Hypertension Flashcards
Definition Hypertension
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
Classification of Hypertension
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
Causes of Hypertension
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
Regulation of Blood Pressure
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
Diuretics Effect and its classes
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
Loop Diuretics Effect and its name
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
Adverse Effects of Loop Diuretics
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)
Thiazide Diuretics effect and its name
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
Adverse Effects of Thiazide Diuretics
Hypokalemia
Metabolic Alkalosis
Hyponatremia
Hyperglycaemia
- exacerbate diabetes
Hyperlipidemia
Potassium
Sparing Diuretics
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
Adverse Effects of K
Sparing Diuretics
• 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
Characteristics of Diuretics
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
Effect of Renin
Angiotensin System
Vasoconstriction
- direct action on smooth muscle
- increased sympathetic function
increased Fluid Retention
- increased Na reabsorption in proximal tubule
- increased release of aldosterone
Names and effect Inhibitors of Renin
Angiotensin System
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
Adverse Effects of ACE Inhibitors /
Angiotensin Receptor Blockers /
Renin Inhibitors
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
Adverse Effects Selective to ACE Inhibitors
Dry Cough
Angioedema
Related to increased level of bradykinin
Sympathoplegic / Sympatholytic
Agents
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
Effect of b Blockers and Adverse Effects of
b Blockers
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
Other Types of
b Blockers
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
Name and effects of a
Adrenoceptor Antagonists
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
Name and effects Adrenergic Neuron Blocking Agents
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
Adverse effects Adrenergic Neuron
Blocking Agents
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)
Name and effect of Centrally
Acting Sympathoplegic Agents
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
Adverse effect of Centrally
Acting Sympathoplegic Agents
Adverse Effects
-central nervous system disturbances
eg sedation, mental depression
Types of Vasodilators
Calcium Channel Blockers
e.g nifedipine amlodipine, diltiazem, verapamil
Nitrovasodilators
eg nitroprusside nitroglycerides
Potassium Channel Openers
eg minoxidil
Hydralazine
Names, Effect and Adverse effect of Calcium channel blockers
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
Names and effect of Nitrovasodilators
•
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
Names, Effect and Adverse Effect of Potassium Channel Openers
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]
Names and Effect and Adverse effect of Hydralazine
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]
Compensatory Responses to Vasodilators
Sodium Retention increased plasma volume
Increased arterial pressure
Increased heart rate
Management of Hypertension
- Non pharmacological approaches
- decreased weight
-decreased sodium intake - Pharmacological monotherapy
- angiotensin inhibitors [
- b adrenoceptor antagonists [B]
- calcium channel blockers [C]
- thiazide diuretics [D] - Alternative choices of monotherapy:
- sympathoplegic agents (not a-adrenoceptor blockers) - Combination Therapy
which is effective blood pressure control while minimizing dose related adverse effects
- thiazide diuretics plus others
Considerations of Anti
Hypertensive Treatment
• 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
