Inotropic/Vasopressor Drugs

Question 1

Shock

Answer 1

inadequate organ perfusion to meet tissue O2 demands + subsequent organ dysfunction

Question 2

Types of shock

Answer 2

1. Hypovolemic = haemorrhage, dehydration
2. Cardiogenic = HF
   - Problem with pump function
3. Distributive = sepsis, anaphylaxis - profound overwhelming hypotension from vasodilator accumulation
4. Obstructive = cardiac tamponade, PE - physical obstruction to filling

Question 3

Features of shock

Answer 3

hypotension/volemia
LV impairment
changes in vascular resistance
confused/sedated = impaired cerebral perfusion
pale/sweaty/cold = poor renal/peripheral perfusion + intense SNS activation

Question 4

Goals of shock resuscitation?

Answer 4

1. Restore BP
2. Normalise systemic perfusion = inotropes/vasopressors
3. Perserve organ function e.g. renal perfusion
4. Treat underlying cause

Question 5

What are causes of cariogenic shock?

Answer 5

ischaemia
valve dysfunction
acute VSD

Question 6

What happens to ventricular function curves in shock

Answer 6

become hypo dynamic - need to preserve adequate fluid status for optimum preload + CO

Question 7

Alpha 1 agonists

Answer 7

“vasopressors”
Act mainly in BVs
increase tone + resistance

Question 8

Beta-1 agonists

Answer 8

“inotropes”
act mainly in heart
increase contractility = +ve inotropes
increase HR = +ve chronotropes

Question 9

Norepinephrine = 1-100micron/min

Answer 9

alpha-agonist = acting via PLC + IP3 to increase intracellular Ca
increased peripheral resistance + systolic/diastolic pressure
Uptake 1 mechanism = pre-synaptic neurons take up

Question 10

Epinephrine = 1-10micron/min

Answer 10

mixed alpha/beta agonist + net vasoconstrictor effect
uptake 2 mechanism = post-synaptic euros
CPR = improve BP in vfib
anaphylaxis = 0.5mg IM adrenaline
- Potent vasopressor increasing BP
- dilates bronchi via B1

Question 11

Dobutamine = 5-20microg/kg/min

Answer 11

synthetic b-agonist = inotrope
T 1/2 = 2min + glucuronide metabolism
Increases cAMP = phosphorylating intracellular kinases

Question 12

What are PDE III inhibitors?

Answer 12

inhibit cAMP breakdown + synergistic effect with dobutamine
Cardiac SM - increase Ca flux (+ve inotrope)
vessels = increase SERCA uptake + vasodilator
SEs = thrombocytopenia, hypotension, arrhythmias

Question 13

Dopamine

Answer 13

Metabolic precursor of NE + short T1/2
uptake 1+2
LOW dose = 0.5-2 - increases RBF/renal perfusion
MOD dose = 2-10 - b-effects + inotrope
HIGH dose = >10 - a-effects + vasopressor
SEs = ischaemia, increased cardiac work (ischaemia/arrhythmias)

Question 14

Digoxin

• Indications
• rate control
• % absorption/protein binding
• T 1/2
• MoA
• Effects in AVN?

Answer 14

Indications = fast AF (rate control), acute/chronic HF
Rate control = good for RESTING HR but not EXERCISING HR
75% oral absorption
20-40% protein binding
T1/2 ~1.6days
Inhibits cardiac Na/K ATPase = increases NCX activity + increases intracellular Ca
AVN = increases vagal tone, decreases conduction

Question 15

What effect does hypokalamia have on digoxin effect?

Answer 15

augments effect
both compete for active site on Na/K ATPase
low K = more digoxin binding + increased toxicity

Question 16

Digoxin toxicities -
Cardiac
GI
CNS

Answer 16

Cardiac = VT/NSVT/bigemmy/2nd degree heart block, "reverse tick" sign, increase PR, reduce QT
GI = anorexia, diarrhoea, abode pain
CNS = fatigue, visual disturbance, dizziness, bizarre dreams

Question 17

Digoxin drug interactions

Answer 17

Metabolic = hypokalaemia/magnesemia increase toxicity
P-GP inhibitors increase GI absorption, CNS access, reduce biliary/renal excretion = quinine, amiodarone, diltiazem, verapamil, cyclosporine, erythromycin