N215 Unit 5 Chapter 14 Drugs Affecting Autonomic Nervous System Flashcards
Describe the following classes of ANS drugs
1) adrenergic agents or sympathomimetics
2) adrenergic-blocking agents or adrenergic antagonists
3) cholinergic or parasympathomimetics
4) cholinergic-blocking agents, anticholinergics,
- Stimulation of the sympathetic nervous system. These drugs are called adrenergic agents or sympathomimetics, and they produce the classic symptoms of the fight-or-flight response. Natural or synthetic agents that produce a sympathomimetic response include the catecholamines and noncatecholamines.
- Inhibition of the sympathetic nervous system. These drugs are called adrenergic-blocking agents or adrenergic antagonists, and they produce actions opposite those of the sympathomimetics. The term sympatholytics is another name for adrenergic antagonists.
- Stimulation of the parasympathetic nervous system. These drugs are called cholinergic or parasympathomimetics, and they produce the characteristic symptoms of the rest-and-digest response.
- Inhibition of the parasympathetic nervous system. These drugs are called cholinergic-blocking agents, anticholinergics, parasympatholytics, or muscarinic blockers, and they produce actions opposite those of the cholinergic drugs.
Name the classes of drugs that affect the autonomic nervous system.
ADRENERGIC DRUGS phenylephrine (Neo-Synephrine)
ADRENERGIC-BLOCKING DRUGS prazosin (Minipress) page 143
CHOLINERGIC DRUGS
- Direct-Acting Parasympathomimetics page 145; bethanechol (Duvoid, Urecholine) page 146
- Cholinesterase Inhibitors page 145 physostigmine (Antilirium) page 147
CHOLINERGIC-BLOCKING DRUGS (ANTICHOLINERGICS) atropine (Atro-Pen) page 151
What are the receptors in the symp. and parasymp. NSs and what are their functions?
Table 13.2.
Types of Autonomic Receptors
1) Norepinephrine (adrenergic)
Alpha1
All sympathetic target organs except the heart
Constriction of blood vessels, dilation of pupils
Alpha2
Presynaptic adrenergic nerve terminals
Inhibition of release of norepinephrine
Beta1
Heart and kidneys
Increased heart rate and force of contraction; release of renin
Beta2
All sympathetic target organs except the heart
Inhibition of smooth muscle
Beta3
Adipose tissue
Lipolysis
2) Acetylcholine (cholinergic)
Nicotinic
Postganglionic neurons
Stimulation of smooth muscle and gland secretions
Muscarinic
Heart
Decreased heart rate and force of contraction
Parasympathetic target: organs other than the heart
Stimulation of smooth muscle and gland secretions
Describe the properties of the following drug
Phenylephrine (Neo-Synephrine)
Phenylephrine (Neo-Synephrine)
Therapeutic Class: Nasal decongestant; mydriatic drug; antihypotensive
Pharmacologic Class: Adrenergic agent (sympathomimetic)
ACTIONS AND USES
Phenylephrine is a selective alpha-adrenergic agonist that is available in different formulations, including intranasal, ophthalmic, IM, subcutaneous, and IV. All its actions and indications are extensions of its sympathetic stimulation.
Intranasal Administration: When applied intranasally by spray or drops, phenylephrine reduces nasal congestion by constricting small blood vessels in the nasal mucosa.
Topical Administration: Applied topically to the eye during ophthalmic examinations, phenylephrine can dilate the pupil without causing significant cycloplegia.
Parenteral Administration: The parenteral administration of phenylephrine can reverse acute hypotension caused by spinal anesthesia or vascular shock. Because phenylephrine lacks beta-adrenergic agonist activity, it produces relatively few cardiac side effects at therapeutic doses. Its longer duration of activity and lack of significant cardiac effects gives phenylephrine some advantages over epinephrine or norepinephrine in treating acute hypotension.
ADMINISTRATION ALERTS
- Parenteral administration can cause tissue injury with extravasation.
- Phenylephrine ophthalmic drops may damage soft contact lenses.
- Pregnancy category C
PHARMACOKINETICS
Onset
Peak
Duration
Immediate IV; 10-15 min IM/subcutaneous
5-10 min IV; 15-30 min IM/subcutaneous
15-20 min IV; 30-120 min IM/subcutaneous; 3-6 h topical
ADVERSE EFFECTS
When the drug is used topically or intranasally, side effects are uncommon. Intranasal use can cause burning of the mucosa and rebound congestion if used for prolonged periods (see chapter 31 ). Ophthalmic preparations can cause narrow-angle glaucoma secondary to their mydriatic effect. High doses can cause reflex bradycardia due to the elevation of blood pressure caused by stimulation of alpha1 receptors.
When used parenterally, the drug should be used with caution in patients with advanced coronary artery disease, hypertension, or hyperthyroidism. Anxiety, restlessness, and tremor may occur due to the drug’s stimulation effect on the CNS. Patients with hyperthyroidism may experience a severe increase in basal metabolic rate, resulting in increased blood pressure and ventricular tachycardia.
Black Box Warning: Severe reactions, including death, may occur with IV infusion even when appropriate dilution is used to avoid rapid diffusion. Therefore, restrict IV use for situations in which other routes are not feasible.
Contraindications: This drug should not be used in patients with acute pancreatitis, heart disease, hepatitis, or narrow-angle glaucoma.
INTERACTIONS
Drug-Drug: Drug interactions may occur with MAO inhibitors, causing a hypertensive crisis. Increased effects may also occur with tricyclic antidepressants, ergot alkaloids, and oxytocin. Inhibitory effects occur with alpha blockers and beta blockers. Phenylephrine is incompatible with iron preparations (ferric salts). Phenylephrine may cause dysrhythmias when taken in combination with digoxin.
Describe the properties of the following drug:
Prazosin (Minipress)
Therapeutic Class: Antihypertensive
Pharmacologic Class: Adrenergic-blocking drug
ACTIONS AND USES
Prazosin is a selective alpha1-adrenergic antagonist that competes with norepinephrine at its receptors on vascular smooth muscle in arterioles and veins. Its major action is a rapid decrease in peripheral resistance that reduces blood pressure. It has little effect on cardiac output or heart rate, and it causes less reflex tachycardia than some other drugs in this class. Tolerance to prazosin’s antihypertensive effect may occur. Its most common use is in combination with other agents, such as beta blockers or diuretics, in the pharmacotherapy of hypertension. Prazosin has a short half-life and is often taken two or three times per day.
ADMINISTRATION ALERTS
- Give a low first dose to avoid severe hypotension.
- Safety during pregnancy (category C) or lactation is not established.
PHARMACOKINETICS
Onset
Peak
Duration
2 h
2-4 h
Less than 24 h
ADVERSE EFFECTS
Like other alpha blockers, prazosin tends to cause orthostatic hypotension due to alpha1 inhibition in vascular smooth muscle. In rare cases, this hypotension can cause unconsciousness about 30 minutes after the first dose. To avoid this situation, the first dose should be very low and given at bedtime. Dizziness, drowsiness, or light-headedness may occur. Reflex tachycardia may result from the rapid fall in blood pressure. Alpha blockade may cause nasal congestion or inhibition of ejaculation.
Contraindications: Safety during pregnancy and lactation is not established.
INTERACTIONS
Drug-Drug: Concurrent use of antihypertensives and diuretics results in extremely low blood pressure. Alcohol should be avoided.
Lab Tests: Prazosin increases urinary metabolites of vanillylmandelic acid (VMA) and norepinephrine, which are measured to screen for pheochromocytoma (adrenal tumor). Prazosin will cause false-positive results.
Herbal/Food: Do not use saw palmetto or nettle root products. Saw palmetto blocks alpha1 receptors, resulting in the dilation of blood vessels and a hypotensive response.
Treatment of Overdose: Overdose may cause hypotension. Blood pressure may be elevated by the administration of fluid expanders, such as normal saline, or vasopressors, such as dopamine or dobutamine.j
Describe the properties of the following drug:
Bethanechol (Duvoid, Urecholine)
CHOLINERGIC DRUGS page 142
Direct-Acting Parasympathomimetics page 145
Therapeutic Class: Nonobstructive urinary retention agent
Pharmacologic Class: Muscarinic cholinergic receptor agent
ACTIONS AND USES
Bethanechol is a direct-acting parasympathomimetic that interacts with muscarinic receptors to cause actions typical of parasympathetic stimulation. Its effects are most noted in the digestive and urinary tracts, where it stimulates smooth-muscle contraction. These actions are useful in increasing smooth-muscle tone and muscular contractions in the GI tract following general anesthesia. In addition, it is used to treat nonobstructive urinary retention in patients with atony of the bladder. Although poorly absorbed from the GI tract, it may be administered orally or by subcutaneous injection.
ADMINISTRATION ALERTS
- Never administer IM or IV.
- Oral and subcutaneous doses are not interchangeable.
- Monitor blood pressure, pulse, and respirations before administration and for at least 1 hour after subcutaneous administration.
- Pregnancy category C.
PHARMACOKINETICS
Onset
Peak
Duration
30-90 min PO; 5-15 min subcutaneous
60 min PO; 15-30 min subcutaneous
6 h PO; 120 min subcutaneous
ADVERSE EFFECTS
The side effects of bethanechol are predicted from its parasympathetic actions. It should be used with extreme caution in patients with disorders that could be aggravated by increased contractions of the digestive tract, such as suspected obstruction, active ulcer, or inflammatory disease. The same caution should be exercised in patients with suspected urinary obstruction or COPD. Side effects include increased salivation, sweating, abdominal cramping, and hypotension that could lead to fainting.
Contraindications: Patients with asthma, epilepsy, or parkinsonism should not use this drug. Safety in pregnancy and lactation and in children younger than 8 years is not established.
INTERACTIONS
Drug-Drug: Drug interactions with bethanechol include increased cholinergic effects from cholinesterase inhibitors and decreased cholinergic effects from procainamide, quinidine, atropine, and epinephrine.
Lab Tests: Bethanechol may cause an increase in serum AST, amylase, and lipase.
Herbal/Food: Cholinergic effects caused by bethanechol may be antagonized by angel’s trumpet, jimson weed, or scopalia.
Treatment of Overdose: Atropine sulfate is a specific antidote. Subcutaneous injection of atropine is preferred except in emergencies when the IV route may be used.
Physostigmine (Antilirium)
CHOLINERGIC DRUGS page 142
Cholinesterase Inhibitors page 145
Therapeutic Class: Antidote for atropine-induced delirium
Pharmacologic Class: Acetylcholinesterase inhibitor
ACTIONS AND USES
Physostigmine is an indirect-acting parasympathomimetic that inhibits the destruction of Ach by AchE. Its effects occur at the neuromuscular junction and at central and peripheral locations where Ach is the neurotransmitter. It reverses toxic and life-threatening delirium caused by atropine, diphenhydramine, dimenhydrinate, Atropa belladonna (deadly nightshade), or jimson weed. Physostigmine is usually administered as an injectable solution, IM or IV, although it is not intended as a first-line agent for anticholinergic toxicity or Parkinson’s disease.
ADMINISTRATION ALERTS
- Administer slowly over 5 minutes to avoid seizures and respiratory distress.
- Continuous infusions should never be used.
- Monitor blood pressure, pulse, and respirations, and look for hypersalivation.
- Pregnancy category C.
PHARMACOKINETICS
Onset
Peak
Duration
Less than 5 min IM/IV
20-40 min IM/IV
1-2 h IM/IV
ADVERSE EFFECTS
Unfavorable effects of physostigmine are bradycardia, asystole, restlessness, nervousness, seizures, salivation, urinary frequency, muscle twitching, and respiratory paralysis.
Contraindications: Use with caution in patients with asthma, epilepsy, diabetes, cardiovascular disease, or bradycardia. Discontinue if excessive sweating, diarrhea, or frequent urination occurs. Physostigmine is not recommended in patients with known or suspected tricyclic antidepressant (TCA) intoxication.
INTERACTIONS
Drug-Drug: Drug interactions with physostigmine include increased effects from cholinergic agents and beta blockers. The levels of physostigmine may be increased by systemic corticosteroids. Physostigmine may decrease effects of neuromuscular-blocking agents.
Lab Tests: Physostigmine may cause an increase in serum ALT/AST and amylase.
Herbal/Food: Toxic effects caused by physostigmine may be enhanced by Ginkgo biloba.
Treatment of Overdose: Due to the possibility of hypersensitivity or cholinergic crisis, atropine sulfate should be available.
atropine (Atro-Pen) page 151
CHOLINERGIC-BLOCKING DRUGS (ANTICHOLINERGICS) page 147
Therapeutic Class: Antidote for anticholinesterase poisoning
Pharmacologic Class: Muscarinic cholinergic receptor blocker
ACTIONS AND USES
By occupying muscarinic receptors, atropine blocks the parasympathetic actions of Ach and induces symptoms of the fight-or-flight response. Most prominent are increased heart rate, bronchodilation, decreased motility in the GI tract, mydriasis, and decreased secretions from glands. At therapeutic doses, atropine has no effect on nicotinic receptors in ganglia or on skeletal muscle.
Although atropine has been used for centuries for a variety of purposes, its use has declined in recent decades because of the development of safer and more effective medications. Atropine may be used to treat hypermotility diseases of the GI tract such as irritable bowel syndrome, to suppress secretions during surgical procedures, to increase the heart rate in patients with bradycardia, and to dilate the pupil during eye examinations. Once widely used to cause bronchodilation in patients with asthma, atropine is now rarely prescribed for this disorder. Atropine therapy is useful for the treatment of reflexive bradycardia in infants and infantile hypertrophic pyloric stenosis (IHPS).
ADMINISTRATION ALERTS
- Oral and subcutaneous doses are not interchangeable.
- Monitor blood pressure, pulse, and respirations before administration and for at least 1 hour after subcutaneous administration.
- Pregnancy category C.
PHARMACOKINETICS
Onset
Peak
Duration
30 min PO; 5-15 min subcutaneously
60-90 min PO; 15-30 min subcutaneously
6 h PO; 4 h subcutaneously
ADVERSE EFFECTS
The side effects of atropine limit its therapeutic usefulness and are predictable extensions of its autonomic actions. Expected side effects include dry mouth, constipation, urinary retention, and an increased heart rate. Initial CNS excitement may progress to delirium and even coma.
Contraindications: Atropine is contraindicated in patients with glaucoma, because the drug may increase pressure within the eye. Atropine should not be administered to patients with obstructive disorders of the GI tract, paralytic ileus, bladder neck obstruction, benign prostatic hyperplasia, myasthenia gravis, cardiac insufficiency, or acute hemorrhage.
INTERACTIONS
Drug-Drug: Drug interactions with atropine include an increased effect with antihistamines, TCAs, quinidine, and procainamide. Atropine decreases effects of levodopa.
Lab Tests: Unknown.
Herbal/Food: Use with caution with herbal supplements, such as aloe, Serona repens (saw palmetto), buckthorn, and cascara sagrada (the name means sacred bark in Spanish), which may increase atropine’s effect, particularly with chronic use of these herbs.
Treatment of Overdose: Accidental poisoning has occurred in children who eat the colorful, purple berries of the deadly nightshade, mistaking them for cherries. Symptoms of poisoning are those of intense parasympathetic stimulation. Overdose may cause CNS stimulation or depression. A short-acting barbiturate or diazepam (Valium) may be administered to control convulsions. Physostigmine is an antidote for atropine poisoning that quickly reverses the coma caused by large doses of atropine.
