Antihypertensive Drugs Flashcards by Anika Gouws

How is blood pressure regulated? (physiologically)

Sympathetic Nervous system –> inc cardiac output, Beta-1 activation

Kidneys

vasoactive substances produced in blood vessel wall (NO, prostacyclin, aldosterone, etc.)

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What influences PVR?

Alpha-1 adrenoceptor stimulation = vasoconstriction

Vasopressin, Angiotensin (AT) II, Aldosterone = vasoconstriction

Locally released substances = adenosine, serotonin, endothelin, prostaglandins

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What are the categories of antihypertensives?

Reduce PVR = vasodilators (inc NO), alpha-1 blockers, AT receptor blockers, centrally acting sympatholytic, ACE inhibitors,

Reduce CO = Beta1-adrenoceptor blockers

Target Na secretion and dec BV = Diuretics

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What suffix helps identify ACE inhibitors?

-pril

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What suffix helps identify ARBs?

-sartan

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What is the MOA of ACE inhibitors?

Block the conversion of angiotensin I to angiotensin II through inhibition of angiotensin converting enzyme.

Also inhibit bradykinin

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List the relevant ACE inhibitors

Captopril, enalapril, fosinopril, lisinopril, perindopril, ramipril

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What effects (NOT ADRs) will ACE inhibitors have?

Reduce AT-II induced vasoconstriction, Na retention, aldosterone release

Reduce effect of AT-II on sympathetic NS activity and growth factor

Cause accumulation of bradykinin

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Name and explain some ADRs of ACE inhibitors

Dry cough = due to bradykinin inhibition, irritating the airways and causing vasodilation

Hypotension, headache, dizziness = drop in blood pressure

Hyperkalaemia = reduced aldosterone secretion

Angioedema, rash (esp captopril), diarrhoea, photosensitivity, psoriasis

Elevated hepatic aminotransferase = start of liver damage

Hyponatraemia = aldosterone inhibition –> reduced Na retention

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Explain the cough associated with ACE inhibitors

Type of cough = persistent, non-productive cough, mild-tolerable

Cough is not dose dependent and occurs days-months after treatment has started

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How long does the ACE inhibitor cough take to subside?

Improves within 1-4 weeks after stopping medication

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How long after commencing treatment of ACE inhibitors could angioedema appear?

First week of treatment (possible months to years later)

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Are ACE inhibitors recommended in diabetic patients?

Yes! It is recommended in patients with albuminuria or inc. serum creatinine

ACE inhibitors have a renoprotective effect

They do carry the risk of renal failure with bilateral renal artery stenosis

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Why do ACE inhibitors increase the risk of renal failure in patients with Bilateral renal artery stenosis?

Due to the renal stenosis, there is already a reduced GFR/blood entering the glomerulus.

ACE inhibitors will act to further decrease this GFR due to inhibition of ACE, preventing an increase in GFR and ATII formation.

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What are the targets of angiotensin? (what are the receptor functions)

AT1 Receptor = contract vascular smooth muscle, secrete aldosterone (adrenal cortex), increase Na+ reabsorption from PCT, increased NA release, stimulation of cell growth in arteries and heart.

AT2 Receptor= influences bradykinin

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What is the MOA of Sartans?

Competitively blocks the binding of ATII to the AT1 receptor with relative selectivity.

Causes a reduction in ATII-induced vasoconstriction, Na reabsorption and aldosterone release.

Also produced reduced ATII effect on sympathetic NS activity and growth factors.

Do sartans pose the same cough risk as ACE inhibitors?

Like ACE inhibitors, Sartans will still cause a cough.

Sartans pose a lower cough risk

Name the relevant Sartans

candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan

Name and explain some ADRs of Sartans

dizziness, headache

hyperkalaemia = due to inhibition of aldosterone –> blocks the insertion of Na transporters in the collecting duct –> prevent Na/K exchange –> inc K+ retention

First dose hypotension, rash, renal impairment, dyspepsia, muscle cramps, diarrhoea, decreased heamoglobin, nasal congestion, insomnia, angioedema

Cough = due to accumulation of bradykinin

Name the main diuretic classes used as antihypertensives (give some examples)

Thiazide and Thiazide like diuretics = hydrochlorothiazide (most common), indapamide, chlorthalidone

Loop diuretics = frusemide, bumetanide, ethacrynic acid

Potassium sparing diuretics = spironolactone, eplerenone, amiloride, triampterene

What are the benefits of thiazide/-like diuretics in hypertension treatment

Well tolerated first line drug (>65 yrs old)

Low dose = maximal antihypertensive w/ minimal hypokalaemia

What are some things to be mindful of when using thiazides as antihypertensives?

Prolonged use = elevated glucose, uric acid (be mindful of this in gout), and lipid derangement

May produce compensatory RAAS production

Osteoprotective = decreased Ca2+ excretion

True or False

Loop diuretics are more effective as antihypertensives in comparison to Thiazides?

FALSE

Loop diuretics are less effective but are very effective in congestive heart failure

Which potassium-sparing diuretic has a lesser anti-androgenic effect?

Eplerenone has a lesser anti-androgenic/anti-testosterone effect compared to spironolactone

What are the benefits of eplerenone use?

Fewer endocrine effects (less anti-androgenic) Reduces left ventricular hypertrophy in HTN patients reduces microalbuminuria in type II diabetes

True or False K+ sparing diuretics are commonly used as monotherapies in hypertension

FALSE K+ sparing diuretics are commonly used in combination with thiazide and loop diuretics to reduce K+ secretion.

Name some centrally acting antihypertensive drugs

Clonidine Methyldopa

What is the general MOA of centrally acting antihypertensives?

Partial alpha-2 receptor agonist --> reduces sympathetic outflow from CNS --> reduces PVR ---> reduces blood pressure Note: Cardiac output will be slightly reduce or unchanged

What are things to be mindful of with methyldopa use as antihypertensive?

Causes immunological effects = causes methyldopa sensitisation ---> immune effects ---> Coombs +ve haemolytic anaemia and autoimmune hepatitis Pregnancy = it does not harm the fetus

What are some things to note with centrally acting anti-hypertensives?

Cause more ADR's, primarily CNS related ones compared to other anti-hypertensives They should not be stopped abruptly = greatly exacerbate the effect/condition that the drug was attempting to treat Rebound hypertension may occur with abrupt stopping of clonidine

What is the role of Hydralazine in treatment of hypertension?

Strong, non-specific vasodilator MOA = potential dec of Ca2+ --> direct relaxation of vascular SM (arteries mainly) ADRs = tachycardia (reflex compensation), oedema (global dilation --> blood pools ---> fluid leaks), peripheral neuritis, systemic lupus

What is the role of sodium nitroprusside in treatment of hypertension?

Strong, non-specific vasodilator MOA = stimulates NO release --> relaxes both arterial and venous smooth muscle ADRs = dizziness, excessive sweating, blurred vision, ataxia, tinnitus, metabolic acidosis, hypotension, muscle twitching

Name some common drugs that interact with Thiazide/-like and loop diuretics

Lithium = increases serum lithium levels NSAIDs = dec renal blood flow --> dec effectiveness of diuretic

Name some common drugs that interact with potassium-sparing diuretics

ACE inhibitors = inc K+ concentration ---> increased risk of hyperkalaemia Potassium supplements = inc risk of hyperkalaemia

Name some common drugs that interact with alpha1-adrenoceptor antagonists (-sin drugs)

other anti-hypertensives (e.g. beta-blocker, diuretics, etc.) = inc risk of hypotension

Name some common drugs that interact with beta-blockers

Beta-blocker (dec HR) = diltiazem, verapamil ---> inc cardiovasc depression NSAIDs = dec hypotensive effect

Name some common drugs that interact with ACE-inhibitors

Lithium = causes inc lithium levels K+-sparing diuretics and K+ supplements = inc risk of hyperkalaemia NSAIDs = dec hypotensive effect

Explain the 'triple whammy' drug effect

Triple whammy drug effect occurs when a patient is given an ACE-inhibitor (or ARB), an NSAID, and a diuretic. NSAID + ACE-inhib (or ARB) + diuretic = dec glomerular blood flow ---> dec GFR ---> detrimental effects on kidney function Further explanation: NSAIDs = block prostaglandin production ---> dec glomerular blood flow Diuretics = dec blood vol ---> reduce glomerular blood flow ACEI or ARBs = efferent arteriole dilation ---> dec GFR

What are the long term effects of thiazide diuretics?

Decreased Na content of SM, dec SM sensitivity to vasopressors, dec PVR dec BP