A22. Drugs used for the treatment of hypertension I: Classification of antihypertensive agents and their mechanisms of action. Pharmacotherapy of hypertension. Flashcards
What are main categories for hypertensive treatment?
- Sympatholytics
- RAAS antagonists
- Direct vasodilators
- Diuretics
List the diuretics used in antihypertensive treatment.
- Hydrochlorothiazide (Thiazide)
- Chlorthalidone (Thiazide)
- Furosemide (Loop diuretic)
What is the MOA of Hydrochlorothiazide and Chlorothalidone?
They both blocks Na+/Cl- transporter in the distal convoluted tubule (DCT).
What is the MOA of Furosemide?
Furosemide is a loop diuretic that works on the loop of Henle. It blocks Na+/K+/2Cl transporter in thick ascending limb (TAL).
List the Sympathoplegics/Sympatholytics.
- Centrally acting: Clonidine and Methyldopa.
- Ganglion blockers: Hexamethonium, Trimethaphan and Mecamylamine.
- Postganglionic neuron blockers: Reserpine and Guanadrel
- Alpha blockers: Prazosin, Doxazosin and Terazosin
- Beta blockers: Propranolol, Atenolol, Metoprolol, Labetalol and Carvedilol
What is the MOA of Clonidine?
Clonidine is a centrally acting sympathoplegics. It is an agonist at the alpha 2 receptors in CNS this leads to SANS (Sympathetic Autonomic Nervous System) outflow.
What is the MOA of Hexamethonium?
Hexamethonium is a ganglion blocker. It’s an Obsolete prototype nicotinic acetylcholine (ACh) receptor blocker in ganglia, blocks all ANS transmission.
What is Guanethidine?
It is similar to guanadrel, and it is withdrawn in US. It’s a antihypertensive agent that acts by inhibiting selectively transmission in post-ganglionic adrenergic nerves. It is believed to act mainly by preventing the release of norepinephrine at nerve endings and causes depletion of norepinephrine in peripheral sympathetic nerve terminals as well as in tissues.
What is the mechanism of action of Reserpine?
Reserpine is a post ganglionic neuron blocker. It blocks vesicular pump (VMAT) in adrenergic neurons.
What is the MOA of Prazosin?
Prazosin is a selective alpha 1 blocker, which reduce peripheral vascular resistance and prostatic smooth muscle tone.
What is the MOA of Propranolol?
Propranolol is a prototype nonselective beta blocker that reduce cardiac output and possible secondary reduction in renin release.
What is the MOA of Captopril?
Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension.
What is the MOA of Aliskiren?
Aliskiren is the first in a class of drugs called direct renin inhibitors. Its current licensed indication is essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit. In December 2011, Novartis halted a clinical trial of the drug after discovering increased incidence of nonfatal stroke, kidney complications, high blood potassium, and low blood pressure in people with diabetes and kidney impairment.
What is the MOA of Methyldopa?
Methyldopa is a centrally acting sympathoplegic. It is a prodrug converted to methylnorepinephrine in CNS, with effects like clonidine.
What is the MOA of Guanadrel?
Guanadrel is a postganglionic neuron blocker. It blocks release of norepinephrine and depletes stores.
What is the MOA of Hydralazine
Hydralazine is a direct-acting vasodilator that is used as an antihypertensive agent. It works by relaxing blood vessels (arterioles more than venules) and increasing the supply of blood and oxygen to the heart while reducing its workload. It also functions as an antioxidant. It inhibits membrane-bound enzymes that form reactive oxygen species, such as superoxides. Excessive superoxide counteracts NO-induced vasodilation.
What are the side effects of Clonidine?
- Sedation
- Dangers of severe rebound hypertension if stopped suddenly.
What is the MOA of Trimethaphan?
Trimethaphan is a nicotinic antagonist that has been used as a ganglionic blocker (obsolete short acting?) in hypertension, as an adjunct to anesthesia, and to induce hypotension during surgery.
What is the MOA of Mecamylamine?
Mecamylamine is a oral ganglion blocker which works several hours and enters CNS.
What is the MOA of Nitroprusside?
Nitroprusside serves as a source of nitric oxide, a potent peripheral vasodilator that affects both arterioles and venules (venules more than arterioles).
What is the MOA of Nifedipine
Nifedipine has been formulated as both a long- and short-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nifedipine prevents calcium-dependent myocyte contraction and vasoconstriction. A second proposed mechanism for the drug’s vasodilatory effects involves pH-dependent inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase. Nifedipine is used to treat hypertension and chronic stable angina.
What is the MOA of Losartan?
Losartan is an angiotensin-receptor blocker (ARB) that may be used alone or with other agents to treat hypertension. Losartan and its longer acting metabolite, E-3174, lower blood pressure by antagonizing the renin-angiotensin-aldosterone system (RAAS); they compete with angiotensin II for binding to the type-1 angiotensin II receptor (AT1) subtype and prevents the blood pressure increasing effects of angiotensin II. Unlike angiotensin-converting enzyme (ACE) inhibitors, ARBs do not have the adverse effect of dry cough. Losartan may be used to treat hypertension, isolated systolic hypertension, left ventricular hypertrophy and diabetic nephropathy. It may also be used as an alternative agent for the treatment of systolic dysfunction, myocardial infarction, coronary artery disease, and heart failure.
What are the clinical indications for starting Clonidine therapy?
- Hypertension
What are the side effects of Hydrochlorothiazide and Chlorothalidone use?
- (Toxicities, interactions)
- Hypokalemia
- Hyperuricemia
- Hyperlipidemia
What are the clinical indications for starting therapy with hydrochlorothiazide and chlorothalidone use?
Hypertension and mild edema
What are the side effects of Reserpine use?
- Sedation
- Severe psychiatric depression (high dose)
What are the side effects of Hexamethonium use?
- Severe orthostatic hypotension
- Constipation
- Blurred vision
- Sexual dysfunction
What are the side effects of Furosemide?
- Hypokalemia
- Hypovolemia
- Ototoxicity
What are the side effects of Propanolol?
- Bronchospasm in asthmatics
- Excessive cardiac depression
- Sexual dysfunction
- Sedation
- Sleep disturbances
What are the side effects of Prazosin?
- First dose orthostatic hypotension
What is the route of administration of hydrochlorothiazide and chlorothalidone? And how long is the DOA?
They are both via oral administration and the duration of action is about 8-12 hrs.
What are the side effects of Methyldopa?
- Sedation
- Induce hemolytic antibodies
What is the route of administration and the DOA of Furosemide?
It is administred via the oral parenteral route. Its duration of action is about 2-3 hrs.
What is the clinical indications to start Furosemide?
- Hypertension
- Heart failure
- Edema
- Hypercalcemia
What are the clinical indications for the use of Clonidine?
- Hypertension
What are the clinical indications for starting Reserpine?
- Obsolete in hypertension
- Huntington’s disease
What are the clinical indications of Hexamethonium?
None
What is the route of administration and what is the DOA of Reserpine?
Administered orally and duration of action of about 5 days.
What is the route of administration of Hexamethonium?
It is administered orally and parenterally.
What is the route of administration of Clonidine?
- It is administered orally or transdermally.
- Oral duration lasts about 2-3 days.
- Transdermal administration last about 1 week.
What are the clinical indications for Propranolol?
- Hypertension
- Many other application…
What are the indications for starting Methyldopa?
1. Hypertension
What is the route of administration of Methyldopa?
Its is given oral orally for 12-24hrs.
What is the route of administration of Propranolol?
It is given orally and parenterally for 6-8 hrs (extended release forms available).
What are the clinical indications for starting Prazosin?
- Mild hypertension
- Benign prostatic hyperplasia
What is the route of administration of Prazosin?
It is given orally for 6-8 hours.
What are the indications of Hydralazine?
It is an antihypertensive drug commonly used in the condition of pregnancy called pre-eclampsia.
Does Hexamethoniums have any CNS effects?
No CNS effects.
What are the indications of Nitroprusside?
Nitroprusside is often administered intravenously to patients who are experiencing a hypertensive emergency.
List the places to influence blood pressure pharmacologically.
- Brain: centrally-acting antihypertensive drugs via α2 agonists.
- Arterioles: α 1 blockers, direct vasodilators
- β1 blockers: block RAAS, heart rate
- Kidney: Aldosterone antagonists
- ACE-inhibitors
- Angiotensin receptor blockers
- Volume: diuretics
Physiology: List the different mechanisms of Blood pressure regulation?
- CNS
- Resistance
- Capacitance
- Heart rate
- RAAS: Angiotensin II
What is the MOA of Doxazosin and Terazosin?
They are similar to prazosin but longer duration of action.
What is the MOA of Atenolol and Metoprolol?
They are like propranolol but beta 1 selective with fewer adverse effects.
What is the MOA of Labetalol and Carvedilol?
They are combined (/mixed) alpha and beta blockers that are orally and parenterally administered.
What is the route of administration fo Guanadrel?
It is given orally for a long duration.
What are the indications for Trimethaphan?
It is given IV for hypertensive emergencies and controlled hypertension.
What are the indications of Guanadrel?
Used to treat and control hypertension.
