A.11

Question 1

Catecholamine

Answer 1

Epinephrine,
Norepinephrine,
Dopamine,
isoprenalin,
dobutamine

Question 2

Epinephrine

Answer 2

MOA: all adrenergic Rs
small dose: β-stimulation predominates (effect: HR,SV,CO,PP↑, TPR,BP↓) ;
large dose: α1-stimulation predominates (TPR, BP↑, reflex bradycardia);
ROA: Parentral ONLY;
IND: Anaphylactic shock (dose: 0.15-0.5mg I.M or 0.05-0.1mg I.V.), ALS (advanced life support)- 1mg I.V or I.O/every4-5min, Refractory asthma attacks, 2nd line in septic shock, inhalation drug in upper airway constriction (e.g. laryngotracheal bronchitis in kids), In combination with anesthetics (e.g. Lidocaine);
Contra-IND: patients taking non-selective β-antagonists (can lead to hypertensive crisis due to α1);
SEs: Hypertension, stroke, MI, Arrhythmia, restlessness, headache, cerebral bleeding

Question 3

Norepinephrine

Answer 3

MOA: α1,α2,β1 agonist;
ROA: parentral ONLY;
Effect: Vasoconstriction;
IND: Septic shock (i.v. infusion pump), Neurogenic shock (after spinal cord injury), Cardiogenic shock (when heart perfusion is impaired), Cardiac arrest, complete heart block;
SEs: Hypertension, Arrhythmias, Vasospasm, Tissue necrosis, Infarction, May impair circulation at injection site (so usually only in central vein);
Extra: Not suitable in anaphylaxis due to no bronchodilatry effect

Question 4

Dopamine

Answer 4

MOA:
1. small dose: D1 (→vasodilation, RBF+GFR↑, Na+ secretion↑),
2. Medium dose: D1,β1 (→+inotropic),
3. Large dose: α1 (→vasoconstriction (TPR,BP↑);
ROA: parentral ONLY;
IND: Cardiogenic Shock (cardiogenic coupled with bradycardia/aortic regurgitation/Aortic stenosis), Renal insufficiency, Acute HF, Severe congestive HF;
SEs: Arrhythmia, tachycardia;
Extra: Cardiac O2 demand increases (→gradual withdrawal)

Question 5

Isoprenalin

Answer 5

MOA: Non-selective β- agonist;
ROA: parentral ;
Effect: +inotropic & chronotropic (β1), Bronchrodilation (β2);
IND: AV block, Bradycardia, β-antagonist overdose;
SEs: Tachycardia, palpitations, arrhythmia, angina pectoris, MI ;
Contra-IND: underlying coronary disease;

Question 6

Receptor activation profile:

Answer 6

Epinephrine: all β>α1 and 2
Norepinephrine: α1 and 2>β1»>β2

note: In organs where SY innervation is missing only circulating epinephrine can stimulate adrenergic receptors (e.g. lungs, β2 receptors → bronchodilation)

Question 7

Synthesis of Epinephrine and Norepinephrine

Answer 7

1. Tyrosine (enters cell via AA transporter) converted to DOPA by Tyrosine hydroxylase →DOPA is converted to Dopamine by DOPA decarboxylase → Dopamine is converted to Norepinephrine by Dopamine-β-hydroxylase → Norepinephrine is converted to Epinephrine by Phenylethanolamine-N-methyl transferase

Question 8

Why can acidemia be fatal?

Answer 8

the effect of catecholamines is decreased during acidemia
note: In acidemia the proteins and enzymes don’t have optimal pH and catecholamines cannot bind their receptors → critical pH= 7.2 below that adrenergic receptors won’t function