Physio Autonomics and Drugs

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Author:
akl273
ID:
201744
Filename:
Physio Autonomics and Drugs
Updated:
2013-02-19 23:06:17
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physio
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autonomics
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  1. G protein for M1, M3,
    • Gq
    • increases phospholipase C
    • increase IP3 and DAG
  2. G protein for M2, M4
    • Gi
    • decrease cAMP
  3. G protein for α1
    • Gq
    • increase of DAG/IP3
  4. G protein for α2
    • Gi
    • decrease cAMP
  5. G protein for β1-3
    • Gs
    • increase cAMP
  6. Main function of M1
    • CNS
    • autonomic ganglia
    • parietal cell
  7. Main function of M2
    SA/AV node
  8. Main function of M3
    • smooth muscle relaxation
    • gland secretion
    • bronchoconstriction
    • vasodilation (corpus cavernosum)
  9. Main function of α1
    • smooth muscle contraction
    • vasoconstriction
    • pupil dilation
    • ejaculation
    • sphincter constriction (GI)
  10. Main function of α2
    • negative feedback
    • closes Ca2+ channels
    • opens K+ channels
    • --> hyperpolarization
    • decrease insulin (beta cells in pancreas)
  11. Main function of β1
    • increase heart contractility (inotropy)
    • increase HR (chronotropy)
    • increases AV conduction velocity
    • increase renin
  12. Main function of β2
    • smooth muscle relaxation
    • (bronchodilation, uterine relaxation)
    • via phosphorylation of MLC kinase
    • metabolic:
    • increase glucagon, etc.
  13. Main function of β3
    increase lipolysis
  14. Gi receptors
    α2; M2
  15. Gs receptors
    β 1, 2, 3
  16. Gq receptors
    M1, M3, α1
  17. Increase Ca2+ receptors
    Gq receptors (M1, M3, α1)
  18. Increase cAMP receptors
    Gs receptors (β1-3)
  19. decrease cAMP receptors
    Gi receptors (α2, M2)
  20. Increased renin
    β1
  21. decreased renin
    α1
  22. increased insulin
    • β2
    • also increases glucagon!
    • glucagon more important - ruling
  23. decreased insulin
    α2
  24. miosis
    M3
  25. sphincter contraction
    α1
  26. sphincter relaxation
    M3
  27. bronchoconstriction
    M3
  28. Bronchodilation
    β2
  29. Mydriasis
    α1
  30. increased heart rate
    β1
  31. Decreased heart rate
    M2
  32. Contraction of vascular SM
    α1
  33. relaxation of vascular smooth muscle
    • β2
    • mostly skeletal muscle during exercise
  34. accommodation
    M3
  35. Salivation
    M3
  36. detrusor contraction
    M3
  37. detrusor relaxation
    β2
  38. erection
    M3
  39. Uterine relaxation
    β2
  40. sweating
    M3
  41. increased glycogenolysis
    β2
  42. lipolysis
    β2/3*
  43. ejaculation
    α1
  44. decrease NE release
    α2 (neg. feedback)
  45. parietal cell secretion
    M1
  46. which receptors do epinephrine favor?
    βs (cAMP and phosphorylation!)
  47. Which receptors do norepinephrine favor?
    α's
  48. Sildenafil
    • blocks degradation of cGMP
    • cGMP created by NO stimulation of guanylate cyclase
    • leads to lack of vasoconstriction in corpora cavernosa
    • only place where M3 will lead to vasodilation
  49. Hemicholinium
    • Prevents choline re-uptake
    • no synthesis of ACH
  50. Vesamicol
    • no vesicular storage of ACH
    • not very useful clinically
    • used for research
  51. Botulinum toxin
    • degrades SNARE
    • no vesicle fusion at synapse
    • no exocytosis
    • used for cosmetics, dystonia (e.g. blepharospasm)
    • excessive sweating (ACH at sweat glands)
  52. AChE inhibitors
    • (Ach esterase)
    • blocks Ach degradation
    • parasympathomimetics (mimics PSNS)
    • Tx of urinary retention/GI atony after anesthesia
    • myasthenia gravis
    • atropine poisoning
    • SE - 2* to muscarinic receptors
    • atropine reverses effect
  53. Edrophonium
    • alcohol AChE inhibitor for diagnosis of:
    • myasthenia gravis; Lambert-Eaton
    • see if condition improves upon administration
    • SE - PSNS effects (bradycardia)
    • atropine reverses effect
  54. Neostigmine
    • Carbamic acid AChE inhibitor
    • Tx of myasthenia gravis
    • does not cross BBB
    • SE - PSNS effects (bradycardia)
    • atropine reverses effect
  55. Physostigmine
    • Carbamic acid AChE inhibitor
    • crosses BBB
    • Tx of atropine poisoning/glaucoma
    • SE - PSNS effects (bradycardia)
    • atropine reverses effect
  56. Rivastigmine
    • AChE inhibitor
    • crosses BBB
    • Tx of dementia
    • SE - PSNS effects (bradycardia)
    • atropine reverses effect
  57. Parathione
    • irreversible AChE inhibitor
    • organophosphate
    • paralysis via depolarization blockade
  58. Pralidoxine
    • treatment for AChE inhibitor poisoning
    • reactivates AChE if given within 24 hours
  59. Atropine
    • treatment for AChE inhibitor poisoning
    • counters PSNS effects of inhibitor
  60. Carbachol
    • muscarinic antagonist
    • not used systemically
    • large side effects 2* to affinity to Nm receptors
  61. Pilocarpine
    • alkaloid muscarinic antagonist
    • Tx glaucoma, Sjogren's syndrome (increase salivation)
  62. Bethanechol
    • muscarinic antagonist
    • (highly selective)
    • increase GI/urinary motility for post-op
    • SE: miosis, bradycardia, salivation, bronchoconstriction
  63. Methacholine
    • muscarinic antagonist
    • Dx asthma
    • "methacholine challenge test"
    • will cause bronchoconstriction (asthmatics more sensitive)
  64. Muscarinic antagonist
    • "parasympatholytics"
    • competitive binding to ACh receptors
  65. Atropine
    • muscarinic antagonist
    • Tx of bradycardia, diarrhea, bladder hypermotility
    • muscarinic/AChE inhibitor poisoning
    • also used during surgery (decrease secretions)
    • reduces "SLUDGE"
  66. What are the signs of atropine poisoning?
    • muscarinic antagonist
    • "hot as a hare" (decreased sweat)
    • photophobia, pupil dilation
    • dryness
    • CNS effects
    • redness (vasodilation)
    • treat with Physostigmine
  67. Scopolamine
    • muscarinic antagonist
    • Tx nausea, motion sickness
    • in divers/astronauts
  68. Pirenzipine
    • muscarinic antagonist
    • alleviate peptic ulcers
  69. Ipratropium
    • muscarinic antagonist
    • reduce bronchial secretions in COPD
    • M3 selective (smooth muscle/gland)
    • used to decrease muscarinic activity by Neostigmine
  70. Nicotinic receptor agonists
    NMJ of somatic NS
  71. Succinylcholine
    • nicotinic agonist
    • depolarizing neuromuscular blocker
    • causes temporary paralysis
    • used for intubation
    • high affinity for Nm/N1 at NMJ
    • SE: arrhythmias
  72. Nicotinic receptor antagonist
    • blocks SNS and PSNS!
    • effect depends on which system is dominant
    • e.g. GI tract/heart/glands --> PSNS dominant
    • with antagonist --> decrease GI motility/tachycardia/xerostomia
    • treatment for HTN
  73. Hexamethonium
    • Nicotinic antagonist
    • treatment of HTN
    • suppresses SNS ruling vasculature
    • --> decrease BP/vasodilation
    • also has PSNS effects on GI, heart, glands
  74. Tubocurarine
    • NMJ nicotinic antagonist
    • non-depolarizing neuromuscular blocker
    • "arrow poison"
  75. Pancuronium
    • NMJ nicotinic antagonist
    • non-depolarizing neuromuscular blocker
    • muscle paralysis during surgery
    • also Vecuronium, Mivacurium
    • Neostigmine (AChE inhibitor) used for reversal
  76. Epinephrine
    • β receptor favored
    • made in adrenal medulla by PNMT
    • Tx anaphylactic shock
    • used with anesthesia to vasoconstrict
  77. Norepinephrine
    • α1 (vasoconstriction)
    • β1 (increase heart rate)
    • Tx of hypovolemic shock
    • Levartenol
  78. Oxymetaxoline
    • α agonist
    • vasoconstriction with 2* reflex bradycardia
    • Tx of nasal decongestion
    • ophthalmic hyperemia
  79. Phenoxybenzmine
    • α antagonist
    • blocks vasoconstriction (α1)
    • 2* reflex tachycardia
    • nonselective/irreversible
    • Tx phenochromocytoma (surgery)
    • SE: postural hypotension, nasal congestion, ejaculation failure
  80. Phentolamine
    • reversible α antagonist
    • preferred for Tx of phenochromocytoma
    • blocks vasoconstriction (α1)
    • 2* reflex tachycardia
  81. Phenylephrine
    • α1 agonist
    • --> vasoconstriction
    • treatment of shock
    • nasal decongestant
  82. Clonidine
    • α2 agonist
    • (-) feedback - decrease NE release
    • Tx HTN, opioid withdrawal
    • block sympathetic tone
    • SE: bradycardia, hypotension
  83. Prazosin
    • selective α1 antagonist
    • Tx HTN, BPH
    • 1st dose postural hypotension
  84. Tamsulosin
    • selective α1A antagonist
    • Tx BPH (α1A in urinary sphincter)
    • less 1st dose postural hypotension
    • SE: tachycardia
  85. Isoproterenol
    • nonselective β agonist
    • Tx arrhythmia, bronchospasm
    • emergency use
    • SE: HTN, palpitations, tremors
  86. Dobutamine
    • selective β1 agonist
    • Tx acute heart failure
    • increase contractility/cardiac output
    • inotropic
    • not for longterm
  87. Albuterol
    • selective β2 agonist
    • Bronchodilator
    • Tx asthma
  88. Salmeterol
    • selective β2 agonist
    • bronchodilator
    • Tx asthma (long duration)
  89. Propanolol
    • nonselective β blocker
    • Tx angina (decrease O2 demand)
    • HTN
    • SE: bronchoconstriction (dyspnea), sedation (CNS)
  90. β blockers
    • β1 block: decrease renin release
    • decrease heart rate
    • β2 block: undesirable
  91. Atenolol
    • selective β1 antagonist
    • Tx Angina, HTN, heart failure
    • not for severe HF
    • pt with DM/impaired pulmonary function
  92. Pindolol
    • Partial β1 agonist
    • (antagonistic function)
    • Tx HTN
    • for pt with DM/bradycardia
    • fewer metabolic side effects
  93. Carvediolol
    • nonselective β and α1 antagonist
    • decreases heart rate
    • vasodilator
    • Tx HTN, chronic HF
    • not for severe HF
  94. Cocaine
    • catecholamine reuptake inhibitor
    • inhibits NET
    • no NE, dopamine, seratonin uptake
    • SE: postural hypotension, tachycardia
  95. Imipramine
    • blocks NET
    • catecholamine reuptake inhibitor
    • Tricyclic antidepressant
    • Tx depression - nonspecific
    • SE: arrhythmia
  96. Reserpine
    • catecholamine storage inhibitor
    • blocks VMAT
    • vascular effects
    • Tx HTN
    • SE: severe depression
  97. Amphetamine
    • catecholamine:
    • displaces NE (and DE)
    • blocks NET (no reuptake)
    • weak inhibitor of MAO (no breakdown)
  98. Phenelzine
    • also Ipronazide
    • nonselective MAOI
    • --> no catecholamine breakdown
    • Tx mild depression
  99. Selegiline
    • selective MAO B inhibitor
    • Tx of mild depression
    • safer than Phenelzine
  100. Tyramine with phenelzine
    • Tyramine = substrate for VMAT
    • blocks NE storage
    • increases [NE] in neuron
    • NET (reuptake) reverses
    • NE released into synapse
    • very very high [NE] because of MAOI
    • 2* sympathetic overload, hypertensive crisis

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