Pharmacology of the Peripheral Nervous System Flashcards Preview

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Flashcards in Pharmacology of the Peripheral Nervous System Deck (86):
1

drugs that affect the ANS are used in what

-anesthesia and emergency medicine
-treatment of allergic reactions, cardiovascular disease, gastrointestinal/urologic disorders, asthma, psychiatric disorders, and glaucoma

2

adverse rxns to PNS drugs are due to

expression through interactions with receptors in the ANS

3

drugs that directly affect somatic responses at skeletal muscles are used when?

-during surgical procedures and in the ICU to limit movement
-in treatment of myasthenia gravis

4

see slides 2&3

see slides 2&3

5

where do neurohumoral transmissions occur

btwn nerve cells (across synapses) and btwn nerve cells and effectors cells (across neuroeffector junctions)

6

what are the 2 major neurotransmitters in the PNS

1. Acetylcholine (ACh)
2. Norepinephrine (NE)

7

what are the steps in neurotransmission

1. synthesis of neurotransmitter
2. sotrage of neurotransmitter
3. release of neurotransmitter
4. receptor binding (recognition) of neurotransmitter
5. inactivation of neurotransmitter

8

see slide 6

see slide 6

9

what type of neurotransmitter is acetylcholine

a cholinergic

10

where is acetylcholine stored

in synaptic vesicles via a proton antiporter

11

see slides 8-12

see slides 8-12

12

what are the adrenergic receptors

alpha1, alpha2 (3 subtupes each)
beta1, beta2, beta3

13

what are the cholinergic receptors

nicotinic receptors: Nn, Nm (sodium channels compromised of 5 subints)

muscarinic receptors: M1,M2,M3,M4,M5

14

where are alpha 1 receptors located

-vascular smooth m.
-pupillary radial m.
-genitourinary smooth m.
-sphincters
-pilomotor smooth m.
-sweat glands

15

what are the physiological responses of Alpha 1 receptors

Contraction (vasoconstriction;  TPR)
Contraction (dilates pupil)
Contraction
Contraction
Contraction (erects hair)
Secretion

16

where are alpha 2 receptors located

Some vascular smooth muscle
Presynaptic (NE, some ACh nerves)
Platelets
Pancreas
CNS

17

what are the physiological responses of Alpha 2 receptor

Contraction (vasoconstriction)
Inhibits NT release
Aggregation
Inhibits insulin release
Multiple sites ( sympathetic outflow)

18

see slides 14-21

see slides 14-21

19

what are the catecholamines

1. epinephrine
2. norepinephrine
3. dopamine

20

what are the uses of Epinephrine

Anaphylaxis, Vasoconstrictor added to local anesthetics, topical hemostatic, cardiac rescue

21

what are the uses of norepinephrine

blood pressure support

22

what are the uses of dopamine

severe CHF; cardiogenic/septic shock

23

see slide 23

see slide 23

24

what are the types of Adrenergic Agonists

1. direct
2. indirect (amphetamine, tyramine)
3. mixed (ephedrine)

25

the clinical effects of alpha receptor agonists are due to what

activation of alpha-adrenergic receptors in vascular smooth m.

26

what are the clinical effects of alpha receptor agonists

-peripheral vascular resistance is increased
-blood pressure is maintained or elevated
-useful in some patients with hypotension or shock
-also are used topically as nasal decongestants

27

what are the direct acting Alpha-1 Selective agonists

-Phenylephrine
-methoxamine
-several "azoline" derivaties

28

what are mixed acting Alpha-1 Selective agonists

Metaraminol

29

what is the therapeutic use of alpha-2 selective agonists

-used for the treatment of hypertension (topically in opthalmology)
-capacity to lower BP results from activation of alpha2- receptors in the CV control centers of the CNS which suppress the outflow of sympathetic nervous system activity form the brain

30

what are the adverse effects of alpha-2 selective agonists

dry mouth and sedation

31

name 3 alpha-2 selective agonists

1. Clonidine
2. Guanfacine, Guanabenz
3. Methyldopa (prodrug)

32

what is the therapeutic use of Beta Receptor Agonists

-treatment of bronchoconstriction in pts with asthma or chronic obstructive pulmonary disease
-occasionally used for cardiac stimulation

33

name 2 nonselective Beta Agonists

1. isoproterenol
2. Epinephrine (also activates alpha receptors)

34

what causes the adverse effects of Beta adrenergic agonists

-stimulation of cardiac Beta-1 receptors
-drugs with preferential affinity for Beta-2 receptors compared with Beta-1 receptors have been developed

35

what are the selective Beta-2 agonists

Metaproterenol
Terbutaline
Albuterol, Pributerol, Fenoterol
Bitolterol (prodrug)
Salmeterol (long acting)
Formoterol (long acting)

36

what are the adverse effects of Beta Agonists

Tachycardia, skeletal muscle tremor, restlessness, apprehension and anxiety, increased plasma glucose, decreased plasma K+

37

see slide 32

see slide 32

38

name a noncompetitive, nonselective alpha blocker

Phenoxybenzamine

39

name 2 competitive, nonselective alpha blocker

Phentolamine; Tolazoline

40

name 5 competitive selective alpha1 blockers

Prazosin, Terazosin, Doxazosin, Alfusozin, Tamsulosin (α1A)

41

what are the adverse effects of alpha blockers

-Decrease in peripheral resistance;  mean blood pressure
-Increase in heart rate and cardiac output (mediated by baroreceptor reflex; less with alpha1 selective blocking agents)
-Improve urine flow in prostatic hypertrophy

42

what are the adverse effects if alpha blocker (continued)

Postural hypotension
Tachycardia
Nasal stuffiness
Weight gain
Psychomotor slowing in some individuals
Inhibition of, or retrograde, ejaculation
Epinephrine “reversal”.

43

what are the clinical uses of alpha blockers

Hypertension
Benign prostatic hypertrophy; urinary flow obstruction
Local vasoconstrictor excess (eg, vasoconstrictor + local anesthetic)
Pheochromacytoma (temporary symptomatic control)

44

how do Beta blockers differ

-in their relative affinity for beta receptors subtypes and pharmacokinetics
-some beta blockers are weak partial agonists of the beta receptors (intrinsic sympathomimetic activity)
-some retain a degree of local anesthetic-like (so-call membrane stabilizing) effect

45

see slide 39

see slide 39

46

what are the side effects of beta blockers

-decreased HR
-lower BP
-enhance cardiac efficiency (improve the balance btwn cardiac oxygen supply and demand)
-antiarrhythmic effects
-lower intraocular pressure
-bronchoconstriction
-metabolic effects
-exacerbate symptoms of PVD
-CNS effects (fatigue, sleep, disturbances, depression)

47

what are the antiarrhythmic effects of beta blockers

-depress SA node
-decrease ectopic pacemaker activity
-slow atrial and AV node refractory pd

48

what are the metabolic effects of beta blockers

-inhibit lipolysis
-delay recovery from, and mask symptoms of hypoglycaemia

49

what are the clinical uses of beta blockers

Hypertension
Supraventricular and ventricular arrhythmias
Angina pectoris
Hypertropic obstructive cardiomyopathy
Post-myocardial infarction (early phase treatment and prophylaxis)
Certain patients with congestive heart failure
Signs and symptoms of hyperthyroidism
Prophylaxis of migraine
Treatment of glaucoma
Social phobia; performance anxiety
Alcohol withdrawal; patients with akathisia

50

see lecture h/o

see lecture h/o

51

see slide 44

see slide 44

52

how is ACh synthesized

choline + acetyl CoA --> Acetylcholine + CoA-SH

53

where is ACh stored

in storage vesicles

54

release of ACh is blocked by what

botulinum toxin; stimulated by spider venom

55

what are the natural alkaloids

1. Muscarine
2. Pilocarpine
3. Nicotinic

56

what is Muscarine isolated from

from the mushroom Amanita muscaria

57

where does muscarine act

almost exclusively at muscarinic receptors

58

where is Pilocarpine isolated from

chief alkaloid obtaiined from the leaflets of S/A shrubs

59

what is the MOA of Pilocarpine

acts on muscarinic agonist

60

what is the therapeutic use of Pilocarpine

-is a MIOTIC agent in the treatment of glaucoma and in the treatment of xerostomia
-sweat and salivary glands are extremely sensitive to the drug

61

what type of receptors are nicotinic receptors

ligand-gated ion channels

62

activation of nicotinic receptors cause what

-a rapid increase in cellular permeability to Na+ and Ca++
-depolarization and excitation

63

what are the 2 agents of Nictonic

-nicotine
-lobeline

64

what are synthetic congeners

chemically related to ACh
-undergo slower rate of hydrolysis
-clinical uses limited to muscarinic effects of bladder and GI-tract

65

what effects do acetylcholinesterase inhibitors cause

-accumulation of Ach at all cholinergic synapses

66

what is the therapeutic use of acetylcholinesterase inhibitors

-myasthenia gravis
-glucoma
- paralytic ileus
-atony of the urinary bladder
-Alzheimer's disease
-as pesticides and chemical warfare agents

67

acetylcholinesterase can reverse the paralysis of

competitive NM blockers and reduce symptoms of atropine-like toxicity

68

what are the side effects of acetylcholinesterase inhibitors

-intoxication manifest as an intense cholinergic response ("cholinergic crisis")
-effects also exerted on skeletal m. and CNS

69

what are the different classification of AChE inhibitors

competitive reversible
alternate substrates; slowly reversible
irreversible (organophophates)

70

what are the effects of AChE inhibitors on eye

miosis; blurred vision; spasm of accommodation

71

what are the effects of AChE inhibitors on the GI

salivation; increased secretions; increased tone and motility; urination; vomiting; diarrhea

72

effects of the AChE inhibitors on respiratory tract

- increased bronchial secretions; watery
nasal discharge; bronchoconstriction; weakness or paralysis of respiratory muscles

73

what are the effects of AChE inhibitors on the cardiovascular system

- bradycardia; decreased cardiac output; hypotension; atrial flutter

74

what are the effects of AChE inhibitors on the CNS

tremor; anxiety; restlessness; convulsions; coma

75

what are the effects of AChE inhibitors on skeletal muscle

fasciculation; increased force of
muscle contraction followed by weakness; muscle paralysis due to depolarizing-type neuromuscular blockade

76

which AChE inhibitors are used to treat Alzheimer's Disease

Tacrine (reversible)
Donepezil (reversible)
Rivastigmine (carbamate)
Galantamine (reversible)

77

what is the function of antimuscarinic such as atropine

-reduces the effect of ACh at muscarinic sites

78

see slide 55

see slide 55

79

what are muscarinic receptor antagonists

-are drugs (organic esters) that inhibit the actions of Ach on autonomic cholinergic nerves and on smooth m. cells that lack parasympathetic innervation

80

what drugs are classificed as belladonna alkaloids

atropine and scopolamine

81

what is the MOA of muscarinic receptor antagonists

-are competitive antagonists of muscarinic agonists competing for a common binding site on the receptor

82

what are the effects of atropine at low doses

Slight cardiac slowing followed by slight increases in heart rate, decreased salivation, inhibition of sweating. At moderate does dryness of mouth is pronounced with tachycardia, mydriasis, and cycloplegia

83

what are the effects of atropine at high doses

Reduced tone and motility in GI tract; decrease in vagus stimulated gastric, pancreatic, intestinal and biliary secretions; urinary retention

84

what are the side effects of atropine

Pulse rapid and weak; iris obliterated; vision very blurred; skin is flushed, hot, and dry; ataxia, restlessness, excitement, hallucinations, delirium, coma

85

what are the clinical uses of muscarinic blockers

Reduce GI tone/motility and bladder voiding
Ocular exams
Anesthesia ( ↓ vagal influences)
Reverse sinus bradycardia
Motion sickness
Treat acute mushroom; AChE(-) poisoning
Adjunct in Parkinson’s disease
Adjunct in bronchial asthma (“tropiums”)

86

what are the limited clinical use of ganglionic blocking agents

controlled hypotension; “bloodless” surgical field