Dawes: Inotropic Drugs Flashcards
(35 cards)
What is an inotrope? what is shock?
An inotrope is a drug that positively or negatively changes the force of contraction.
Shock: This is a state characterised by inadequate organ perfusion to meet the tissues oxygenation demand leading to organ dysfunction.
What are the different categories of shock?
- Hypovolemic
- Haemorrhage and Dehydration
- Cardiogenic
- Heart Failure
- Distributive
- Sepsis and Anaphylaxis
- Obstructive
- Cardiac Tamponade and Pulmonary Embolism.
What are the features of patients in shock?
They will usually be very unwell and as a result in an intensive treatment unit/high dependency unit. As well as this they will present with hypotension, hypovolemia, LV impairment, changes in vascular resistance, poor renal/peripheral perfusion and will be disorientated.
What are the goals of shock resuscitation?
- Restore Blood Pressure
- Ensure euvolemic
- Normalise Systemic Perfusion
- Inotropes and Vasopressors
- Preserve organ function
- Renal Perfusion
- Treat Underlying Cause
- Antibiotics or Relieve Tamponade
You will need to individualise treatment,
What is the mortality rates post cardiogenic shock?
>80% mortality!! In these people we use - intropes and vasopressors and the negative side effects far outweigh the rate of death!
What are the causes of cardiogenic shock? Characterised by?
- Ischaemia
- Valve Dysfunction
- Acute VSD
- High Systemic Resistance - Due to increased sympathetic activity.
- Low Cardiac Output.
What is the first phase of septic shock?
This is the warm/hyperdynamic phase which is characterised by high cardiac output and low peripheral resistance. This is to compensate for the diminished plasma volume.
What is the late stage of septic shock?
This is the cold/hypodynamic phase characterised by subnormal temperature, low white blood cell counts and profound hypotension and hypoperfusion. This is caused by a considerable decrease in the cardiac output.
How do inotropic agents act to treat the effects of shock?
They augment contractility after preload has been established, thus improving cardiac output. This increased cardiac output acts to improve global perfusion. However, it does risk the patient becoming tachycardiac and increases myocardial oxygen consumption.
What are the vasopressors/inotropic agents?
They are alpha- and beta-adrenoreceptors agonists such as norepinephrine, epinephrine, dobutamine and dopamine.
What are the functions of each adrenergic receptor?
What is the function of Beta-1 receptors? EG?
They mainly have effects on the heart
- increase contractility (positive inotrope)
- increase heart rate (positive chronotrope)
Dobutamine
What is the function of alpha-1 receptors? Eg?
These are mainly found in the blood vessels themselves
- increase tone
- increase vascular resistance
Norepinephrine
What is the relationship between vasoconstrictors and inotropes/chronotropes?
Inotropes/Chronotropes effects are mainly generated by the binding of drugs to beta-receptors whereas vasoconstrictors are those drugs that bind to alpha-receptors. As a result, a drugs ability to act as a vasoconstrictor/inotrope/chronotrope is affected by its’ affinity to alpha- or beta-receptors.
What is the relationship between alpha- and beta-receptors and pressure?
Alpha-Receptors act to generate high blood pressures as they function as vasoconstrictors. This is in comparison to Beta-Receptors which result in lower blood pressures being generated.
What is norepinephrine?
This is a first choice vasopressor which acts as a potent alpha-adrenergic agonist. It has minimal affinity for beta-1 receptors and therefore does not show high levels of inotropy or chronotropy. It instead acts to increase peripheral resistance and systolic/diastolic BP and is given via continuous intravenous infusion at 1-100 ug/min.
How does norepinephrine function?
- Binds to alpha-1 receptors.
- GDP is converted to GTP.
- GTP acts to stimulate phospholipase C.
- Phospholipase C acts to convert PIP2 into DAG and IP3
- IP3 causes the release of stored calcium leading to activation of Ca2+ dependent protein kinases.
- Results in contraction of the vascular smooth muscle.
- Vasoconstriction.
What is epinephrine?
Epinephrine is a mixed alpha- and beta-receptor agonist and therefore can cause vasoconstriction and vasodilation. It is a potent inotrope and chronotrope and is used in cardiac arrest situations. The risk with this drug is that it increases myocardial oxygen consumption, particularly in coronary heart disease. Epinephrine is given as a continuous intravenous infusion at 1 - 10ug/min. Uptaken by the uptake 2 channels (non-specific postsynaptic)
Why is epinephrine a good treatment for anaphylaxis?
It activates both alpha- and beta-receptors and therefore
- Is a potent vasopressor
- increases blood pressure
- dilate bronchi.
What is dobutamine?
This is a beta-1 agonist that acts as a potent inotrope and variable chronotrope. It has a short half-life of 2 minutes due to its hepatic metabolism and is therefore given intravenously at a rate of 5-20 ug/kg/minute. Caution must be taken in hypotensive patients as it may precipitate tachycardia or worse hypotension due to its vasodilatory effects.
What is the mechanism behind dobutamine?
- Binds to beta-receptor.
- Activate a stimulatory G-protein.
- Stimulatory G-protein activates adenylyl cyclase.
- Adenylyl Cyclase converts ATP into cAMP.
- Increased cAMP and Phosphodiesterase
- Stimulation of Protein Kinase C.
- Phosphorylation of enzymes (Enzyme-PO4)
- Biological Effect - Vasoconstriction.
What is dopamine?
Dopamine is a metabolic precursor of norepinephrine with a short half-life.
If taken in low doses (0.5 - 2 ug/kg/min) it has a dopaminergic effect and acts to increase renal blood flow via D1 receptors.
If it is taken in moderate doses (2 - 10ug/kg/min) it has beta-effects.
If it is taken in high doses (>10ug/kg/min) it has alpha-effects.
What are the side effects of vasopressors?
In shock, the sympathetic activity is already very high and as a result, further vasoconstriction - caused by alpha-agonism - can lead to ischaemia. Beta- and alpha- agonism can also increase cardiac work leading to cardiac ischaemia and arrhythmias.
What are vasopressins and angiotensin IIs role in vasoconstriction?
Vasopressin is a vasopressor that also works through the IP3 mechanism - like norepinephrine. It undergoes liver and renal metabolism.
Angiotensin II is useful in catecholamine-resistant shock.
