Cardiovascular System Pharmac😍

Cardiovascular System

CONGESTIVE HEART FAILURE

• In low output CHF:
• Heart is not able to pump enough blood.
• Results in accumulation of fluid in various parts of body.

ACUTE (DECOMPENSATED) CHF

BNP analogue :

• Nesiritide (IV)

• Metabolized by :
• Neprilysin (Neutral endopeptidase).

Aim of treatment of Acute CHF:

• ↓ FLUID → Loop Diuretics

• ↑ PUMPING → Inotropics
• b1 Agonists:
• Dopamine
• IV Dobutamine (DOC)
• Nor-adrenaline
• Isoprenaline
• Phosphodiesterase Inhibitors
  [PDE 3 → Inodilators]:
• Amrinone
• Milrinone

• Naseer (Neriritide) got CHF when Dog (Dobutamine) went Miles (Milrinone) away

CHRONIC CHF (COMPENSATED)

• Aim of Treatment in Chronic CHF:
• ↓ Work
• Vessel Dilators
• ↓ Fluid
• Diuretics
• ↓ LVH [Cardiac Remodeling]
• 4 pillars
• Inotropic action
• Digoxin

1. ↓ Work → Vasodilators:

• Venodilators:
• ↓ Preload
• Nitrates

• Arteriolar dilators:
• ↓ Afterload
• Hydralazine
• Used in renal failure with HF.
• Hydralazine + Isosorbide dinitrate (Combination)

• Veno + Arteriolar Dilators:
• ↓ Preload and ↓ Afterload
• Na Nitroprusside
• ACE inhibitors
• Angiotensin receptor blockers

2. ↓ Fluid → Loop Diuretics

3. ↓ LVH [Cardiac Remodeling]:

• It results due to excessive aldosterone.

• HFrEF (Heart Failure with reduced Ejection Fraction):
• 4 Pillars: ↓ Mortality
1. RAAS blockers: ARNI > ACEi > ARBs
2. β-blockers
3. Mineralocorticoid receptor antagonist (MRA)
4. SGLT2 antagonist

• Other drugs ↓ mortality
1. Ivabradine
2. Vericiguat ( ↑cGMP).
3. Hydralazine.

Sacubitril+Valsartan (ARNI):

• Preferred RAAS blocker

• Sacubitril is a Neprilysin inhibitor (↑BNP) /Neutral endopeptidase inhibitor

• S/E: Angioedema,

• C/I: ACEI.

What is the name of the drug that has an effect on both the indicated regions?

ANS

• Omapatrilat

Omapartilat

• Dual inhibitor of Neural endopeptidase + ACE

4. Contractility (Ionotropics)

DIGOXIN:

• Only inotropic drug that can be given Orally.

• DOC for AF with Heart Failure

• t1/2 = 40 hrs

• MOA in Atrial Fibrillation:
• Vagomimetic effect lead to ↓ AV conduction.
• Mnemonic: Vagomonil Dig cheyyan poi → Naakku (⛔Na K) kaalum (↓ Ca) attu poi

• MOA in CHF:
• Inhibit Na+- K+ pump → ↑↑ intracellular calcium and thus inotropic action.
• Hypokalemia → ↑ binding of digoxin with Na K pump → ↑↑ toxicity

• Adverse Effects:
• Mnemonic: DIGOXIN
• Dialysis, defibrillation C/I
• Increases K⁺
• Gynaecomastia
• Ocular S/E: Green halos
• Xanthopsia / Yellow Vision.
• Increases risk of arrhythmia
• MC arrhythmia → Ventricular bigeminy.
• Most specific → NPAT (Non Paroxysmal Atrial Tachycardia) with AV Block.
• Nausea, Vomiting [MC]

• Mnemonic: Dig () cheythu → Queen (Quinidine) Clara (Clarithromycin) kku nu VATan (Verapamil, amiodarone, thiazide) → Apo wolf (Wolf) vannu → Pottanem (↓ K) mandenem (↓ Mg) kalanjitt kalum (↑ca) eduth Odi

ANGINA PECTORIS

• Drugs for Angina Pectoris:
• I. Nitrates
• II. Calcium Channel Blockers
• III. Beta Blockers
• IV. Potassium Channel Openers

I. Nitrates

• S/E → Methemoglobinemia
• Nitroprusside → Cyanide toxicity

• Mechanism of action:

• → MOA of nitrates in classical angina - ↓ Preload.

• → MOA of nitrates in variant angina → Dilation of coronary arteries.

• Drugs:
• Isosorbide Mononitrate [IMN] → has minimum 1st pass metabolism.
• Mnemonic: Iska Metabolism Nahi hota
• Isosorbide Dinitrate [IDN]
• Glyceryl Trinitrate / Nitroglycerine [GTN/ NTG]
• Penta Erythrital Tetra Nitrate [PETN] → Longest acting
• Amyl Nitrite [AN]

• GTN/NTG and IDN:
• DOC for acute attack of angina.
• Have high 1st pass metabolism.
• Sublingual route preferred.
• Try (Trinitro) Wen Dying (Dinitro)

Applied

• Tolerance
• Occurs, if nitrates are continuously present in blood.
• To avoid, 6-8 hours of Nitrate Free Period should be maintained.

II. L-Type (voltage gated) Calcium Channel Blockers

• DOC for variant angina → CCB like verapamil and diltiazem.

• Mnemonic: Variant → Verapamil

• Dihydropyridines are not used because they can worsen angina due to reflex tachycardia.

III. Potassium Channel Opener:

• NICORANDIL:
• NO Releaser + K+ channel opener.
• Mnemonic:
• N → NO releaser
• ICO → KO → Potassium Opener
• DIL → Dil pain
• Mnemonic: Nicoranndil → Nikkar (Nicorandil) thorannu (Open) → Pottante (Potassium) → Pottan Noo (NO release) nnu prnju

IV. Beta Blockers:

• Useful in classical angina (Act by ↓ HR).

• Contraindicated in variant angina.

V. Metabolic Modulators:

• Making heart to utilize glucose instead of fatty acids.

• Fatty Acids require more oxygen for same energy production than glucose.

• Drugs:
1. Trimetazidine
2. Ranolazine:
• MOA: inhibition of Late Inward Na channels.

• Mnemonic:
• Metabolism kuuttan 3 meter (trimeta) odi (ran → ranolazin)
• Ran (Ranolazine) → still Late (Late inward Na channel)

New Drugs for Angina Pectoris

Bradycardiac Agent

Ivabradine:

• Ivabradine inhibit Na+ channel [Funny current] in SA node

• Only bradycardia → No effect on BP

• S/E → ↓ Visual acuity (Phosphenes).

Rho Kinase Inhibitor

• Fasudil

• Mnemonic: Rocky (Rho Ki I) Fasil (Fasuldil) → Fasil (bradycardia) and ↓ Angina

MYOCARDIAL INFARCTION (MI)

• Non-STEMI: Mona
• M → Morphine
• O → Oxygen
• N → Nitrates
• A → Aspirin

• STEMI: Sonam
• S → Streptokinase
• O → Oxygen
• N → Nitrates
• A → Aspirin
• M → Morphine

HYPERTENSION

ESC 2024 Blood Pressure Targets

• In all age group > 18 years and comorbidities
• SBP target: 120–129 mmHg
• Diastolic BP: 70 - 79 mmHg

Condition	DOC
• HTN in pregnancy	Oral Labetalol > Methyldopa
• HTN Emergency in pregnancy	IV Labetalol
• HTN Emergency	Nicardipine > Nitroprusside
• Hypertensive urgency • Cheese Reaction	Clonidine
• Resistant Hypertension ↳ >140/90 mmHg ↳ Instead of ≥ 3 drugs including thiazides	Spironolactone
• HTN with Diabetes	Telmisartan
• HTN with Gout	Losartan
HTN with • edema • osteoporosis • Renal stones/colic	Thiazide like diuretics
HTN with • Nephrotic syndrome • Scleroderma • CKD	ACE I/ARBS
• HTN with renal insufficiency (eGFR <40)	↳ Loop diuretics is preferred ↳ if no response - add metalazone
• HTN induced by cyclosporin • Raynauds D/s	CCBs
• HTN with BPH	Prazosin
HTN with • Migraine • Hyperthyroidism • Stable Angina • Anxiety disorder • Essential tremor	β Blocker

Essential Tremor

• High-frequency tremor with sustained posture

• Tremor increases with activity, anxiety

• Initially tremor → then smoothens

• Decreases with alcohol

• Familial

• DOC: Propranolol

Intentional tremor

• Cerebellar tremor

• Start fine → tremor by the end

First Line Drugs:

• A – ACE inhibitors and ARB

• B – Beta Blockers (Not considered first line drugs now)

• C – Calcium channel blockers

• D – Diuretics

ACE Inhibitors:

• Name ends with pril.

• Features
• C → Cough
• A → Angioedema → (caused by bradykinin)
• P → Prodrugs except Captopril & Lisinopril
• T → Taste alteration [Dysgeusia]
• O → Orthostatic / Postural hypotension [max with captopril]
• P → C/l in Pregnancy
• Oligohydramnios
• Renal agenesis
• R → C/l in B/L Renal Artery Stenosis
• I → C/I in Increased K+
• L → Lower the risk of Diabetic Nephropathy

ARBs [Angiotensin (AT1) Receptors Blockers]:

• Name ends with ‘SARTAN‘.

• All points about ACE inhibitors apply to ARB
• Except → do not cause cough and angioedema
• ARB are not prodrugs.

• Telmisartan
• PPAR-γ agonist
• reverse insulin resistance.
• DOC: HTN with DM

• Losartan
• Mnemonic : PUT
• PPAR-γ agonist
• ↑ Uric acid excretion : HTN with gout DOC
• Mnemonic: Lost (Losar) Goat (Gout)
• ⛔ Thromboxane A2 : ⛔ Platelet aggregation

Direct Renin Inhibitor

• Aliskiren
• Treatment of diabetic nephropathy

PULMONARY ARTERY HYPERTENSION (PAH)

Definition

• Mean pulmonary arterial pressure > 20 mmHg.

• Pulmonary vascular resistance of ≥3 wood units.

Revised WHO Classification of PAH: DANA Point classification

• Group I: Pulmonary arterial hypertension (PAH)
• Idiopathic
• Hereditary: BMPR2
• Associated with
• Connective tissue diseases
• HIV infection
• Portal Hypertension
• Congenital heart disease
• Schistosomiasis
• Chronic haemolytic anaemia

• Group II: Pulmonary hypertension
• with left heart disease

• Group III: Pulmonary hypertension
• with lung diseases and/or hypoxemia
• CREST syndrome (m/c)

• Group IV: Pulmonary hypertension
• due to chronic thrombotic and/or embolic disease (CTEPH)
• Plexiform arteriopathy → Overgrowing of fibrosis around Pulm artery

• Group V: Pulmonary hypertension
• due to miscellaneous causes → unclear multifactorial

• Pulmonary artery is dilated due to increased pressure.

• Jug handle appearance of pulmonary artery (Image 1).

• ↓↓ peripheral pulmonary vascularity → Pruning → RVH → Obliterates the retrosternal space.

• On CT (Image 2):
• Diameter of pulmonary artery > Diameter of aorta.
• PA/AA > 1.

Clinical Features

• Early symptoms:
• Exertional dyspnea
• Chest pain
• Fatigue
• Lightheadedness

• Progression → Right ventricular dysfunction:
• Syncope
• Abdominal distention
• Ascites
• Peripheral edema

Management

First line

• Diuretics, Oxygen, Digoxin, Anticoagulant

• DODA

Vasoreactivity Test

• Via Right heart catheterisation

• Agents used:
• Inhaled nitric oxide
• IV epoprostenol (PGI 2 ⛔)
• IV adenosine
• Inhaled iloprost (PGI 2 ⛔)

• Positive test criteria:
• Mean pulmonary arterial pressure (mPAH) 
• ↓↓ by ≥ 10 mmHg → mPAH ≤ 40 mmHg.
• Without a decrease in cardiac output (CO).

PGI 2 :

1. epoprostenol → IV

2. Iloprost → Inhaled

• Selexipag:
• → Can be given orally.
• SELE → Selective
• XI → Non injectable [Oral]
• P → PGI2
• AG → Agonist

Management

• Riociguat → Guanylate cyclase +

• Reserved for refractory cases:
• Lung transplantation
• Atrial septostomy

• Mnemonic: Selective (Selexipag) ayitt Pulmonary (PGI) Pressure (PDEI) kuraykkunna Endo (Endothelin) Agents

ANTI-ARRHYTHMIC DRUGS

 

Vaughan Williams Classification

• Based on predominant mechanism of action
1. Class I → Na+ Channel Blockers
1. 1a → K Blocker
2. 1b → K Opener
3. 1c → No effect
2. Class II → β Blockers
3. Class III → K+ channel blockers
4. Class IV → Ca2+ Channel Blockers
5. Class V → Others

Class I Drugs

• Na+ Channel blockers

• ↓ Slope of Phase 0

Class II

• Beta Blockers

• Used in Tachyarrhythmias

• Sotalol has both Class III [Major] & class II Actions

Class III

• K+ Channel Blockers

• Amiodarone → Dronedrone → Ibutilide → Fetalide

• Drugs (BIN DASS mnemonic):
• B → Bretylium
• I → Ibutilide
• N D → Dofetilide, Dronedarone
• A → Amiodarone
• S → Sotalol

AMIODARONE

• Longest acting [t1/2 → > 3wks]
• Longest acting: Amiodarone.
• Shortest acting: Adenosine.

• MOA:
1. K+ channel Blocker [Main action]
2. Beta-Blocker (Non-competitive)
3. Na+ channel Blocker
4. Calcium channel blocker

• Adverse effect of amiodarone:
• The Thyroid (hypo/hyper) (40% iodine is present in amiodarone)
• Periphery of Peripheral neuropathy
• My Myocardial depression
• Lung Lung fibrosis
• Liver Liver toxicity
• Cornea is Corneal deposits
• Photosensitive Photosensitivity (Rash on exposure to sun)
• (Bluish: Blue man syndrome)

Class IV

• L-Ca2+ Channel Blockers:
• Verapamil
• Diltiazem
• DHPs [Not Used]

• Used in Tachyarrhythmias

Class V

• Digoxin: 
• Used for AF (in patients with CHF)
• S/E
• CHB → Digibind (Antibody against digoxin)
• Arrythmia → Lidocaine

• Atropine: 
• DOC for Bradycardia & AV block

• Adenosine: 
• Shortest acting antiarrhythmic drug (t1/2 < 10s)
• DOC for PSVT

ANTI-DYSLIPIDEMIC DRUGS

Statins

• Cholesterol → EEE + MTP → Ezetimibe, Evolumab, Evanicumab + Lomitapide

• Mnemonic: Try IF → Trigyceride - Icosapent, Fibrates

• CYP3A4 Inhibitors
• ↑ Statin levels (esp. Simvastatin, Lovastatin, Atorvastatin)
• ↑ myopathy risk.

• CYP2C9 Inhibitors (e.g., fluconazole):
• Affect Fluvastatin, Rosuvastatin.

Examples:

• Atorvastatin
• Atorvastatin 10-40 mg (Moderate-intensity)
• Atorvastatin 40-80 mg (High-intensity)

• Rosuvastatin [Longest Acting]
• DOC
• Rosuvastatin 5-10 mg (Moderate-intensity)
• Rosuvastatin 20-40 mg (High-intensity)
• Longest acting statin
• Maximum ↓LDL effect.
• Pitavastatin > Rosuvastatin are Most potent ?

• Pravastatin

• Simvastatin

Important Points:

• Given at late evening/night except
• Atorvastatin & Rosuvastatin
• Long acting
• Can be given at anytime of the day

Adverse Effects:

• Myopathy
• Risk further ↑ with
• Fibrates
• Enzyme inhibitors → clarithromycin and erythromycin.

• Hepatotoxicity

• Hyperglycemia: ↑ Risk of new onset DM.

• Pleiotropic Effects:
• Additional benefits
• PL → Plaque Stabilization
• E → ↓ Endothelial dysfunction
• I → ↓ Inflammation
• O → ↓ Oxidative Stress
• TR → ↓ Thrombosis

PCSK-9 Inhibitors (Pre Protein Convertin Subtilisin Kexin Type 9)

• PCSK-9 binds to LDL receptors → Directs them to lysosomes → Degradation of LDL receptors

• Subcutaneous

• Metabolism → Proteolysis

• PCSK-9 Inhibitors prevent degradation
→ More LDL receptors remain → More LDL-cholesterol uptake from blood

• Drugs:
• Alirocumab
• Evolocumab
(Both are monoclonal antibodies against PCSK-9)