Cardio: Adrenergic Drugs

Question 1

• Affects:
  
  • α1, α2
  • β1

Answer 1

Norepinephrine

Question 2

• Affects:
  
  • α1, α2
  • β1, β2, β3

Answer 2

Epinephrine

Question 3

• Affects:
  
  • β1, β2, β3
  • D1 (& D5), D2 (& D3, D4)
  • At high concentrations: α1

Answer 3

Dopamine

Question 4

Adrenergic receptors of the
Heart

Answer 4

• β1 = Increased contractility
• β1 = Increased automaticity
• β1 = Increased conduction velocity

Question 5

Adrenergic receptors fo the
Blood Vessels

Answer 5

• α1 = Arteriolar constriction
• β2 = Arteriolar dilation of Skeletal muscle and Liver
• D1 = Arteriolar dilation of Kidney and Mesentry
• α1 = Venoconstriction
• β2 = Venodilation

Question 6

Adrenergic receptors of the
Bronchioles

Answer 6

• β2 = Bronchodilation

Question 7

Adrenergic receptors of the
Iris

Answer 7

• α1 = Radial muscle contraction –> mydriasis

Question 8

Adrenergic receptors of the
GI Tract and Urinary Bladder

Answer 8

• α1 = Sphincter contraction
• β2 = Decreased motility

Question 9

Adrenergic receptors of the
Uterus

Answer 9

• β1 = Relaxation of uterus

Question 10

Metabolic affects of adrenergic receptors on the
Liver

Answer 10

• α1 / β2 = Gluconeogenesis, Glycogenolysis

Question 11

Metabolic affects of adrenergic receptors on the
Fat

Answer 11

• β1 / β3 = Lipolysis

Question 12

Metabolic affects of adrenergic receptors on the
Pancreas

Answer 12

• α2 = Decreased insulin secretion

Question 13

Metabolic affects of adrenergic receptors on the
Kidney

Answer 13

• β1 = Renin secretion

Question 14

• These receptors include typical postsynaptic receptors mediating smooth-muscle contraction

Answer 14

α1

Question 15

• These receptors include presynaptic autoregulatory and postsynaptic receptors
  
  • Activation of prysynaptic autoregulatory inhibits NE release while blockage of the presynaptic receptors enhances NE releaase
  • Postsynaptic receptors exist in extrasynaptic vascular smooth muscle, ciliary, epithelium, and in the brain

Answer 15

α2

Question 16

Mechanism of Transduction
β1

Answer 16

• Gs protein
• Increases adenylyl cyclase activity
• Opens L-type Ca²⁺ channels

Question 17

Mechanism of Transduction
β2

Answer 17

• Gs protein
• Increases adenylyl cyclase activity

Question 18

Mechanism of Transduction
β3

Answer 18

• Gs protein
• Increases adenylyl cyclase activity

Question 19

Mechanism of Transduction
α1

Answer 19

• Gq protein
• Increases phospholipase C –> *Increases *IP3
• -> Increases Ca²⁺
• *Increases *phospholipase D (Minor effectors)
• Gq, Gi/Go
• Increases phospholipase A2 (Minor effectors)

Question 20

Mechanism of Transduction
α2

Answer 20

• Gi protein
• decreases adenylyl cyclase activity
• Gi (via βy subunits)
• Opens K⁺ channels (L- and N- types)
• Go
• Closes Ca²⁺ channels

Question 21

Epinephrine cardiac effects

Answer 21

• β1 actions
• Increases automaticity, Heart Rate, Conduction velocity, Myocardial contractile force (MCF), Cardiac output (CO), and O₂ consumption
• Accelerates phase 4 diastolic depolarization in Purkinje fibers and further facilitates activation of latent pacemaker cells
• Can cause ventricular arrhythmias (especially in the presence of halogenated hydrocarbon anesthetics)

Question 22

Epinephrine vascular effects on
peripheral resistance and blood pressure

Answer 22

• Increases Cutaneous, Mesenteric, and Renal vascular resistance (α1 receptor)
• Decreases Skeletal and Liver vascular resistance at low concentrations (β2 receptor > α1 receptor) –> dilation
• Increases Skeletal and Liver vascular resistance at high concentrations (α1 receptor > β2 receptor) –> constriction
• Low Dose Epi - decrease BP (β2) vasodilation, *increase HR (β1), **decrease* or no change in Mean Blood Pressure (MBP)
• High Dose Epi - Increase MBP (α1) both Sys / Dia

Question 23

Epinephrine nonvascular effects on
Bronchiole Smooth Muscle

Answer 23

• Relaxes Bronchal smooth muscle (β2)
• Most evident when bronchial muscle is contracted due to disease or drugs

Question 24

Epinephrine Metabolic effects

Answer 24

• Hyperglycemia occurs due to gluconeogenesis and glycogenolysis in the Liver (α1 / β2)
• Inhibition of insulin release (α2) from Pancreas
• Lipolysis elevates free Fatty Acids in the blood (β1 and β3)

Question 25

Norepinephrine effects the
Blood pressure and Vasculature

Answer 25

• Increases peripheral resistance in most vascular beds (α1) with no dilation anywhere
• Increases Total peripheral resistance (TRP)
• Increases Mean Blood Pressure (MBP)
• Decreases Blood flow in the Skin, Kidney, Liver, and Skeletal muscle w/ flow to CNS not reduced

Question 26

Norepinephrine cardiac effects

Answer 26

• β1 actions same as Epinephrine
• Heart rate decreases due to compensatory Vagal reflex activity initiated by the elevated MBP; overcomes the direct cardioacceleratory action of β1 receptor activation

Question 27

α receptor general locations

Answer 27

• α1 - post-synaptic
• α2 - pre and post-synaptic (β cells of the Pancreas)

Question 28

β receptor general locations

Answer 28

• β1 - post-synaptic
• β2 - extra-junctional on EO (end organs)
  
  • NEVER at synaptic nerve terminal
• β3 -

Question 29

D receptor general locations

Answer 29

• D1 - post-synaptic
• D2 - pre and post-synaptic