Download DRUGS ACTING ON THE CARDIOVASCULAR SYSTEM

UNIVERSITY OF LUSAKA
DRUGS ACTING ON THE
CARDIOVASCULAR SYSTEM
ANATOMY & PHYSIOLOGY
• The heart is the pump resposible for
maintaining adquate circulation of oxyginated
blood around the vascular network of the
body.It is a four charmber pump with the rt
side receiving deoxy blood from the body at a
low pr (pulmonary circulation) and the the left
side receiving oxy blood frm the lungs and
pumping at high pr(systemic circulation).The
myocardium are joined by specialised cells.
Anatomy & PHY Continued
• The contraction of each cell is produced by the
rise in intracellular calcium leads to
depolarisation.For this to be effective there is
a specialized conducting system i.e SA
Node,AV Node and His-Purkinje system.
• SA NODE: Under normal circustances SA node
is the pace maker and dominates all other
pontencial pacemakers.
ANA & PHY CONT”D
• AV NODE: Impulses originating in the atria must
travel in order to reach the ventricles.Impulses
reaching the AV node are delayed before nodal
exitation.This delay provides time blood to fill the
ventricles prior to ventricular contraction.
• His purkinje system:Specialised nervous
tissue.The function is to conduct electrical
excitation in all parts of the ventrical.Stimulation
His-Purkinje is caused by impulses leaving the AV
Node.
ANA & PHY CONT”D
• This depolarisation and contraction is
controlled by this specialised cells.The cells
genarate rhythmical depolarisation which
spreads over the atria to the AV Node.The
atria then contract,pushing blood in the
ventricles.The electrical conduction passes via
the AV Node to the bundle of His,which
divides into the right and left branches and
then spreads from the base of the ventricles…
Cont”d
• ….across the myocardium.This leads to a
“bottom-up “contraction of the
ventricles,forcing blood up and out into the
pulmonary artery(right) and Aorta (left).The
atriaen refills as the myocardium relaxes.The
“squeeze” is called systole and normally lasts
about 250 ms.The relaxation period,when the
atria and ventricles refill is called diastole,
time depends on the heart rate.
Cardiovascular drugs
a)
b)
c)
d)
Cardiac gylycosides
Anti-angina agents
Antihypertensives
Haematologic drugs -heamatenicsAnticoagulants –blood derivatives –
Thrombolytic enzymes
e) Fluid and electrolytes balance i.e eletrolytes
and replacement solutions –Acidifiers and
alkaliners
Cardiac glyco cont”d
• Acute digoxin poisoning-nausea &
vomiting,hyperkalaemia,bradycardia,ectopic
rhyms,heart block
• Treatment of overdose: Lignocaine IV,
Phenytoin.severe poisoning –digoxin specific binding
fragment(Fab)
• Drug interactions- hypokalemia enhances digoxin toxic
effects therefore drugs that deplete potassium eg
diuretics,adrenal
steroids,verapamil,nifedipine,quinidine,amiodarone
increase plasma digoxin,verapamil and beta blockers
increase the AV Block caused by digoxin.
Anti-arrhythmic agents
• An arrhythmia is an abnormality in the rate or regularity of the
heartbeat.Arrhythmias can lead to lowering of cardiac output and
therefore associated with a high degree of morbidity and mortality.
• Phases of the cardiac cycle :phase 0-depolarisation of cell
membrane in response to soduim channels,phase 1-repolarisation
in response to potassium ions, phase 2-delay in repolarisation
mainly caused slow movement of calcuim ions from the exterior
into the cell.The membrane pontencial remains the stable.Phase 3rapid repolarisation caused by extrution of potassium ions from the
cell.Phase 4-repolarised state potassium ions move back into then
soduim and calcuim move out the cell.During this phase the interior
of the walls that discharge automatically gradually less negative i.e
membranes undergoe depolarisation until zero threshold(phase 0)
is reached and the process is repeated.Cells that do not discharge
spontaneously rely on action pontencial from another cell to initiate
depolarisation.
Causes of Arrhythmias
1. Disturbances of automaticity i.e discharge of SA
Node,AV node and His purkinge system
changes(changes caused by injury or influence
on the autonomic nervous system,tissues which
do not normally express automaticity(ectopic
pacemaker)
2. Disturbances of conduction-AV Block which
result in varying degrees i.e 1ST,2nd and 3rd
degree block.Reentry circuits – these form when
there is partial conduction block.
ANTI-DYSARRHYTHMICS
• Vaughan-william clasification based on phases of
cardiac cycle.Class one blocks sodium
channels.subdivided into class Ia,Ib and Ic.
• Ia i.e quinidine,procainamide and disopyramide
• Side effects- quinidine(hypotention,cardiac
failure) Disopyramide-has lesser effects than
quinidine(hypotention,heart failure,GI
effects,agranulocytosis) Procainamide(similar to
quinidine)
Class IB
• Lignocaine,phenytoin
• Side effectsLignocaine(convulsions,dizziness,slurred
speech,sweating)
Phenytoin(hiccup,tremor,drowsiness)
• Class IC-Flecainamide,propafenone-Side effectsFlecainamide(prolongs effects on
ECG)contraindicated in cardiac failure,myocardial
infarction.Propafenone(worsens cardiac
failure,exacerbates ventricular dysarrthmias)
Class II
• Beta adrenoceptor antagonists-propranolol,Labetolol
• Adverse effects: overdosage can cause heart block or
even cardiac arrest
• Class III-lengthen refractoriness without sodium
blockade-Amiodarone and Bretylium.Side
effects:Amiodarone(heart
block,photophobia,hepatatis.interactions displaces
digoxin frm binding sites,inhibits metabolism of
warfarin.Bretylium(vomitting,hypotension and
bradycardia
Class IV
• Calcium channel blockers-calcium is involved
in the contraction of cardiac smooth muscle
cells.Pacemaker cells rely on the slow inflow
of calcium(phase 4)Verapamil,Diltiazem
• Side
effects:nausea,consitipation,headache,fatigue
and heart block.
Anti-Angina Drugs
•
•
Angina pectoris: Angina pectoris, commonly
known as angina, is chest pain due to ischemia
(a lack of blood, thus a lack of oxygen supply and
waste removal) of the heart muscle, generally
due to obstruction or spasm of the coronary
arteries (the heart's blood vessels)
Pathophysiology:Angina results from transient
episode of ischemia due to an imbalance
between myocardial oxygen supply and
demand.
Types of Angina
• Stable angina
• Also known as effort angina, this refers to the more
common understanding of angina related to
myocardial ischemia. Typical presentations of stable
angina is that of chest discomfort and associated
symptoms precipitated by some activity (running,
walking, etc.) with minimal or non-existent symptoms
at rest. Symptoms typically abate several minutes
following cessation of precipitating activities and
reoccur when activity resume. Also caused by
atherosclosis
Types Angina cont”d
• Unstable angina
• Unstable angina (UA) (also "crescendo angina;" this is a
form of acute coronary syndrome) is defined as angina
pectoris that changes or worsens.
• It has at least one of these three features:
• it occurs at rest (or with minimal exertion), usually
lasting >10 min;
• it is severe and of new onset (i.e., within the prior 4–6
weeks); and/or
• it occurs with a crescendo pattern (i.e., distinctly more
severe, prolonged.
Angina cont”d
• Micro vascular angina(variant)
• Micro vascular Angina or Angina Syndrome X is
characterized by angina-like chest pain, but has
different causes. The cause of Micro vascular
Angina is unknown, but it appears to be the result
of poor function in the tiny blood vessels of the
heart, arms and legs. Since micro vascular angina
isn't characterized by arterial blockages, it's
harder to recognize and diagnose, but its
prognosis is excellent.
Anti-Anginal Drugs
1. Organic nitrates
2. Beta adrenergic blockers
3. Calcium channel blockers
Organic Nitrates
• Nitroglycerine,isosorbite dinitrate,isosorbite
mononitrate and amyl nitrate
• Mech of action:Bind to nitrate receptor in the
vascular smooth muscle releasing nitric oxide
which is a vasodilator or inhibiting entry of
calcium which leads to vasodilation.
• Side
effects:flushing,hypotention,dizzness,tachycar
dia,
Therapautic uses of organic nitrates
1.
2.
3.
4.
5.
Angina
CHF
Acute myocardial infarction-IV Nitroglycerin
Spasmolytics-UTIs and GIT
Cyanide poisoning-sodium nitrite IV
1. Precaution during nitrate therapy
1. Nitroglycerin tabs should not be put in direct
sunlight
2. Expiry date checked i.e replenish every 3
months
3. Start with small dose to minimise side effects
4. Transdermal formulations are long Acting
BETA BLOCKERS
• Propranolol,Atenolol
• Mech of action;They improve the balance btn
myocardial oxygen supply and demand.They
increase oxy demand by increasing coronary
blood flow and reduce oxy demand by
reducing heart rate and reducing BP
Calcium channel blockers
• Nifedipine,Amlodipine
• Mech of action;Inrease oxy supply and
improve coronary blood flow and produce
coronary vasodilation
1. MANAGEMENT OF ANGINA
• Avoid risk factor:
smoking,diet,diabetis,hypertention,hyperlipid
emia
• Decrease risk myocardial infarction i.e antiplatelets eg Aspirin
• Take Anti-anginal drugs
Anti-Hypertensives
• Hypertension; is the most common
cardiovascular disease.It is defined as
sustained increase in BP >140/90 mmHg.It
associated with an increase in peripheral
resistance. BP=Cardiac output(CO)*Peripheral
resistance(PR).
• Etiology:Essential hypertension(no specific
cause ),Family history,Enviromental
factors(stress,obesity,sodium,smoking)
Regulation of BP
1. Four anatomical sites:arterioles,post capillary
venules,heart and kidney.
2. Systems that control arterial pr:symphathetic nervous system,reninangiotesin system(ras),endothelium derived
autocoids i.e nitric oxide and endothelin-1
3. Factors that increase arterial BP:Increased
cardiac output and increased peripheral
resistance.
Classification of Antihypertensive
Drugs
1. DIURETICS
2. SYMPATHOLYTICS:centrally acting(clonidine)B
adrenergic blockers(atenolol)Alpha adrenergic
blokers(prazocin)adrenergic blokers(reserpine)
3. Angiotensin converting enzyme inhibtor(ACE)
4. Angiotensin II receptor blockers
5. Calcium channel blockers
6. Vasodilators
Diuretics
• Hydrochlorothiazide
• Diuretics reduce BP by depleting sodium
stores and reducing blood volume.
• Toxicity:hypokalemia,hypomagnesia,hyperuricaemia,s
exual impairment
•B-adrenergic blockers
• Atenolol,Propranalol
• Beta blockers provide effective therapy for all
grades of hypertension.They do not produce
postural hypertension,no salt and water
rentetion and can be used with vasodilators.
• Propranolol: non-selective-lipophilic
• Atenolol-selective-hydrophilic
Angiotensin converting enzyme
inhibitors
• Enalapril,lisinopril
• They inhibit angiotensin converting enzyme,
which is responsible for the formation of
angiotensin II –which is a vasoconsitrictor.
• ACEIs inhibit angiotensin II formation in
tissues(heart and vessels) preventing
myocardial hypertrophy.
ACEIs adverse effects and
contraindications
1.
2.
3.
4.
5.
6.
Hypotension-start with small dose
Skin rash
Dry cough
Temporary loss of taste
Nephrotic syndrome
Fetopathic(hypotension,anuria,renal
failure)therfore contraindicated in pregnancy
Angiotensin receptor blockers
• Losartan,valsartan
• Pharmacology:They produce more complete
inhibition of the effect of angiotensin II.They
have no effect on bradykinin metabolism.They
do not induce cough which are bradykinin
mediated.
• Side
effects:Fetopathic,hypotension,hyperkalemia.
Calcium channel blockers
• Nifedipine,amlodipine
• Mech of action;Block sensitive calcium
channel-relax arterial smooth muscle leading
to vasodilatation
• Side
effects;dizziness,hypotension,consitipation,oe
dema
VASODILATORS
•
•
•
•
Hydralazine,Minoxidil
Dilates arterioles not veins
Used in severe hypertension
Side effects:headache,flushing,Angina
Choice of Anti-hypertensives
1. Hypertensive emergencies:frusemide
IV,diazoxide IV ,Na nitroprusside IV, Labetalol
2. Hypertension and heart failure-ACEIs –
diuretics.B blockers and CCBs are
contraindicated
3. Hypertension in pregnancy-methydopa-B
blocker eg
atenolol,Hydralazine.ACEIs(teratogenic)and
diuretics(volume depletion)
choice of Anti-hpy”s cont”d
 Htn & peripheral vascular disease:CCBs .B
blockers are contraindicated.
 Htn & asthma: CCBs,diuretics.B blockers are
contraindicated
 Htn & ischemic heart disease: CCBs(all types
of angina) B-blockers(except in variant angina)
 Htn & diabetes: ACEIs