1. 18
Drugs Used to Treat Autonomic Nervous System Conditions

2. Two Major Body Systems Nervous system and endocrine system
Involve high-level integration in the brain
Able to influence processes in distant regions of the body and use negative feedback
Both use chemicals to transmit information

3. Endocrine System Chemicals
Called hormones
Released into blood circulation
Travel to interact with receptors in target tissue
Endocrine system will be covered in Chapter 25.

4. Nervous System Chemicals
Called neurotransmitters
Released from nerve terminals in the synaptic cleft
Interact with receptors on neurons or effectors

5. Figure 18-1 Divisions of the nervous system.

6. Central Nervous System (CNS)
Brain and spinal cord
Receives and processes information and initiates action

7. Peripheral Nervous System (PNS)
Outside the brain and spinal cord
Autonomic nervous system (ANS) is one division; has motor and sensory neurons
Motor neurons: sympathetic nervous system (fight-or-flight responses) and parasympathetic nervous system (rest- and-digest responses)

8. Neuron Basic functional unit cell of nervous system
Neurons communicate at the synapse (junction over which nerve impulses pass).
Originating neuron is termed presynaptic.
Receiving neuron is called postsynaptic.

9. Neurotransmitters
Neurotransmitters: chemicals that bridge the synapses
In ANS, the two main chemicals are acetylcholine (ACh) and norepinephrine (NE).

10. Neurotransmitters
When neurotransmitters cross the synapse they reach a receptor.
Drugs work like neurotransmitters: They can enhance neurotransmitter activity or block neurotransmitters from reaching receptor.

11. Figure 18-2A In the autonomic pathway (A), nerve impulses (B; shown as arrows) travel along a presynaptic neuron to reach the junction between two neurons called the synapses. Chemicals called neurotransmitters (shown as triangles) must cross the synapses to carry the nerve impulse to the postsynaptic neuron. When the neurotransmitters cross the synapses, they reach a receptor (C). Many drugs act as neurotransmitters or they act by blocking the neurotransmitters from reaching a receptor or enhancing the activity of neurotransmitters so that more of them reach the receptor.

12. Figure 18-2B In the autonomic pathway (A), nerve impulses (B; shown as arrows) travel along a presynaptic neuron to reach the junction between two neurons called the synapses. Chemicals called neurotransmitters (shown as triangles) must cross the synapses to carry the nerve impulse to the postsynaptic neuron. When the neurotransmitters cross the synapses, they reach a receptor (C). Many drugs act as neurotransmitters or they act by blocking the neurotransmitters from reaching a receptor or enhancing the activity of neurotransmitters so that more of them reach the receptor.

13. Figure 18-2C In the autonomic pathway (A), nerve impulses (B; shown as arrows) travel along a presynaptic neuron to reach the junction between two neurons called the synapses. Chemicals called neurotransmitters (shown as triangles) must cross the synapses to carry the nerve impulse to the postsynaptic neuron. When the neurotransmitters cross the synapses, they reach a receptor (C). Many drugs act as neurotransmitters or they act by blocking the neurotransmitters from reaching a receptor or enhancing the activity of neurotransmitters so that more of them reach the receptor.

14. Sympathetic Nervous System
Ganglion: aggregation of nerve cell fibers
Acetylcholine: neurotransmitter released by preganglionic neurons of CNS
Norepinephrine: main neurotransmitter released by postganglionic neurons

15. Receptors Cholinergic: receptors to which acetylcholine binds
Adrenergic: receptors to which norepinephrine, dopamine, and epinephrine bind

16. Parasympathetic Nervous System
Parasympathetic preganglionic fibers exit the CNS through cranial nerves and sacral spinal roots and travel to innervated tissues.
Both parasympathetic preganglionic and postganglionic neurons release acetylcholine.

17. Figure 18-3A Receptors in the autonomic nervous system
Figure 18-3A Receptors in the autonomic nervous system. A: Sympathetic pathways (acetylcholine [ACh] and norepinephrine [NE]).

18. Figure 18-3B Receptors in the autonomic nervous system
Figure 18-3B Receptors in the autonomic nervous system. B: Parasympathetic pathway (ACh).

19. Figure “Rest and digest” effects of the parasympathetic nervous system; “fight-or-flight” effects of the sympathetic nervous system.

20. Table 18-1 Autonomic Regulation of Target Organs and Tissues

21. Table 18-1 (continued) Autonomic Regulation of Target Organs and Tissues

22. Adrenergic Receptors
Two main types: alpha (α) and beta (β) which are divided again into α1, α2, β1, and β2.
Alpha-adrenergic receptors are found in vascular smooth muscle.
Beta-adrenergic receptors are found smooth and cardiac muscle.

23. Cholinergic and Cholinergic-blocking Drugs
Drugs that bind to cholinergic receptors are cholinergic agonists; these drugs act like acetylcholine.
Drugs that prevent acetylcholine from acting on receptors are cholinergic-blocking agents or anticholinergics.
Similarly, drugs that bind to adrenergic receptors are called adrenergic agonists or sympathomimetics.

24. Adrenergic Agonists Also called sympathomimetics
Some sympathomimetics are catecholamines:
Norepinephrine (released at nerve terminals)
Epinephrine (released from adrenal medulla)
Dopamine (released from sites in brain, kidneys and GI tract)

25. Drug Effects on ANS
Sympathomimetics (adrenergic agonists): stimulate sympathetic nervous system (fight-or-flight)
Parasympathomimetics (cholinergic agonists): stimulate parasympathetic nervous system (rest-and-digest)

26. Drug Effects on ANS
Adrenergic blockers (sympatholytics) inhibit the sympathetic nervous system.
Anticholinergics (cholinergic blockers) inhibit the parasympathetic nervous system.

27. Focus on Fatty Acids
Essential fatty acids, which cannot be manufactured by the body, are most commonly found in polyunsaturated vegetable oils.
Both omegas 3 and 6 fatty acids are converted in the body to prostaglandins, which affect almost every biologic function including regulation of smooth muscle and autonomic reflexes.

28. Table 18-2 Classifications of Sympathomimetic Drugs

29. Table 18-2 (continued) Classifications of Sympathomimetic Drugs

30. Table 18-2 (continued) Classifications of Sympathomimetic Drugs

31. Alpha1-Receptor Agonists: Uses
Located on blood vessels, muscles of iris, smooth muscle of GI and reproductive tracts, liver cells, sweat glands, and bladder sphincters
Cause vasoconstriction, mydriasis, decreased GI motility, sphincter contraction, increased sweat, decreased bile secretion

32. Alpha1-Receptor Agonists: Uses
Used to treat hypotension, nasal congestion, subconjunctival hemorrhage (red eye)

33. Alpha1-Receptor Agonists: Adverse Effects
Common: blurred vision, constipation, urine retention, gooseflesh, sweating, hypertension

34. Alpha1-Receptor Agonists: Contraindications
Should not be used in patients with glaucoma, severe cardiovascular disease, hypovolemia, acute kidney disease, thyrotoxicosis, supine hypertension, ventricular tachycardia
Should not be given to pregnant or lactating women or children
Numerous drugs interact with these agents.

35. Alpha1-Receptor Agonists: Patient Information
Instruct patients to report hypertension, hyperthyroidism, enlarged prostate, glaucoma, or breastfeeding to physician.
Instruct patients to report use of antihypertensives, thyroid medications, decongestants, and TCAs.

36. Alpha2-Receptor Agonists: Uses
Thought to be located on presynaptic neurons; seem to control neurotransmitter release by presynaptic neurons
Inhibit sympathetic vasomotor centers
Used to treat hypertension (alone or with diuretics)

37. Alpha2-Receptor Agonists: Adverse Effects
Common: hypotension, peripheral edema, dry mouth and eyes, constipation, drowsiness, dizziness, rash, pruritus, impotence, nausea and vomiting, hepatitis, hallucinations, depression, and recurrent herpes simplex

38. Alpha2-Receptor Agonists: Contraindications
Do not give to pregnant or lactating women, children.
Those with scleroderma, hepatitis, cirrhosis, pheochromocytoma, blood dyscrasias, or polyarteritis nodosa should not use these.

39. Alpha2-Receptor Agonists: Contraindications
These drugs interact with alcohol, other CNS depressants, antidepressants, beta-blockers, calcium channel blockers, amphetamines, ephedrine, haloperidol, levodopa, digoxin, and lithium.

40. Alpha2-Receptor Agonists: Patient Information
Instruct patients to report use of other drugs and to check with the physician before taking OTC drugs.
Advise patients to avoid foods with high sodium levels.

41. Beta1-Receptor Agonists: Uses
Receptors are located on myocardium, sphincters and smooth muscle of GI tract, and renal arterioles.

42. Beta1-Receptor Agonists: Uses
Work to increase rate and force of heart contractions, increase lipolysis in adipose tissue, decrease digestion and GI motility, and increase glomerular filtration
Used to treat circulatory shock, hypotension, and cardiac arrest

43. Beta1-Receptor Agonists: Adverse Effects
Hypertension
Tachycardia
Constipation

44. Beta1-Receptor Agonists: Contraindications
Patients with ventricular tachycardia or who are pregnant or lactating should not take these agents.
Avoid in patients after myocardial infarction.
Interactions occur with general anesthetics, beta-blockers, and antidepressants.

45. Beta1-Receptor Agonists: Patient Information
Alert patients that sputum and saliva may turn pink after inhalation of isoproterenol.
Warn women not to breast feed.
Instruct patients not to change doses, omit doses, or change intervals between doses.
Instruct patients to immediately report chest pain.

46. Beta2-Receptor Agonists: Uses
Receptors are located in smooth muscle of bronchioles; skeletal muscle; blood vessels supplying the heart, brain, kidneys, and skeletal muscle; uterus; and liver cells.
Cause bronchodilation, increased muscle excitability, vasodilation, and uterine relaxation

47. Beta2-Receptor Agonists: Uses
Used to treat chronic obstruct airway disease, circulatory shock, premature labor, peripheral vascular disease

48. Beta2-Receptor Agonists: Adverse Effects
Common: muscle tremor in hands, increased muscle tension, feelings of warmth
Also cause hyperglycemia

49. Beta2-Receptor Agonists: Contraindications
Should not be used in pregnancy or lactation, by children, or in those with cardiac arrhythmias, hyperthyroidism, preeclampsia, eclampsia, hypertension, diabetes, hypovolemia, coronary artery disease, or glaucoma
Interact with beta-blockers, corticosteroids, epinephrine, other bronchodilators, antidepressants

50. Beta2-Receptor Agonists: Patient Information
Demonstrate how to use inhaler correctly.
Warn patients not to change dose or frequency of dose.
Explain that these drugs may cause dizziness or tremors.
Advise patients to check with their physician before using any OTC drugs.

51. Adrenergic Antagonists (Sympatholytics)
Direct acting: have affinity for receptor, but block normal response
Indirect acting: block adrenergic nerve transmission by inhibiting release of neurotransmitter or depleting stores of neurotransmitter

52. Table 18-3 Adrenergic Antagonists

53. Table 18-3 (continued) Adrenergic Antagonists

54. Table 18-3 (continued) Adrenergic Antagonists

55. Table 18-3 (continued) Adrenergic Antagonists

56. Table 18-3 (continued) Adrenergic Antagonists

57. Alpha-Receptor Antagonists: Uses
Inhibit actions of adrenoreceptors, producing vasodilation in arterioles and veins
Used to control hypertension and treat peripheral vascular disease, urine retention, and adrenal medulla tumor

58. Alpha-Receptor Antagonists: Adverse Effects
Nasal congestion and stuffiness
Postural hypotension
Inhibition of ejaculation
Lack of energy

59. Alpha-Receptor Antagonists: Contraindications
Contraindicated in patients with known sensitivity to these drugs
Interact with diuretics, ephedrine, epinephrine, methoxamine, norepinephrine, other hypotensive agents, NSAIDs, and phenylephrine

60. Alpha-Receptor Antagonists: Patient Information
Advise patients to change positions slowly and to avoid driving after first dose to determine side effects.
Warn women not to breast feed.
Warn patients to check with their physician before taking OTC drugs for coughs, colds, or allergies.

61. Beta-Receptor Antagonists: Uses
Most work by occupying beta receptors to block all activation.
Used to treat hypertension, cardiac arrhythmias, myocardial infarction, tachycardia, angina pectoris, pheochromocytoma, hypertrophic subaortic stenosis

62. Beta-Receptor Antagonists: Adverse Effects
Dizziness
Lethargy
Insomnia
Diarrhea

63. Beta-Receptor Antagonists: Contraindications
Should not be used in patients with heart block, severe heart failure, cardiogenic shock, circulatory disorders, asthma, or chronic obstructive airway disorders, or in lactating women
Interact with phenothiazines, atropine, beta-agonists, antidepressants, diuretics, antacids and other drugs

64. Beta-Receptor Antagonists: Patient Information
Teach patients to take their heart rate and blood pressure and report decreases in either.
Advise patients to change positions slowly and not drive until side effects are known.

65. Beta-Receptor Antagonists: Patient Information
Warn patients not to stop drugs abruptly.
Tell patients to check with their physician before taking OTC drugs for cough, colds, or allergies.

66. Parasympathomimetics (Cholinergic Agonists)
Stimulate parasympathetic nervous system by mimicking acetylcholine
Two types: muscarinic and nicotinic
Muscarinic innervate smooth muscle and slow heart rate
Nicotinic affect skeletal muscle

67. Table 18-4 Cholinergic Agents

68. Table 18-4 (continued) Cholinergic Agents

69. Parasympathomimetics: Uses
Used to treat glaucoma, constipation, congenital megacolon, postpartum intestinal ileus, reflux esophagitis, neurogenic bladder with retention
Used to diagnose atrial tachycardia and asthma

70. Parasympathomimetics: Adverse Effects
Common: flushing, sweating, abdominal cramps, headache, nausea and vomiting, diarrhea
Serious: convulsions at high doses

71. Parasympathomimetics: Contraindications
Should not be used in patients with atrioventricular arrhythmias, coronary insufficiency, hyperthyroidism, asthma, peptic ulcer
Interact with beta-adrenergic blockers, other cholinesterase inhibitors, atropine, and other drugs

72. Parasympathomimetics: Patient Information
Advise patients to report all other drugs they are taking.
Caution patients to change positions slowly.
Warn patients not to breast feed.
Explain that increased sweating and urination may occur.

73. Cholinergic Blockers
Also called parasympatholytics or anticholinergics
Affect the heart, respiratory tract, bladder, eyes, GI tract, and sweat glands

74. Atropine (Atropair, AtroPen): Uses
Acts by selectively blocking muscarinic responses to acetylcholine
Used to treat symptoms of GI disorders, ophthalmic disorders, cardiac conditions, bronchial conditions, chronic obstructive airway disease, and upper respiratory infections

75. Atropine: Adverse Effects
Common: dry mouth, decreased perspiration, blurred vision, tachycardia, constipation, urine retention
Serious: coma

76. Atropine: Contraindications
Should be avoided in patients with glaucoma, obstructive uropathy, intestinal atony, paralytic ileus, GI obstructions, ulcerative colitis, toxic megacolon, tachycardia, acute hemorrhage, and myasthenia gravis
Interacts with antihistamines, antidepressants, phenothiazines, and other drugs

77. Atropine: Patient Information
Encourage patients to use mouth rinses, chew gum, or suck ice to relieve dry mouth.
Caution patients to avoid driving.
Warn patients not to breast feed while taking this drug.
Tell patients to report a fast heartbeat or palpitations.

78. Ecstasy and the ANS
The illegal drug known as Ecstasy (XTC) was originally patented as an appetite suppressant.
Data now show that this drug may be toxic to the brain.
Studies have shown a 20 to 60% reduction in healthy serotonin cells in the brains of Ecstasy users, damaging their ability to remember and learn.