Antihypertensive Drugs Flashcards
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.)
What influences PVR?
Alpha-1 adrenoceptor stimulation = vasoconstriction
Vasopressin, Angiotensin (AT) II, Aldosterone = vasoconstriction
Locally released substances = adenosine, serotonin, endothelin, prostaglandins
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
What suffix helps identify ACE inhibitors?
-pril
What suffix helps identify ARBs?
-sartan
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
List the relevant ACE inhibitors
Captopril, enalapril, fosinopril, lisinopril, perindopril, ramipril
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
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
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
How long does the ACE inhibitor cough take to subside?
Improves within 1-4 weeks after stopping medication
How long after commencing treatment of ACE inhibitors could angioedema appear?
First week of treatment (possible months to years later)
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
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.
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
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
