Ionotropes & Vasoconstrictors

Question 1

A1 stimulation:

• location of receptor
• action when stimulated
• mechanism

Answer 1

• located in vascular smooth muscle
• vasoconstriction
• Gq-coupled phospholipase C activated: increases IP3: increases CA2+

Reflex bradycardia through baroreflex (increased SVR)

Question 2

B1 stimulation

Answer 2

Iontropy; especially in chronically failing hearts.

Vasodilation in splanchnic and skeletal muscle beds.

Question 3

B2 stimulation

Answer 3

iontropy, arterial smooth muscle dilation

Question 4

Adrenaline

Answer 4

• Adrenergic drug
• A1, A2, beta-receptors

CVS:
Low dose- beta effects: increased CO, increased myocardial O2 demand, lowers arrhythmia threshold and coronary artery dilation.

High dose/ bolus/ infusion- alpha effects: increase SVR

Question 5

Noradrenaline

Answer 5

• A1, B1
• vasoconstrictor and increases vascular tone
  Powerful iontrope with potent B1 activity

Question 6

Isoprenaline

Answer 6

• b1, b2
• powerful iontropy that results in unfettered tachycardia, no vasoconstriction.
• used to treat bradycardia

Question 7

Salbutamol

Answer 7

• b2

- treat bronchospasm

Question 8

Dopamine

Answer 8

• natural catecholamine
• ## A1, B1

Question 9

Dobutamine

Answer 9

• A1, b1
• relatively selective B1 agonist, causes less tachycardia for given iontropy given A1 activity.
• causes bradycardia indirectly through baroreflex.

Question 10

Dopexamine

Answer 10

• B1

- splanchnic vasodilation through B1 and dopaminergic receptors

Question 11

What are inodilators?

Answer 11

Drugs that enhance adrenergic activity through phosphodiesterase inhibition.
Ie. Milrinone and Exoximone

Enhance and restore b-adrenoreceptor function

Question 12

Levosimendan
?class of drug
?action

Answer 12

• class of iontropes and inodilators
• calcium sensitiser for myocardium
• binds to Troponin C, stabilises the complex and inhibits Troponin I - improves myocardial contraction.
• vasodilation due to antagonism of ATP-K+channel and PDE3 inhibitor
• increases cardiac output

Question 13

V1 Receptor effect

Answer 13

• vasoconstriction, especially in the gut, skin and skeletal muscle and platelet aggregation

Question 14

V2 receptor effect

Answer 14

Opens aquaporin channels in renal collecting duct, reduces urine volume

Releases Von Willebrand factor

Question 15

V3 receptor effect

Answer 15

Mainly CNS activity including ACTH release

Question 16

Main functions of vasopressin (physiology)

Answer 16

• regulates plasma osmolality
• when plasma osmolarity increases, plasma vasopressin conc increases in step
  But
  When blood volume reduces there is little effect until loss is significant - at least 10% loss after which plasma vasopressin conc increases exponentially.

Question 17

Uses of Terlipressin

Answer 17

management of bleeding from oesophageal varices

• vasoconstriction
• reduces portal venous pressure by splanchnic vasoconstriction

Question 18

Vasopressin uses

Answer 18

• receptors are not found in pulmonary vasculature
• Vasoconstrictor of choice in patients with pulmonary hypertension.
• Haemorrhagic shock, cardiac arrest, hypotension after cardiac surgery, sepsis

Question 19

Desmopressin uses

Answer 19

Treatment of diabetes insipidus of extrarenal origin

Question 20

Hydrocortisone uses in CVS physiology

Answer 20

Hypertensive effects of A1 stimulation fades in sepsis and other shock conditions, but hydrocortisone has shown to improve responsiveness to A1 agonists.

Question 21

Methylene Blue uses

Answer 21

Can restore vascular tone in certain circumstances;

Excess Nitric oxide causes vasodilation and hypotension in sepsis, methylene blue inhibits second messenger guanylate cyclase in nitric oxide vasodilation.

Causes methaemoglobinaemia in high doses 4mg/kg

Question 22

Phosphodiesterase inhibitors effect on blood pressure?

Answer 22

Increase cardiac output due to the decrease in SVR usually leads to reduction in blood pressure.

Therefore increases blood pressure.

Question 23

Patient with poor LVF, is hypotensive after cardiac bypass, which drugs appropriate to give immediately?

Answer 23

Adrenaline and Noradrenaline for B1 and B2 activity, need to increase myocardial contractility and cardiac output immediately.

Question 24

In patient who is hypotensive with poor LVF what supplemental therapy maybe appropriate?

(Methylene blue, vasopressin, noradrenaline, milrinone, levosimendan)

Answer 24

a PDE inhibitor would enhance response to adrenaline eg Milrinone but vasodilation May become a problem.

Levosimendan - added iontropic effect.

Question 25

Septic patient in ITU is peripherally dilated and hypotensive, which would be appropriate to use?

(Adrenaline, vasopressin, noradrenaline, milrinone, levosimendan, methylene blue)

Answer 25

Vasopressin- vasoconstriction
Noradrenaline- potent to increase SVR.

Needs increased vascular tone

NOT:
Adrenaline - improves numbers not outcome.
Milrinone- reduces SVR
Levosimendan- vasodilation 
Methylene blue- not first line Tx