Pharmacy

1. 22-May-23 1

2.  The most common form of heart disease
 The single most important cause of
premature death world wide
 Death: Male: 1 in 3, Female 1in 4
 It is due to atheroma and it complications –
thrombosis - in coronary arteries
 CAD, CHD, IHD all synonym
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3.  Risk factors of CAD:
◦ High blood cholesterol levels
◦ High B.P
◦ Cigarette smoking
◦ Obesity
◦ Diabetes mellitus
◦ Sedentary life
◦ Genetic predisposition & Gender
Anginal Drugs

4.  The main cause of CAD
◦ Atherosclerotic plaques formation in coronary
arteries
 atherosclerotic plaques
◦ A type of lesions formed in the walls of
large and medium sized coronary arteries
◦ Reduces the blood supply to myocardium
Anginal Drugs

5.  Unstable angina
◦ Ischaemia caused by dynamic obstruction of
coronary arteries
◦ Due to rupture of atheromatus plaque
◦ Associated with coronary vasospasm
 Variant angina (Prinzmetal’suncommon form)
◦ Attacks occurs at rest or during sleep
◦ Due to recurrent localized vasospasm of
atheromatized coronary arteries
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6.  Myocardial Infarction (MI)
◦ Myocardial necrosis caused by acute occlusion of
an artery:
◦ Due to plaque rupture and thrombosis
 Heart failure
◦ Myocardial dysfunction due to infarction or
ischaemia
 Arrhythmia
◦ Altered conduction due to ischaemia or infarction
 Sudden Death
◦ Ventricular arrhythmia, asystole or massive MI
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7.  Pharmacotherapy
◦ Drugs for
 Angina, MI, Heart failure, Cardiac arrhythmias,
Dyslipidemia, Preventing coagulation
 Surgical Procedure
◦ Coronary artery bypass grafting (CABG)
 A Non surgical Procedure
◦ Percutaneous tansluminal coronary angioplasty
(PTCA)
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9. 9

10.  Severe chest pain caused
by transient myocardial
ischaemia
 Occurs due to an
imbalance between
myocardial oxygen
supply and demand
 Constitute a clinical
syndrome
 The Cause: Coronary
atheroma
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11.  Common form; Attacks predictable; Provoked
by exercises, eating, emotions
 Cause:
◦ Ischaemia is due to fixed atheromatous stenosis of
larger coronaries
◦ Blood flow fails to meet the increased demand
◦ Results in an acute & reversible LVF, Left ventricular
failure
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12.  Left Ventricle end diastolic pressure rises from
5 to 25 mm Hg
◦ Diastolic subendocardial crunch
◦ Ischaemia aggravated in the region
 Aims of the drug therapy:
◦ To reduce work load on heart
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13. 13

14.  Uncommon form
◦ Attacks occur at rest / in sleep
 Cause:
◦ Transient spasm of localized portion of
atheromatized coronary arteries
 Aims of drug therapy:
◦ To prevent and reduce vasospasm
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15.  Rapid increase in duration and severity of
attacks
 Ischaemia caused by dynamic obstruction of
coronary arteries
◦ Rupture of atheromatous plaque
◦ Platelets deposition at the site
◦ Progressive occlusion of the artery
 Associated with coronary vasospasm
 Aim: To reduce the vasospasm
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16.  Dynamism of
coronary arteries
 During Classical
and variant angina
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17.  Drugs that relieve the ischaemic (anginal)
pain
1. Nitrates
◦ Short acting
 Glyceryl trinitrate (GTN)
◦ Long acting
 Isosorbide dinitrate
 Isosorbide mononitrate
 Erythrityl tetranitrate
 Pentaerythritol tetranitrate
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18.  Beta blockers
◦ Propranolol, Metoprolol, Atenolol
 Calcium channel Blockers
◦ Phenly alkylamine: Verapamil
◦ Benzothiazepine: Diltiazem
◦ Dihydropyridines: Nifedipine, Felodipine, Amlodipine
Nimodipine Nitrendipine, Lacidipine, Larcanidipine,
Benidipine
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19.  Potassium channel openers
◦ Nicorandil
 Antiplatelet drugs
◦ Aspirin, Clopidogrel, Dipyridamole
 Miscellaneous
◦ Trimetazidin, Oxyphedrine
 Drugs for acute attacks
◦ GTN, Isosorbide dinitrate
 Drugs for prophylaxis: All drugs
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20. Anginal Drugs
Ma
llik
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• Glyceryl trinitrate
- A Prototype organic nitrate
- A direct non-specific smooth
muscle relaxant

21. Anginal Drugs
Step No 1:
Generation of
reactive Free
Radical NO (nitric
oxide) by ONs
How does it happen:
-Through
Glutathione-S-
transferase

22. Anginal Drugs

23.  In classical angina the nitrates:
◦ Reduce cardiac work load
◦ Increase blood flow to ischaemic area
 In Variant angina:
◦ Reduce coronary vasospasm by
dilating larger coronaries
Anginal Drugs

24.  How exactly nitrates relieve
pain in classical angina
◦By decreasing work load on heart
 By reducing preload
 By reducing after load
◦By redistributing the coronary
flow to affected area
Anginal Drugs

25. 25

26.  In classical angina the nitrates:
◦ Reduce cardiac work load
◦ Increase blood flow to ischaemic area
◦ By reducing preload
◦ By reducing after load
◦ By redistributing the coronary flow to affected area
 In Variant angina
◦ Reduce coronary vasospasm by dilating larger
coronaries
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27.  Dilatation of
◦ Cutaneous vessels: Flushing
◦ Meningeal vessels: Headache
 Reduction of Splanchinic and renal blood flow
◦ Shifting of blood from lungs to systemic circulation
◦ Decongestions of lungs
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28.  Relaxation of SM of
◦ Bronchial
◦ Biliary tract
◦ Oesophagus
◦ Genitourinary tract
 Variable and insignificant
◦ Intestine
◦ Ureters, and Uterus
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29.  Reduce platelet aggregation through
increased GC-cGMP pathway
 NO, oxidizes the ferrous iron of Hb to Ferric
state, Methemoglobin:
◦ Low affinity for O2
◦ Pseudocyanosis, Tissue hypoxia
◦ Death in high doses
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30.  Lipid soluble molecules
 Well absorbed from skin, buccal mucous and
intestine
 Extensive First Pass Metabolism
 Denitrated by GSH-reductase
 GTN acts rapidly and short acting
sublingually, long acting orally
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31.  Fullness in head, throbbing headache
 Flushing weakness, sweating, palpitation,
dizziness, and fainting
 Methemoglobinemia
 Rashes
 Tolerance
 Dependence
 Drug interactions with sildenafil
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32.  Explosive liquid stuffed in tablets
 Route: Sublingual for acute attacks
◦ Onset: 1- 2 min, t1/2= 2 min
 Sublingual spray: Very rapid effect
 Oral dosage forms: For prophylaxis
◦ Dose: Large (5-15 mg)
 For long acting: Sustained release dosage
forms for chronic prophylaxis
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33.  Transdermal patch: Onset – 60 min
◦ For 24 hr action
◦ Limitations: Tolerance
 Transmucosal patch: Onset - 5 min
◦ For 4 - 6 hr
 IV infusion: For rapid and steady effect
◦ Used for unstable angina, coronary vasospasm, LVF
with MI, Hypertension
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34.  Solid substance
 Properties same as GTN
 Sublingually for acute attacks
 Orally for chronic prophylaxis
 Pronounced pre-systemic effect by p.o.
 t1/2: 40 min; SR: 6-10 hr
 Last dose to be taken: Before 6pm
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35.  Metabolite of isosorbide dinitrate
 Less first pass effect, given orally
 High bio-availability
 Long acting; t1/2 4-6 hrs
 Last dose: In the afternoon
 SR tablet: OD in the morning
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36.  Long acting nitrates
 Used only for chronic prophylaxis
 SR preparation on BD- QID dosing
 First pass metabolism is saturated on daily
dosing
 Duration of action: 4-6 hrs
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37.  Angina Pectoris
◦ Questions: How are nitrates useful in angina?
◦ What are the limitations of nitrates?
◦ Are nitrates effective in unstable angina?
 Myocardial infarction
◦ Question: How is GTN useful in MI?
 CCF and acute LVF
◦ Question: Explain the rationale behind the use of
IV GTN in LVF
 Interventional cardiac procedures
 Biliary colic due to disease or morphine:
Sublingual GTN
 Oesophageal spasm: Sublingual GTN before
food
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38.  In Cyanide poisoning: The Rationale use
 Haemoglobin
↓ NaNO2 iv (10 ml, 3%)
 Methaemoglobin
↓ Cyanide molecules
 Cyanomethaemoglobin
↓ Hypo iv (50ml, 30%)
 Methaemoglobin + Sod. thiocynate (Urine)
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39.  Drugs that block the voltage sensitive L –type
of calcium channels
 Calcium channels- L-Type
◦ Muscles: Excitation and contraction
◦ SA and AV nodes: Conduction
◦ Endocrine cells: Hormone release
◦ Neurones: Transmitter release
 Blockers
◦ Nifedipine, diltiazem, verapamil
 Inactivation rate: Slow
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40.  Phenyl alkylamine
◦ Hydrophilic compounds
◦ Eg: Verapamil
 Benzothiazepine
◦ Hydrophilic compounds
◦ Eg., Diltiazem
 Dihydropyridine (DHP)
◦ Lipophilic and most potent drugs
◦ Eg., Nifedipine, Amlodipine, Felodipine
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41.  Inhibit calcium mediated slow channel AP in
cardiac and smooth muscles
 Smooth muscle relaxation
◦ Vascular and others
 Negative inotropic and chronotropic actions
on heart
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42.  Markedly dilate arterioles
 Mild relaxation effects on veins smooth
muscles
 Extra-vascular muscles relaxed
◦ Bronchial, Biliary, Intestinal and Uterine
 DHPs eg., Nifedipine & Amlodipine have got
prominent action on smooth muscles
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43.  Action on atrial and ventricle muscles
◦ Negative inotropic
 Actions on conducting tissues
◦ SA and AV Nodes: Reductions in slope of Phase-4 →
Reduced automaticity
◦ AV Nodal conduction: Prolonged
 Verapamil > Diltiazem; DHPs: Nil
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44.  Dilates arterioles
 Blocks alpha receptors as well
 Decreases tPVR → BP falls
 COP maintained due to Preload
 Coronary flow is increased
 -ve inotropic and chronotropic
 Contraindicated in CCF
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45.  Common effects
◦ Nausea, Constipation, Bradycardia
 Less common
◦ Flushing, headache, ankle edema
 Conduction defects
◦ Contraindicated in AV-bocks, CCF
 Cardiac arrest upon iv in Sick Sinus
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46.  With β-blockers
◦ Additive sinus depression
◦ Conduction defects or asystole occur
 With digoxin
◦ Increases the concentration of Digoxin
 Should not be given with cardiac depressants
like disopyramide or quinidine
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47.  Less potent vasodilator
 Cardiac action equal to verapamil
 Normal doses: Consistent fall in BP
 Little change in heart rate
 Dilates coronary arteries
 Low incidence of side effects
◦ Same profile as verapamil
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48.  A most prominent arteriolar dilator
 ↓ in tPVR → Rapid fall in BP
 A weak –ve inotropic effect (Nil)
 No conduction blockade action
 Reflex sympathetic stimulation
◦ Tachycardia is pronounced
 ↑ COP and coronary out flow
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49.  Frequent effects
◦ Palpitation, flushing, ankle edema, hypotension,
headache, drowsiness
 Enhances the frequency of angina
◦ Paradoxical effect in post MI cases
 Safe with beta-blockers/digoxin
 Difficulty in urination
 Reduces insulin release
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50.  Pharmacokinetically distinct DHP
 Complete and slow oral absorption
 Higher and most consistent oral bio-availability
 Very long duration of action
◦ 5-10 mg OD
 S(-) amlodipine effective at ½ dose& less incidences
of ankle edema
 Early vasodilator effects are largely avoided
(Palpitation,flushings, headache, postural dizziness)
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51. 1. Angina pectoris: Classical and variant.
◦ The short acting DHPs harmful in MI
 A drop in coronary out flow
 Reflex tachycardia
 Coronary steal
◦ Best CCBs in MI: Verapamil or diltiazem
2. Hypertension: All three class of drugs
3. Arrhythmias: Only verapamil in PSVT & SVT
4. Premature labour: Nifedipine
5. In Raynaud’s episodes: DHPs
6. Nocturnal leg cramps: Verapamil
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52.  Felodipine
 Nitrendipine
 Lacidipine
 Nimodipine
 Lercanidipine
 Benidipine
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53.  Different types of K+ channels
◦ Voltage sensitive,
◦ Ca++ activated,
◦ receptor operated,
◦ ATP sensitive,
◦ Na+ activated
◦ Cell volume sensitive
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54.  Nicorandil, Pinacidil, Cromakalim
 Opens potassium channel → outflow of K+ →
hyperpolerisation → muscle relaxation
 Diazoxide ↓ insulin secretion
 Sulfonylureas (glybenclamide) ↑ Insulin
secretion by blocking same K+ channels
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55.  Angina pectoris
 Hypertension
 CHF
 Myocardial salvage
in MI
 Antihypoglycemic
(Insulinoma)
 Alopecia
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• Bronchial asthma
• Urinary urge
incontinence
• Peripheral vascular
disease
• Erectile dysfunction
• Premature labour

56.  Dipyridamole
◦ Inhibits platelet agregation by PGI2 pathway and ↑
cAMP in platelets
◦ Powerful arteriodialator
◦ Failure of this drug is because of coronary steel
phenomena
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57.  Trimetazidine
◦ Novel antianginal drug acts by non-hemodynamic
mechanisms
◦ MOA is not known but proposed MOAs as follows
 Inhibiting Mitochondrial long chain 3- ketoacyl CoA
thiolase (LC3-KAT) a key enzyme for fatty acid
oxidation. It has been labeled as pFOX (fatty acid
oxidation pathway) inhibitor
 Limiting the intracellular acidosis and Ca, Na,
accumulation during ischemia
 Protecting the Free Radical induced damage
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58.  Trimetazidine
◦ Absorbs orally
◦ Partly metabolised, Excreted unchanged in urine
◦ T1/2 is 6 hrs
◦ ADRs : GI burning, Dizziness, fatigue, Muscle
cramps, reversible Parkinsonism
 It is also advocated in Visual disturbances,
Tinnitus, Meneir’s disease, etc
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59.  Ranolazine
◦ Trimetazidine congener LC3-KAT inhibitor
◦ Orally absorbed Bioavailability is 30-50%
◦ T ½ is 7 hrs
◦ ADRs: Dizziness, Weakness, constipation, postural
hypotension, Headache, dyspepsia, Prolongation of
QT interval, torsade de pointes is a risk
◦ Used along with Atenolol, amlodipine, diltiazem
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60.  Pain, anxiety, apprehension
◦ Morphine/ pethidine or Diazepam
 Oxygenation: Inhalation of O2
 Maintenance of Blood volume, tissue
perfusion & microcirculation
◦ Saline/ Low molecular weight dextran
 Correction of acidosis
◦ Sod bicarbonate iv
 Prevention & treatment of arrhythmia
◦ i.v β blockers subsequently by lidocaine etc
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61.  Pump failure:↑ CO by
◦ Frusemide / Vasodilators like ON
◦ Inotropic drugs: dopamine/ dobutamine
 Prevention of thrombus extension,
embolism & venous thrombosis
◦ Aspirin (165-325 mg chewing/ swallowing)
 Thrombolytics & reperfusion
◦ Thrombolytics Streptokinase/ Urokinase/
alteplase
 Prevention of remodeling & subsequent CHF
◦ ACE inhibitors/ ARBs
 Prevention of future attacks
◦ Aspirin/ β blockers / Hypolipidemic drugs
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