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DRUGS ACTING ON CVS
Presented by
Dr. Sannithi Nagarjuna
Coordinator for RIPER-GPAT Cell,
Hyderabad Academy &
Online GPAT Academy
7899107907
9885784793
ATHEROSCLEROSIS
Atherosclerosis is characterized by deposition of lipids and lipid
related materials like cholesterol, triglycerides and lipoproteins in
blood vessels particularly in Coronary Blood Vessels.
As a result of this condition blood/oxygen supply decreases to
muscle of the heart (Myocardium).
This condition further leads to angina pectoris and finally results in
Myocardial Infaraction.
LIPOPROTEINS
Lipoprotein, any member of a group of substances containing
both lipid (fat) and protein.
Lipoproteins in blood plasma have been intensively studied
because they are the mode of transport for cholesterol through
the bloodstream and lymphatic fluid.
Cholesterol is insoluble in the blood, and so it must be bound
to lipoproteins in order to be transported.
Two types of lipoprotein are involved in this function: low-
density lipoproteins (LDLs) and high-density lipoproteins
(HDLs).
LDLs transport cholesterol from its site of synthesis in
the liver to the body’s cells, where the cholesterol is
separated from the LDL and is then used by the cells for
various purposes.
HDLs probably transport excess or unused cholesterol from
the body’s tissues back to the liver, where the cholesterol is
broken down to bile acids and is then excreted. About 70
percent of all cholesterol in the blood is carried by LDL
particles, and most of the remainder is carried by HDLs. LDL-
bound cholesterol is primarily responsible for the
atherosclerotic buildup of fatty deposits on the blood
vessel walls, while HDL particles may actually reduce or retard
such atherosclerotic buildups and are thus beneficial to health.
Source: Google
Source: Google
Atherosclerosis is a disorder which mainly occurs due to
disturbance in homeostasis (Balance) between synthesis
and metabolism of cholesterol.
↑ HMG-CoA Reducatse ǂ ↓ Lipoprotein Lipase
(Enzyme involved in the (Enzyme involved in the
synthesis of cholesterol) metabolism/breakdown of cholesterol)
Based on this, mechanisms used to treat atherosclerosis
include
1. HMG-CoA Reducatse Inhibitors
2. Lipoprotein Lipase Activators
HMG-COA REDUCATSE INHIBITORS
(STATINS)
Source: Google
Source: Google
Ex:
LOVASTATIN – first introduced drug obtained from
Aspergillus terreus
ATORVASTATIN - high potent drug
ROSUVASTATIN - high potent drug
FLUVASTATIN - least potent drug
CERIVASTATIN - withdrawn from the market due to severe
hepatotoxicity
Stains are advised at bedtime because synthesis of
cholesterol is maximum in the midnight.
Side effects include
Myopathy (Muscle weakness)
Myalgia ( Muscle pain)
Rhabdomyolysis (Breakdown of muscles)
FIBRATES
Which activate lipoprotein lipase and they promote lipolysis.
Ex:
Clofibrate
Fenofibrate
Gemfibrozil
The first two are prodrugs and in the body they converted to
clofibric acid and fenofibric acid.
Side effects:
GIT disturbances
NIACIN
Which is also known as Vitamin B3 or Nicotinic acid.
Which is chemically Pyridine-3-carboxylic acid.
Mechanism of action:
Which inhibits the transportation of free fatty acids from adipose to
liver, where free fatty acids are converted to cholesterol and
lipoproteins
Which also increases HDL levels.
Side effects:
Skin allergic reactions due to release of PGs which will be suppressed
by NSAIDs
BILE ACID SEQUESTRANTS
Usually cholesterol is converted to bile acids which are used for
the emulsification of fats.
These are drugs which form complex with bile acids that result
in the formation of large complexes which are having poor
absorption.
Unabsorbed complexes are eliminated through stools.
Further due to this mechanism cholesterol is converted to bile
acids.
These drugs act by increasing the excretion of bile acids by
which increase the conversion of cholesterol to bile acids as a
result the levels of cholesterol will be decreases.
Ex:
Cholestyramine
Colestipol
Colesevelam
DRUGS WHICH INHIBIT
CHOLESTEROL ABSORPTION
Ex:
Ezetemibe
Gum Guggul (Guggullipids)- Obtained form
Commiphora molmol
Commiphora mukul
Commiphora weightii
Dietary Fibres
ANGINA PECTORIS
Which is a pain syndrome characterized by the
development of pain in the chest due to insufficient
oxygen/blood supply to muscle of the heart
(Myocardium).
Hence it is otherwise called as Myocardial
Ischemia/Myocardial Hypoxia.
Further angina pectoris results in Myocardial infaraction
(Heart attack).
Angina pectoris is a disorder which mainly occurs due to
disturbance in homeostasis (Balance) between oxygen
demand and oxygen supply.
The two major reasons for angina pectoris include
↑ Oxygen Demand ǂ ↓ Oxygen Supply
↑ Oxygen Demand ǂ ↓ Oxygen Supply
Ex: During Exercise Coronary Artery Disease
Increase in heart rate a) Vasoconstriction
b) Deposition of lipids
(Atherosclerosis)
c) Deposition of clots
d) Platelet aggregation
Drugs used in angina pectoris should either decrease the oxygen demand or increase the oxygen supply
↑ Oxygen Demand ǂ ↓ Oxygen Supply
(Drugs ↓ Oxygen Demand) (Drugs ↑ Oxygen Supply)
Coronary Artery Disease
Increase in heart rate a) Vasoconstriction
(Calcium channel Blockers, (Vasodilators)
β blockers) b) Deposition of lipids
(Drugs used in Atherosclerosis specially statins)
c) Deposition of clots
(Anticoagulants, Thrombolytics)
d) Platelet aggregation
(Antiplatelet drugs)
Source: Google
Source: Google
Source: Google
VASODILATORS
These are drugs which dilate blood vessels specially
coronary blood vessels by which they improve blood
supply to myocardium.
Hence they are otherwise called as Coronary Vasodilators.
Best examples are Organic Nitrates.
ORGANIC NITRATES
Organic Nitrates Organic Nitrate Reducatse__>> NO
(Nitric Oxide, EDRF)
Stimulates Guanyl Cyclase
GTP cGMP
Smooth muscle
relaxation
NO otherwise called as EDRF which causes vasodilation
due to increased levels of cGMP.
EDRF means Endothelial Derived Relaxing factor causes
vasodilation and derived from endothelium.
Organic Nitrates also cause dilation of Cranial blood
vessels which results in cerebro vasodilaton lead to
headache.
They are classified into 2 types based upon duration of
action
1. Short Acting Ex: Nitroglycerine (Glyceryl Trinitrate)
which undergoes high first pass metabolism.
Not suitable for oral route and given by sublingual route.
Onset of action is within 2min and duration of action is
upto 30 min
2. Long Acting Ex: Isosorbide dinitrate
Isosorbide-2-mononitrate
Isosorbide-5-mononitrate
CALCIUM CHANNEL BLOCKERS
1. Phenyl Alkyl Amines Ex: Verapamil (Which blocks calcium
channels only in heart)
2. Benzothiazepines Ex: Diltiazem (Which blocks calcium channels
both in heart & blood vessels)
3. Dihydropyridines Ex: Amlodipine, Nifedipine, Nimodipine
Nicardipine, Nitrendipine
(Which blocks calcium channels only in
blood vessels)
They are classified into 2 types
1. Nonselective β blockers – Bronchoconstriction side effect
Ex: Propranolol, Pindolol, Timolol, Sotalol
2. Selective β1 blockers
Ex: Atenolol, Acebutalol, Bisoprolol, Nebivolol
β blockers
OTHER DRUGS
1. DIPYRIDAMOL – Antiplatelet as well as direct acting coronary
vasodilator
2. TRIMETAZIDINE – Antioxidant property
3. RANOLAZINE -- Direct acting coronary vasodilator
Stable angina
pectoris
Variant angina
pectoris
Unstable angina
All drugs used in
atherosclerosis
specially statins
Vasodilators
Vasodilators Statins
Anticoagulants
Vasodilators
Atherosclerosis
Coronary artery disease
Angina pectoris
Myocardial infaraction
Atherosclerosis Coronary artery
disease
Angina pectoris Myocardial
infaraction
Atherosclerosis Coronary artery
disease
Angina pectoris Myocardial
infaraction
Statins
Fibrates
Niacin
Bile acid
Sequesterants
All drugs used in
atherosclerosis
Anticoagulants
Thrombolytics
Antiplatelet
drugs
Vasodilators
All drugs used
in angina
pectoris
Calcium
Channel
blockers
β blockers
All drugs
used in
angina
pectoris
ANTIHYPERTENSIVE AGENTS
Which are used for the treatment of hypertension
Increase in blood pressure called as hypertension
Normal blood pressure is 120/80 mm of Hg
> 140/90 mm of Hg is considered as beginning stage of
hypertension
Blood Pressure -- It is the pressure exerted by circulating blood on the
walls of blood vessels.
Cardiac output -- It is the volume of blood pumped by the heart per one
minute. It is approximately 5L.
Heart Rate – It is the number of heart beats/min. It is approximately
72 beats/min.
Stroke Volume – It is the volume of blood pumped by the heart per one
heart beat. It is approximately 70 mL.
Cardiac Output → Heart rate * Stroke Volume
72 * 70
= 5040 mL Approximately 5L
Peripheral Vascular Resistance (PVR) -- It is the resistance offered by
peripheral blood vessels for blood flow.
Blood Pressure = Cardiac output * Peripheral Vascular Resistance
Heart rate * Stroke Volume
Hypertension= ↑ Blood Pressure = ↑ Cardiac output * ↑ PVR
↑ Heart rate * ↑ Stroke Volume
TYPES OF HYPERTENSION
1. Essential/ Primary hypertension
Which is idiopathic and primarily genetics
2. Nonessential/ Secondary hypertension
due to secondary reasons like renal defects, cushings
syndrome, renal artery stenosis
Gestational Hypertension
Hypertension during pregnancy
Malignant hypertension/Hypertensive emergency
It is extremely high blood pressure that develops rapidly
and causes some type of organ damage. A person
with malignant hypertension has a blood pressure that's
typically above 180/120.
Different reasons for hypertension include
1. Increase in Cardiac output
2. Increase in Heart rate
3. Increase in Stroke volume
4. Increase in force of contraction
5. Vasoconstriction
The proposed mechanisms involved in the development
of hypertension include:
1. Increased activity of Renin-Angiotensin-Aldosterone
System (RAAS)
2. Increased activity of Sympathetic Nervous System
3. Increased activity of L type Calcium Channels
4. Excessive Vasoconstriction
5. Increased fluid and sodium retention
Source: Google
The other action of ACE is involved in the inactivation of
bradykinin.
Bradykinin
ACE
Inactive
Angiotensin-I is converted into angiotensin –II by the action of
another enzyme Chymase
Angiotensin-I
Chymase
Angiotensin-II
DRUGS WHICH INHIBIT RAAS INCLUDE
1. Renin Release Blockers Ex: β1 Blockers
2. Renin Activity Inhibitors Ex: Enalkiren, Aliskiren
3. ACE inhibitors
4. Angiotensin- II antagonists
5. Aldosterone antagonists Ex: Spiranolactone
6. Vasodilators
7. Diuretics
Source: Google
ACE INHIBITORS
Source: Google
Side effects of ACE inhibitors include
1. Dry cough & Angioedema ( due to increased levels of
bradykinin)
2. Hyperkalaemia
3. Unable to stop the conversion mediated through
Chymase
ANGIOTENSIN-II ANTAGONISTS
Which block the actions of angiotensin-II mediated through AT1
receptors and they will not have any action on ACE.
Advantages over ACE inhibitors include
1. No dry cough, No angioedema
2. No chymase mediated problem but these agents are also having
Hyperkalaemia
Ex:
Azilsartan
Candesartan
Eprosartan
Irbesartan
Losartan
Olmesartan
Telmisartan
Valsartan
Both ACE inhibitors and angiotensin-II antagonists are
preferably used in diabetic patients because they reduce the
development of diabetic nephropathy.
Both ACE inhibitors and angiotensin-II antagonists are
contraindicated in pregnant women because they produce
kidney defects in the fetus.
Both ACE inhibitors and angiotensin-II antagonists are having
hyperkalaemia side effect.
SYMPATHETIC NERVOUS SYSTEM
Noradrenaline is the neurotransmitter in sympathetic
nervous system.
All actions of sympathetic nervous system are mediated
through Noradrenaline.
Noradrenaline acts through the receptors called as
adrenergic receptors which include α and β receptors.
Type of
receptor
Second
Messenger
Location Pharmacological actions
α1 Gq ❖ Blood vesselsVasoconstriction,
increase in blood
pressure
α2 Gi ❖ CNSNo Action
Type of
receptor
Second
Messenger
Location Pharmacological actions
β1 GS ❖ HeartIncrease in force of
contraction,
Increase in cardiac output,
Increase in blood
pressure,
Increase in heart rate
β2 GS ❖ Smooth muscles
❖ Bronchi
❖ Liver
❖ Smooth muscle
relaxation
❖ Bronchodilation
❖ Glycogenolysis
β3 GS ❖ Adipose tissue❖ Lipolysis
The overall activity of sympathetic nervous system
(Noradrenaline) is increase in blood pressure through α1 and
β1 receptors.
Sympathetic nervous system increases blood pressure as a
part of homeostasis in balance with parasympathetic nervous
system.
But hypertension occurs due to increased activity of
sympathetic nervous system hence we are using α1 and β1
receptor blockers.
α BLOCKERS
1. Nonselective α blockers
Ex: Phenoxybenzamine, Phentolamine
2. Selective α1 blockers
Ex: Prazosin, Terazosin, Doxazosin
Which are also used to treat prostatic hyperplasia
β BLOCKERS
1. Nonselective β blockers
Ex: Propranolol, Pindolol, Timolol, Sotalol
❖ Having bronchoconstriction side effect
❖ Propranolol is also used for migraine treatment
❖ Timolol is also used for glaucoma treatment
❖ Sotalol acts as both class II & class III antiarrhythmic agent
2. Selective β1 (Cardioselective β blockers) blockers
Ex: Atenolol, Acebutalol, Bisoprolol, Nebivolol
α and β receptor blockers
Ex: Labetalol, Carvedilol
❖Which block α1, β1, & β2 receptors but no affinity for α2
receptors
❖ Carvedilol has antioxidant property
CENTRALLY ACTING ANTIHYPERTENSIVES
❖ Which act through α2 receptors located in CNS.
❖ α2 receptors are autoreceptors.
❖ Always stimulation of autoreceptors results in decrease of
further release of neurotransmitters.
❖ Stimulation of α2 receptors results in decrease of further
release of noradrenaline.
❖ Hence they are named as Centrally acting antihypertensives.
Ex:
Clonidine,
α- Methyldopa.
❖ α- Methyldopa in the body converted to α- Methyl
norepinephrine
❖ which stimulates α2 receptors located in CNS and
causes decrease in further release of noradrenaline.
❖ α- Methyl norepinephrine called as false transmitter
CALCIUM CHANNEL BLOCKERS
There are 3 types of calcium channels present
1. L (Longitudinal) located in CVS (Heart & Blood vessels)
2. T (Transient) located in CNS
3. N (Neuronal) located in neurons
ROLE OF CALCIUM
Heart
Influx of calcium
Interacts with troponin C
Increases phosphorylation between actin and myosin
Increases force of contraction
Increases cardiac output
Increases blood pressure
Blood Vessels
Influx of calcium
Interacts with Calmodulin
Increases phosphorylation between actin and myosin
Causes vasoconstriction
Increases peripheral vascular resistance
Increases blood pressure
Increased activity of L type Calcium channels results in
hypertension.
Hence we are using L type Calcium channel blockers.
They prevent the entry of calcium ions through L type Calcium
channels hence which are otherwise called as Calcium Entry
Blockers.
PHARMACOLOGICAL ACTIONS
1. Inotropic action (Force of contraction)
2. Dromotropic action (Impulse conduction)
3. Chronotropic action ( No of contractions/
No of heart beats)
PHARMACOLOGICAL ACTIONS
1. -Ve Inotropic action (↓ Force of contraction)
2. -Ve Dromotropic action ( ↓Impulse conduction)
3. - Ve Chronotropic action (↓ No of contractions/
↓ No of heart beats)
4. Vasodilation
THERAPEUTIC USES
1. As antihypertensive agents ( Due to -Ve Inotropic action ,
-Ve Dromotropic action, - Ve Chronotropic action & vasodilation)
2. As antiarrhythmics (due to -Ve Dromotropic action,
- Ve Chronotropic action)
3. As antianginals ( due to -Ve Dromotropic action,
- Ve Chronotropic action & vasodilation)
But they are contraindicated in CHF ( due to -Ve Inotropic action )
Ex:
1. Phenyl alkyl amines Ex: Verapamil – which block
calcium channels only in heart
2. Benzothiazepines Ex: Diltiazem- which block calcium
channels both in heart & blood vessels
3. Dihydropyridines Ex: Amlodipine, Nifedipine,
Nimodipine, Nitrendipine – which block calcium
channels only in blood vessels
VASODILATORS
Which dilate blood vessels specially peripheral blood
vessels and they decrease peripheral vascular
resistance and they decrease blood pressure.
They are classified into 2 types
ARTERIAL VASODILATORS
1. HYDRALAZINE - releases NO
- causes SLEs
( Systemic lupus erythematous syndrome)
2. MINOXIDIL - Potassium channel opener
- Causes Hypertrichosis (Excess hair growth)
- used to treat Alopecia
3. DIAZOXIDE - Potassium channel opener
- Causes Hyperuricemia and hyperglycemia
ARTERIAL & VENOUS VASODILATORS
Ex: SODIUM NITROPRUSSIDE
SODIUM NITROPRUSSIDE NO + CN
Rhodanese
Thiocyanates
Excreted through urine
Rhodanese enzyme is absent in infants hence contraindicated in
pregnancy and infants
Condition Indicated Drugs Contraindicated
drugs
Gestational
Hypertension
Centrally acting
antihypertensives,
Calcium channel
blockers
ACE Inhibitors,
Angiotensin-II
blockers,
Sodium
nitroprusside,
Diuretics
Hypertension with
diabetes
ACE Inhibitors,
Angiotensin-II
blockers
Diazoxide
Hypertension with
asthma
------- Nonselective β
blockers
Hypertension with
gout
------- Diazoxide
Hypertensive
emergencies
------- Sodium
nitroprusside
Presented by
Dr. Sannithi Nagarjuna
Coordinator for RIPER-GPAT Cell,
Hyderabad Academy &
Online GPAT Academy
7899107907
9885784793