synthetic catceholamines and non-catecholamines

Question 1

Phenylephrine mechanism

Answer 1

Direct acting sympathomimetic amine with potent alpha1 agonist actions.
Causes a rapid rise in systemic vascular resistance and BP. No effect on beta receptors

Question 2

Phenylephrine presentation and uses

Answer 2

Presented as a clear solution containing 10mg in 1mL. Bolus doses of 50-100mcg are used IV. Continuous infusion of 20-100mcg per minute are used too.
It is used to increase SVR associated with spinal anaesthesia or systemically administered drugs.

Question 3

Phenylephrine effects

Answer 3

CVS - Raises SVR and BP in may result in a reflex bradycardia (BRR response).
CNS - nil
Renal - RBF decreases

Question 4

Phenylephrine kinetics

Answer 4

Rapid rise in BP lasts about 5-10 minutes.

Metabolised by MAO

Question 5

Isoprenaline

Answer 5

Highly potent synthetic catecholamine with actions at B1 and B2 receptors. Has no alpha effects

Question 6

Isoprenaline Presentation and uses

Answer 6

Clear solution containing 1mg/mL for IV infusion.

Used IV to treat severe bradycardia associated with complete heart block of beta-blocker overdose

Question 7

Isoprenaline effects

Answer 7

CVS - Stimulation of B1 receptors increases heart rate, myocardial contractility, automaticity and cardiac output.
Effects on BP are varied. B2 effects may drop SVR so that the increase in CO is not enough to maintain MAP.
Respiratory - Potent bronchodilator and inhibits histamine release in the lungs. V/Q mismatch will increase.
CNS - stimulant effects
Splanchnic - mesenteric and RBF increased
Metabolic - B effects = increased blood glucose

Question 8

Isoprenaline kinetes

Answer 8

Low bioavailability due to extensive first pass metabolism.

Rapidly metabolised by COMT in the liver.

Question 9

Dobutamine

Answer 9

Direct acting synthetic catecholamine derivative of isoprenaline. B1 effects predominate but has a small affect at b2 receptors

Question 10

Dobutamine presentation and uses

Answer 10

Presented in 20mL of water containing 250mg dobutatmine and sodium metabisulfite.
Used to increase cardiac output in patients with heart failure or cardiogenic shock
Dose range 0.5-20mcg/kg/min

Question 11

Dobutamine effects

Answer 11

CVS - Main actions are direct stimulation of b1 receptors = increased contractility, heart rate, myocardial 02 requirement. Blood pressure usually increased due to increased CO (more than b2 activation).
May precipitate arrhythmias due to increased AV conduction

Question 12

Dobutamine kinetics

Answer 12

Only administered IV. Rapidly metabolized by COMT in the liver to inactive compounds which are excreted in the urine. Half life 2 min.

Question 13

Ephedrine presentation and uses

Answer 13

Clear solution for injection containing 30mg/mL.

Used IV to treat hypotension associated with anaesthesia. Can also be used to treat bronchospasm

Question 14

Ephedrine mechanism of action

Answer 14

Has both direct and indirect sympathomimetic actions.
Activates alpha and beta receptors directly (b1, B2, alpha1) but also inhibits the actions of MAO on noradrenaline and decreases uptake plus increases release from vesicles. This causes increased norad present in the synapse for longer periods of time.
Due to its indirect actions it is prone to tachyphylaxis as norad stores in vesicles deplete.

Question 15

Ephedrine effects

Answer 15

CVS - increases CO, HR, BP, myocardial 02 consumption. May precipitate arrhythmias
Respiratory - bronchodilation
Renal - RBF and GFR decreased
Interactions - should be used in extreme caution in patients taking MAOI

Question 16

Ephedrine kinetics

Answer 16

Not metabolised by MAO or COMT so has longer duration of action and elimination half life of four hours.

Question 17

Metaraminol mechanism of action

Answer 17

Synthetic amine with both direct and indirect sympathomimetic actions. Acts mainly via alpha 1 receptor but retains some beta adrenoreceptor activity
Also stimulates noradrenaline release from vesicles

Question 18

Metaraminol presentation and uses

Answer 18

Clear solution, 10mg/mL. Used as IV bolus 0.5-1mg or infusion 0.5-10mg/hr.
used for hypotension associated with anaesthesia, haemorrhage etc

Question 19

Metaraminol effects

Answer 19

CVS - Increase SVR. Often causes a decreased CO due to increased SVR with little beta stimulation

Question 20

Milrinone mechanism of action

Answer 20

Selective PDE III inhibitor.
Decreases hydrolysis of cAMP leading to increased IC concentration which in turn increases calcium concentration in myocardium and vascular smooth muscle.

Question 21

Milrinone preparation and uses

Answer 21

Yellow solution containing 1mg/mL. Stored at room temp. Should be diluted before administering.
Used for short term management of cardiac failure

Question 22

Milrinone effects

Answer 22

CVS - increased inotropy and vascular smooth muscle dilatation = increased cardiac output
Decreased pulmonary artery pressures and SVR
Can decrease platelet aggregation