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pharm - Autonomatic Nervous System > ANS > Flashcards

ANS Flashcards

1
Q

Parasympathetic neurotransmitter

A

acetylcholine

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2
Q

Sympathetic neurotransmitters

A

epinephrine, norepinephrine, and dopamine

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3
Q

Adrenergic (sympathetic)

symptoms

A 
Dry mouth 
Dilated pupils,
Increased contractility,
Increased heart rate,
Bronchodilation,
Relaxation of the bladder fundus, sphincter contraction
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4
Q

Cholinergic (parasympathetic)

symptoms

A 
Increased saliva
Constricted pupils 
Bronchoconstriction 
Increased gastrointestinal mucous 
Bladder fundus contraction
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5
Q

Alpha 1 receptors

A

excitation; found in eye, salivary glands, arterioles, post-capillary venules, and GI/GU sphincters; norepinephrine, epinephrine

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6
Q

alpha 2 receptors

A

relaxation; found in presynaptic nerve terminals of smooth muscle, islet cells of pancreas, salivary glands, skin, mucosa; epinephrine

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7
Q

beta 1 reecptors

A

found in heart, brain, kidney, lipocytes; norepinephrine, epinephrine

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8
Q

beta 2 receptors

A

found in smooth muscle of eye, arterioles, venules, bronchioles, liver, pancreas, GI, and GU; epinephrine

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9
Q

α-adrenergic physiological activities

A

Vasoconstriction of arterioles resulting in higher blood pressure
Pupil dilation
Relaxation of the gut

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10
Q

β-adrenergic physiological activities

A

Cardiac acceleration and increased contractility
Vasodilatation of arterioles supplying skeletal muscles
Bronchial relaxation
Uterine relaxation

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11
Q

Primary use depends on the receptors activated:

Alpha1 receptors:

A

nasal congestion, hypotension, dilation of pupils for eye examination

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12
Q

Primary use depends on the receptors activated:

Alpha2 receptors:

A

HTN

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13
Q

Primary use depends on the receptors activated:

Beta1 receptors

A

cardiac arrest, heart failure, shock

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14
Q

Primary use depends on the receptors activated:

Beta2 receptors

A

asthma and premature labor contractions

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15
Q

Alpha2 Agonists

A

Decreases peripheral vascular resistance, renal vascular resistance, heart rate and blood pressure

Reduction of sympathetic tone and increased parasympathetic tone via receptors in the medulla

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16
Q

Alpha2 Agonists

clonidine

A

Lowers blood pressure and heart rate

Used for treatment of withdrawal symptoms of etoh, nicotine, and opioids; ADHD

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17
Q

Alpha2 Agonists

clinical use

A

Second or third line treatment in mild to moderate HTN;

methyldopa is first line in pregnancy

Can cause retention of sodium and fluid (as compensation for lowered BP), so may be used in combination with diuretic

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18
Q

Alpha2 Agonists ADR

A

Drowsiness, dry mouth, hypotension, constitpation urinary retention, impotence

May be inappropriate to use is elderly due to affects on cognitive
function

Result in down regulation of alpha 2 receptors in chronic use, therefore cannot be stopped abruptly—rebound hypertension, especially if also on a beta blocker

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19
Q

alpha2 agonists pharmacokinetics

A

Generally absorbed well PO (clonidine also via skin)
Liver metabolism
Kidney excretion

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20
Q

Alpha2 Agonists Pharmacotherapeutics:

A

Cautious use in pts with severe coronary insufficiency, recent MI, renal impairment, severe cerebrovascular resistance, depression

Methyldopa is the dug in the class that could be used in pregnancy and in pediatrics

Interactions: additive sedative effects, additive hypotensive effects, interaction with psychiatric meds

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21
Q

Alpha2 Agonists monitoring/education

A

Blood pressure
Fluid status and weight
Dose adjustment in renal impairment—check creatinine before initiation of treatment and at a regular intervals thereafter
Check liver function studies at initiation, 6 and 12 months
Take a missed dose as soon as remembered, unless close to time for next dose.; doses should not be doubled
Report any weight gain or swelling

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22
Q

Beta2 Agonists

A

Bronchodilation is main use of these drugs

Albuterol: bronchodilation

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23
Q

Alpha Blockers

A

Block alpha receptors in vascular smooth muscles leading to vasodilation; also receptors in smooth muscle of the bladder neck and prostate
Results in arterial and venous dilation

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24
Q

Alpha Blockers meds

A

Doxazosin (Cardura)
Used for HTN
Tamulosin (Flomax)
Used to relieve outflow obstruction in BPH

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25
Q

Alpha Blockers clinical use

A

Used to treat HTN and benign prostatic hyperplasia (BPH)
Not used as first line treatment in HTN due to increased risk for heart failure (doxazosin, ALLHAT trial) and general side effects, however treatment of choice for older men with HTN and BPH
Tamulosin, alfuzosin, and silodosin have increased selectivity for receptors in the prostate (therefore little effect on BP)
Doxazosin lowers LDL levels, enhance insulin sensitivity, cause regression of LV hypertrophy
Tamulosin and Doxazosin can be used for expulsion of ureteral stones

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26
Q

alpha blockers ADR

A

Orthostatic hypotension with syncope within 30 – 90 minutes

fluid retention

To reduce risk of/consequences of orthostatic hypotension: start with low dose and titrate up, take before bed
Doxazosin is least likely to produce postural hypotension and fluid retention

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27
Q

alpha blokcers pharmacokinetics

A

Tamulosin administered 30 minutes after same meal each day
Liver metabolism
Tamulosin metabolized via CYP450 enzymes
Doxazosin has significant first-pass metabolism and is eliminated biphasic due to enterohepatic recycling
Kidney and feces excretion

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28
Q

alpha blockers pharmacotherapeutics

A

Contraindicated in setting of volume depletion
Peripheral vasodilation leads to decreased venous return and can precipitate heart failure—may be associated with fluid retention
No dosage changes required for renal or hepatic impairment
Safety and efficacy is not established in children; not to be used in pregnancy
Interactions: additive or contradictory effects with antihypertensives, alcohol and nitrates—doxazosin has the fewest interactions

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29
Q

alpha blockers monitoring/education

A

Monitor: BP, weight change, WBC count, liver function tests
Cancer screening with BPH dx
Take a missed dose as soon as remembered, unless close to time for next dose.; doses should not be doubled
Avoid NSAIDs
Teach pts about BPH symptoms, weight gain/edema, orthostatic hypotension, and to report impotence

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30
Q

Beta Blockers

A

Selective vs. non-selective beta blockers
Drugs can be “selective” to beta1 receptors or to beta2 receptors
Antagonizes or blocks the effects of catecholamines
Angina, HTN, heart failure, post MI, migraine prophylaxis, arrhythmias, hyperthyroid, essential tremor

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31
Q

Beta Blockers meds

A

Metoprolol, atenolol

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32
Q

Beta Blockers clinical use beta1

A

The highest concentration of beta1 receptors is in the heart and influence heart rate (SA node), slow conduction (AV node) and myocardial contractility (atria and ventricles) – lead to clinical effects of reduced angina, reduced dysrhythmias with rapid rhythms, reduced BP, reduced reflex orthostatic tachycardia (reduced oxygen demand)
Used in combo with diuretics to reduce morbidity and mortality for HTN
Decreases mortality in post-MI pts

Blockade of beta1 receptors in the juxtaglomerular apparatus reduces the release of renin, leading to less angiotensin II mediated

33
Q

Beta Blockers clinical use beta2

A

Blockade of beta2 receptors initially causes vasoconstriction and increased peripheral vascular resistance (PVR), but with chronic administration, through a central mechanism, the PVR reduces

34
Q

Beta Blockers: blockade of beta2 receptors in lungs

A

bronchoconstriction

35
Q

Beta Blockers: blockade beta2 receptors in liver

A

inhibits lipolysis, leading to increased TG and cholesterol and decreased HDL; inhibits gluconeogenesis and insulin secretion

36
Q

Beta Blockers ADR

A

bradycardia, hypotension, fatigue (18/1000), dizziness

most mild and transient

37
Q

Beta Blockers pharmacokinetics

A

Well absorbed PO
Propranolol with highest CNS penetration
Liver metabolism—dosage decreases needed in pts with hepatic impairment
Elimination via bile and feces
Dosage adjustment needed in renal impairment as varying percentages of beta blockers are excreted unchanged via the kidneys

38
Q

Beta Blockers pharmacotherapeutics

A

Beta blockade can be dangerous in pts who’s heart is severely damaged
Upregulation of beta1 receptors occurs with chronic blocker use and therefore the drug cannot be abruptly withdrawn—can cause severe angina, MI arrhythmias, and death
Contraindicated in pts with respiratory conditions that include bronchospasm—even though beta1 drugs have less effect on beta2 receptors, there had been no beta blocker that eliminates the pulmonary risk. Beta1 drugs at high doses show beta2 effects.
Contraindicated in AV Block, peripheral vascular disease
Cautious use in heart failure, older adults, diabetics
Pindolol and Sotalol are pregnancy category B, however side effects are seen in the neonate at birth. Contraindicated in first trimester and must be withdrawn prior to delivery
Metoprolol and atenolol are drugs of choice in kids
Interactions: additive hypotension with antihypertensives, etoh, or nitrates; bradycardia with digoxin; altered effectiveness with hypoglycemic drugs; hypertension and tachycardia with OTC cold remedies; life threatening HTN with clonidine withdrawal
Can cause increased BUN, K+, TG, lipoprotein, uric acid, ANA, blood glucose levels

39
Q

Beta Blockers monitoring/education

A

Monitor the condition being treated: # of angina attacks, BP, HR, etc.
Home BP and HR monitoring
For those with renal impairment, check renal labs
For those with liver impairment, check liver function tests
Teach diabetic pts signs of hypoglycemia, especially diaphoresis, as all the traditional symptoms, except diaphoresis will be masked by beta blockers
Must not stop drug abruptly due to potential for life-threatening arrhythmias, HTN, and myocardial ischemia
Take meds consistently either with or without food
Call first prior to taking OTC meds, especially cold remedies
In the case of angina, teach when to call 911

40
Q

Combined Blockers

A

Blockade of both alpha and beta receptors
Dominated by alpha blockade makes them less likely to cause bradycardia or reduced cardiac output
Nonselective beta blockade
Cause peripheral vasodilation and decrease myocardial oxygen demand and cardiac workload

41
Q

Combined Blockers: meds

A

Carvedilol and labetalol

42
Q

Combined Blockers: carvedilol, labetolol

A

Both treat HTN, however carvedilol is used to reduce progression of heart failure and treat left ventricular dysfunction after MI

43
Q

Combined Blockers ADR

A

Essentially the same as beta blockers, fewer cardiac reactions and CNS reactions; higher risk of orthostatic hypotension
Most common reactions include hypotension, bradycardia, dizziness, and drowsiness

44
Q

Combined Blockers pharacokinetics

A

Rapidly absorbed, widely distributed; carvedilol is more protein bound
Carvedilol should be taken with food
Rapid first-pass metabolism
Excreted in bile and feces, carvedilol more than labetalol

45
Q

Combined Blockers pharmacotherapeutics

A

Sympathetic blockade can be dangerous in pts who’s heart is so severely damaged that it requires sympathetic stimulation for adequate ventricular function
Contraindicated in bronchospastic respiratory conditions, overt NYHA class IV heart failure, 2 and 3rd degree heart block, bradycardia.
Carvedilol does have an indication in class II and III heart failure
Cautious use in diabetics and thyroid disease, liver disease, older adults (carvedilol)
Interactions similar to beta blockers
Cannot withdraw abruptly
Labetalol can be used in pregnancy; Contraindicated in first trimester and must be withdrawn prior to delivery
Safety and efficacy has not been established in kids

Monitoring and Education:

46
Q

combined blockers Monitoring and Education:

A

Labetalol can screen urine positive for amphetamines
Liver function tests when initiating and adjusting dosages
Renal functions tests prior to administration and at regular intervals
Must not stop drug abruptly due to potential for life-threatening arrhythmias, HTN, and myocardial ischemia
Doses should not be skipped or doubled
Call first prior to taking OTC meds, especially cold remedies
Teach diabetic pts signs of hypoglycemia, especially diaphoresis as the traditional symptoms will be masked by blockers

47
Q

Cholinergic Agents: agonists

A

parasympathomimetics, muscarinic agonists

48
Q

Cholinergic Agents: antagonists

A

parasympatholytics, muscarinic antagonists, anticholinergics, cholinergic blocker

49
Q

Direct-acting cholinergic drugs

A

Prototype: bethanechol
Prototype: pilocarpine

50
Q

Indirect-acting cholinergic drugs

A

Cholinesterase inhibitors

Prototype: neostigmine bromide

51
Q

Cholinergic blockers

A

Prototype: atropine
Prototype: oxybutynin

52
Q

cholinergic agents: There are two subtypes of acetylcholine receptors in the autonomic nervous system.

A

Nicotinic receptors are present at the ganglia of both the sympathetic and parasympathetic arms of the ANS as well as on the adrenal medulla. Muscarinic receptors are activated by ACh released by the postganglionic parasympathetic nerves and thus mediate the actions of the parasympathetic nervous system.

53
Q

Cholinergic (parasympathetic) side effects

A 
Constricted pupils 
Increased saliva
Bronchoconstriction 
Increased gastrointestinal mucous 
Bladder fundus contraction
54
Q

Agonists mimic the actions of acetylcholine (ACh)

A

Direct agonist effect

Indirect prevention of breakdown of ACH by acetylcholinesterase (AChE)

55
Q

Uses of Cholinergic Drugs

A

To decrease intraocular pressure in glaucoma
To treat atony of gastrointestinal tract and urinary bladder
To diagnose and treat myasthenia gravis
To treat Alzheimer’s dementia
Atropine used to treat cholinergic toxicity
Physostigmine used to treat anticholinergic toxicity

56
Q

Muscarinic Agonists

A

Stimulate release of Ach from PNS nerves to alter organ function and inhibit release of neurotransmitters

57
Q

Muscarinic Agonists: Bethanechol

A

Increases tone of detrusor muscle and causes bladder contractions to initiate micturation
Increases gastric tone/motility

58
Q

Muscarinic Agonists clinical use

A

Urinary retention

59
Q

Muscarinic Agonists ADR

A

Rare after PO administration, more common with SQ
Abdominal pain, flushing, sweating, salivation
Atropine is the antidote to toxicity

60
Q

Muscarinic Agonists pharmacokinetics

A

PO doses taken 1 hour before or 2 hours after meals to avoid nausea/emesis
Different susceptibility to AChE, bethanechol has little susceptibility to AChE
PO or SQ administration, doses vary by route
Selective so few nicotinic symptoms (muscle fasciculations,cramping,weakness, hypertension, tachycardia, mydriasis,pallor and diaphragmatic failure)
Metabolism and excretion unknown

61
Q

Muscarinic Agonists pharmacotherapeutics

A

Contraindicated in peptic ulcer disease (excessive acid secretion), intestinal obstruction, urinary tract obstruction, bladder wall weakness, bronchospastic disorders, hyperthyroidism, hypotension, bradycardia, and cardiovascular disease
Unknown if causes fetal harm, benefits must outweigh risks
Interactions: additive effects with cholinesterase inhibitors, histamine blockers antagonize effects

62
Q

Muscarinic Agonists monitoring/education

A

Educate to potential adverse effects

63
Q

Cholinesterase Inhibitors

A

Prevents degradation of ACh by AChE

Intensify ACh activity in the synapses

64
Q

Cholinesterase Inhibitors meds

A

Neostigmine and pyridostigmine
Myasthenia gravis

Donepezil
Alzheimer’s disease has profound cholinergic depletion

65
Q

2 categories of Cholinesterase Inhibitors

A

Reversible inhibitors have a moderate duration of action, e.g. pyridostigmine, donepezil

Irreversible inhibitors are highly toxic and effects last until new AChE can be generated, e.g. organophosphates

66
Q

Cholinesterase Inhibitors clinical use

A

Myasthenia gravis
Alzheimer’s dementia
Reversal of non-depolarizing neuromuscular blockade

67
Q

Cholinesterase Inhibitors ADR

A

abdominal pain, flushing, sweating, salivation

Drugs with increased CNS affinity have increased ADRs
Donepezil general well tolerated. Most common ADRs are headache, nausea, diarrhea, insomnia. Pts with h/o GI complaints may experience reoccurrence or exacerbation
Atropine is antidote for toxicity

68
Q

Cholinesterase Inhibitors pharmacokinetics

A

PO absorption is poor for pyridostigmine and neostigmine
Donepezil may be taken with food, good PO absorption
Pyridostigmine and neostigmine metabolized minimally in the liver and excreted by kidneys; require dosage adjustments for renal disease
Donepezil metabolized extensively in the liver, excreted in the urine and feces; possible adjustment in liver disease but not for kidney disease; titrate to response, not specific dosage

69
Q

Cholinesterase Inhibitors Pharmacotherapeutic

A

As dementia progresses, there are less functional cholinergic neurons and therefore cholinergic drugs will no longer have benefit
Pyridostigmine and neostigmine contraindications: mechanical intestinal and/or urinary obstruction, possible h/o reaction to bromides; use in pregnancy only when benefits clearly outweigh risks due to uterine irritability and neonate muscular weakness; safety and efficacy not established in kids (although it is used)
Donepezil safety not established in pregnancy
General contraindications: peptic ulcer disease (excessive acid secretion), intestinal obstruction, urinary tract obstruction, bladder wall weakness, bronchospastic disorders, hyperthyroidism, hypotension, bradycardia, and cardiovascular disease
Interactions: additive effects with cholinergic agonists, antagonistic effects with anticholinergic meds, meds metabolized by CYP450
Donepezil does not interact with warfarin, furosemide, or digoxin
Pyridostigmine and neostigmine interactions: aminoglycoside antibiotics, atropine, belladonna, corticosteroids, magnesium

70
Q

Cholinesterase Inhibitors monitor/education

A

Watch for symptoms of increased gastric acid secretion and GI bleed
Donepezil requires routine monitoring of chemistry and hematology
Late doses of pyridostigmine and neostigmine can cause myasthenic crisis and early doses could result in cholinergic crisis. Doses should not be doubled. Pts may need to set an alarm to remember as doses can be taken every 3 – 4 hours.
Missed doses of donepezil should be skipped and taken the following day
Educate to potential adverse effects

71
Q

Uses of Anticholinergic Drugs

A

Block vagal impulses to heart
Suppress or decrease
Respiratory secretions (pre-op medication)
Bladder spasms
Relax sphincter muscle of iris
Treat tremors/rigidity of Parkinsonism
Treat side effects of psychotropic medications

72
Q

Cholinergic Blockers

A

Competitively and selectively block muscarinic receptors against action of ACh

GI motility, motion sickness, urinary smooth muscle spasm, asthma and COPD, Parkinson’s Disease, extrapyramidal symptoms, ophthalmic procedures

73
Q

Cholinergic Blockers: med

A

atropine

74
Q

Cholinergic Blockers rational drug selection

A

Scopalamine: motion sickness
Benztropine: extrapyramidal symptoms
Oxybutynin: bladder spasms

75
Q

Cholinergic Blockers clinical uses

A

Bronchodilation (useful in COPD) and reduction of bronchial secretions (not useful in COPD)
Prolongation of gastric emptying time and intestinal transit time—irritable bowel syndrome
Anti-secretory properties in the GI tract – peptic ulcer disease
Motion sickness
Incontinence due to bladder/ureter spasm and overactivity
Tremor in Parkinson’s Disease and parkinsonism (adjuncts, not first-line therapy)
Extrapyramidal symptoms and akathisia

76
Q

Cholinergic Blockers ADR

A

Tachycardia, xerostomia (dry mouth), anhidrosis (reduced sweating—increased risk of hyperthermia), constipation, urinary hesitancy and retention (urinary infection), agitation, hallucinations, dizziness, confusion or delirium, drowsiness, mydriasis, cycloplegia, increased intraocular pressure, blurred vision, photophobia, respiratory infection (thickening of respiratory secretions), impotence

77
Q

Cholinergic Blockers pharmacokinetics

A

Atropine and oxybutynin are absorbed well PO
Liver metabolism
Renal excretion

78
Q

Cholinergic Blockers pharmacotheuraputics

A

Competitively block the receptor from neurotransmitters that would activate the receptor, but they do not activate the receptor
Contraindicated in glaucoma (mydriasis and cycloplegia)
Cautious use in GI obstruction and urinary obstruction (including BPH), HTN, tachycardia, other arrhythmias, older adults (CNS effects)
Not many studies on pregnancy safety, should only be used with benefits outweigh risks; oxybutynin is classified as category B
Safety and efficacy mostly unestablished in kids, except atropine in kids down to 7lbs and oxybutynin in kids older than 6
Interactions: additive effects to antihistamines, antipsychotics, TCAs, alcohol, opioids, sedative hypnotics; due to altered GI transit time drug absorption may also be altered which can cause previously stable drug therapies to become unstable particularly if the therapeutic index is narrow.

79
Q

Cholinergic Blockers monitoring/education

A

Educate to potential adverse effects
Teach pts to monitor HR and report if > 100
Drink fluids to keep secretions thin and help with constipation (also fiber intake)
Missed doses should be taken as soon as remembered unless it is almost time for the next dose, doses should not be doubled

pharm - Autonomatic Nervous System (1 decks)

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