Question 8

College Answer

Pharmacodynamics  imply  what  the  drug  does  to  the  body.  Consideration  should  be given  to mechanism of action, effects on various organs, relationship of dose to effect. indications  for use, and type of adverse effects. These drugs are essential parts of the intensivist's armamentarium, and a good level of understanding should have been displayed.

Dopamine:
•  Immediate  precursor  of  noradrenaline,  and  also  serves  as  a  neurotransmitter  in central  and peripheral nervous systems,
•  Doses of Q.5 to 2 meg/kg/min  (via stimulation  of DA-1  and DA-2  receptors)  increase  renal blood flow, urine flow and sodium excretion (inhibit  sodium resorption in proximal tubules)
•  Haemodynamic  effects are due to noradrenaline release (up to 500/o) and direct stimulation  of alpha,  beta  and  noradrenergic   receptors.  Can  lose  effect  with  time  (due  to  depletion  of noradrenaline stores in periphery and heart).
•  Doses of 2-5 meg/kg/min increase cardiac contractility and cardiac output with minimal change in heart rate/BP/SVR. Increasing dose up to 10 meg/kg/min increase CO/HR. and BP.
•  Doses above 10 meg/kg/min result in increasing alpha adrenergic mediated vasoconstriction.
•  Can increase intrapulmonary shunt (increase CO), but pulmonary vasoconstriction can occur.
•  Dopamine also stimulates  receptors in the zona glomerulosa  of the adrenal cortex to decrease aldosterone secretion.
•  A selective  increase  in  renal  and  splanchnic  blood  flow  occurs,  and  low  doses  have  been thought to prevent the vasoconstrictive effects of other agents. The clinical significance of these effects are controversial (?harm to GIT via shunting from mucosa).
•  Dopamine  inhibits  TSH  and  prolactin  release  as  well as other  potential  negative  effects  on anterior pituitary function.
•  Other  side  effects  include  nausea/emesis,  tachyarrhythm.ias (particularly  AF),  anginal pain, profound  vasoconstriction  (including  if local  extravasation  (treat  with  phentolamine]),  and impairment of hypoxic ventilatory drive.
•  Used to increase cardiac output and as a mild vasopressor (cardiogenic or septic shock), and as a diuretic (no evidence to support renal protective role).

Dobutamine:
•  Racemic  mixture  of  + and  - isomers.  + isomer  stimulates  both  beta-adrenergic  receptors. - isomer is potent selective  alpha-1-ad.renergic agonist   No indirect stimulation  of receptors. Metabolite (3-0-methlydobutamine) is potent inhibitor of alpha receptors. Net effect is balance between various receptor effects.

•  At commonly used dose ranges (2-15 meg/kg/min) increases contractility, with little effect on HR at doses < I0  meg/kg/min. Usually little effect on SVR and PVR as balance between alpha- 1 and beta-2 effects (CVP and PAWP usually decrease). Some tolerance with time but less than with dopamine.
•  Enhances urine  output  by  increasing cardiac output. No  other  significant  metabolic or endocrine effects.
•  Side  effects  include  dysrhythmias  (less  than dopamine),  tachycardia,  headaches,  anxiety, tremors, changes in BP. •
•  Used to increase cardiac output without need to effect peripheral resistance (cardiogenic or septic shock) or desire to have metabolic/endocrine effects of dopamine. Also used to assess for myocardial ischaemia (stress test).

Discussion

Though it may be tempting to unload a massive amount of pharmacological knowledge onto such a question, the candidate is reminded that these days we only have 10 minutes per question.