CVS 1 - Heart failure Flashcards
Physiology
SA node - non contractile muscle tissue and spontaneously fires action potentials at a certain freq.
Action potential cause atria to contract.
Signal is slowed down at AV node
Blood is returned from the periphery via vena cava into right atrium . As right atrium contacts it forces blood into right ventirlce so atrium has to ocntract before the ventricle.
From the right ventrilce the blood exits and passesinto the lungs where the blood is oxygenated and returns from via the pulmonary vein into the left atria
after the left ventricle contacts blood ases into the aorta
Sympathetic Nervous system
switched on if Blood pressure is low
SinoAtrial node – noradrenaline bind β1 increase pacemaker current (increase slope of phase 4) Atrial-Ventricular node – noradrenaline binds, increases Ca2* current (increases slope of phase 0) and hence conduction velocity
Also increase contractility of myocytes (heart)
Parasympathetic Nervous system
switched on if Blood pressure is high
Sinoatrial node – ACh (vagus nerve) binds muscarinic receptors and slows depolarization (opens K+ channel, inhibits Na+ channel opening, reduces slope of phase 4)
Atrial-Ventricular node ACh binds muscarinic receptors and decrease conduction velocity (decreases slope phase 0)
Autonomic regulation of cardiac function
• Autonomic nervous system - innervation of SA node
– sympathetic (noradrenaline,↑rate of SA node firing)
– parasympathetic (acetylcholine, ↓rate of SA node firing)
• Baroreceptors
– aortic
– carotid
– send afferent nerve fibres to cardiac control centre (medulla)
• If Increased bp
– baroreceptors activate parasympathetic outflow to inhibit SA firing rate
– parasympathetic outflow inhibits sympathetic nervous system from inducing vasoconstriction (parasympathetic ns causes little direct vasodilation)
• If Decreased bp
– baroreceptors activate sympathetic outflow to increase SA firing rate
– sympathetic nervous system → ↑vasoconstriction →↑venous return→↑ cardiac output
Treatment of heart failure
• When the output of the heart is insufficient to meet the needs of the body (c.f. angina)
– insufficient cardiac output (eg reduced left ventricular contractility)
– inadequate venous return (eg inadequate diastolic relaxation)
– symptoms
» » »
tachycardia (compensation) shortness of breath, easily tired oedema
• Several underlying causes possible:
– coronary artery disease, hypertension, myocardial disease, previous M.I., valve dysfunction, arrhythmia, congenital defects
• Acute left ventricular failure
– inadequate output→pulmonary oedema
– inadequate output → reflex arterial/venous contraction →increased venous return → exacerbate problem
– Treatment goal –reduce venous return (preload)
» Loop diuretic (→ venous dilation & pooling even prior to diuresis) eg furosemide
» glycerol trinitrate (dilate venous capacitance vessels)
» opioid analgesic
• Cardiogenic shock
– sudden impairment to left ventricle systole (eg after acute M.I.) impairs organ perfusion
– treatment goal – resuscitation
– dobutamine (inotropic b agonist) to increase tissue perfusion
• Chronic heart failure
– myocardium disease due to excess load because of eg ischaemic heart disease, valve dysfunction, hypertension
– treatment goal
» reduce compensatory mechanisms triggered by failing heart (vasoconstriction, fluid retention) and/or increase output
– ACE inhibitor – first line!
» vasodilation reduces afterload
» Reduced aldosterone secretion reduce preload
– Diuretics – furosemide (reduce preload)
– Paradoxically β1 antagonists
» block reflex activation of RAAS by SNS?
– Digoxin (positive inotrope)
Positive inotropic drugs: Digoxin
Digitalis glycosides
– (a.k.a. cardiac glycosides),
– originially isolated from foxglove (Digitalis purpura) 1785
• Mechanism
– inhibits Na+/K+ ATPase in myocyte cell membrane, → ↓ Ca2+ efflux by Na+/Ca2+ exchanger → ↑ Ca2+ in sarcoplasmic reticulum→ positive inotrope
– slows heart rate (activates vagus nerve, slows SA node and AV conduction - “AV block”)
» Because slows ventricular response, so can be useful to treat arrhythmia
– can cause arrhythmia
» AV block
» ↑ membrane potential & ↓ Ca2+ efflux →spontaneous Ca2+ release from s.r.)
» arrhythmia “bigeminy” (normal beat followed by ectopic beat), ventricular tachycardia, ventricular fibrillation.
– binds Na+/K+ ATPase in neurons in CNS and PNS – multiple effects
digoxin: indications, pk, adr, caution, contraindication
• Indications
– symptom relief in heart failure
– supraventricular arrhythmia (eg atrial fibrillation)
– NB often used in sub-milligram dose (1000 mg = 1 mg)
• PK
– Good Foral ~ 75% but i.v. possible for rapid onset
– long t1/2 ~ 40 h, large Vd (~ 640L/70 kg; binds Na+/K+ ATPase in skeletal muscle)
– elimination mainly through kidney by PgP → ↑ t1/2 in patients with renal
impairment • ADR
– narrow therapeutic window.
– Cardiac arrhythmia is most important ADR
– GI effects (nausea, vomiting)
– Neurological effects: fatigue, confusion, impaired coloured vision
– Treatment of toxicity – see stage 2, overdose
• Cautions
– Hypokalemia can exacerbate digoxin toxicity see diagram
» K+ inhibits digoxin binding to Na+/K+ ATPase hypokalemia promotes pharmacological and toxic effects of digoxin see diagram
– Hypothyroidism (see diagram) – potential for increased toxicity (see PK)
– elderly more susceptible (renal impairment - see PK)
• Contraindications
– heart block (digoxin inhibits AV node conduction)
Effect of thyroid hormones on renal system
Thyroid hormones increase:
• renal blood flow, GFR
Hypothyroidism leads to reduced GFR
- can promote toxicity induced by digoxin
Hypokalaemia, Diuretics and digoxin
draw
Interaction between
positive and negative
inotropes
draw
Interaction between β- antagonists and Digoxin
draw
A brief reminder –adrenergic receptors
• β1
– Heart – increased rate & force of contraction
– Kidney (juxtaglomerular cells) - renin release
• β2
– some vascular smooth muscle – dilation (skeletal muscle)
– Bronchial muscle – relaxation
– GI tract – relaxation
– Liver & pancreas – glycogenolysis, gluconeogenesis, lipolysis
– Uterus –relaxation
– Bladder – detrusor muscle relaxation
• β3
– adipose tissue - lipolysis
• α1
– some vascular smooth muscle – constriction
• α1 &α2
– Liver & pancreas- glycogenolysis, gluconeogenesis, lipolysis
– Uterus –contraction
– Bladder sphincter – contraction
– Pupil -dilation
Sympathomimetic inotropes
• β1 selective preferred to non-selective sympathomimetics – avoid α1 agonism (peripheral vasoconstriction)
• Dobutamine
– short t1/2 – i.v. not oral
– only used for acute emergencies
– repeated use can cause receptor down regulation and do opposite of what trying to achieve!
• Dopamine
– Is a neurotransmitter but also β1 agonist
– doesn’t cross blood brain barier
• Other β1 agonists avoided
– increase heart rate
– peripheral vasoconstriction α1
PDE inhibitors
avoids receptor down regulation
• Enoximone
– selective for PDE III found in cardiac/smooth muscle ↑cAMP (hence also cause arterial vasodilation)
– avoids receptor down-regulation
– increase cardiac output
– can cause arrhythmia – need ECG monitoring so not for chronic therapy
Hydralazine
- Vasodilator – relaxes smooth muscle, but uncertain mechanism of action
- Tolerance develops and causes reflex tachycardia so not widely used
