Drugs in Cardiovascular disease Flashcards
What are the main functions of the CVS?
Transport
Protection
Regulation
The cardiovascular system is responsible for the transport of…
Oxygen
Nutrients
Hormones
Waste products
How does the CVS contribute towards protection of the body?
Contain:
Leukocytes
Antibodies
Complement proteins
Clotting factors
The CVS is responsible for the regulation of …
Temperature
pH
Hydration (water content)
List cardiovascular diseases that affect the heart
Arrhythmias
Angina
Acute or chronic heart failure
Congenital heart disease
Aortic valve/mitral valve disease
List cardiovascular diseases that affect the blood vessels
Hypertension
Hyperlipidaemia
Thrombosis
Atherosclerosis/ Atheroma
In what ways can drugs have an effect on the heart?
They can affect:
-rate and rhythm
-myocardial contraction
-metabolism and blood flow
The conduction of the electrical impulse through the heart corresponds to an ECG trace. True or false
True
Briefly state the route of the cardiac action potential
SA node —> Atrium —> AV node —> Purkinje fibres —> ventricle
What is an arrhythmia/Dysrhythmia?
An irregular heartbeat
How are arrhythmias/dysrhythmias clincally classified?
- the site of abnormality- atrial, junctional or ventricular
-whether the rate is increased (tachycardia) or decreased (bradycardia)
Give examples of tachyarrhythmias
- atrial fibrillation
- supraventricular tachcardia (SVT)
- ventricular tachycardia
- ventricular fibrillation
Give examples of bradyarrythmias
SA node dysfunction
AV block
What are the 4 basic phenomena that underlie disturbances of cardiac rhythm?
- delayed after depolarisation
- re-entry (circus movement)
- ectopic pacemaker activity
- Heart block
Delayed after- depolarisation is caused by …
an inward current associated with an increase in calcium ion influx
What is delayed after depolarisation?
They are transient depolarisations in the diastolic phase following an action potential which has been linked to arrhythmogenesis in cardiac diseases
What is re-entry (circus movement)
occurs when parts of the myocardium are depolarised as a result of disease
occurs when a propagating impulse fails to die out after normal activation of the heart and persists to re-excite the heart after expiration of the refractory period
Ectopic pacemaker activity occurs as a result of…
increased sympathetic activity in non-nodal tissue (e.g. during disease)
Heart block is often a result of …
fibrosis/ischaemic damage to the conducting system
What is the mechanism of Class Ia antidysrhythmic drugs? Give an example
Sodium channel blocker (intermediate dissociation)
Disopyramide
What is the mechanism of Class Ib anti-dysrhythmic drugs? Give an example
Sodium channel blocker (fast dissociation)
Lidocaine
What is the mechanism of Class Ic anti-dysrhythmic drugs? Give an example
Sodium channel blocker (slow dissociation)
Flecainide
What is the mechanism of Class II anti-dysrhythmic drugs? Give an example
Beta blocker
Propanolol
What is the mechanism of Class III anti-dysrhythmic drugs? Give an example
Potassium channel blocked
Amiodarone
What is the mechanism of Class IV anti-dysrhythmic drugs? Give an example
Calcium channel blocker
Verapamil
Briefly describe the phases of a cardiac membrane potential
Phase 4: Na+, Ca2+ channels are closed, open K+ rectifier channels keep the membrane potential stable at -90mV
Phase 0: Rapid influx of Na+ through open fast Na+ channels
Phase 1: transient K+ channels opening and efflux of K+ to help membrane potential return to 0
Phase 2: influx of Ca2+ through L type channels which is electrically balanced by K+ efflux through delayed rectifier K+ channels
Phase 3: calcium channels close but delayed rectifier K+ channels remain open and the membrane potential returns to -90mV
What phase of cardiac potential are B-agonist most relevant ? Elucidate your reasons why.
Phase 4
Pacemaker potential
result in increased cardiac stimulation
Phase 2 (Plateau)
Beta agonists bind to betaadrenoceptors which are coupled to Gproteins which lead to cAMP dependent activation of pKA.
pKA phosphorylates L- type calcium channels which leads to an increased influx of calcium ions
Class I and II anti-dysrhythmic drugs block what phase?
Phase 0
prevent the influx of Na+ via Na+ channels
Class IV anti-dysrhythmic drugs block what phase?
Phase 2 (plateau)
block ca2+ ion channels
Class III and Ia anti-dysrhythmic drugs block what phase?
Phase 3
Repolarisation phase
What is the function of anti-dysrhythmic drugs?
to restore normal rhythm and conduction
How is cardiac output (L/min) calculated
SV (stroke volume- ml) X heart rate (beats per minute)
Heart rate is controlled by the __________ nervous system
autonomic
What is the stroke volume?
volume of blood ejected from the ventricle with each heartbeat
What are the categories of the factors that affect stroke volume
Intrinsic myocardial contractility
Extrinsic circulatory factors
List some factors that affect the heart rate
Autonomic innervation
hormones
fitness levels
age
List some factors affecting stroke volume
heart size
fitness levels
gender
contractility
duration of contraction
Preload (EDV)
Afterload (resistance)
The intrinsic contractility of cardiomyocytes is dependent on …
Ca2+ ions and ATP availability
Ca2+ entry across the plasma membrane
Ca2+ release from stores (sacroplasmic reticulum?)
What are the extrinsic circulatory factors that affect myocardial contraction?
- elasticity and contractile state of arteries and veins
- volume and viscosity of the blood
- these together determine the cardiac load (preload and after load)
What is preload?
This is the initial stretching of the cardiac myocytes (muscle cells) prior to contraction. It is related to ventricular filling
What is afterload?
force or load the heart must pump against to eject blood to the lungs or the body. Afterload goes down when aortic pressure and systemic vascular resistance decreases through vasodilation
What is heart failure?
this is where the cardiac output is not suffcient to meet the demands of the body
Heart failure is often a result of …
conditions which reduce the efficacy of the heart (damaged or increased workload)
Consequences of heart failure are often observed during exercise, but as the disease progresses it is also observed at ______.
rest
Heart failure is divided into …
Systolic dysfunction
Diastolic dysfunction
Systolic dysfunction results from …
a loss of intrinsic contractility by alterations in signal transduction mechanisms
Diastolic dysfunction results from
less compliant ventricles (become stiffer) which impairs ventricular relaxation/filling and causes less ejection of blood
What is an important consequence of heart failure?
Oedema
How does heart failure cause oedema?
less renal retention of sodium and water, this increases blood volume and venous pressure
Results in oedema of peripheral tissues (swelling of legs) and lungs (breathlessness)- promotion of fluid extravasation
sodium and water reabsorption is promoted in the kidneys during heart failure
Drugs that treat heart failure improve cardiac function by …
reducing blood volume
reduce clinical symptoms e.g. oedema, shortness of breath
The heart is poorly perfused compared to its oxygen consumption and metabolic need. True or false
True
What can lead to an increase in coronary blood flow?
Increased cardiac activity
Increased oxygen consumption
Coronary blood flow is controlled by …
Auto-regulation of perfusion pressure (60-200mmHg)
Vasodilation by mediators (adenosine, nitric oxide)
Autonomic innervation is less important in coronary blood flow
When coronary blood flow is reduced, what can this lead to?
Angina
Coronary blood flow can be reduced by …
Transient constriction of the coronary arteries (vasospasm)
Chronic narrowing of a coronary artery (i.e fixed stenosis) caused by atherosclerosis
Formation of a blood clot within the vessel lumen (i.e. coronary thrombosis)
Vasospasms, fixed stenosis and a thrombus in coronary arteries can lead to…
Angina (chest pain)
Increased heart rate, contractility, afterload and preload leads to …
Increased oxygen consumption
Increased oxygen consumption and decreased coronary blood flow can lead to…
Angina (chest pain)
Angina is caused by…
insufficient oxygen supply to the myocardium which leads to pain distributed in the chest, arm (left) and back
Decreased coronary blood flow
Increased oxygen consumption
What is ischaemia
This is when there is insufficient blood flow to provide adequate oxygenation
Blood flow and thus oxygen is restricted or reduced in a certain part of the body
What are the types of angina recognised clincally?
Stable angina
Unstable angina
Variant angina
What is stable angina?
chest pain on exertion (exercise) produced by increased demand on the heart
What causes stable angina?
fixed narrowing of blood vessels by atheroma
coronary vessels ???
Angina is referred to as unstable when …
pain is experienced even at rest
What causes unstable angina
thrombi from ruptured plaques form leading to decreased blood flow
This is without complete occlusion
Variant angina is uncommon. What does it result from?
coronary artery spasm
Drugs that increase blood flow in the heart have what effect?
increased oxygen supply
Drugs that decrease oxygen demand in the heart lead to …
a decrease in myocardial oxygen consumption
What are the effects of sympathetic innervation on the heart (via B adrenoceptors)?
- increased heart rate
- increased force of contraction
- increases automaticity- spontaneous activity of pacemaker cells
- reduces cardiac efficiency- O2 consumption in relation to cardiac work
An increase in heart rate demonstrates a positive _________ effect.
chronotropic
An increase in contractility/force of contraction demonstrates a positive ________ effect.
inotropic effect
What is the effect of parasympathetic innervation on the heart (via muscarinic M2 receptors- smooth muscle and heart)
- Decrease heart rate
- decrease force of contraction- in the atria only
- reduces automaticity- spontaneous activity of pacemaker cells
- inhibits atrio-ventricular conduction
Inhibition of AV conduction is also referred to as…
negative dromotropy
A decrease in heart rate demonstrates a negative _________ effect
chronotropic
What are drugs that affect the myocardial cells directly?
Autonomic neurotransmitters and related drugs (B blockers)
Anti-dysrhythmic drugs (calcium channel blockers)
Cardiac glycosides (digoxin- inhibits Na+/K+ ATPase)
What is the mechanism of action of digoxin?
Inhibits Na+/K+ ATPases in cardiac myocytes
Increases intracellular Na+
This in turn increases intracellular Ca2+ ions
This increases cardiac contractility
Give examples of drugs that affect cardiac function indirectly (effect is elsewhere in vascular system)
Nitrates
Diuretics
ACEIs
Nitrates are used to treat…
Angina
Diuretics and ACEIs are used to treat…
heart failure
Calcium antagonists are a category of drugs that affect cardiac function in what ways?
both directly and indirectly
What is the mechanism of action of ACEIs
Prevent production of Angiotensin II
Angiotensin II raises blood pressure
In what ways is angiotensin II able to raise blood pressure?
Vasoconstriction
Increased aldosterone synthesis
Sympathetic nervous stimulation
B1 adrenoceptor subtypes have a ________ effect. Give examples of tissues they can be expressed in
stimulatory effect
Heart, juxtaglomerular apparatus (kidney)
B2 adrenoceptor subtypes have a _______ effect. Give examples of tissues they are expressed in.
relaxation effect
bronchial, vascular, uterine smooth muscle
B3 adrenoceptors are often found in __________ tissue
Adipose
For lipolysis
What is the mechanism of action of B-blockers
competitively bind to B-adrenergic GPCRs
block sympathetic effects of adrenaline and noradrenaline
What are the cardiac effects of Beta- blockers ?
- decreased contractility (negative inotropy)
- decrease relaxation rate (nageive lusitropy)
- decreased heart rate (negative chronotropy)
- decreased conduction velocity ((negative dromotrophy)
What are the vascular effects of beta- blockers?
smooth muscle contraction (mild vasoconstriction)
What are the therapeutic indications for beta- blockers?
Angina
Heart failure
Arrhythmia
Hypertension
Open angle glaucoma, hyperthyroidism, anxiety, tremor
Why are beta blockers indicated for angina?
Reduces heart rate, contractility, arterial pressure, workload and oxygen demand of the heart
This improves O2 supply/demand ration which can relieve anginal pain
Why are beta blockers indicated for heart failure?
blockade of excessive, chronic sympathetic input to the heart (poorly understood)
Why are beta blockers indicated for arrhythmias?
decreased sinus (heart rate) and conduction velocity and inhibit aberrant pacemaker activity.
increase action potential duration and effective refractory period (in non pacemaker cells).
effective in blocking re-entry arrhythmias
Why are beta blockers indicated for HTN?
- reduce cardiac output
- inhibit renin release by kidneys- enhanced renal loss of sodium and water and further diminishes arterial pressure
- decrease in blood pressure
List some B1/B2 non selective betablockers (B adrenoceptor antagonists)
Carvedilol
Labetalol
Nadolol
Pindolol
Propanolol
Sotalol
Timolol
What B1/B2 non-selective Beta blockers are indicated for therapeutic use against hypertension and angina?
Carvedilol
Labetalol
Nadolol
Pindolol
Propanolol
Sotalol
Timolol
What B1/B2 non-selective beta blockers are indicated for therapeutic use against arrhythmias?
Nadolol
Propanolol
Sotalol
What B1/B2 non-selective beta blockers are indicated for therapeutic use as prophylaxis after MI?
Propanolol
Timolol
What B1/B2 non-selective beta blocker is indicated for therapeutic use as an adjunctive therapy in heart failure
Carvedilol
What are some other therapeutic uses of nadolol?
Migraine prophylaxis
Thyrotoxicosis
What are some other therapeutic uses of propanolol?
Migraine prophylaxis
Thyrotoxicosis
Anxiety (palpitation, sweating and tremor)
Pheochromocytoma
What are some other therapeutic uses of timolol?
Open- angle glaucoma
Migraine prophylaxis
Give examples of B1 cardio-selective beta- blockers
Acebutolol
Atenolol
Betaxolol
Bisoprolol
Esmolol
Metoprolol
Nebivolol
Give examples of B1 cardio-selective beta- blockers indicated for hypertension
Acebutolol
Atenolol
Bisoprolol
Esmolol
Metoprolol
Nebivolol
Give examples of B1 cardio-selective beta- blockers indicated for angina
Acebutolol
Atenolol
Bisoprolol
Metoprolol
Give examples of B1 cardio-selective beta- blockers indicated for arrhythmias
Acebutolol
Atenolol
Esmolol
Metoprolol
Give examples of B1 cardio-selective beta- blockers indicated for use as early intervention within 12 hours of MI
Atenolol
Metoprolol
Give examples of B1 cardio-selective beta- blockers indicated for use as adjuncts in heart failure
Acebutolol
Bisprolol
Nebivolol
What are other therapeutic uses of atenolol?
Migraine prophylaxis
What are other therapeutic uses of betaxolol?
Open- angle glaucoma
What are other therapeutic uses of metoprolol?
Migraine prophylaxis
Hyperthryroidism (adjunct)
In surgery
List some common/ very common side effects of beta blockers
Abdominal discomfort
Bradycardia
Bronchospasm
Confusion
Constipation
Depression
Diarrhoea
Dizziness
Dry eye
Dyspnoea- shortness of breath
Erectile dysfunction
Fatigue
Headache
Heart failure
Nausea
Parasthesia
Peripheral coldness
Peripheral vascular disease
Rash
Sleep disorders
Syncope
Visual impariment
Vomiting