Pharmacology Exam 3- Chand

Blood pressure formula

Cardiac output x peripheral vascular resistance

• Short term control: baroreceptor reflexes

• Long term control: Kidney; plasma volume and renin-angiotensin-aldosterone system

#1 cause of CV disease

HTN

Primary HTN

Of unknown cause

Secondary HTN

Pheochromocytoma, renovascular disease (pallor, edema, bruit), aldosteronism (buffalo hump, truncal obesity, purple striae), coarctation of the aorta

Menopause increases the risk of heart disease due to

Decreased estrogen in the patient

• Estrogen is cardioprotective

HTN according to 2025 guidelines

Anything above 130/80

Normal BP (2025)

<120/<80 mmHg

Elevated BP (2025)

120-129/>80 mmHg

Stage 1 HTN (2025)

130-139/80-89 mmHg (one or the other)

• Prescribe medications if- pt has a risk of CV event or has had one previously, or if presence of DM, CKD, or atherosclerosis risk

Stage 2 HTN (2025)

Systolic least 140 or diastolic at least 90 mmHg

HTN crisis (2025)

Systolic over 180 and/or diastolic over 120

• Acute elevation in BP with end organ damage

HTN causes ________ in the body

Target organ damage

• LVH, MI, CABG, HF

• CVA/TIA

• CKD

• PAD, retinopathy

Common causes of HTN

• Anti-hypertensive drug withdrawal→ Clonidine

• Autonomic hyperactivity→ Sympathetic

• Collagen vascular disease→ Systemic Erythematous Lupus (SLE)

• Renal disease→ acute/chronic renal failure

• Trauma to the head→ concussion/contusion

• Neoplasia→ pheochromocytoma (adrenaline secreting tumor)

• Pre-eclampsia→ Eclampsia

• Recreational drugs→ cocaine, meth, mushrooms

Anti-Hypertensive Drugs

• Alpha blockers

• Centrally acting antihypertensives

• Vasodilators

• Diuretics

• ACE Inhibitors

• Angiotensin receptor blockers

• Calcium channel blockers (CCB)

• B-Blockers

Diuretics (anti-HTN drugs)

• MOA: work in various sites in the nephron to increase urine production and inhibit sodium reabsorption

• Types: High ceiling (Loop), thiazide, potassium sparing, carbonic anhydrase inhibitors, osmotic diuretics, others

High Ceiling (Loop) Diuretic

Furosemide (Lasix), Bumetanide, Ethacrynic Acid

• MOA: work on the ascending loop of Henle to inhibit Na, K, Cl reabsorption

Furosemide

• MOA: High ceiling diuretic that acts on the ascending loop of henle; By blocking this transporter, it reduces sodium, potassium, and chloride reabsorption, causing increased urinary excretion of water and electrolytes

• SE: hypokalemia, ototoxicity, dehydration, HoTN

• Drug interactions: Digoxin, Aminoglycosides, lithium

Thiazide Diuretic

Hydrochlorothiazide, Chlorothiazide, Indapamide

• MOA: block reabsorption of Na and Cl in the distal convoluted tubule, increase renal excretion of Na, Cl, K, H2O

• Not used in immediate diuresis

Hydrochlorothiazide (HCTZ)

• MOA: Thiazide diuretic; block reabsorption of Na and Cl in the distal convoluted tubule and increase renal excretion of Na, Cl, K, H2O

• SE: hypokalemia, hyperuricemia, hyperlipidemia, hyperglycemia

• CI: pregnancy and sulfa allergies

Potassium Sparing Diuretics

Epithelial sodium channel blockers (Amiloride, Triamterene) and aldosterone receptor antagonists (Spirnolactone)

• MOA: act in the distal convoluted tubule to decrease Na absorption and decrease K excretion

  • Counteracts K loss induced by loop or thiazide diuretics

• SE: hyperkalemia, endocrine effects

• Use: tx and prevent hypokalemia, primary hyper aldosteronism, PCOS, hirsutism

Epithelial sodium channel blockers

Subtype of potassium sparing diuretics

• Amiloride, Triamterene

Aldosterone receptor antagonists

Spirnolactone

• MOA: block sodium retention (get rid of Na) and K excretion (retain K)

• Blocks action of aldosterone (decrease Na uptake, increase K retention)

Osmotic Diuretics

Mannitol, Isosorbide, Urea, Glycerol

• MOA: freely filtered in the glomerulus, increase osmotic pressure of tubular fluid and decrease water reabsorption

Carbonic Anhydrase Inhibitors

Other diuretic

• MOA: block sodium bicarbonate reabsorption causing sodium bicarbonate diuresis

Uses for diuretics

CVD, HTN, renal dz, endocrine abnormalities, tx of glaucoma, increased ICP

Angiotensin Converting Enzyme Inhibitors (ACE-I)- Antihypertensive

“Pril”- Enalapril, Ramipril, Lisinopril, Catopril, Fosinopril

• MOA: decrease peripheral resistance by inhibiting ACE (ace activates Angiotensin II→ vasoconstrict)

• SE: rash, dry cough (lisinopril)

• Use: HTN, HF, post MI, diabetic neuropathy

• CI: loop and thiazide diuretics, anti-HTN, lithium, drugs that increase K levels, pregnancy, renal failure

Angiotensin II Receptor Blockers

“Sartan”- Losartan, Olmesartan, Telmisartan, Valsartan

• MOA: block vasoconstrictor effect d/t angiotensin II blockage on blood vessels, dilate arterioles, increase Na and H2O excretion (blocked aldosterone), no significant effect on K

Losartan

Angiotensin II receptor blocker

• SE: low incidence of dizzy

• Contraindicated: pregnancy in the 2 and 3 trimesters, renal disease

Beta-Blockers (anti-HTN)

“Olol”- Propranolol, Metoprolol, Atenolol (cardio selective), Timolol, Esmolol, Labetolol

• MOA: Sympathetic antagonists at beta receptors in heart and blood vessels, decreased pulse and O2 demand of the heart muscle (negative ionotropic (force), negative chronotropic (rate))

Beta blockers might mask

Signs of hypoglycemia and hypothyroidism

• B2 (non-selective) can cause vasoconstriction

Propranolol

Non-selective beta blocker

• MOA: decrease BP, CO, and inhibit stimulation of renin production

• CI: 1st degree heart block, CHF, cardiogenic shock, COPD, bronchial asthma

Metoprolol

Cardio-selective beta blocker

• MOA: blocks B1

• Use: HTN, angina, MI, CHF (good in pts with asthma, DM, PVD)

• Masks hypoglycemia and hypothyroidism

Labetolol

Alpha 1 and beta 1 and 2 blocker

• Use: Clonidine withdrawal, pheochromocytoma

Timolol

Decreased IOP (used in glaucoma)

CCB (anti-HTN)

Dihydropyridines (Nifedipine, Amlodipine), Non-dihydropyridines (Diltiazem, Verapamil)

• MOA: inhibit smooth muscle contraction leading to a vasodilation of arterioles and negative ionotropic and chronotropic effects on the heart

• SE: dizzy, HA, syncope, tachycardia, drug induced gingival overgrowth

  • High risk of bradycardia and HoTN if used in combo with beta blockers

Angina

Pain in the chest syndrome; retrosternal pain radiating to the left arm/chest/jaw, tight or pressure like sensation

• S/S: N/V, feeling of doom

• imbalance between the myocardial O2 supply and demand

• ST depression on ECG

Pharmacological management of angina (6)

Decrease O2 demand or increase blood supply to the heart

1. Organic nitrates- nitroglycerin

2. CCB- Nifedipine, Verapamil

3. B-Blocker- Propranolol, Atenolol

4. Antiplatelet anticoagulant- Aspirin

5. Ranolazine (chronic angina)

6. Trimetziadine (metabolic control)

Nitrates (anti-angina)

Nitroglycerin

• MOA: converted to NO which causes vasodilation of blood vessels, dilate coronary and pulmonary blood vessels→ raise cGMP levels to promote dephosphorylation of myosin light chains leading to smooth muscle relaxation

  • reduces preload (decrease in myocardial wall stress), dilate arterial vessels (reduce afterload)

• Cannot be stored in plastic, HA are common (use Tylenol)

• Forms: patch, sublingual, spray, ointment

• Nitro patches

  • Tachyphylaxis, need a 12 on 12 off (need nitrate free period)

  • SE: HA, dizzy, HoTN, lightheaded

Immediate Management of unstable angina

1. Hospitalization

2. High intensity statins

3. DAPT

4. Anticoagulants

5. Possible revascularization (CABG)

Stable (chronic) Angina

Predictable chest pain on exertion or emotional stress

• usually relieved by nitro

Unstable Angina

Acute change in frequency/intensity of angina episode, often occurring at rest (more dangerous)

Prinzmetal (variant) Angina

Coronary vasospasm, transient ST elevation, occurs at rest

• responds to CCB and nitrates

1st line for chronic stable angina

Beta-blockers

B-Blocker (anti-anginal)

• MOA: prevent catecholamines from binding to B1 receptors (decreased HR, contractility, conduction velocity, decreased O2 requirements)

  • Non-selective: Propranolol, Carvedilol (also A1)

  • Selective: Metoprolol, Bisoprolol, Atenolol (B1 selective)

• Use: Stable angina (1st line), post MI management, HTN

• SE: bradycardia, fatigue/exercise intolerance, bronchospasm (non-selective), exacerbation of PVD

CCB (anti-anginal)

Dihydropyridine, Non-dihydropyridine

• MOA: decrease in calcium influx across cardiac and smooth muscles, diminish contractility and promote vasodilation

• Use: Prinzmetal’s angina, stable angina, HTN and angina combo

Dihydropyridine CCB (anti-anginal)

Amlodipine, Nifedipine

• MOA: target vascular smooth muscle and arterial dilation and drop in afterload

• SE: peripheral edema, HA, flushing, reflex tachycardia

Non-Dihydropyridine CCB (anti-anginal)

Decreased HR and contractility in SA and AV nodes- Diltiazem and Verapamil

• SE: bradycardia, AV node blockage, constipation, negative ionotropy

Ranolazine (anti-anginal)

Good in chronic stable angina, preserve BP and HR with a b-blocker or CCB

• MOA: inhibit late sodium current and decrease Ca and intracellular wall tension, decrease O2 demand

• SE: QT prolongation (especially with “azalea” or “thromycin”), dizzy, HA, constipation

Antiplatelet Therapy

Aspirin, Clopidogrel (Plavix), Prasugrel (Effient)

• MOA: prevent acute coronary syndrome

Aspirin (anti-anginal)

Anti-platelet

• Low dose

• MOA: irreversible inhibition of COX-1

• SE: GI irritation, bleeding risk, rare hypersensitivity

Clopidogrel/Prasugrel (anti-anginal)

Anti-platelet, Clopidogrel (Plavix), Prasugrel (Effient)

• MOA: block ADP mediated platelet aggression; often combines with ASA for high risk or stent placement

Statins (anti-anginal)

Atorvastatin, Rosuvastatin

• MOA: reduce atherosclerotic progression, improve endothelial function and stabilize plaques; inhibit HMG-COA reductase (cholesterol synthesis) and lower LDL cholesterol

• SE: myalgia/myopathy, LFT abnormality, new onset DM risk