Inotropic drugs Flashcards
Define inpotrope and shock
Inotrope: changing force on contraction of heart
Shock: inadequate organ perfusion to meet the tissue’s oxygenation demand leading to organ dysfunction
Categories of shock
Hypovolemic: haemorrhage, dehydration
Cardiogenic: HF
Distributive: sepsis, anaphylaxis ** most common type
Obstructive: cardiac tamponade, PE in RV obstructing flow
Features of patients with shock
ICU, HDU with central lines, catheters, etc
- Hypotension
- LV impairment
- Changes in vascular resistance
- Poor renal/peripheral perfusion
- Confused/sedated
How do inotropes work, rationale and risks
Once euvolemic (preload established), augments contractility, increasing CO
Rationale: ^ CO ^ global perfusion
Risk: Tachycardia and increased myocardial O2 consumption
Examples of vasopresser/ inotropic agents
alpha and beta receptor agonists
NE, E, dobutamine; dopamine
Receptors and location
A1: vascular SM, increase tone, NE A2: presynaptic B1: heart, increase chronotropy and inotropy- dobutamine B2: respiratory and uterine SM B3: adipocytes
Drug affinities for receptors
Alpha1: Phenylephrine > NE > E > dopamine > dobutamine > isopreterenol
beta is opposite
NE: what line in shock; results in; administration
1st line in shock, potent vasoconstrictor, a1 agonist. Minimal beta effect.
Increase TPR, increases BP
Continuous IV infusion, can titrate according to BP, short half life but fast uptake by presynaptic
GPCR, increase phospholipase C and IP3, increased calcium
E: effects what receptors; causes what?; used for
Alpha and beta receptors, can cause vasoconstriction and dilation. Net effect is constriction when infused. (NB ramchandra leccy)
Inotrope and chronotrope, so cardiac arrest.
IV dose
So vasopression + inotropy on heart + relaxes bronchi
Anaphylactic shock (0.5mg 1:1000 IM), uptake 2 mechanism on post synaptic. Short t1/2
Dobutamine: ? agonist; half life; metabolism; caution in ?; mechanism
B1 agonist, potent. Is a potent inotrope, variable chronotrope
2 mins
Hepatic (glucoronide)
Hypotension, may cause tachy or worsen hypotension
Adenylyl cyclase, increasing cAMP and subsequent effect occurs.
cAMP breakdown and significance
Phosphodiesterase breaks down. If blocked, can prolong activity, whatever it may be
Dopamine: precursor?; low dose; moderate dose; high dose
NE precursor
Low dose: dopaminergic receptors in kidneys, vasodilating in kidney, increasing renal blood flow
Moderate: B agonist (+ inotropy and chronotropy)
High: alpha agonist (vasopresser)
Vasopresser side effects
- In shock, adding to what is already a high sympathetic drive
- Vasoconstriction through alpha agonism, ischaemia in heart, limb, gut, brain
- Increase cardiac work (alpha and beta agonism), cardiac ischaemia, or arrythmias
Other vasopresser agents
vasopressin
A2
Phosphodiesterase inhibitiors for shock
Amrinone and milrinone
often used with dobutamine IV
However: thrombocytopenia; hypotension as vasodilates; arrythmias due to ^ cAMP; mortality risk up
Levosimendan
Calcium sensitiser, new and IV use.
enhances tropnonin sensitivity to ca2+, increases inotropy. However pro-arrythmic
Digoxin class and inication
Glycoside, from a plant, is lipophilic and long half life
Atrial fibrillation as slows HR, improves cardiac work. Acute and chronic HF
Mechanism of action of digoxin 2.
For first, if hypokalaemic, result is?
1: Blocks Na+/K+ ATPase. Normally, three sodium out, 2 K+ in. Block will cause [Na+]i (intacellular) to increase. This is noted by NCX. Result is more Na+ extrusion, and increased calcium in the cell, this increases inotropy
NB: hypokalaemia, allows digoxin to inhibit more, more liekly to have side effects
2: Acts at AVN, by augmenting vagal tone, slows conduction and thus ventricular rate
Digoxin: half life and clinicaluse
Long half life, up to 36 hours with 1.5mg. Dependent on renal function though. Fast effect will be maintenance dose
Acute heart failure with atrial fibrillation
Afib 3rd line rate control (note 1st line beta blocker, 2nd line diltiazem for RATE CONTROL), often to us synergy if can not stand one
Digoxin toxicity/side effets
Cardiac:
- Various arrythmias: bigeminy, NSVT, VT, 2nd or 3rd degree heart block
- ECG change: reverse tick sign in ST segment
Non cardiac: Nasuea/vomiting/anorexia; fatigue; visual complaints; muscular weakness; abdo pain; dizziness; funny dreams; diarrhoea
Digoxin drug interactions and why
Excreted by P-glycoproteins in kidney. Also decreases GI absorption, increases biliary loss and decreases CNS access.
PGP inhibitors: quinidine, amiodarone, verapamil, diltiazem, erythromycin, cyclosporin. Will increase digoxin levels, more likely to be toxic
Metabolic: also low K+ like said above and low magnesium, so be careful with diuretic use
