiants are examples of such drugs.
3- A mixed-acting sympathomimetic both directly stimulates the receptor by binding to it and indirectly stimulates the receptor by causing the release of neurotransmitter stored in vesicles at the nerve endings. Ephedrine and pseudoeohedrine are an example of a mixed-acting adrenergic drug.
✓ Drug effects:
← Stimulation of alpha1-adrenergic receptors on smooth muscles results in
➢ Vasoconstriction of blood vessels
➢ Relaxation of GI smooth muscles (decreased motility)
➢ Constriction of bladder sphincter
➢ Contraction of uterus
➢ Contraction of pupillary muscles of the eye (dilated pupils)
← Stimulation of alpha2-adrenergic receptors, actually tend to reverse sympathetic activity but is not of great significance either physiologically or pharmacologically.
← Stimulation of beta1-adrenergic receptors on the myocardium, AV node, and SA node results in cardiac stimulation
➢ Increased force of contraction (positive inotropic effect)
➢ Increased heart rate (positive chronotropic effect)
➢ Increased conduction through AV node (positive dromotropic effect)
← Stimulation of beta2-adrenergic receptors results in
➢ Bronchodilation (relaxation of the bronchi)
➢ Uterine relaxation
➢ Relaxation of GI smooth muscles (decreased motility)
✓ Indications:
Their selectivity for either alpha- or beta- adrenergic receptors and their affinity for certain tissues or organs determine the settings in which they are most commonly used.
Respiratory indications:
Certain adrenergic drugs have an affinity for the adrenergic receptors located in the respiratory system and are classified as bronchodilators. They tend to preferentially stimulate the beta2-adrenergic receptors and cause bronchodilation. The beta2 agonists are helpful in treating conditions such as asthma and bronchitis. Some common bronchodilators that are classified as predominantly beta2-selective adrenergic drugs include (salbutamol, formetrol, salmeterol and terbutaline).
Indications for topical nasal decongestants
The intranasal application of certain adrenergics can cause the constriction of dilated arterioles and reduction in nasal blood flow, which thus decreases congestion. These adrenergic drugs work by stimulating alpha1-adrenergic receptors and have little or no effect on beta-adrenergic receptors. The nasal decongestants include epinephrin, pseudoephedrine, naphazoline, oxymetazoline, phenylephrine, and tetrahydrozoline.
Ophthalmic indications
Some adrenergics are applied to the surface of the eye. These drugs are called ophthalmics, and they affect the vasculature of the eye. When administered, they stimulate alpha-adrenergic receptors located on small arterioles in the eye and temporarily relieve conjunctival congestion by causing arteriolar vasoconstriction. The ophthalmic adrenergics include epinephrine, naphazoline, phenylephrine, and tetrahydrozoline.
Adrenergics can also used to reduce intraocular pressure and dilate the pupils (mydriasis), properties that make them useful in the treatment of open-angle glaucoma, as well as for diagnostic eye examinations. They produce these effects by stimulating alpha-or-beta2-adrenergic receptors, or both. The two adrenergics used for this purpose are epinephrine and dipivefrin.
Cardiovascular indications
Cardioselective sympathomimetics they are used to support the cardiovascular system during cardiac failure or shock these drugs have a variety of effects on the various alpha- and beta-adrenergic receptors, and these effects can also be related to the specific dose of the adrenergic drug. Common vasoactive adrenergic drugs include dobutamine, dopamine, ephedrine, epinephrine, fenoldopam, midodrine, norepinephrine, and phenylephrine.
✓ Contraindications: The only contraindications to the use of adrenergic drugs are known drug allergy and severe hypertension
✓ Adverse effects:
Alpha-Adrenergic Adverse Effects
← CNS: Headache, restlessness, excitement, insomnia, euphoria
← Cardiovascular: Palpitations (dysrhythmias), tachycardia, vasoconstriction, hypertension
← Other: Loss of appetite, dry mouth, nausea, vomiting, taste changes (rare)
Beta-Adrenergic Adverse Effects
← CNS: Mild tremors, headache, nervousness, dizziness
← Cardiovascular: Increased heart rate, palpitations (dysrhythmias), fluctuations in BP
← Other: Sweating, nausea, vomiting, muscle cramps
✓ Drug profiles:
1- Epinephrine:
It acts directly on both the alpha- and beta-adrengic receptors of tissues innervated by the SNS.
Therapeutic uses:
a. Bronchospasm: Epinephrine is the primary drug used in the emergency treatment of respiratory conditions when bronchoconstriction has resulted in diminished respiratory function.
b. Anaphylactic shock: Epinephrine is the drug of choice for the treatment of type I hypersensitivity reactions (including anaphylaxis) in response to allergens.
c. Cardiac arrest: Epinephrine may be used to restore cardiac rhythm in patients with cardiac arrest.
d. Anesthetics: Local anesthetic solutions may contain low concentrations (for example, 1:100,000 parts) of epinephrine. Epinephrine greatly increases the duration of local anesthesia by producing vasoconstriction at the site of injection. This allows the local anesthetic to persist at the injection site before being absorbed into the systemic circulation.
At low dosages it stimulates mostly beta1-adrenergic receptors, increasing the force of contraction and heart rate. It is used to treat acute asthma and shock at these dosages. At high dosages, it stimulates mostly alpha-adrenrgic receptors, causing vasoconstriction, which elevates the blood pressure.
2- Dobutamine.
Is a beta1-selective vasoactive adrenergic drug that is structurally similar to the naturally occurring catecholamine dopamine. Through stimulation of the beta1 receptors on heart muscle (myocardium), it increases cardiac output by increasing contractility (positive inotropy), which increases the stroke volume, especially in patients with heart failure. Dobutamine is available only as an intravenous drug is given by continuous infusion.
3- Dopamine:
Dopamine is a naturally occurring catecholamine in the SNS. It has potent dopaminergic as well as beta1- and alpha1- adrenergic receptor activity, depending on the dosage.
Dopamine, when used at low dosages, can dilate blood vessels in the brain, heart, kidney, and mesentery, which increases blood flow to these areas (dopaminergic receptor activity).
At higher infusion rates dopamine can improve cardiac contractility and output (beta1-adrenergic receptor activity).
Use of the drug is contraindicated in patients who have a catecholamine-secreting tumor of the adrenal gland known as a pheochromocytoma. The drug is available only as an intravenous injectable drug and is given by continuous infusion.
Therapeutic uses:
Dopamine is the drug of choice for cardiogenic and septic shock and is given by continuous infusion.
It raises blood pressure by stimulating the β1 receptors on the heart to increase cardiac output and α1 receptors on blood vessels to increase total peripheral resistance. In addition, it enhances perfusion to the kidney and splanchnic areas.
Increased blood flow to the kidney enhances the glomerular filtration rate and causes diuresis. It is also used to treat hypotension and severe heart failure, primarily in patients with low or normal peripheral vascular resistance and in patients who have oliguria.
Nursing Implications:
← Follow administration guidelines carefully
← Intravenous administration
← Check IV site often for infiltration
← Use clear IV solutions
← Use an infusion pump
← Infuse drug slowly to avoid dangerous cardiovascular effects
← Monitor cardiac rhythm
← Monitor for therapeutic effects (cardiovascular uses)
← Decreased edema
← Increased urinary output
← Return to normal vital signs
← Improved skin color and temperature
II: Adrenergic-Blocking Drugs:
Overview:
The adrenergic blockers have the opposite effect of adrenergic agonists and therefore referred to as antagonists. They also bind to adrenergic receptors but in doing so inhibit or block stimulation by the SNS. They are also referred to as sympatholytics because they “lyse:, or inhibit, SNS stimulation. At adrenergic receptors the adrenergic blockers act, and they are classified by the type of adrenergic receptor they block-alpha or beta or, in few cases, both. Hence, they are called alpha-blockers, beta-blockers, or alpha/beta-blockers.
Pharmacology overview:
1- Alpha-Blockers:
✓ Mechanism of action and drug effects:
These drugs have a greater affinity for the alpha-adrenergic receptor than do norepinephrine and can chemically displace norepinephrine molecules from the receptor.
Adrenergic blockade at these receptors leads to effects such as vasodilatation, reduced blood pressure, miosis (papillary constriction), and reduced smooth muscle tone in organs like the bladder and prostate.
✓ Indications:
The alpha-blockers such as doxazosin, prazosin, and terazosin cause both arterial and venous dilation. This reduces peripheral vascular resistance and blood pressure, and these drugs are used to treat hypertension.
The alpha-adrenergic receptors are also present in the prostate and bladder. By blocking stimulation of alpha1 receptors, these drugs reduce smooth muscle contraction of the bladder neck and the prostatic portion of the urethra. For this reason, alpha-blockers are given to patients with benign prostatic hyperplasia (BPH) to decrease resistance to urinary outflow. This reduces urinary obstruction and relieves some of the effects of BPH.
Tamsulosin and alfuzosin are used exclusively for treating BPH, whereas terazosin and doxazosin can be used for both hypertension and BPH.
✓ Contraindications:
Contraindications to the use of alpha-blocking drugs include known drug allergy and peripheral vascular disease and may include hepatic and renal disease, coronary artery disease, peptic ulcer, and sepsis.
✓ Adverse effects:
Body System Adverse Effects
• Cardiovascular Palpitations, orthostatic hypotension, and edema.
• CNS Dizziness, headache, drowsiness, anxiety, depression, vertigo,
weakness, numbness, fatigue
• Gastrointestinal Nausea, vomiting, diarrhea, constipation, abdominal pain
2- Beta-Blockers:
✓ Mechanism of action and drug effects:
The beta-adrenergic-blocking drugs (beta-blockers) block SNS stimulation of the beta-adrenergic receptors by competing with the endogenous catecholamines norepinephrine and epinephrine. The beta-blockers can be either selective or nonselective, depending on the type of beta-adrenergic receptors they antagonize.
As mentioned earlier, beta1-adrenergic receptors are located primarily in the heart. Beta-blockers selective for these receptors are sometimes called cardioselective beta-blockers or beta1-blocking drugs.
Other beta-blockers block both beta1- and beta2- adrenergic receptors, the latter of which are located primarily on the smooth muscles of the bronchioles and blood vessels. These beta-blockers are referred to as nonselective beta-blockers.
Two beta-blockers, carvedilol, and labetalol, also have an alpha receptor-blocking activity, especially at higher dosages.
Cardioselective beta1-blockers reduces myocardial stimulation, which in turn reduces heart rate, slows conduction through the atrioventricular (AV) node, prolongs sinoatrial (SA) node recovery, and decreases myocardial oxygen demand by decreasing contractility. Nonselective beta blockers also have these cardiac effects, but they block beta2 receptors on the smooth muscle of the bronchioles and blood vessels as well.
✓ Indications:
Indications for beta-blockers include angina, MI, cardiac dysrhythmias, hypertension, and heart failure.
Beta-blockers are also considered to be cardioprotective because they inhibit stimulation of the myocardium by circulating catecholamines. Catecholamines are released during myocardial muscle damage such as that caused by an MI, or heart attack. Catecholamines would further increase the heart rate and the contractile force and thereby increase myocardial oxygen demand. When a beta-blocker drug occupies myocardial bata1 receptors, circulating catecholamines molecules are prevented from binding to the receptors. Thus the beta-blockers protect the heart from being stimulated by these catecholamines. Because of this characteristic, beta-blockers are commonly given to patients after they have experienced an MI to protect the heart.
Conduction in the SA node is slowed by beta-blockers, which results in a decreased heart rate. These drugs also slow conduction through the AV node. These effects of the beta-blockers on the conduction system of the heart make them useful drugs in the treatment of dysrhythmias.
The ability to reduce SNS stimulation of the heart, including reducing heart rate and the force of myocardial contraction, renders beta-blockers useful in treating hypertension. Certain beta-blockers such as carvedilol and metoprolol have produced the best results in treating heart failure to date.
Because of their lipophilicity some beta-blockers can easily gain entry into the central nervous system and are used to treat migraine headaches. In addition, the topical application of timolol to the eyes has been very effective in treating ocular disorders such as glaucoma.
✓ Adverse effects:
Body System Adverse Effects
Blood Agranulocytosis, thrombocytopenia
Cardiovascular Bradycardia, heart failure, peripheral vascular insufficiency
CNS Dizziness, mental depression, lethargy, hallucinations, unusual dreams
Gastrointestinal Nausea, dry mouth, vomiting, diarrhea, cramps, ischemic colitis
Other Impotence, rash, alopecia, bronchospasm
← Nonselective beta-blockers may interfere with normal responses to hypoglycemia (tremor, tachycardia, nervousness)
➢ May mask signs and symptoms of hypoglycemia
Nursing Implications:
← Assess for allergies and history of COPD, hypotension, cardiac dysrhythmias, bradycardia, heart failure, or other cardiovascular problems
➢ Any preexisting condition that might be exacerbated by the use of these drugs might be a contraindication to their use
← Remember that alpha-blockers may precipitate hypotension, and that some beta-blockers may precipitate bradycardia, hypotension, heart block, heart failure, and bronchoconstriction
← Avoid over-the-counter medications because of possible interactions
← Encourage patients to take medications as prescribed, and instruct patients that these medications should never be stopped abruptly. Rebound hypertension or chest pain may occur if this medication is discontinued abruptly
← Teach patients to change positions slowly to prevent or minimize postural hypotension with alpha-blockers.
← Monitor for therapeutic effects of beta-blockers
➢ Decreased chest pain in patients with angina
➢ Return to normal BP and HR
➢ Other specific effects, depending on the use
← Inform patients that they may notice a decrease in tolerance for exercise (dizziness and fainting may occur with increased activity), and have patients notify the physician if these problems occur
← Inform patients to report the following to their physician if he take alpha-blockers and beta-blockers:
➢ Weight gain of more than 2 pounds in 1 day or 5 pounds in 1 week
➢ Edema of the feet or ankles
➢ Shortness of breath
➢ Excessive fatigue or weakness
➢ Syncope or dizziness
III: CHOLINERGIC DRUGS:
Overview:
Cholinergics, cholinergic agonists, and parasympathomimetics are all terms that refer to the class of drugs which stimulate the parasympathetic nervous system. For a better understanding of how these drugs work, it is helpful to know how the parasympathetic nervous system operates in relation to the rest of the nervous system.
Parasympathetic nervous system:
The parasympathetic nervous system is the branch of the autonomic nervous system with nerve functions generally opposite those of the SNS. The neurotransmitter responsible for the transmission of nerve impulses to effector cells in the parasympathetic nervous system is acetylcholine. A receptor that binds acetylcholine and mediates its actions is called a cholinergic receptor. There are two types of cholinergic receptors, as determined by their location and their action once stimulated. Nicotinic receptors are located in the ganglia of both the parasympathetic nervous system of both the parasympathetic nervous system and sympathetic nervous system. They are called nicotinic because they can also stimulated by the alkaloid nicotine that is found in the tobacco plant. The other type of cholinergic receptor is the muscarinic receptors. These receptors are located postsynaptically in the effector organs (I.e., smooth muscle, cardiac muscle, and glands) supplied by the parasympathetic fibers. They are called muscarinic because they are stimulated by the alkaloid muscarine, a substance isolated from mushrooms. The figure below shows how the nicotine and muscarinic receptors are arranged in the parasympathetic nervous system.
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Pharmacology overview:
Cholinergic drugs:
✓ Mechanism of action:
Cholinergic drugs can stimulate cholinergic receptors either directly or indirectly.
1- Direct-acting cholinergic agonists bind directly to cholinergic receptors and activate them.
2- Indirect-acting cholinergic drugs work by inhibiting the action of acetylcholinesterase, the enzyme responsible for breaking down acetylcholine.
The indirect-acting cholinergic drugs bind to cholinesterase in one of two ways: reversibly or irreversibly. Reversible inhibitors bind to cholinesterase for a period of minutes to hours. Irreversible inhibitors bind to cholinesterase and form a permanent covalent bond. The body must then generate new enzymes to override the effects of the irreversible drugs.
When acetylcholine directly binds to its receptor, stimulation occurs. Once binding takes place on the membranes of an effector cell, the permeability of the cell changes, and calcium and sodium are permitted to flow into the cell. This then depolarizes the cell membrane and stimulates the effector organ.
Acetylcholine is needed for normal brain function. It is in short supply in patients with Alzeheimer’s disease. At recommended dosages, cholinergics primarily affect the muscarinic receptors, but at high dosages the nicotinic receptors can also be stimulated. The desired effects come from muscarinic receptor stimulation; many of the undesirable adverse effects are due to nicotinic receptor stimulation.
✓ Drug effects:
← SLUDGE acronym
➢ Salivation
➢ Lacrimation
➢ Urinary incontinence
➢ Diarrhea
➢ Gastrointestinal cramps
➢ Emesis
← Stimulate intestine and bladder
➢ Increased gastric secretions
➢ Increased gastrointestinal motility
➢ Increased urinary frequency
← Stimulate pupils
➢ Constriction (miosis)
➢ Reduced intraocular pressure
← Increased salivation and sweating
← Cardiovascular effects
➢ Decreased heart rate
➢ Vasodilatation
← Respiratory effects
➢ Bronchial constriction, narrowed airways
✓ Direct-acting cholinergic agonists
A. Acetylcholine:
Although it is the neurotransmitter of parasympathetic and somatic nerves as well as autonomic ganglia, it lacks therapeutic importance because of its multiplicity of actions (leading to diffuse effects) and its rapid inactivation by the cholinesterases.
B. Bethanechol:
In urologic treatment, bethanechol is used to stimulate the atonic bladder, particularly in postpartum or postoperative, nonobstructive urinary retention. Bethanechol can be administered orally or subcutaneous injection. When given, it causes increased bladder and GI tract tone and motility, which thereby increases the movement of contents through these areas. It also causes the sphincters in the bladder and the GI tract to relax, which allows them to empty.
C. Carbachol and pilocarpine:
Are used topically to reduce intraocular pressure in patients with glaucoma or in those undergoing ocular surgery. They are poorly absorbed orally because they have large quaternary amines in their chemical structure. This limits their use mostly to topical application.
✓ Indirect-acting cholinergic agonists (Reversible):
A. physostigmine:
The drug increases intestinal and bladder motility, which serves as its therapeutic action in atony of either organ. Physostigmine is also used in the treatment of overdoses of drugs with anticholinergic actions, such as atropine.
Indirect-acting drugs cause skeletal muscle contraction and therefore used to diagnosis and treatment of myasthenia gravis like neostigmine and Pyridostigmine
In the treatment of Alzeheimer’s disease, cholinergic drugs increase concentrations of acetylcholine in the brain and thereby improve cholinergic function. The ability of the drugs to increase acetylcholine levels in the brain by inhibiting acetylcholinesterase helps to enhance and maintain memory and learning capabilities. The most commonly used drug is Donepzil.
✓ Adverse effects:
The primary adverse effects of cholinergic drugs are the consequence of overstimulation of the parasympathetic nervous system.
✓ Interactions:
Anticholinergics (Atropine), antihistamines, and sympathomimetics may antagonize cholinergic drugs and lead to reduced response to them. Other cholinergic drugs may have additive effects.
Nursing Implications:
← Note that these drugs will stimulate the PSNS and mimic the action of ACh
← Assess for allergies, presence of GI or GU obstructions, asthma, peptic ulcer disease,
or coronary artery disease
← Medications should be taken as ordered and not abruptly stopped
← Doses should be spread evenly apart to optimize the effects of the medication. Overdosing can cause life-threatening problems. Patients should not adjust dosages unless directed by their physician
← Encourage patients with myasthenia gravis to take medication 30 minutes before eating to help improve chewing and swallowing. When cholinergic drugs are prescribed for Alzheimer’s disease, be honest with caregivers and patients that the drugs are for management of symptoms (not a cure) and the therapeutic effects of anti-Alzheimer’s drugs may not occur for up to 6 weeks
← Atropine is the antidote for cholinergics, and it should be available in the patient’s room for immediate use if needed
←
← Patients should notify their physician if they experience muscle weakness, abdominal cramps,
diarrhea or difficulty breathing
← Monitor for therapeutic effects
← In postoperative patients with decreased GI peristalsis, monitor for:
← Increased bowel sounds
← Passage of flatus
← Occurrence of bowel movements
← In patients with urinary retention/hypotonic bladder, urination should occur within 60 minutes of bethanechol administration
← Also monitor for adverse effects
IV: Cholinergic-antagonists:
Pharmacology overview:
Cholinergic-Blocking Drugs:
Cholinergic blockers, anticholinergics, parasympatholytics, and antimuscarinic drugs are all terms that refer to the class of drugs that block or inhibit the actions of acetylcholine in the parasympathetic nervous system.
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✓ Mechanism of action and drug effects:
Cholinergic-blocking drugs block the action of the acetylcholine. Acetylcholine released from a stimulated nerve fiber is then unable to bind to the receptor site and fails to produce a cholinergic effect. Blocking the parasympathetic nerves allows the sympathetic nervous system to dominant.
Cholinergic blockers are largely competitive antagonists. They compete with acetylcholine for binding at the receptors. Once they have bound to the receptor, they inhibit cholinergic nerve transmission. This occurs at muscarinic receptors. Cholinergic blockers have little effect at the nicotinic receptors.
The blockade of acetylcholine causes the pupils to dilate (mydriasis) and increase intraocular pressure. In the GIT, cholinergic blockers cause a decrease in GI motility, GI secretions, and salivation. In the CVS these drugs cause an increase in heart rate. In the genitourinary system, anticholinergics lead to decrease bladder contraction, which can result in urinary retention. In the skin they reduce sweating, and in the respiratory system they dry mucous membranes and bronchial dilation.
A. Atropine
Atropine acts both centrally and peripherally. Its general actions last about 4 hours, except when placed topically in the eye, where the action may last for days.
Therapeutic uses:
a. Ophthalmic: Topical atropine exerts both mydriatic and cycloplegic effects, and it permits the measurement of refractive errors without interference by the accommodative capacity of the eye.
Shorter-acting antimuscarinics (cyclopentolate and tropicamide) have largely replaced atropine due to prolonged mydriasis observed with atropine (7 to 14 days vs. 6 to 24 hours with other agents).
b. Cardiovascular: The drug is used to treat bradycardia of varying etiologies.
c. Antisecretory: Atropine is sometimes used as an antisecretory agent to block secretions in the upper and lower respiratory tracts prior to surgery.
d. Antidote for cholinergic agonists: Atropine is used for the treatment of organophosphate (insecticides, nerve gases) poisoning, of overdose of clinically used anticholinesterases such as physostigmine, and in some types of mushroom poisoning (certain mushrooms contain cholinergic substances that block cholinesterases). Massive doses of atropine may be required over a long period of time to counteract the poisons. The ability of atropine to enter the central nervous system (CNS) is of particular importance in treating central toxic effects of anticholinesterases.
B. Scopolamine:
The therapeutic use of scopolamine is limited to prevention of motion sickness and postoperative nausea and vomiting.
C. Ipratropium and tiotropium
These agents are approved as bronchodilators for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). Ipratropium is also used in the acute management of bronchospasm in asthma. Both agents are delivered via inhalation.
D. Oxybutynin, and tolterodine:
These synthetic atropine-like drugs are used to treat overactive bladder. By blocking muscarinic receptors in the bladder, intravesical pressure is lowered, bladder capacity is increased, and the frequency of bladder contractions is reduced. Side effects include dry mouth, constipation, and blurred vision, which limit tolerability of these agents if used continually.
.
✓ Contraindications:
These known drug allergy, angle-closure glaucoma, and GI or GU obstruction.
Adverse effects:
Body System Adverse Effects
Cardiovascular Increased heart rate, dysrhythmias
CNS CNS excitation, restlessness, irritability, hallucinations, delirium
Eye Dilated pupils, decreased visual accommodation, increased intraocular pressure
Gastrointestinal Decreased salivation, decreased gastric secretions, decreased motility
Genitourinary Urinary retention
Glandular Decreased sweating
Respiratory Decreased bronchial secretions
Nursing Implications:
← Blurred vision may cause problems with driving or operating machinery
← Dry mouth may occur; can be handled by chewing gum, frequent mouth care, and hard candy
← Check with physician before taking any other medication, including over-the-counter medications
← Antidote for atropine overdose is physostigmine
← Anticholinergics taken by the elderly patient may lead to higher risk for heatstroke because of the effects on heat-regulating mechanisms. Teach patients to limit physical exertion and avoid high temperatures and strenuous exercise and emphasize the importance of adequate fluid and salt intake
← Patients should report the following symptoms to their physician: urinary hesitancy and/or retention, constipation, palpitations, tremors, confusion, sedation or amnesia, excessive dry mouth (especially if they have chronic lung infections or disease), or fever
← Monitor for therapeutic effects
← For patients with Parkinson’s disease:
fewer tremors and decreased salivation and drooling
← For patients with urologic problems: improved urinary patterns, less hypermotility, increased time between voiding
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Direct-Acting agents:
• Dobutamine.
• Dopamine.
• Epinephrine.
• Norepinephrine.
• Fenoldopam.
• Salbutamol.
• Formetrol.
• Salmetrol.
• Terbutaline.
Indirect-Acting agents:
• Amphetamine.
• Cocaine.
Mixed action:
• Ephedrine.
• Pseudoephedrine.
Nonselective adrenergic blockers:
• Carvedilol.
• Labetalol
Nonselective alpha blockers:
• Phentolamine.
Alpha-1 blockers:
• Alfuzosin (Xatral).
• Doxazosin (Cardura).
• Tamsulosin (Omnic).
• phenoxybenzamine
Beta blockers:
• nonselective:
• Carteolol (Carteol E/D).
• Propranolol (Inderal).
• Timolol.
• Cardioselective beta-1 blockers:
• Atenolol (Tenormin).
• Betaxolol (Kerlone).
• Bisoprolol (Concore).
• Metoprolol (Betaloc Zok).
Direct acting drugs:
• Bethanechol.
• Carbachol.
• Pilocarpine.
• Succinylcholine.
Indirect-Acting Drugs:
Reversible:
• Donepezil.
• Physostigmine.
• Pyridostigmine.
Irreversible:
• Echothiophate.
Reactivation of acytelcholinestarase:
• Pralidoxime.
Natural plant alkaloids:
• Atropine.
• Belladonna.
• Hyoscyamine.
• Scopolamine.
Synthetic/Semisynthetic:
• Oxybutynin.
• Tolterodine.
• Clidinium.
• Ipratropium.
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