ANTIHYPERTENSIVE DRUGS

ANTI-ANGINALS
HEART FAILURE DRUGS
RAY ALBERT R. CABIGAN, MD
INTERNAL MEDICINE
INTERVENTIONAL CARDIOLOGIST
PERPETUALITE
“Type a quote here.”

–Johnny Appleseed
“Type a quote here.”

–Johnny Appleseed
 “Type a quote here.”

–Johnny Appleseed

Blood Pressure = Cardiac output x Peripheral Resistance

BP = (Stroke volume x HR) x Peripheral Resistance
“Type a quote here.”

–Johnny Appleseed
“Type a quote here.”

–Johnny Appleseed
“Type a quote here.”

–Johnny Appleseed
Preload Afterload
Amount of
Amount of
pressure
pressure in
against
the ventricle
which the
at the end of
ventricle has
diastole
to contract
DID YOU KNOW
INHIBITORS OF
ANGIOTENSIN
4 Classes of drugs that
woek on the RAAS

ACE inhibitors

ARBs

Aliskiren

Aldosterone receptor inhibitors

Angiotensin Converting
Enzyme Inhibitors
Captopril, enalapril(converted to enalaprilat after
hydrolysis), Benazepril, fosinopril, moexipril, perindopril,
quinapril, ramipril, and trandolapri

Decreases peripheral vascular resistance

Contraindicated during the second and third trimesters

of pregnancy because of the risk of fetal hypotension,
anuria, and renal failure, sometimes associated with fetal
malformations or death. Teratogenic on the 1st trimester.

NSAIDs impair effects by blocking bradykinin

Angiotensin Receptor
Blockers
Losartan, valsartan, Azilsartan, candesartan,
eprosartan, irbesartan, olmesartan, and
telmisartan

No effect on bradykinin metabolism

Same hazards as ACEi in pregnancy

Combination with ACEi and/or aliskiren is NOT

RECOMMENDED
ACEi beneficial for HFrEF ARBs beneficial for HFrEF

Captopril Losartan

Ramipril Candesartan

Enalapril Valsartan
DIURETICS
Potassium sparing
diuretics
Spironolactone is a synthetic steroid that acts as a competitive
antagonist to aldosterone. Inhibits androgen receptor. Reduce Na+
absorption in the collecting tubules and ducts

Eplerenone is a spironolactone analog with much greater selectivity for the

mineralocorticoid receptor. It is several hundredfold less active on
androgen

Amiloride and triamterene are direct inhibitors of Na+ influx in the CCT
via ENaC

Spironolactone and eplerenone are used in HF, Aldosteronism,

Hypertension

Hyperkalemia risk is increased in renal failure, use of BB, NSAIDs, Aliskiren

or ACEi/ARBs
Loop Diuretics
Selectively inhibit NKCC2,
luminal Na/K/2Cl transporter
in the Thick Ascending Loop

Non-sulfonamide base:
ethacrinic acid

Sulfinamide base: furosemide,

bumetanide, torsemide

Clinical use: edema,

hyperkalemia, acute renal
failure, anion overdose
Loop Diuretics

Toxicity: hypokalemic metabolic alkalosis,

reversible ototoxicity, hyperuricemia,
hypomagnesemia, hyponatremia, hypocalcemia

Contraindication: allergy to sulfonamides

Thiazides
Inhibit NaCl reabsorption from the DCT by blocking
the Na+/Cl− transporter (NCC)

Enhanced Calcium reabsorption via volume depletion

at the PCT leads to enhanced Na+ and passive Ca2+
reabsorption. In the DCT, blockade of Na+ entry,
increases overall reabsorption of Ca2+ = prevents
calcium containing kidney stones

Indications: hypertension, heart failure, kidney stones

from hypercalciuria, nephrogenic diabetes insipidus
Thiazides

Toxicity: hypokalemia, impaired carbohydrate

tolerance, hyperlipidemia, impaired uric acid
metabolism and gout

Thiazides have a weak, dose-dependent, off-

target effect to stimulate ATP-sensitive K+
channels and cause hyperpolarization of beta cells,
thereby inhibiting insulin release
Aquaretics
Osmotic diuretic = mannitol.

Not reabsorbed from the PCT, and descending

loop after being filtered from the glomerulus

Excreted by the kidneys in 30-60mins after

administration

Used to reduce intracranial and intraoccular

pressure
Aquaretics
ADH Antagonist = vaptans

Conivaptan inhibits V1 (brain)

and V2 (kidneys)

Tolvaptan, lixivaptan,
mozavaptan, and satavaptan are
selectively active against the V2
receptor

lithium and demeclocycline

reduce ADH-induced cAMP by
unknown mechanisms

Use: SIADH, HF, AD-PCKD

Preload Afterload
Amount of
Amount of
pressure
pressure in
against
the ventricle
which the
at the end of
ventricle has
diastole
to contract
Carbonic anhydrase inhibitors
Blocks carbonic anhydrase primarily at the PCT, blunting NaHCO3
reabsorption and causing diuresis.

The prototypical carbonic anhydrase inhibitor is acetazolamide.

Excretion of the drug is by secretion in the proximal tubule S2

segment

Toxicity: significant HCO3- losses and hyperchloremic metabolic

acidosis, renal stones, potassium wasting

Clinical use: glaucoma, urinary alkalinization for cystinuria and uric

acid, metabolic alkalosis

Diuretic effect: 2-3days only

Contraindication: cirrhosis due to decreased NH4+ Excretion

Sodium Glucose Cotransporter
2 (SGLT2) Inhibitor
Works on the PCT SGLT2, causing excretion of
30-50% of filtered glucose

Dapagliflozin, canaflozin, empagliflozin,

ipragliflozin

3rd line therapy for Diabetes Mellitus, reduces

HBA1C by 0.5-1.0%. Low incidence of
hypoglycemia

Weak diuretic
DID YOU KNOW
CALCIUM CHANNEL BLOCKERS
(CCBS)
Non-dihydropyridines
Verpamil and diltiazem

Less-selective CCB (L-type

calcium channel blockers)

Class 4 antoarrhythmic

Decreases HR and CO
(verapamil > diltiazem)

They block tachycardias in

calcium-dependent cells, eg,
the atrioventricular node, more
selectively than do the
dihydropyridines.
Verapamil
Toxic effects are dose-related and usually avoidable

A common error has been to administer intravenous

verapamil to a patient with ventricular tachycardia
misdiagnosed as supraventricular tachycardia

Verapamil can induce AV block

The half-life of verapamil is approximately 4–7 hours

Hepatic metabolism

Has negative inotropic effects

Dihdropyridines
Amlodipine, felodipine,
isradipine, nicardipine,
nifedipine (prototype),
nisoldipine, and nitrendipine

Newest: Clevidipine, IV only

Nifedipine: short acting,

associsted with increased
risk of MI

Sustained release CCBs are

appropriate for chronic HPN
BETA ADRENOCEPTOR
BLOCKING AGENTS
Selectivity
B1 selective: metoprolol, atenolol, betaxolol,
bisoprolol, esmolol (shortest half life: 9-10mins)

Non-selective: propranolol, nadolol, carteolol

B-blocking with vasodilating effects: labetalol,

carvedilol, nebivolol (via NO release)

Partial B agonists: Pindolol, acebutolol, and

penbutolol
Beta blockers
Decreased heart rate, blood pressure, and contractility
decreases myocardial oxygen requirements at rest and
during exercise and increases in diastolic perfusion time

Also used for heart failure and is a Class 2 antiarrhythmic

These agents can prevent recurrent infarction and sudden

desth n patients with AMI

Contraindications to the use of β blockers are asthma

and other bronchospastic conditions, severe bradycardia,
atrioventricular blockade, bradycardia-tachycardia
syndrome, and severe unstable left ventricular failure
Beta blockers proven
beneficial for HFrEF

Bisoprolol

Carvedilol

Metoprolol

Nebivolol
ALPHA1 BLOCKERS
Alpha Blockers
Prazosin, terazosin, and
doxazosin selectively blocks
α1 receptors in arterioles
and venules - less reflex
tachycardia

Phentolamine is a non-
selective α1 blocker.may be
used to diagnose and treat
pheochromocytoma

First dose phenomenon =

orthostatic hypotension
SODIUM NITROPRUSSIDE
AND NITRATES
Sodium nitroprusside
Dilates both arterial and
venous vessels. effects
disappear within 1–10
minutes after
discontinuation

Most serious toxicity is

related to accumulation of
cyanide; metabolic
acidosis, arrhythmias,
excessive hypotension, and
death
Nitrates
Nitroglycerin

Nitric oxide released from

nitroglycerin stimulates guanylyl
cyclase

Deactivated by nitrate reductase in

the liver reducing oral bioavailability
to <10-20%

The 5-mononitrate metabolite of

isosorbide dinitrate is an active
metabolite of the latter drug and is
available for oral use as isosorbide
mononitrate. It has a bioavailability
of 100%.
Nitrates
Tocixity: orthostatic
hypotension, tachycardia,
and throbbing headache

Contraindicstion: elevated
intracranial pressure

Tachyphylaxis: rapid
diminishing response to a
drug

Combination with sildenafil

(PDE-5 inhibitor) may cause
profound hypotension
DID YOU KNOW
HYDRALAZINE
Hydralazine

Dilates arterioles but not veins.

Causes tachyphylaxis

The most common adverse effects of hydralazine

are headache, nausea, anorexia, palpitations,
sweating, and flushing
MINOXIDIL
Minoxidil

Opens potassium channels in smooth muscle

Dilates arterioles but not veins

Associated with reflex sympathetic stimulation and

sodium and fluid retention. Minoxidil must be used
in combination with a β blocker and a loop
diuretic.
DIAZOXIDE
Diazoxide
Long-acting potassium channel opener that
causes hyperpolarization in smooth muscle and
pancreatic β cells

Dilates arterioles

Diazoxide is similar chemically to the thiazide

diuretics but has no diuretic activity.

Lowers BP in 5mins, lasts 4-12hours

FENOLDOPAM
Fenoldopam

Dilates arterioles, auses natriuresis

D1 agonist

Used for hprrtensive emergencied

 CENTRALLY ACTING
SYMPATHOPLEGIC DRUGS
Centrally acting
sympathoplegics
Methyldopa is an analog of L-
dopa and is converted to α-
methyldopamine and α-
methylnorepinephrine which
stimulates central α adrenoceptors

Clonidine partially α receptors

agonist/inhibitor. Reduces
sympathetic and increases
parasympathetic tone. Binds to a
nonadrenoceptor site, the
imidazoline receptor, which may
also mediate antihypertensive
effects.