Pharmacology - HYPERTENSION & ANTIHYPERTENSIVES (MADE EASY)

Aug 24, 2023

Pharmacology - HYPERTENSION & ANTIHYPERTENSIVES (MADE EASY)

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Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure such as heart attack and stroke. This pharmacology lecture covers topics such as pathophysiology of hypertension, regulation of blood pressure, cardiac output, systemic vascular resistance, baroreceptors, alpha \u0026 beta receptors, vasoconstriction, vasodilation, renin-angiotensin-aldosterone system, bradykinin, nitric oxide. Mechanism of action of antihypertensive drugs and their side effects; adrenergic antagonists; alpha \u0026 beta blockers, centrally acting adrenergic agents, dihydropyridine \u0026 nondihydropyridine calcium channel blockers, loop, thiazide, potassium-sparing diuretics, renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor type 1 blockers (ARBs), endothelin receptor antagonist, dopamine-1 receptor agonist, peripheral vasodilators. Drugs mentioned include; Doxazosin, Prazosin, Clonidine, Methyldopa, Amlodipine, Felodipine, Nicardipine, Nifedipine, Diltiazem, Verapamil, Furosemide, Hydrochlorothiazide, Triamterene, Spironolactone, Aliskiren, Benazepril, Captopril, Enalapril, Lisinopril, Quinapril, Ramipril, Candesartan, Irbesartan, Losartan, Olmesartan, Valsartan, Bosentan, Fenoldopam, Sodium Nitroprusside, Nitroglycerin, Hydralazine, and Minoxidil.

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0:00 Pathophysiology of hypertension
2:55 Alpha-1 blockers
3:10 Beta blockers
4:01 Centrally-acting adrenergic drugs
4:49 Calcium channel blockers
7:27 Diuretics
8:57 Inhibitors of renin-angiotensin-aldosterone system
12:25 Miscellaneous antihypertensives

Content

0 -> in this lecture I'm going to talk about pharmacology of antihypertensive drugs

5.15 -> so let's get right into it hypertension or high blood pressure is a

10.86 -> quite common disorder affecting many people who typically don't even notice

15.059 -> any symptoms now in order to gain a better understanding of pharmacology of

20.33 -> antihypertensive agents first we need to review a basic physiology of blood

24.84 -> pressure regulation so when we talk about blood pressure we are generally

30.33 -> referring to the force or tension of blood pressing against the artery walls

34.61 -> now this pressure in the arteries is maintained by among other things

38.87 -> contraction of the left ventricle systemic vascular resistance elasticity

44.309 -> of the arterial walls as well blood volume in other words blood pressure is

49.379 -> simply a product of cardiac output and systemic vascular resistance there are a

56.129 -> couple of major systems involved in blood pressure regulation first arterial

61.32 -> blood pressure is regulated by pressure sensitive neurons called baroreceptors

66.02 -> located in the aortic arch and carotid sinuses so for example if blood pressure

73.89 -> falls too low those baroreceptors can send signals to the adrenal medulla

78.17 -> causing release of catecholamines and thus increase in sympathetic activity through

83.9 -> activation of alpha and beta receptors so activation of beta-1 receptors causes

90.54 -> increase in heart rate and stroke volume and thus increased cardiac output which

96.09 -> leads to increase in blood pressure on the other hand activation of alpha-1

100.92 -> receptors on smooth muscle causes vasoconstriction and thus increase in

105.75 -> vascular resistance which again leads to increase in blood pressure now another

111.18 -> major system involved in blood pressure regulation is the

114.979 -> renin-angiotensin-aldosterone system so we also have baroreceptors in the

120.299 -> kidneys that respond to fall in blood pressure or reduction of blood flow by

124.86 -> releasing enzyme called renin additionally renin secretion is also

130.05 -> stimulated by sympathetic activation of beta-1 receptors

133.47 -> in the kidneys now renin is necessary for the production of angiotensin II

139.34 -> angiotensin II is a very potent vasoconstrictor which constricts systemic

144.27 -> blood vessels thus increasing peripheral resistance angiotensin II also

149.97 -> constricts renal blood vessels and stimulates aldosterone secretion which

154.2 -> leads to sodium and water retention thereby increased blood volume cardiac

158.52 -> output and ultimately increased blood pressure now let's switch gears and

163.68 -> let's talk about antihypertensive agents so there are several major

168.03 -> classes of antihypertensive drugs which work by interrupting different parts of

172.68 -> this blood pressure regulating system first we have alpha-1 blockers such as

177.93 -> Doxazosin and Prazosin which block alpha-1 receptors on the smooth muscle

182.94 -> thus causing decrease in systemic vascular resistance and ultimately

187.26 -> decrease in blood pressure next we have selective beta blockers such as Atenolol

193.02 -> and Metoprolol which selectively block beta-1 receptors on the heart thus

198.33 -> causing decrease in cardiac output and thereby decrease in blood pressure as

203.519 -> you may remember we also have non-selective beta blockers such as

207.42 -> Labetalol and Carvedilol that can additionally block alpha-1 receptors and

212.13 -> thus simultaneously decrease vascular resistance furthermore beta blockers can

218.13 -> inhibit beta-1 receptors present on the kidneys and thus suppress release of

222.81 -> renin formation of angiotensin II and secretion of aldosterone so these

228.39 -> effects result in decrease in systemic vascular resistance and again fall in

233.34 -> blood pressure to learn more about alpha and beta blockers make sure you check

237.989 -> out my video about adrenergic antagonists now the next major class of

242.85 -> antihypertensive agents are centrally acting adrenergic drugs which work by

247.92 -> blocking sympathetic activity within the brain example of drugs that belong to

252.989 -> this class are Clonidine and Methyldopa now Clonidine selectively stimulates

258.63 -> presynaptic alpha-2 receptors thus providing negative feedback to reduce

263.19 -> catecholamine production and release this leads to decrease

267.5 -> in systemic vascular resistance and cardiac output and ultimately decreased

272.039 -> blood pressure Methyldopa on the other hand also lowers blood pressure through the

277.53 -> same mechanism however unlike Clonidine it is not an

281.25 -> agonist itself so first it must be converted to its active metabolite

285.96 -> called methylnorepinephrine now let's move on to another major class of

292 -> antihypertensive agents that is calcium channel blockers so calcium channel

298.169 -> blockers are divided into two main subclasses dihydropyridines and

303.8 -> nondihydropyridines now dihydropyridines selectively inhibit L-type calcium

309.389 -> channels in the vascular smooth muscle under normal conditions when calcium

315.539 -> enters the smooth muscle cell it causes it to contract which leads to increased

320.219 -> vascular resistance and thus increase in blood pressure so when dihydropyridine drug

326.699 -> blocks the entry of calcium into the vascular smooth muscle cell the

331.139 -> contraction is inhibited which leads to decreased resistance to blood flow and

335.219 -> thus lowering of blood pressure example of drugs that belong to this group are

341.31 -> Amlodipine Felodipine Nicardipine and Nifedipine when it comes to side

348.3 -> effects of dihydropyridines they're related to systemic vasodilation so you

354.12 -> can expect dizziness headache flushing and peripheral edema another side effect

359.909 -> that may occur with this class is swelling of gums also known as gingival

364.83 -> hyperplasia now let's move on to nondihydropyridines which are non selective

370.889 -> inhibitors of L-type calcium channels in other words they are not only capable of

376.11 -> blocking calcium channels on vascular smooth muscle but also calcium channels

380.43 -> on cardiac cells such as those of SA node and AV node which leads to reduced

385.469 -> myocardial contractility slower heart rate and slower conduction that's why these

391.11 -> agents exhibit significant antiarrhythmic properties for more

395.819 -> details make sure you check out my video about antiarrhythmic drugs

400.74 -> now it's important to remember that even though decreased heart contractions

404.52 -> typically result in decreased cardiac output

406.94 -> nondihydropyridines do not significantly decrease cardiac output

411.6 -> most likely because of the reflex tachycardia that occurs as a result of

415.83 -> vasodilation currently there are only two drugs that belong to this group

421.29 -> namely Diltiazem and Verapamil now when it comes to side-effects nondihydropyridines

427.8 -> can cause excessive bradycardia and cardiac conduction abnormalities

432.71 -> additionally Verapamil which happens to be the least selective calcium channel

437.07 -> blocker can exert significant inhibition of calcium channels in the smooth muscle

442.05 -> that lines the GI tract which can lead to constipation

446.9 -> now the next major class of antihypertensive agents are diuretics there

452.31 -> are three major classes of diuretics that are used in the treatment of

455.61 -> hypertension first we have loop diuretics such as Furosemide which

460.17 -> work by reducing reabsorption of sodium chloride in the kidneys leading to

464.07 -> significant diuresis with less volume in the vascular space less blood returns to

469.41 -> the heart so cardiac output decreases this in turn leads to decrease in blood

473.79 -> pressure particularly in patients with volume-based hypertension and chronic

478.44 -> kidney disease secondly we have thiazide diuretics such as Hydrochlorothiazide

483.72 -> which also reduce reabsorption of sodium chloride in the kidneys but to a much

488.73 -> smaller degree than loop diuretics this leads to initial decrease in

493.08 -> intravascular volume decrease in cardiac output and ultimately lower blood

497.25 -> pressure however the long term effects on blood volume are minimal and

501.48 -> sustained antihypertensive effects are thought to be produced by thiazide induced

506.1 -> vasodilation lastly we have potassium-sparing diuretics such as Triamterene

512.31 -> and Spironolactone which increase diuresis by either interfering with the

516.63 -> sodium potassium exchange in the kidneys or by blocking the actions of

520.95 -> aldosterone potassium-sparing diuretics are often used in combination

525.12 -> with loop and thiazide diuretics to reduce loss of potassium that can occur with

530.94 -> the use of these drugs for more details make

534.5 -> sure you check out my video about diuretics now let's move on to another

539.03 -> group of antihypertensive agents that is agents that work on the

543.88 -> renin-angiotensin-aldosterone system so here we have three pharmacological

548.99 -> targets that can be used to reduce the activity of angiotensin II which is

553.4 -> ultimately responsible for causing blood pressure to increase first we have renin

559.07 -> the enzyme responsible for conversion of angiotensinogen to precursor of

564.35 -> angiotensin II that is angiotensin I so renin is the target of renin inhibitors

571.31 -> which selectively inhibit this enzyme thus decreasing production of

575.57 -> angiotensin II the example of drug that belongs to this class is Aliskiren

581.98 -> secondly we have angiotensin-converting enzyme that is responsible

585.71 -> for conversion of angiotensin I to angiotensin II this enzyme is the target

592.94 -> of ACE inhibitors so just like inhibition of renin inhibition of

597.23 -> angiotensin-converting enzyme also leads to decreased production of angiotensin II

602.3 -> however what makes ACE inhibitors different is that in addition to

606.26 -> lowering angiotensin II levels they can also elevate bradykinin levels

610.93 -> bradykinin is a peptide that causes blood vessels to dilate by stimulating

615.8 -> the release of nitric oxide and prostacyclin

618.67 -> however normally angiotensin-converting enzyme inactives bradykinin so it's

624.2 -> inhibition leads to bradykinin induced vasodilation the example of drugs

630.71 -> that belong to this class are Benazepril Captopril Enalapril

635.47 -> Lisinopril Quinapril and Ramipril finally we have

641.27 -> angiotensin II receptors type 1 or AT1 receptors for short so binding

647.96 -> of angiotensin II to these receptors is actually responsible for most of the

653 -> effects of angiotensin II including vasoconstriction and stimulation of

657.26 -> aldosterone release these receptors are the target of angiotensin II receptor

662.839 -> blockers or ARBs for short the example of drugs that

667.49 -> belong to this class are Candesartan Irbesartan Losartan Olmesartan and

674.24 -> Valsartan so in summary the agents that work on

679.22 -> this renin-angiotensin-aldosterone system either block the production of

683.569 -> angiotensin II or block its actions on the AT1 receptors this in turn leads to

689.629 -> decreased systemic vascular resistance but without significant changes in

693.559 -> cardiac output additionally these agents reduce the effects of angiotensin II on

699.35 -> renal hemodynamics specifically angiotensin II constricts the efferent

704.899 -> arteriole thereby generating back pressure in the glomerulus which can

709.699 -> lead to injury so by reducing activity of angiotensin II these agents also

715.759 -> improve renal blood flow and thereby reduce the risk of renal injury now when

721.73 -> it comes to side effects because these agents suppress aldosterone release

725.6 -> their use can contribute to development of hyperkalemia furthermore

730.85 -> ACE inhibitors in particular may cause dry cough or in rare cases angioedema

736.1 -> which can be life-threatening this is thought to be due to increased

740.809 -> levels of bradykinin and substance P now before we end this lecture I wanted to

747.499 -> briefly discuss few other antihypertensive agents that do not fall

751.699 -> into any of the classes that we covered thus far so first we have Bosentan

757.279 -> which is a competitive antagonist of a potent vasoconstrictor called endothelin-1

763.4 -> which acts on the endothelin-A and endothelin-B receptors located

768.379 -> on pulmonary vascular cells by blocking the action of endothelin-1 on

773.809 -> these receptors Bosentan leads to vasodilation which decreases pulmonary

778.549 -> vascular resistance for that reason Bosentan is often a drug of choice for

783.709 -> treatment of pulmonary hypertension next we have Fenoldopam which is a selective

791.48 -> dopamine-1 receptor agonist the dopamine-1 receptors are located on the

797.149 -> smooth muscle cells in the peripheral vasculature

800.529 -> as well as the renal coronary cerebral and mesenteric arteries by stimulating

806.769 -> dopamine-1 receptors Fenoldopam produces generalized arterial vasodilation

811.6 -> which leads to decreased peripheral resistance and thus lower blood pressure

817.29 -> additionally Fenoldopam inhibits tubular sodium reabsorption which

821.86 -> results in natriuresis and diuresis due to its rapid onset of action and

827.68 -> short duration of action Fenoldopam is often used in the

831.339 -> hospitals for short-term management of severe hypertension another fast-acting

837.85 -> agents that are also used for hypertensive emergency are

841.7 -> Sodium Nitroprusside and Nitroglycerin which simply serve as a source of nitric oxide

847.209 -> a potent peripheral vasodilator lastly we have direct acting smooth muscle

853.54 -> relaxants namely Hydralazine with mechanism of action that has not been

858.22 -> entirely determined yet and Minoxidil which works by stimulating opening of

863.559 -> ATP-activated potassium channels in the smooth muscle which leads to membrane

868.75 -> stabilization making vasoconstriction less likely while these agents

874.089 -> significantly decrease peripheral resistance they also produce significant

878.47 -> compensatory reflex tachycardia and renin release for that reason these

883.93 -> drugs are typically administered in combination with a diuretic and a beta

888.279 -> blocker on the flip side topical application of Minoxidil promotes hair

893.68 -> growth which is why this drug is used more often for treatment of baldness

897.73 -> rather than hypertension and with that I wanted to thank you for watching I hope

902.86 -> you enjoyed this video and as always stay tuned for more

Source: https://www.youtube.com/watch?v=V2sEay-E-Ro