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Pharmacology > Hypertension > Flashcards

Hypertension Flashcards

1
Q

Definition Hypertension

A

Most Common Cardiovascular Disease

Persistent increased Blood Pressure
lead to increased risk of coronary thrombosis, strokes and renal failure

Asymptomatic
lead to symptoms only reported when there is end organ damage

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2
Q

Classification of Hypertension

A 
Normal Blood Pressure
< 120
And
< 80
Elevated Blood Pressure
120-129 And < 80

Stage 1 Hypertension
130-139 Or 80-89
Stage 2 Hypertension
larger or equal to140 Or larger or equal to 90

Blood pressure based on an average of 2 careful readings obtained on 2 occasions

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3
Q

Causes of Hypertension

A 
Essential or Primary Hypertension
-unknown cause
-multifactorial
genetic inheritance
psychological stress
dietary factors e g increased intake of sodium and cholesterol
life styles e g smoking
existing conditions e g obesity, diabetes

Secondary Hypertension
specific cause
eg pheochromocytoma Cushing’s disease, primary aldosteronism renal artery constriction

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4
Q

Regulation of Blood Pressure

A

Heart
cardiac output X blood pressure

Arterioles

Capacitance vessels
which these two regulates peripheral vascular resistance X bp

Kidney
-regulate intravascular fluid (Blood volume)

Sympathetic Nervous System

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5
Q

Diuretics Effect and its classes

A

Increased Fluid Excretion
which decreased blood volume

Classes of Diuretics
-loop diuretics
eg furosemide, ethacrynic acid
- thiazide diuretics
eg hydrochlorothiazide, chlorthalidone
-potassium sparing diuretics
eg amiloride spironolactone
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6
Q

Loop Diuretics Effect and its name

A

e.g. furosemide, ethacrynic acid
Inhibit Na +/K+ /2Cl- co-transport in the thick ascending loop of Henle
which inhibit Na and Cl reabsorption
-lead to increased renal excretion of water and Na
-lead to decreased reabsorption of Mg 2 and Ca 2

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7
Q

Adverse Effects of Loop Diuretics

A 
Hypokalemia
due to loss of K in collecting tubule
lead to exacerbate cardiac arrhythmias
-reversed by decreased  Na intake
or K replacement
Metabolic Alkalosis
due to loss of H in collecting tubule lead to compromise cardiac function
Hyponatremia
- due to depletion of Na
lead to extracellular fluid depletion
(hypotension,
reduced glomerular filtration rate, circulatory collapse, thromboembolic episodes,
hepatic encephalopathy)
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8
Q

Thiazide Diuretics effect and its name

A

e.g. hydrochlorothiazide,
chlorthalidone

Inhibit Na ++/Cl co transport in the distal convoluted tubule

  • which inhibit Na and Cl reabsorption
  • lead to increased re absorption of Ca 2
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9
Q

Adverse Effects of Thiazide Diuretics

A

Hypokalemia

Metabolic Alkalosis

Hyponatremia

Hyperglycaemia
- exacerbate diabetes

Hyperlipidemia

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10
Q

Potassium

Sparing Diuretics

A

e. g. amiloride,
- inhibits epithelial Na channel activity in the collecting tubule

spironolactone, eplerenone
-antagonize aldosterone receptor

inhibit Na influx and K efflux in the collecting tubule
lead to inhibit reabsorption of Na
lead to decrease excretion of K

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11
Q

Adverse Effects of K

Sparing Diuretics

A 
•
Hyperkalemia
-due to decreased excretion of K+
lead to exacerbate cardiac arrhythmias
enhanced in renal diseases, or with intake of drugs
which inhibit renin angiotensin system
[eg β blockers, NSAIDs, renin inhibitors, angiotensin converting enzyme inhibitors]
-reversed by thiazide diuretics

Metabolic Acidosis
-due to dcreased excretion of H+ lead to compromise cardiac function

Gynecomastia, impotence, menstrual irregularities
- selective to spironolactone [not with eplerenone]
therefore spironolactone is also an antagonist for androgen and progesterone receptors

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12
Q

Characteristics of Diuretics

A

Efficacy
-loop diuretics >thiazide diuretics >K sparing diuretics
[most Na has been reabsorbed at sites before reaching the distal tubule]

Loop Diuretics

  • more severe hypertension
  • shorter acting

Thiazide Diuretics

  • mild to moderate hypertension lead to decreased 10 15 mmHg
  • longer acting with slightly safer profile which is for chronic use

K Sparing Diuretics [limited blood pressure lowering effect]

Multiple Drug Regimen
combine with other antihypertensive drugs
lead to enhance blood pressure lowering effect

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13
Q

Effect of Renin

Angiotensin System

A

Vasoconstriction

  • direct action on smooth muscle
  • increased sympathetic function

increased Fluid Retention

  • increased Na reabsorption in proximal tubule
  • increased release of aldosterone
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14
Q

Names and effect Inhibitors of Renin

Angiotensin System

A

Angiotensin Converting Enzyme (ACE) Inhibitors
-decreasd Formation of Angiotensin II
eg captopril enalapril lisinopril quinapril

Angiotensin Receptor Blockers (ARB)
Inhibit the Actions of Angiotensin II
eg losartan valsartan

Renin Inhibitors
- which decreased the Activity of Renin e g aliskiren

lead to decreased vasoconstriction which lead to decreased peripheral vascular resistance lead to decreased blood volume (slightly diuretic) lead to decreased oedema

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15
Q

Adverse Effects of ACE Inhibitors /
Angiotensin Receptor Blockers /
Renin Inhibitors

A

Severe Hypotension e g in patients with fluid loss

Acute Renal Failure

Hyperkalemia therefore caution with K sparing diuretics

Risk of Fetal Hypotension, Renal Failure or Malformation
which is contraindicated during pregnancy

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16
Q

Adverse Effects Selective to ACE Inhibitors

A

Dry Cough
Angioedema
Related to increased level of bradykinin

17
Q

Sympathoplegic / Sympatholytic

Agents

A

Adrenoceptor Antagonists

  • inhibit b-adrenoceptors in heart e.g propranolol, metoprolol, pindolol
  • inhibit a-adrenoceptors in blood vessels e-g prazosin doxazosin

Adrenergic Neuron Blocking Drugs
- inhibit release of neurotransmitters ( from
postganglionic sympathetic neurons e g reserpine

Centrally Acting Drugs
-affect sympathetic nervous system in the brain
eg methyldopa, clonidine

18
Q

Effect of b Blockers and Adverse Effects of

b Blockers

A

Inhibit b Adrenoceptors in Heart
which lowers rate and force of contraction of heart which decreases cardiac output

Inhibit b-Adrenoceptors in Kidneys lead to decreased activation of renin production lead to decreased Na and water retention

Adverse Effects of
b Blockers
-Inhibit b Adrenoceptors in Respiratory Tract lead to bronchospasm

-Inhibit b Adrenoceptors in the Liver lead to increased risk of hypoglycemia

both Less with
metoprolol because of its
cardiac selectivity

Inhibit b Adrenoceptors in Heart
=lead to decreased rate and force of contraction of heart
lead to increased risk of arrhythmias and heart failure
Less with pindolol because it has small effect on heart function

19
Q

Other Types of

b Blockers

A

β-Blockers With Vasodilator Effects
- inhibit β and α adrenoceptors e.g labetalol and carvedilol
inhibit β adrenoceptors and stimulates release of nitric oxide from endothelial cells
e.g nebivolol

Short Acting β-Adrenoceptor Antagonist e.g esmolol
- inhibits β 1 adrenoceptors
- short half-life 9-10 minutes)
therefore constant intravenous infusion
which for management of intraoperative and postoperative hypertension, and for hypertensive emergencies

20
Q

Name and effects of a

Adrenoceptor Antagonists

A

prazosin , doxazosin

Inhibit a 1 Adrenoceptors in Arterioles and Venules
-lead to dilate arterioles and veins
which decreases peripheral vascular resistance

Selectivity at a1 Adrenoceptors
-which has mild unwanted effects e.g dizziness, palpitations ,headache

lead to Reflex Tachycardia and Retention of Na and Water
which oppose antihypertensive action
which is more effective when used in combination with diuretics or b-adrenoceptor blockers

21
Q

Name and effects Adrenergic Neuron Blocking Agents

A

Reserpine
- inhibit the uptake and storage of biogenic amines into aminergic transmitter
vesicles

  • lead to depletion of neurotransmitters ( in central and peripheral neurons which decreases peripheral vascular resistance and thus decreases cardiac output
  • relatively safe at low doses for mild and moderate hypertension
22
Q

Adverse effects Adrenergic Neuron

Blocking Agents

A

Gastrointestinal disturbances
-lead to increased gastric acid secretion therefore avoided in patients with peptic ulcer)

Ccentral nervous system disturbances
e.g sedation, mental depression (not common with low doses)

23
Q

Name and effect of Centrally

Acting Sympathoplegic Agents

A

e.g. methyldopa, clonidine

Central Nervous System
lead to decresaed stimulation of a2- adrenoceptors in presynaptic nerve endings
lead to decreased adrenergic outflow

Clonidine (less with methyldopa) which decreases heart rate which decreases cardiac output

24
Q

Adverse effect of Centrally

Acting Sympathoplegic Agents

A

Adverse Effects
-central nervous system disturbances
eg sedation, mental depression

25
Q

Types of Vasodilators

A

Calcium Channel Blockers
e.g nifedipine amlodipine, diltiazem, verapamil

Nitrovasodilators
eg nitroprusside nitroglycerides

Potassium Channel Openers
eg minoxidil

Hydralazine

26
Q

Names, Effect and Adverse effect of Calcium channel blockers

A

e.g.
nifedipine and amlodipine (dihydropyridines) dihydropyridines), diltiazem, verapamil

Inhibit Calcium Channels in Blood Vessels
-lead to reduced vasoconstriction lead to lowered peripheral vascular resistance

Inhibit Calcium Channels in the Heart
lowered rate and force of contraction lead to decreased cardiac output

Adverse Effects
-vascular selective blockers eg nifedipine dihydropyridines
lead to reflex tachycardia
-cardiac selective blockers eg verapamil
lead to heart failure
27
Q

Names and effect of Nitrovasodilators

A

•
Dilators of Arteries and Veins
-lead to reduced peripheral vascular resistance
-lead to decreased amount of blood returning to the heart

Nitroprusside
- intravenous infusion therefore limited clinical use
- rapidly decreased blood pressure and short acting
therefore for hypertensive crisis e g during surgery
-break down to thiocyanate
lead to thiocynate toxicity [e g disorientation, convulsions]
therefore only short term treatment [risk increased if infused for 24-48 hours]

Organic Nitrates e g nitroglycerin
-tolerance lead to not useful for long term management of high blood pressure

28
Q

Names, Effect and Adverse Effect of Potassium Channel Openers

A

e.g. minoxidil

Dilators of Arterioles
lead to decreased peripheral vascular resistance
-activation of ATP sensitive potassium channels
which increases potassium efflux lead to hyperpolarization and relaxation of smooth muscle

Adverse Effects
-reflex tachycardia
-reflex retention of Na and water both lead to
Myocardial ischemia in patients with
cardiovascular diseases
-excessive hair growth on face, back, arms and legs

Used as Last Resort to Treat Severe Hypertension
[in combination with other antihypertensive drugs especially in male patients with renal insufficiency]

29
Q

Names and Effect and Adverse effect of Hydralazine

A

Dilators of Arterioles
lead to decreased peripheral vascular resistance [mechanism not clear]

Adverse Effects
-headache, nausea, flushing, hypotension, dizziness
-reflex tachycardia and reflex retention of Na and water
which may precipitate angina and myocardial ischemia
- autoimmune reactions
lead to lupus syndrome [ arthritis and fever higher risk in female and in Caucasians]
hemolytic anemia, vasculitis, and rapidly progressive glomerulonephritis
[relieved by discontinuation of hydralazine]

Used as Last Resort to Treat Severe Hypertension [in combination with other
antihypertensive drugs], And Hypertensive Emergencies [especially preeclampsia in
pregnant women]

30
Q

Compensatory Responses to Vasodilators

A

Sodium Retention increased plasma volume

Increased arterial pressure

Increased heart rate

31
Q

Management of Hypertension

A
  1. Non pharmacological approaches
    - decreased weight
    -decreased sodium intake
  2. Pharmacological monotherapy
    - angiotensin inhibitors [
    - b adrenoceptor antagonists [B]
    - calcium channel blockers [C]
    - thiazide diuretics [D]
  3. Alternative choices of monotherapy:
    - sympathoplegic agents (not a-adrenoceptor blockers)
  4. Combination Therapy
    which is effective blood pressure control while minimizing dose related adverse effects
    - thiazide diuretics plus others
32
Q

Considerations of Anti

Hypertensive Treatment

A 
•
Lifelong Treatment
compliance of treatment
- oral preparation
- monotherapy versus multiple drugs
therefore monitor of unwanted/adverse effects
Choices of Drugs
- level of blood pressure
- concomitant diseases
e,g hypertension+angina
- b-adrenoceptor antagonists /calcium channel blockers
hypertension+heart failure
- diuretics ACE inhibitors
hypertension+asthma avoid b-adrenoceptor antagonists

Pharmacology (30 decks)

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