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PREPARED BY: REYSAN S.

COSAS, RPh
• Lesson 1 – Antihypertensive Drugs
• Lesson 2 – Vasodilators & the Treatment of Angina Pectoris
• Lesson 3 – Drugs Used in Heart Failure
• Lesson 4 – Agents used in Cardiac Arrhythmias
• Lesson 5 – Lipid Lowering Drugs
• Lesson 6 – Drugs Used in Disorders of Coagulation
• Lesson 7 – Agents Used in Anemias: Hematopoeitic Growth Factors
LEARNING OBJECTIVES
1. Define blood pressure and hypertension;
2. Describe the etiology & pathophysiology of hypertension and the
mechanisms for blood pressure regulation;
3. Classify the drugs used in hypertension;
4. Identify the mechanism of action for each class of antihypertensive
agents; and
5. Determine the clinical uses and adverse effects of each
antihypertensive agents.
• It is the outward pressure of
blood against blood vessel
wall, is the product of blood
flow from the heart and
inward resistance of blood
vessel walls.
• BP is directly proportional to
cardiac output and peripheral
vascular resistance.

BP = CO x PVR
• Hypertension is defined as either a sustained systolic blood pressure of
greater than 140 mm Hg or a sustained diastolic blood pressure of greater
than 90 mm Hg.
• American Heart Association (AHA) : >140/90 mm Hg
• World Health Organization (WHO): >160/95 mm Hg
Systolic/Diastolic Pressure
Category
(mm Hg)
< 120/80 Normal
120–135/80–89 Prehypertension
≥ 140/90 Hypertension
140–159/90–99 Stage 1 HTN
≥ 160/100 Stage 2 HTN
From the Joint National Committee on prevention, detection, evaluation, and treatment of high
blood pressure. JAMA 2003;289:2560.
Systolic/Diastolic Pressure
Category
(mm Hg)
< 120/80 Normal
120–129/ < 80 Elevated
130–139/80–89 Stage 1 HTN
≥ 140/90 Stage 2 HTN
≥ 180/120 Hypertensive crisis
From new ACC/AHA guidelines for the detection, prevention, management and treatment of high
blood pressure, November 2017.
What are the complications of Hypertension?
• CHF
• CAD
• Renal Disease
• Ischemic Stroke
• Atherosclerosis
• Retinal Disease
Renal disease
• Aneurysm atherosclerosis
CHF
• Cardiomyopathy
• ESSENTIAL OR PRIMARY HYPERTENSION
• no specific cause
• heritability is 30%
• SECONDARY HYPERTENSION
• with a specific etiology
• renal artery constriction, coarctation of the aorta, pheochromocytoma,
Cushing's disease, and primary aldosteronism
• multifactorial
ANATOMIC SITES OF BLOOD PRESSURE CONTROL

Cardiac output
(CO)

PVR

Regulates
the volume
• BARORECEPTOR REFLEX ARCH
• Baroreflexes are responsible for rapid, moment-to-moment adjustments in
blood pressure, such as in transition from a reclining to an upright posture
• RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
• By controlling blood volume, the kidney is primarily responsible for long-term
blood pressure control.
Baroreceptor Reflex Control of BP (↑ Pressure)

Carotid Sinus

Decreased
↑ Arterial Arterial
Pressure
Pressure

VASOMOTOR
↑Decreased
Arterial Arterial
CENTER
Pressure Aortic Arch
Pressure

Decreased Inotropy &


Chronotropy
Baroreceptor Reflex Control of BP (↓ Pressure)

Carotid Sinus

Increased
↓ ArterialArterial
Pressure
Pressure

VASOMOTOR
↓Increased
Arterial Arterial
CENTER
Aortic Arch
Pressure
Pressure

Increased Inotropy &


Chronotropy
Normal Regulation of BP

Renal response to
decreased BP
• Reduction of the sign itself by drugs whose mechanisms of
action at the system level are altered:
• blood volume
• cardiac output
• peripheral vascular resistance

• Limit development of subsequent organ pathology


1. DIURETICS
2. SYMPATHOPLEGIC AGENTS
3. DIRECT VASODILATORS
4. ANGIOTENSIN ANTAGONIST/MODIFIERS (AGENTS THAT
BLOCK PRODUCTION OR ACTION OF ANGIOTENSIN)
MAJOR CLASSES OF ANTIHYPERTENSIVE AGENTS
Sites of action of the
major classes of
antihypertensive drugs
Lower blood pressure by depleting the body of sodium and reducing blood
volume and perhaps by other mechanisms.
Drugs used in renal disorders

Drugs that modify Drugs that modify


Salt excretion Water excretion

Osmotic diuretics ADH


PCT TAL DCT CCT
agonists
ADH
antagonists
K+-sparing
Thiazides
Loop
CAI
LOOP DIURETICS POTASSIUM-SPARING
• Ethacrynic acid DIURETICS
• Bumetanide • Spironolactone
• Furosemide • Triamterene
• Torsemide • Amiloride
• Muzolamine • Eplerenone
THIAZIDE DIURETICS
• Hydrochlorothiazide
• Chlorthiazide
• Chlorthalidone
• Metolazone
• Indapamide
CARBONIC ANHYDRASE ADH ANTAGONISTS
INHIBITORS
• Demeclocycline
• Acetazolamide
• Brinzolamide • Lithium
• Dorzolamide
MERCURIAL DIURETICS
OSMOTIC DIURETICS
• Mannitol • Mercaptomerin
• Urea ACIDIFYING SALTS
• Isosorbide
• Ammonium chloride
XANTHINE DIURETICS
• Caffeine
• Theobromine
• Theophylline
The Nephron
and the sites of action of Diuretics
MOA OF CARBONIC
ANHYDRASE INHIBITORS
Inhibition of Carbonic Anhydrase:
↓ Bicarbonate
concentration in the blood
MOA OF LOOP DIURETICS

↓ Potassium, Sodium, Chloride,


Magnesium, Calcium reabsorbed

Block the Na+/K+/2Cl- symporter (cotransporter)


in thick ascending loop of Henle
MOA OF THIAZIDE DIURETICS

Regulated by PTH

Block the Na+/Cl- cotransporter in the DCT


MOA OF POTASSIUM SPARING DIURETICS

Spironolactone,
Amiloride Eplerenone
Triamterene

Amiloride and Triamterene – inhibit the Na+ influx through ion


channel (ENaC)
Spironolactone, Eplerenone – antagonize the effect of
aldosterone (mineralocorticoid)
MOA OF AQUARETICS

• MANNITOL
• ADH AGONISTS
• ADH ANTAGONISTS
Electrolyte Changes Produced by
Diuretic Drugs
Urine
Drug Group NaCl NaHCO3 K+ Ca 2+ Body pH

CAI ­ ­­­ ­ - Acidosis

Loop ­­­­ - ­ ­­ Alkalosis

Thiazides ­­ ­ ­ ¯¯ Alkalosis

K+-Sparing ­ (+) ¯ - Acidosis


• EDEMATOUS STATES
• Edema associated with Heart failure
• Kidney disease and renal failure
• Hepatic cirrhosis
• Idiopathic edema
• NON-EDEMATOUS STATES
• High salt intake resulting to Hypertension
• Nephrolithiasis
• Hypercalcemia
• Diabetes Insipidus
• Renal & cardiac protection
• THIAZIDES
• For mild to moderate hypertension

• LOOP DIURETICS
• For severe hypertension

• POTASSIUM-SPARING DIURETICS
• Useful both to avoid excessive potassium depletion and enhance the natriuretic
effects of other diuretics
• Diuretics enhance the efficacy of ACE inhibitors and vasodilators
• THIAZIDE DIURETICS • LOOP DIURETICS
• HTN • Acute Pulmonary edema, and
• Mild heart failure other edematous condition
• Chronic calcium stone formation • Acute hypercalcemia

• Nephrogenic diabetes insipidus • Hyperkalemia


• Acute Renal Failure
• Anion overdose
• POTASSIUM SPARING DIURETICS CARBONIC ANHYDRASE INHIBITORS
• Hyperaldosteronism • Glaucoma
• Primary – Conn’s syndrome, ectopic ACTH • CAIs reduce aqueous humor formation =
production decrease IOP
• Secondary – evoked by heart failure, hepatic • Urinary alkalinization
cirrhosis, nephrotic syndrome
• Metabolic alkalosis
• Alternative to loop and thiazide
diuretics, if K+ wasting is to be • Acute mountain sickness
• CAIs decrease CSF formation and the pH of CSF
avoided and brain = increase ventilation and diminish
symptoms of mountain sickness
• Eplerenone – reduce myocardial
perfusion defects • Adjuvants in the treatment of epilepsy
• Amiloride – Liddle’s syndrome • Increase urinary phosphate excretion
during severe hyperphosphatemia
• Finerenone – Cardioprotectant
• Attributable to diuretic property
• Metabolic alkalosis
• Hypokalemia
• Hypocalcemia
• Hypovolemia
• Hypotension
• Hypomagnesemia
• Not directly related to diuretic property
• Hyperuricemia
• Ototoxicity
• Attributable to diuretic property
• Metabolic alkalosis
• Hypokalemia
• Hyponatremia
• Hypercalcemia
• Hypovolemia
• Hypotension
• Hypomagnesemia
• Not directly related to diuretic property
• Hyperuricemia
• Hyperglycemia
• Hyperlipidemia
• Attributable to diuretic property
• Metabolic acidosis
• Hyperkalemia
• Not directly related to diuretic property
• Menstrual disorders
• Impotence/ gynecomastia
• Loss of libido
• Hirsutism
* Reported with Spironolactone but not reported with eplerenone
• Others:
• Acute Renal Failure –Triamterene + Indomethacin
• Kidney stones – with triamterene
OSMOTIC DIURETICS
ADH AGONISTS
ADH ANTAGONISTS
XANTHINE DIURETICS
UREARETICS
OTHERS
• MANNITOL – prototype agent
• Large amount of impermeant solute in the tubular fluid
• Water reabsorption causes the solute concentration and osmolarity to rise
• Prevents water reabsorption

• CLINICAL USES
• Increase urine volume
• Reduction of ICP and IOP
• ADVERSE EFFECTS
• Extracellular volume expansion
• Dehydration, Hyperkalemia, and hypernatremia
• Hyponatremia – when used with patient with diminished renal function
• Acute renal failure
• VASOPRESSIN AND DESMOPRESSIN
• Used in the treatment of central diabetes insipidus
• LITHIUM & DEMECLOCYCLINE – nonselective agents
• CONIVAPTAN
• TOLVAPTAN, LIXIVAPTAN, AND SATAVAPTAN
• CLINICAL USES
• To manage SIADH
• Used in other conditions where there is elevated ADH (CHF)
• Autosomal Dominant Polycystic Kidney Disease
• ADVERSE EFFECTS
• Nephrogenic diabetes insipidus
• Renal failure, dry mouth and thirst
• Two families of urea transporters:
• UT-A is present in inner medullary collecting duct cells and the thin descending limb of
Henle.
• UT-B is present in the descending vasa recta and several extrarenal tissues.

• Urearetics are aquaretics that increase urea and water excretion but not
sodium excretion.
• These agents may prove to be useful in edematous states and even in
SIADH
• CAFFEINE • SODIUM GLUCOSE
• Weak diuretic COTRANSPORTER 2 (SGLT2)
• Nonspecifically and weakly blocks INHIBITORS
adenosine receptors that participate • Weak diuretic
in the control of proximal tubule Na+
• Dapagliflozin, Canagliflozin,
reabsorption
Empagliflozin, and Ipragliflozin
• Third-line therapy for diabetes
mellitus
• Loop diuretics and Thiazides
• Can mobilize a large amount of fluid
• K+-wasting

• Loop agents or thiazides and Potassium sparing