PHYS - CV Autonomic Pharmacology

Question 1

AUTONOMIC RECEPTORS

Answer 1

• Adrenergic
  
  • α1 – SM of viscera and BVs (PLC → IP3/DAG → Ca2+/PKC*)
    
    • Increase systolic pressure
    • Increase MAP
  • α2 – SM BVs and presynaptic nerve terms (Inhibit AC and nerve Ca2+ channels)
  • β1 – CM; glomerular jxns (AC* → cAMP)
    
    • Increase TPR = increase systolic pressure
    • Increase pulse pressure
    • Stimulates renin secretion
  • β2 – SM of visceral and BVs, CM (AC* → cAMP)
    
    • Lowers diastolic pressure
    • Lowers systolic pressure
  • β3 – adipocytes (AC* → cAMP)
• Cholinergic
  
  • N­_N/N_M = neurons/neuromuscular jxns → open NSCCs
  • M1/3/5 = BVs, exocrine glands, CNS (PLC* → IP3/DAG → Ca2+/PKC*)
  • M2,4 = CM(2)/CNS (K+ channels*, inhibit AC)
    
    • M2 increase HR and MAP

Question 2

CV AUTONOMIC RESPONSES

Answer 2

• Heart
  
  • SA Node
    
    • Symp β1 = +chronotropic
    • Para M2 = -chronotropic
  • AV Node
    
    • Symp β1 = +dromotropic
    • Para M2 = -dromotropic
  • Ventricular muscle
    
    • Symp β1 = +inotropic
    • Para M2 = -inotropic
• Blood Vessels
  
  • Sympathetic
    
    • α = vasoconstriction
    • β2 = vasodilation
  • Parasympathetic
    
    • No effect EXCEPT face, tongue, GU

Question 3

SYMPATHOMIMETICS

(Adrenergic Agonists)

Answer 3

• Norepinephrine
  
  • RECEPTORS: B1/A1 > A2 > B2
  • TREATMENT: severe hypoT, septic shock
  • Decreased HR, increased BP/PP, increased TPR
• Epinephrine
  
  • RECEPTORS: B1/B2 > A1/A2
  • TREATMENT: anaphylaxis, cardiogenic shock, cardiac arrest, local vasoconstriction
  • Low dose E = similar to ISO (TPR increase less dramatic)
  • High dose E = similar to NE
• Isoproterenol
  
  • RECEPTORS: B1/B2
  • TREATMENT: cardiogenic shock, bradycardia, AV block
  • Increases HR, increased PP, decreased TPR
• Dobutamine
  
  • RECEPTORS: B1>B2>A1
  • TREATMENT: acute HF, cardiogenic shock
• Dopamine
  
  • RECEPTORS: D1 > B1/B2 > A1
  • TREATMENT: acute HR, cardiogenic shock, acute renal failure
  • Low doses, only D receptors
  • High doses, B stimulation; higher doses, A stimulation
• Phenylephrine
  
  • RECEPTORS: A1>A2
  • TREATMENT: local vasoconstriction, decongestant, autonomic testing
  • No B component = no effect on HR
• Clondine
  
  • RECEPTORS A2>A1
  • TREATMENT: HT, a2* inhibits NT release to reduce sympathetic tone
• Tyramine
  
  • Naturally occurring in aged cheese/meat, beer
  • Uptaken into nerve terminal by NET, normally metabolized by MAO
  • People on MAOIs, tyramine can displace endogenous NTs → spontaneous NT release → HT crisis

Question 4

TYPES OF SHOCK

Answer 4

• Hypovolumic: loss of blood vol → decreased MAP → decreased Q → reflex sympathetic stimulation → vasoconstriction to increase BP
  
  • Need immediate fluid volume replacement because vasoconstriction decreases Q (tissue perfusion) further
• Cardiogenic: poor contractility → reduced CO → reflex sympathetic activity vasoconstriction to increase BP → poor Q → increased venous pressure
  
  • Treat with B agonists: isoproterenol, dobutamine, dopamine
• Vasodilator: sepsis/anaphylaxis → dilated arteries → decreased TPR → decreased MAP and Q → decreased VR and decreased CO
  
  • Sepsis: immune response to bacterial toxins
  • Anaphylaxis: immune response to vasoactive allergens

Question 5

SYMPATHOLYTICS

(Adrenergic Agonists)

Answer 5

• Phentolamine
  
  • BLOCKS: A1/A2
  • TREATMENT: severe HT, pheochromocytoma
• Prazosin
  
  • BLOCKS: A1 > A2
  • TREATMENT: HT
• Propranolol
  
  • BLOCKS: B1/B2
  • TREATMENT: HT, angina, arrhythmia
• Metaprolol
  
  • BLOCKS: B1 > B2
  • TREAMENT: HT, angina, HF
• Carvedilol
  
  • BLOCKS: A1/B1 > B1/B2
  • TREATMENT: HT, HF

Question 6

CHOLINOMIMETICS

(Cholinergic Agonists)

Answer 6

• Acetylcholine: M1-5/N
• Digitoxin: increases Ca2+ availability = + inotrope
  
  • Used to treat atrial fibrillation b/c increases parasympathetic tone
  • Slows conduction through AV node

Question 7

CHOLINOLYTICS

(Cholinergic Antagonists)

Answer 7

• Atropine M1-5 > > N
  
  • Used to treat bradycardia and heart block
• Trimethaphan N_N > N_M
  
  • Used to treat HT crisis

Question 8

WHAT DRUGS?

Answer 8

1. Increased PP, increased HR, decreased diastolic
   
   1. Isoproterenol
2. No change in PP, decreased HR, increased BP
   
   1. Phenylephrine
   2. No B component, no PP change
3. Increased PP, increased HR, decreased diastolic, not drastic
   
   1. Low dose epinephrine

Question 9

WHAT BLOCKERS?

Answer 9

1. Increased HR, increased PP, decreased BP
   
   1. Not a beta-blocker
   2. phentolamine, prasozin