Cardiovascular System Drugs and Hemodynamics

Cardiovascular System Drugs

• Drugs affecting the cardiovascular system impact the heart, blood vessels, and blood.

Hemodynamics Review

• Hemodynamics studies blood flow throughout the circulatory system, including regulatory mechanisms and driving forces.
• Primary functions of the cardiovascular system include delivering oxygen, nutrients, hormones, electrolytes and other essentials to cells, and removing carbon dioxide and metabolic wastes from cells.

Blood Distribution

• An adult's blood volume is approximately 5 liters.
• A large portion of blood volume is stored in the venous system, acting as a reservoir.

Blood Flow and Resistance

• Blood flow within vessels is driven by a pressure gradient, exceeding resistance to flow.
• In pharmacology, vessel diameter is the most important determinant of resistance.
• Larger vessels have lower resistance.

Renin-Angiotensin-Aldosterone System (RAAS)

• The RAAS is a crucial determinant of blood pressure.
• It's activated when blood flow to the kidneys decreases.

ACE Inhibitors

• These drugs prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor and aldosterone stimulator.
• Common ACE inhibitors include benazepril, captopril, enalapril, enalaprilat, fosinopril, lisinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril.

Therapeutic Actions and Indications

• ACE inhibitors lower blood pressure and aldosterone secretion, resulting in slight serum potassium increase and reduced sodium and fluid.
• Often used in hypertension treatment, alone or in combination with other medications.
• Can be used with digoxin and diuretics to treat heart failure and left ventricular dysfunction.

Pharmacokinetics

• ACE inhibitors are usually administered orally and can be administered intravenously when oral availability is limited or rapid onset is required.
• They are well absorbed, metabolized in the liver, and excreted through the urine and feces.
• ACE inhibitors have been detected in breast milk and can cross the placenta.

Contraindications and Cautions

• Caution is advised for patients with allergies, impaired renal function, or heart failure, as the drugs can affect cardiovascular dynamics.
• ACE inhibitors are contraindicated during pregnancy due to potential adverse effects on the fetus.
• These agents may cause reduced milk production and affect the neonate during lactation.

Adverse Effects

• Common adverse effects include vasodilation, altered blood flow, GI irritation, ulcers, constipation, liver injury, renal problems, skin reactions, and alopecia.

Drug-Drug Interactions

• Allopurinol (xanthine oxidase inhibitor) can lead to hypersensitivity reactions with ACE inhibitors.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect.
• Oral ACE inhibitors' absorption decreases with food; they should be administered one hour before or two hours after meals.

Angiotensin II Receptor Blockers (ARBs)

• ARBs include azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan.

ARBs - Therapeutic Actions and Indications

• ARBs bind selectively with angiotensin II receptors, preventing vasoconstriction and aldosterone release.
• They are used to treat hypertension alone or in combination with other medications.
• These agents are used in patients who cannot tolerate ACE inhibitors.

ARBs - Pharmacokinetics

• ARBs are generally administered orally, well absorbed, and metabolized in the liver, and excreted through urine and feces.
• ARBs can cross the placenta, but it's unknown if they pass into breast milk.

ARBs - Contraindications and Cautions

• ARBs use should be approached cautiously in patients with impaired renal function or liver disorder.
• They may not be suitable for use during pregnancy, specifically in the second and third trimesters, as there's a link to potential fetal abnormalities.

ARBs - Adverse Effects

• Common side effects include headache, dizziness, syncope, weakness, gastrointestinal problems (diarrhea, abdominal pain, nausea, dry mouth, tooth pain), upper respiratory tract infections, cough, skin reactions (rash, dry skin, alopecia), and hypotension.

Drug-Drug Interactions (ARBs)

• Concurrent use of ARBs with phenobarbital, indomethacin, or rifamycin may lead to decreased serum levels and reduced effectiveness.
• Drug interactions can occur with ketoconazole, fluconazole, or diltiazem.

Calcium Channel Blockers

• Calcium channel blockers lower blood pressure, reduce cardiac workload, and lower myocardial oxygen consumption.
• Effectively used in angina treatment.
• Common forms of calcium channel blockers include immediate-release and sustained-release as in amlodipine, felodipine, isradipine, nicardipine. Additional agents include nifedipine and clevidipine.

Calcium Channel Blockers - Therapeutic Actions and Indications

• Calcium channel blockers prevent calcium ions from moving into myocardial and arterial muscle cells, hindering action potentials and blocking muscle contraction.
• This effect reduces myocardial contractility, slows cardiac impulse formation, relaxes arteries, and reduces venous return.
• These drugs are indicated in treating hypertension and angina.

Calcium Channel Blockers - Pharmacokinetics

• Oral administration, liver metabolism, urine and feces excretion are the primary aspects.
• Calcium channel blockers pass through the placenta and may transfer into breast milk.
• Nicardipine and clevidipine are available intravenously for short-term use.

Calcium Channel Blockers - Contraindications and Cautions

• Caution is advised for patients with heart block or sinus syndrome.
• Caution is needed in patients with renal or hepatic impairment.
• During pregnancy, a benefit-risk assessment for the mother and fetus is crucial.

Calcium Channel Blockers - Adverse Effects

• Possible symptoms include CNS issues (dizziness, lightheadedness, headache, fatigue), GI distress (nausea, hepatic issues), cardiovascular problems (hypotension, bradycardia, peripheral edema, heart block), skin reactions (flushing, rash), and others.

Calcium Channel Blockers - Drug-Drug Interactions

• A significant concern is the interaction between calcium channel blockers and grapefruit juice, which can lead to increased drug concentration and potentially toxic levels.
• Other drug interactions can occur, like between calcium channel blockers and cyclosporine.

Vasodilators

• Vasodilators are used when other treatments fail to reduce blood pressure effectively.
• Common examples include hydralazine, minoxidil, and nitroprusside.

Vasodilators - Therapeutic Actions and Indications

• Vasodilators directly relax vascular smooth muscles, leading to vasodilation and a decrease in blood pressure.
• They are primarily used in cases of severe hypertension or hypertensive emergencies.

Vasodilators - Pharmacokinetics

• Nitroprusside's administration is intravenous, while hydralazine and minoxidil are given orally, intravenously, or intramuscularly.
• Vasodilators are known to be rapidly absorbed and widely distributed, metabolized in the liver, and primarily excreted in the urine.
• Drugs generally cross the placenta and enter breast milk.

Vasodilators - Contraindications and Cautions

• Caution is needed in patients with cerebral insufficiency, peripheral vascular disease, coronary artery disease, heart failure, or tachycardia.
• Pregnancy use should be considered cautiously.

Vasodilators - Adverse Effects

• Common symptoms include dizziness, anxiety, headache, reflex tachycardia, heart failure, chest pain, edema, skin rashes, GI upset, nausea, vomiting, cyanide toxicity, ataxia, loss of consciousness, dilated pupils, distant heart sounds, shallow breathing, hypothyroidism, and others.

Other Antihypertensive Agents

• Diuretics (e.g., metolazone, chlorothiazide, hydroflumethiazide, amiloride, spironolactone, triamterene) increase sodium and water excretion from the kidneys, often used in mild hypertension.
• Renin inhibitors (e.g., aliskiren) block renin, which lowers blood pressure by decreasing aldosterone release.
• Sympathetic nervous system blockers: beta-blockers (e.g., atenolol, metoprolol, nebivolol, esmolol, propranolol) inhibit the sympathetic nervous system response, lowering heart rate, and reducing cardiac output, renin release; alpha-blockers (e.g., doxazosin, prazosin, terazosin) work by limiting postsynaptic alpha-1 receptors, resulting in a fall in blood pressure.

Antihypertensive Agents Treatment of Low Blood Pressure

• If blood pressure drops too low, the brain and body tissues may not receive adequate oxygenated blood for proper function, posing a serious risk.
• The condition frequently requires immediate treatment to prevent life-threatening complications.

Sympathomimetic Drugs

• Used to restore blood pressure during shock or severe hypotension.
• These drugs include dobutamine, dopamine, ephedrine, epinephrine, isoproterenol, norepinephrine, and phenylephrine.

Sympathomimetic Drugs - Therapeutic Actions and Indications

• These drugs stimulate sympathetic adrenergic receptors resulting in increased blood pressure, blood volume, and improved cardiac muscle contraction.
• This response is important in restoring cardiovascular balance while treating underlying causes of shock.

Sympathomimetic Drugs - Adverse Effects

• Likely side effects linked include reduced GI activity (nausea, constipation), increased heart rate, changes in blood pressure, headache, peripheral blood flow modifications, numbness, skin problems, and potential gangrene.

Alpha-Specific Adrenergic Agents

• A specific type of adrenergic agent employed to address orthostatic hypotension.
• Midodrine is a prime example although it is no longer available.

Alpha-Specific Adrenergic Agents - Therapeutic Actions and Indications

• Midodrine activates alpha-receptors in arteries and veins, increasing blood vessel tone and raising blood pressure.
• It is often used for symptomatic orthostatic hypotension.

Alpha-Specific Adrenergic Agents - Adverse Effects

• Potential adverse events include piloerection, chills, rash, hypertension, bradycardia, dizziness, vision problems, vertigo, headache, and urination difficulties.