Inotropic vasopressor drugs - Dawes Flashcards
What is an inotrope
changes the force of cardiac muscle contractions
positive or negative
What is shock?
Inadequate oxygen perfusion to meet the tissues oxygenation demand leading to organ dysfunction
The types of shock
Hypovolemic - dehydration, haemorrhage
Cardiogenic - HF
Distributive - sepsis, anaphylaxis
Obstructive - Cardiac tamponade. PE
Features of patient in shock
Hypotension / hypovolemia LV impairment Changes in vascular resistance Poor renal / peripheral perfusion Confused / sedated
Goals of shock resuscitation
Restore BP - IV fluids - positive inotropes Normalise systemic perfusion - postitive inotropes Reverse organ function - renal perfusion Treat underlying cause - antibiotics - relieve tamponade
Cariogenic shock,
causes?
Characterised by?
Ischaemia
Valve dysfunction
Actue VSD
High systemic resistance (sympathetic activity)
Low CO
Treatment of cardiogenic shock
Fluids first to improve preload
inotropes
intra aortic balloon pump
Inotropic agents
what
risk
rationale
arguments contractility, after preload established, thus improving cardiac output
rationale: increased cardiac output improves global perfusion
Risk, tachycardia and increased myocardial oxygen consumption
alpha and beta adrenoreceptor agonists
Norepinephrine
epinephrine
Dobutamine
Dopamine
Beta 1 agonists
mostly in heart
increase contractility - positive inotrope
increase heart rate - positive chronotrope
DOBUTAMINE
alpha 1 agonists
mostly in BV’s increase tone/ resistance = vasopressor
NOREPINEPHRINE
Alpha and beta agonists and BP
Beta agonists affecting the heart have very little effect on BP, whereas alpha agonists raise BP significantly
norepinephrine
= noradrenaline potent alpha vasoconstrictor minimal beta adrenergic agonism minimal inotropic chronotropic effect Causes: increased peripheral resistance increased systolic/ diastolic BP Continuous IV infusion
Epinephrine
= adrenaline
Mixed alpha and beta adrenergic effects
can vasoconstrict and vasodilate
potent inotrope and chronotrope, used in cardiac arrest
Increases myocardial oxygen consumption particularly in coronary heart disease
continuous IV infusion
epinephrine for anaphylaxis
activates both alpha and beta receptors potent vasopressor blood pressure increase dilates bronchi = symptomatic treatment of anaphylactic shock
Dobutamine
beta agonist - potent inotrope variable chronotrope
hepatic metabolism - glucoruonide
Caution in hypertension, inadequate volume may precipitate tachycardia or worsen hypertension
increases adenylate cyclase activity
Dopamine
metabolic precursor of norepinephrine at low dose - dopaminergic (inc renal blood flow) via D1 receptors Moderate dose - beta effects High dose - alpha effects * although used from time to time as an agonist, has quirky pharmacology so haven't seen much improvement in patient outcomes.
vasopressor side effects
in shock sympathetic activity already high
vasoconstriction
- Ischaemia
increase cardiac work (alpha and beta agonism)
- cardiac ischaemia
- arrhythmias
vasopressin
Vasopressor (VA1 receptor - VSMC)
IP3 mechanism
liver/ renal metabolism
can use when alpha agonist wont work because same effect different mechanism
Angiotensin II
2017
Catecholamine resistant shock
When resistant to noradrenaline
Amrinone / milrinone
Phosphodiesterase III inhibitor
- vascular / vasodilate
- cardiac smooth muscle / postitive inotrope
increase CAMP –> activates protein kinase
- myocardium = inc Ca2+ flux
- Vessels Ca2+ uptake into SR
Most often added as dobutamine as second agent
Need ITU environment
Block the breakdown of CAMP
phosphodiesterase inhibitors - main side effects
thrombocytopenia hypotension (vasodilation) Arrhythmias from inc CAMP Increased mortality *are used but because of side effects need close observation therefore expensive
What are the calcium sensitiser drugs
Levosimendan
Digoxin
Levosimendan
New I.V Emerging role in treatment of shock Calcium sensitiser - Enhances troponin sensitivity to Ca2+ - inc inotropy Arrhythmias increase mortality
Digoxin
- indications
- why is it good to use?
- atrial fibrillation: rate control slows HR improves cardiac work Acute / chronic HF - no effect on mortality - Improves symptoms - reduces hospital admissions
Digoxin MoA
Normally sodium / potassium ATPase is chucking sodium out of the cell. Digoxin inhibits this therefore increasing the amount of intracellular sodium, which is picked up by the Na/Ca channel, which is activated to continue extruding sodium in exchange for inc inCa2+
But if patient has low K+, digoxin much more able to inhibit the channel therefore digoxin induced side effects
Why is digoxin good for coronary perfusion?
Coronary perfusion occurs during diastole therefore by slowing heart rate inc time for diastolie = more time for coronary perfusion.
AF rate control = 3rd line digoxin
1st = beta blockers
2nd = diltiazem calcium channel blocker
You often need synergy of two of the 3 drugs to get an effect.
Digitalis toxicity
Various arrhythmias (2nd or 3rd degree heart block) Changes in ECG
Non cardiac
- Nausea / vomiting / anorexia
- Fatigue
- Visual complaints
- Muscular weakness
- Abdominal pain
- Dizziness
- Dreams
- Diarrhoea
Digitalis interactions
Metabolic
A decrease in K+ or Mg2+ will increase the digoxin effect and side effects, care with use of diuretics
Quinidine, amiodarone, verapamil, diltiazem, erythromycin, cyclosporin.
PGP inhibitors
