Drugs Affecting the Autonomic Nervous System Flashcards
1
Q
Sympathetic effect is the same as
A
Adrenergic effect or
Anticholinergic effect
2
Q
Parasympathetic effect is the same as
A
Cholinergic effect or
Muscarinic effect
3
Q
Stimulation of Alpha-2 receptors creates
A
creates a negative feedback loop and inhibits sympathetic outflow (aka sympatholytic).
Alpha2 Adrenergic Agonists Sympathetic effects: Dry mouth, constipation, nausea and gastric upset. Sympatholytic effects (similar to parasympathetic): Bradycardia, hypotension, and impotence.
4
Q
The following drugs have sympathetic effects
A
Adrenergic Agonists
Anticholinergics
5
Q
The following drugs have parasympathetic effects
A
Cholinergic Agonists
Alpha Adrenergic Antagonists
Beta Adrenergic Antagonists
Anticholinesterase (AChE) inhibitors
6
Q
NE receptors (adrenergic):
A
Norepinephrine is the neurotransmitter at the synapse between the postganglionic sympathetic neuron and the effector tissue.
7
Q
Epinephrine is released
A
Epinephrine is released from the adrenal medulla with sympathetic stimulation.
8
Q
Norepinephrine receptors are subdivided into:
A
Alpha-1 (postsynaptic) Alpha-2 (presynaptic) Beta-1 Beta-2 Dopamine
9
Q
Alpha-1 receptors
A
Alpha-1 (postsynaptic) causes vasoconstriction, mydriasis (radial muscles of eye contract), GI/bladder sphincter contraction
10
Q
Alpha-2 receptors
A
Alpha-2 (presynaptic) negative feedback loop inhibiting subsequent release of neurotransmitter.
VASODILATION = lowers BP
Up- and down-regulation are known to occur in response to decreased or increased activation of receptors.
Alpha-2 receptors are also present at extrasynaptic sites in blood vessels and in the CNS. Stimulation of central alpha-2 receptors in the brainstem decreases sympathetic outflow. Stimulation of alpha-2 receptors in the pancreas inhibits insulin release.
11
Q
Beta-1 receptors
A
Beta-1 (predominately cardiac) stimulation produces increase in heart rate and strength of contraction.
Some drugs seem to have a greater effect on strength of contraction than on rate.
12
Q
Beta-2 receptors
A
Beta-2 (predominately non-cardiac) receptors are found on smooth muscle [e.g., bronchi; large blood vessels], bronchodilation, vasodilation, GI relaxation, uterine relaxation, glycogenolysis (hyperglycemia).
Beta-2 receptors also promote insulin release, and, in liver & muscle, gluconeogenesis & glycogenolysis as well as lipolysis in fat cells.
13
Q
Dopamine receptors
A
Dopamine-1 (postsynaptic) receptor activation is responsible for vasodilation in splanchnic & renal circulations.
Dopamine-2 (presynaptic) receptors initiate a negative feedback loop.
At least five varieties of dopamine receptors are found in brain.
14
Q
ACh receptors
A
Cholinergic receptors are designated as:
Muscarinic
Nicotinic
15
Q
Muscarinic receptors
A
Muscarinic - found at postganglionic parasympathetic endings (heart; smooth muscle; glands).
16
Q
Nicotinic receptors
A
Nicotinic - found in autonomic ganglia, adrenal medulla, CNS (and at neuromuscular junction in skeletal muscle – somatic nervous system as listed above).
17
Q
ANS receptors
A
- NE receptors
2. Cholinergic receptors
18
Q
Postganglionic neurotransmitter sympathetic effect
A
NE released
19
Q
Postganglionic neurotransmitter parasympathetic effect
A
Ach released
20
Q
Name(s) for agonists
A
-mimetic
21
Q
Name(s) for antagonists
A
-lytic
Inhibitor
Blocker
22
Q
Adrenergic drugs
A
Adrenergic agonist Sympathomimetic Catecholamines Alpha (-1 or -2) adrenergic, beta (-1 or -2) adrenergic "-ine"
23
Q
Adrenergic-blocking drugs
A
Alpha-antagonist Alpha-adrenergic antagonist Sympatholytic Anti-adrenergic Alpha (-1 or -2) blockers, beta (-1 or -2) blockers
24
Q
Cholinergic drugs
A
Muscarinic agonist
Parasympathomimetic
Cholinomimetic
25
Cholinergic-blocking drugs
Cholinergic antagonist
Anticholinergic
Antimuscarinic
Parasympatholytic
26
Uses of Adrenergic Drugs
Eye: Mydriasis (dilate eyes for eye exam)
Resp: Cause bronchodilation and manage anaphylactic shock
CV: Improve myocardial contractility, increase in heart rate and blood pressure
GI/GU: Decrease peristalsis
Endocrine: Increases blood sugar
Prolong local anesthetics
27
General ADRs of Adrenergic Drugs
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Fear
Restlessness
Headache
Tremor
Palpitations
Pallor
Serious ADRs
Stroke
V-Fib
```
28
Phenylephrine (Neo-synephrine)
Receptor: Selective Alpha-1 Agonist
Action: Vasopressor
Uses: Treat congestion, hypotension, uveitis
29
Clonidine (Catapres)
Alpha-2 Agonist
MOA: Causes vasodilation by stimulating inhibitory alpha-adrenergic receptors in the brain (centrally)
Uses:
Lowers blood pressure (2nd or 3rd line) and heart rate
Used for treatment of withdrawal symptoms (ETOH, nicotine, heroin)
Used for attention deficit hyperactivity disorder
Adverse drug reactions (ADRs):
Sedation, dry mouth, and postural hypotension occur but these usually decrease after several weeks of therapy. Sodium and water retention may occur. Bradycardia, Skin rashes, constipation, urinary retention, impotence, and nightmares may occur .
Abrupt discontinuation of clonidine can result in Rebound Hypertension as soon as 8 and as late as 36 hours after the last dose. Gradually taper over 4 days.
Rational drug selection: Caution in elderly because they are at risk for orthostatic hypotension and fluid retention. Cat C Pregnancy
Monitoring: Dose may need adjustment in renal pts
Education: Teach the pt to not stop the drug suddenly.
30
Methyldopa (Aldomet)
Alpha2 Agonist
MOA: Causes vasodilation by stimulating inhibitory alpha-adrenergic receptors in the brain (centrally)
Uses: Lowers blood pressure
Adverse drug reactions (ADRs):
Sedation, hepatotoxicity (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. Retention of sodium and weight gain may occur during treatment.
Abrupt discontinuation can result in rebound hypertension as soon as 8 and as late as 36 hours after the last dose. Gradually taper over 4 days.
Rational drug selection: Cat B Pregnancy, Pts with renal impairment need adjustment of dosing frequency.
31
Dobutamine (Dobutrex)
Beta-1 Agonist
Receptor: Beta-1
Use: Cardiac Decompensation
ADR: Increases heart rate and blood pressure; angina
32
Albuterol
Relatively selective Beta-2 Agonist
Use: Bronchodilation
ADRs: CNS stimulation, palpitation, tremors, shakiness, hyperactivity, headache, and nausea & vomiting. May cause irritable behavior in infants.
Clinical use in adults and children as young as 4 y/o
Rational drug selection:
Caution: Patients at risk include diabetics, hyperthyroidism, subjects with seizures disorders, and the elderly.
Excessive use may cause death, cause unknown but probably cardiac arrest. Oral use may delay preterm labor.
33
Epinephrine (Adrenalin)
Receptors: Alpha 1 & 2; Beta 1 & 2
Uses: Prolong local anesthetics, Treat allergic reactions, CPR, Status Asthmaticus
34
Norepinephrine (Levarterenol)
Receptors: Alpha 1; Less Beta 1
Uses: Treat hypotension
35
Dopamine (Intropin)
Receptors: Dopamine; Beta-1; Alpha 1 (dose dependent)
Causes: Renal Vasodilation; Stimulates heart
Use: Shock syndrome
ADR: Palpitations, hypotension
36
Pseudoephedrine (Sudafed)
Receptors: Alpha & Beta-2
Uses: Decongestant
ADR: Nervousness, insomnia, arrhythmias, tachycardia, headache
Warnings: HBP, CAD, glaucoma, hyperthyroidism, BPH, DM
37
Amphetamine/ Methylphenidate (Ritalin)
Receptors: Direct and Indirect Adrenergic
Uses: ADHD, Narcolepsy
ADR: Nervousness, insomnia, arrhythmias, tachycardia, headache
Warnings: HBP, CAD, glaucoma, hyperthyroidism, BPH, DM
38
Alpha-1 Blockers
“-zosin”
Prazosin (Minipress), Doxazosin (Cardura), Terazosin (Hytrin): Used for HTN
Tamsulosin (Flomax): Used for BPH
ADRs: fluid retention, orthostatic HTN, dry mouth, constipation, urinary retention, etc.
Warning: 1st dose effect = excess postural hypotension that can occur within 30-90 min of the first few doses
The patient will adjust to the medication with successive doses.
To avoid: Take at bedtime; start at 1mg, and titrate up every 2 weeks.
Rational Drug Selection: Doxazosin less likely to cause 1st dose effect.
39
Beta Blockers
"-olol”
Propranolol (non-selective) vs. atenolol (selective)
Uses: Angina, HTN, HF, arrhythmias, migraine prophylaxis, thyrotoxicosis
ADRs:
Dizziness, lethargy/ fatigue, nightmares, mental status changes in elderly, impotence
Warning: DO NOT STOP ABRUPTLY (life threatening, especially in pts with angina and CAD) d/t up-regulation.
Myocardial ischemia or cardiac arrhythmias may occur.
40
ADRs of Beta-1 Blockers
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).
41
ADRs of Beta-2 Blockers
Bronchoconstriction and hypoglycemia (from inhibition of glycogenolysis).
42
Contraindications of Beta Blockers
(Esp. non-selective) Asthma or any bronchospastic condition.
Caution in diabetics: masks hypoglycemic symptoms EXCEPT diaphoresis.
Avoid in pregnant & nursing women.
43
Interactions of medications with Beta Blockers
OTC Cold remedies (pseudoephedrine, ephedrine, phenyephrine) - can have unopposed alpha-adrenergic stimulation (excessive HTN & tachycardia); Clonidine (fatalities).
44
Combined Beta Blockers
Combined Beta Blockers (nonselective) with alpha blocking activity (e.g., labetalol [Normodyne]) & carvedilol [Coreg]).
Used to reduce the progression on heart failure because they cause vasodilation of the peripheral vasculature
Especially effective in African Americans
45
Beta Blockers for asthmatics and diabetics
```
Cardioselective beta blockers avoid bronchoconstriction.
Beta blockers depend on the location of the receptor on the smooth muscle.
Nonselective BB (eg. propanolol) affect both Beta-1 and Beta-2 receptors and result in decreases in heart rate, myocardial contractility, myocardial oxygen demand, blood pressure, AND bronchoconstriction, AND hypoglycemia. Thus, we would not give this medication (non-selective BB) to an asthmatic or diabetic.
```
46
Dosing in renal patients
Loading doses usually do not need to be adjusted in patients with chronic kidney disease.
Maintenance dosing adjustments: dose reduction, lengthening the dosing interval, or both.
Dose reduction involves reducing each dose while maintaining the normal dosing interval.
This approach maintains more constant drug concentrations, but it is associated with a higher risk of toxicities if the dosing interval is inadequate to allow for drug elimination.
Normal doses are maintained with the extended interval method, but the dosing interval is lengthened to allow time for drug elimination before redosing.
Lengthening the dosing interval has been associated with a lower risk of toxicities but a higher risk of subtherapeutic drug concentrations, especially toward the end of the dosing interval.
47
Cholinergic Agonists are also called
parasympathomimetics, muscarinic agonists
48
Direct-acting cholinergic drugs
Prototype: bethanechol (Urecholine)
Prototype: pilocarpine (Pilocar)
Two types of drugs are used: derivatives of acetylcholine (carbachol, bethanechol [Urecholine]) and cholinomimetic alkaloids (pilocarpine).
49
Indirect-acting cholinergic drugs
Cholinesterase inhibitors
Peripheral-Acting: Prototype: neostigmine bromide (Prostigmin)
Central-Acting: Donepezil (Aricept)
50
Main Uses of Cholinergic Drugs
Eyes: Decrease intraocular pressure in glaucoma, miosis
Resp: Stimulates secretions in the tracheobronchial tree, produces bronchoconstriction
Cardiovascular: Decrease in heart rate and force of contractility is due to cholinergic innervation of the SA and AV nodes and atrial muscle.
GI: Increased tone and amplitude of contraction, peristaltic activity, and secretory action.
Urinary tract: Increase in ureteral peristalsis and contraction of the detrusor muscle.
Neuromuscular: Treat Myasthenia gravis, Reverse neuromuscular block
51
General ADRs of Cholinergic Drugs
```
GI discomfort (nausea, vomiting, diarrhea, belching, salivation, and intestinal cramps)
Bradycardia
Bronchoconstriction
```
52
Bethanechol (Urecholine)
Direct-acting cholinergic drug
MOA:
Increases tone of detrusor muscle and causes bladder contractions
Increases tone of the lower esophageal sphincter
Clinical Indications:
Urinary retention (Post-op & post-partum)
ADRs:
Initially: Abdominal discomfort/ epigastric pain, salivation, flushed skin, sweating, nausea, vomiting, and miosis are common.
Toxic reactions: include intense cramping, diarrhea, urination, bradycardia, and bronchoconstriction.
Contraindications: COPD, asthma, hyperthyroidism, peptic ulcer
Education: To avoid nausea & vomiting, take 1 hour before or 2 hours after meals.
53
Pilocarpine (Pilopine)
Used primarily as an ophthalmic solution in the treatment of open-angle glaucoma where, by contracting the ciliary muscle, outflow of aqueous humor is improved and intraocular pressure reduced within minutes.
Used also to treat of xerostomia and Sjogren ’s syndrome because it increases salivation.
54
Prototype of (Acetyl)cholinesterase inhibitors
```
neostigmine bromide (Prostigmin);
Also use pyridostigmine (Regonol)
```
55
MOA, Uses and ADRs of (Acetyl)cholinesterase inhibitors
MOA:
These drugs produce reversible inhibition of AChE (which destroys Ach) by formation of a carbamyl-ester complex which dissociates slowly, hence provides longer action of Ach.
They act preferentially at the neuromuscular junction (NMJ) and restore skeletal muscle strength by increasing the availability of acetylcholine.
Use: Myasthenia gravis and Nondepol Neuromuscular Blockade Reversal
ADRs: nausea, diarrhea, and excessive salivation.
Caution in patients with asthma. If muscarinic effects of such therapy are prominent, they can be controlled by the administration of atropine.
Note that there is a short amount of time between the occurrence of ADRs and Toxicity.
Toxicity- emergency treatment needed if you see fasciculations of voluntary muscles.
56
Donepezil (Aricept)
Central (acetyl)cholinesterase inhibitor
MOA: inhibits AChE; thus causing an increase in Ach
Use: treatment of mild to moderate Alzheimer's disease. Among those who benefit, improvements are seen in quality of life and cognitive functions (eg, memory, thought, reasoning). There is no evidence the drug leads to substantial functional improvement or prevents progression of Alzheimer’s.
ADRs: Most ADRs are related to increased cholinergic (muscarinic) effects including GI effects such as nausea and diarrhea, increases gastric acid secretion (monitor for occult bleeding), syncope, bradycardia (thus should be taken at bedtime)
Has advantages over other drugs such as Tacrine- (once-a day dosing), lower side effect profile, and does not require LFTs for hepatoxicity.
57
Anticholinergic Drugs
MOA: Block Ach at muscarinic receptors
Prototype: atropine
58
Uses for Anticholinergic Drugs
```
Eyes: Mydriasis
CV: Block vagal impulses to heart; Reverse sinus bradycardia (increase heart rate)
Resp: Bronchodilation, Suppress respiratory secretions pre-op
GI: Decreased secretions and tone
GU: Bladder spasms
CNS
Treat tremors/rigidity of Parkinsonism
Treat EPS from psychotropic medications
Sedation
Motion Sickness
```
59
General ADRs of Anticholinergics
```
Photophobia
Increased Intraocular Pressure
Dry Mouth
Constipation
Urinary retention
Drowsiness
Central Anticholinergic Syndrome/ Anticholinergic toxicity (antidote is physostigmine salicylate- increases Ach)
Scopolamine (and to lesser extent, atropine) can enter the CNS and produce symptoms characterized as the central anticholinergic syndrome. Symptoms range from restlessness and hallucinations to somnolence & unconsciousness. The main symptoms are drowsiness, coma, excitation, agitation, hallucinations, motor incoordination, short-term memory loss, disorientation, emotional instability, central hyperpyrexia, and shivering.
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60
Atropine
Used to reverse severe sinus bradycardia in adults and neonates, especially when due to parasympathetic influence (e.g., digoxin, beta blockers)
Atropine decreases the tone of the smooth muscle of the biliary tract & ureter and produce relaxation.
61
Glycopyrrolate [Robinul]
A quaternary amine, is devoid of sedative effect
62
Scopolamine
(Or Atropine) is administered prior to induction of anesthesia to protect heart from vagal reflexes and prevent excessive salivary & 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.
63
Ipratropium (Atrovent)
Bronchoconstriction: Anticholinergic drugs can relax bronchial smooth muscles by blocking the constrictor effects of the vagus nerve.
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 should be used cautiously in asthmatic patients because of drying of secretions and increased risk of mucus plugs.
64
Oxybutynin (Ditropan XL)
Prototype of overactive bladder drugs.
Oxybutynin is both an antimuscarinic and an antispasmodic. It easily crosses the blood-brain barrier, thus has a higher rate of CNS adverse effects.
Inform the patient that adverse effects include xerostomia (70%) constipation, urinary retention, and blurred vision. Alcohol may enhance the drowsiness.
65
Tolterodine (Detrol)
Commonly advertised drug for overactive bladder.
66
Diphenhydramine [Benadryl]
Often recommended to alleviate extrapyramidal symptoms (EPS) associated with conventional antipsychotic agents.
67
Benztropine [Cogentin]
Centrally acting antimuscarinic drugs reduce Parkinsonian tremor and rigidity seem to result from a relative excess of cholinergic activity in the basal ganglia system.
