3. Hypertension
Systolic Blood
Pressure (SBP(
Diastolic Blood
Pressure (DBP(
<140mmHg <90mmHg
****************************************************
Hypertension β The Silent Killer
Hypertension, also known as high blood pressure, is defined as systolic blood
pressure of 140 mmHg or higher and/or diastolic blood pressure of 90 mmHg or
higher
3
4. Types of
Hypertension
Essential Secondary
A disorder of unknown origin affecting the
Blood Pressure regulating mechanisms
Secondary to other disease processes
Environmental
Factors
Stress Na+ Intake Obesity Smoking
****************************************************
4
5. ο Hydraulic equation:
Blood Pressure = Cardiac output (CO) X
Resistance to passage of blood through
precapillary arterioles (PVR)
ο Physiologically CO and PVR is
maintained minute to minute by β
arterioles (1) postcapillary venules (2)
and Heart (3)
ο Kidney is the fourth site β volume of
intravascular fluid
ο Baroreflex, humoral mechanism and
renin-angiotensin- aldosterone system
regulates the above 4 sites
ο Local agents like Nitric oxide
ο In hypertensives β Baroreflex and renal
blood-volume control system β set at
higher level
ο All antihypertensives act via interfering
with normal mechanisms
5
7. ο Long-term blood pressure control β by controlling blood volume
ο Reduction in renal pressure - intrarenal redistribution of
pressure and increased absorption of salt and water
ο Decreased pressure in renal arterioles and sympathetic activity
β renin production β angiotensin II production
ο Angiotensin II:
ο Causes direct constriction of renal arterioles
ο Stimulation of aldosterone synthesis β sodium absorption and
increase in intravascular blood volume
7
9. ο Diuretics:
ο Thiazides: Hydrochlorothiazide, chlorthalidone
ο High ceiling: Furosemide
ο K+ sparing: Spironolactone, triamterene and amiloride
MOA: Acts on Kidneys to increase excretion of Na and H2O β decrease in blood
volume β decreased BP
ο Angiotensin-converting Enzyme (ACE) inhibitors:
ο Captopril, lisinopril., enalapril, ramipril and fosinopril
MOA: Inhibit synthesis of Angiotensin II β decrease in peripheral resistance and
blood volume
ο Angiotensin (AT1) blockers:
ο Losartan, candesartan, valsartan and telmisartan
MOA: Blocks binding of Angiotensin II to its receptors
9
10. ο Centrally acting:
ο Clonidine, methyldopa
MOA: Act on central Ξ±2A receptors to decrease sympathetic outflow β fall in BP
ο Γ-adrenergic blockers:
ο Non selective: PropranololΒ (others: nadolol, timolol, pindolol, labetolol)
ο Cardioselective: MetoprololΒ (others: atenolol, esmolol, betaxolol) Β
MOA: Bind to beta adrenergic receptors and blocks the activity
ο Γ and Ξ± β adrenergic blockers:
ο Labetolol and carvedilol
ο Ξ± β adrenergic blockers:
ο Prazosin, terazosin, doxazosin, phenoxybenzamine and phentolamine
MOA: Blocking of alpha adrenergic receptors in smooth muscles -
vasodilatation
10
11. ο Calcium Channel Blockers (CCB):
ο Verapamil, diltiazem, nifedipine, felodipine, amlodipine, nimodipine etc.
MOA: Blocks influx of Ca++ in smooth muscle cells β relaxation of
SMCs β decrease BP
ο K+ Channel activators:
ο Diazoxide, minoxidil, pinacidil and nicorandil
MOA: Leaking of K+ due to opening β hyper polarization of SMCs
β relaxation of SMCs
ο Vasodilators:
ο Arteriolar β Hydralazine (also CCBs and K+ channel activators)
ο Arterio-venular: Sodium Nitroprusside
11
12. ο Drugs causing net loss of Na+ and water in urine
ο Mechanism of antihypertensive action:
ο Initially: diuresis β depletion of Na+ and body fluid volume β
decrease in cardiac output
ο Subsequently after 4 - 6 weeks, Na+ balance and CO is regained
by 95%, but BP remains low!
ο Q: Why? Answer: reduction in total peripheral resistance (TPR)
due to deficit of little amount of Na+ and water (Na+ causes
vascular stiffness)
ο Similar effect is seen with sodium restriction (low sodium diet)
12
13. ο Adverse Effects:
ο Hypokalaemia β muscle pain and fatigue
ο Hyperglycemia: Inhibition of insulin release due to K+ depletion
(proinsulin to insulin) β precipitation of diabetes
ο Hyperlipidemia: rise in total LDL level β risk of stroke
ο Hyperurecaemia: inhibition of urate excretion
ο Sudden cardiac death β tosades de pointes (hypokalaemia)
ο All the above metabolic side effects β higher doses (50 β 100 mg
per day)
ο But, its observed that these adverse effects are minimal with low
doses (12.5 to 25 mg) - Average fall in BP is 10 mm of Hg
13
14. ο Effects of low dose:
ο No significant hypokalaemia
ο Low incidence of arrhythmia
ο Lower incidence of hyperglycaemia, hyperlipidemia and hyperuricaemia
ο Reduction in MI incidence
ο Reduction in mortality and morbidity
ο JNC recommendation:
ο JNC recommends low dose of thiazide therapy (12.5 β 25 mg per day) in
essential hypertension
ο Preferably should be used with a potassium sparing diuretic as first
choice in elderly
ο If therapy fails β another antihypertensive but do not increase the
thiazide dose
ο Loop diuretics are to be given when there is severe hypertension with
retention of body fluids
14
15. ο K+ sparing diuretics:
ο Thiazide and K sparing diuretics are combined therapeutically β
DITIDE (triamterene + benzthiazide) is popular one
ο Modified thiazide: indapamide
ο Indole derivative and long duration of action (18 Hrs) β orally 2.5
mg dose
ο It is a lipid neutral i.e. does not alter blood lipid concentration, but
other adverse effects may remain
ο Loop diuretics:
ο Na+ deficient state is temporary, not maintained round βthe-clock
and t.p.r not reduced
ο Used only in complicated cases β CRF, CHF marked fluid retention
cases
15
16. What is Renin - Angiotensin?
(Physiological Background)
16
17. ο Renin is a proteolytic enzyme and also called angiotensinogenase
ο It is produced by juxtaglomerular cells of kidney
ο It is secreted in response to:
ο Decrease in arterial blood pressure
ο Decrease Na+ in macula densa
ο Increased sympathetic nervous activity
ο Renin acts on a plasma protein β Angiotensinogen (a glycoprotein
synthesized and secreted into the bloodstream by the liver) and
cleaves to produce a decapeptide Angiotensin-I
ο Angiotensin-I is rapidly converted to Angiotensin-II (octapeptide) by
ACE (present in luminal surface of vascular endothelium)
ο Furthermore degradation of Angiotensin-II by peptidases produce
Angiotensin-III
ο Both Angiotensin-II and Angiotensin-III stimulates Aldosterone
secretion from Adrenal Cortex (equipotent)
ο AT-II has very short half life β 1 min
17
19. 1. Powerful vasoconstrictor particularly arteriolar β direct action and release of
Adr/NA release
ο Promotes movement of fluid from vascular to extravascular
ο More potent vasopressor agent than NA β promotes Na+ and water reabsorption
ο It increases myocardial force of contraction (CA++ influx promotion) and increases
heart rate by sympathetic activity, but reflex bradycardia occurs
ο Cardiac output is reduced and cardiac work increases
1. Aldosterone secretion stimulation β retention of Na++ in body
2. Vasoconstriction of renal arterioles β rise in IGP β glomerular damage
3. Decreases NO release
4. Decreases Fibrinolysis in blood
5. Induces drinking behaviour and ADH release by acting in CNS β increase thirst
6. Mitogenic effect β cell proliferation
19
20. ο What are the ill effects on chronic ?
ο Volume overload and increased t.p.r
ο Cardiac hypertrophy and remodeling
ο Coronary vascular damage and remodeling
ο Hypertension β long standing will cause ventricular hypertrophy
ο Myocardial infarction β hypertrophy of non-infarcted area of
ventricles
ο Renal damage
ο Risk of increased CVS related morbidity and mortality
ο ACE inhibitors reverse cardiac and vascular hypertrophy and
remodeling
20
21. 1. Mineraocorticoid secretion
2. Electrolyte, blood volume and pressure homeostasis: Renin is
released when there is changes in blood volume or pressure or
decreased Na+ content
ο Intrarenal baroreceptor pathway β reduce tension in the afferent
glomerular arterioles by local production of Prostaglandin β
intrarenal regulator of blood flow and reabsorption
ο Low Na+ conc. in tubular fluid β macula densa pathway β COX-2 and
nNOS are induced β release of PGE2 and PGI2 β more renin release
ο Baroreceptor stimulation increases sympathetic impulse β via beta-1
pathway β renin release
ο Renin release β increased Angiotensin II production β
vasoconstriction and increased Na+ and water reabsorption
ο Long term stabilization of BP is achieved β long-loop negative
feedback and short-loop negative feedback mechanism
3. Hypertension
4. Secondary hyperaldosteronism
21
23. ο Sulfhydryl containing dipeptide and abolishes
pressor action of Angiotensin-I and not
Angiotensin-II and does not block AT receptors
ο Pharmacokinetics:
ο Available only orally, 70% - 75% is absorbed
ο Partly absorbed and partly excreted unchanged in
urine
ο Food interferes with its absorption
ο Half life: 2 Hrs, but action stays for 6-12 Hrs
23
24. 1. In Normal:
ο Depends on Na+ status β lowers BP marginally on single dose
ο When Na+ depletion β marked lowering of BP
1. In hypertensive:
ο Lowers PVR and thereby mean, systolic and diastolic BP
ο RAS is overactive in 80% of hypertensive cases and contributes to the
maintenance of vascular tone β inhibition causes lowering of BP
ο Initially correlates with renin-angiotensin status but chronic administration is
independent of renin activity
ο Captopril decreases t.p.r on long term β arterioles dilate β fall in systolic and
diastolic BP
ο No effect on Cardiac output
ο Postural hypotension is not a problem - reflex sympathetic stimulation does
not occur
ο Renal blood flow is maintained β greater dilatation of vessels
24
25. ο Cough β persistent brassy cough in 20% cases β inhibition of bradykinin
and substanceP breakdown in lungs
ο Hyperkalemia in renal failure patients with K+ sparing diuretics, NSAID and
beta blockers (routine check of K+ level)
ο Hypotension β sharp fall may occur β 1st
dose
ο Acute renal failure: CHF and bilateral renal artery stenosis
ο Angioedema: swelling of lips, mouth, nose etc.
ο Rashes, urticaria etc
ο Dysgeusia: loss or alteration of taste
ο Foetopathic: hypoplasia of organs, growth retardation etc
ο Neutripenia
ο Contraindications: Pregnancy, bilateral renal artery stenosis, hypersensitivity
and hyperkalaemia
25
26. ο Itβs a prodrug β converted to enalaprilate
ο Advantages over captopril:
ο Longer half life β OD (5-20 mg OD)
ο Absorption not affected by food
ο Rash and loss of taste are less frequent
ο Longer onset of action
ο Less side effects
26
27. ο Itβs a popular ACEI now
ο It is also a prodrug with long half life
ο Tissue specific β Protective of heart and kidney
ο Uses: Diabetes with hypertension, CHF, AMI
and cardio protective in angina pectoris
ο Blacks in USA are resistant to Ramipril β
addition of diuretics help
ο Dose: Start with low dose; 2.5 to 10 mg daily
27
28. ο Itβs a lysine derivative
ο Not a prodrug
ο Slow oral absorption β less chance of 1st
dose
phenomenon
ο Absorption not affected by food and not
metabolized β excrete unchanged in urine
ο Long duration of action β single daily dose
ο Doses: available as 1.25, 2.5, 5, 10 1nd 20 mg
tab β start with low dose
28
29. ο 1st
line of Drug:
ο No postural hypotension or electrolyte imbalance (no fatigue or
weakness)
ο Safe in asthmatics and diabetics
ο Prevention of secondary hyperaldosteronism and K+ loss
ο Renal perfusion well maintained
ο Reverse the ventricular hypertrophy and increase in lumen size of
vessel
ο No hyperuraecemia or deleterious effect on plasma lipid profile
ο No rebound hypertension
ο Minimal worsening of quality of life β general wellbeing, sleep and
work performance etc.
29
31. Angiotensin Receptors:
ο Specific angiotensin receptors have been discovered, grouped and
abbreviated as β AT1 and AT2
ο They are present on the surface of the target cells
ο Most of the physiological actions of angiotensin are mediated via
AT1 receptor
ο Transducer mechanisms of AT1 inhibitors: In different tissues show
different mechanisms. For example -
ο PhospholipaseC-IP3/DAG-intracellular Ca++ release
mechanism β vascular and visceral smooth muscle contraction
ο In myocardium and vascular smooth muscles AT1 receptor
mediates long term effects by MAP kinase and others
ο Losartan is the specific AT1 blocker
31
32. ο Competitive antagonist and inverse agonist of
AT1 receptor
ο Does not interfere with other receptors except
TXA2
ο Blocks all the actions of A-II - vasoconstriction,
sympathetic stimulation, aldosterone release
and renal actions of salt and water
reabsorption
ο No inhibition of ACE
32
33. ο Theoretical superiority over ACEIs:
ο Cough is rare β no interference with bradykinin and other ACE
substrates
ο Complete inhibition of AT1 β alternative remains with ACEs
ο Result in indirect activation of AT2 β vasodilatation (additional benefit)
ο Clinical benefit of ARBs over ACEIs β not known
ο However, losartan decreases BP in hypertensive which is for long period (24
Hrs)
ο heart rate remains unchanged and cvs reflxes are not interfered
ο no significant effect in plasma lipid profile, insulin sensitivity and
carbohydrate tolerance etc
ο Mild uricosuric effect
33
34. ο Pharmacokinetic:
ο Absorption not affected by food but unlike ACEIs its bioavailability is low
ο High first pass metabolism
ο Carboxylated to active metabolite E3174
ο Highly bound to plasma protein
ο Do not enter brain
ο Adverse effects:
ο Foetopathic like ACEIs β not to be administered in pregnancy
ο Rare 1st
dose effect hypotension
ο Low dysgeusia and dry cough
ο Lower incidence of angioedema
ο Available as 25 and 50 mg tablets
34
35. ο Non selective: PropranololΒ (others: nadolol, timolol, pindolol, labetolol)
ο Cardioselective: MetoprololΒ (others: atenolol, esmolol, betaxolol)
ο All beta-blockers similar antihypertensive effects β irrespective of additional
properties
ο Reduction in CO but no change in BP initially but slowly
ο Adaptation by resistance vessels to chronically reduced CO β antihypertensive
action
ο Other mechanisms β decreased renin release from kidney (beta-1 mediated)
ο Reduced NA release and central sympathetic outflow reduction
ο Non-selective ones β reduction in g.f.r but not with selective ones
ο Drugs with intrinsic sympathomimetic activity may cause less reduction in HR
and CO Β
35
36. ο Advantages:
ο No postural hypotension
ο No salt and water retention
ο Low incidence of side effects
ο Low cost
ο Once a day regime
ο Preferred in young non-obese patients, prevention of sudden cardiac
death in post infarction patients and progression of CHF
ο Drawbacks (side effects):
ο Fatigue, lethargy (low CO?) β decreased work capacity
ο Loss of libido β impotence
ο Cognitive defects β forgetfulness
ο Difficult to stop suddenly
ο Therefore cardio-selective drugs are preferred now
36
37. ο Advantages of cardio-selective over non-selective:
ο In asthma
ο In diabetes mellitus
ο In peripheral vascular disease
ο Current status:
ο JNC 7 recommends - 1st
line of antihypertensive along with
diuretics and ACEIs
ο Preferred in young non-obese hypertensive
ο Angina pectoris and post angina patients
ο Post MI patients β useful in preventing mortality
ο In old persons, carvedilol β vasodilatory action can be given
37
38. ο Non selective alpha blockers are not used in chronic essential
hypertension (phenoxybenzamine, phentolamine), only used
sometimes as in phaechromocytoma
ο Specific alpha-1 blockers like prazosin, terazosin and
doxazosine are used
ο PRAZOSIN is the prototype of the alpha-blockers
ο Reduction in t.p.r and mean BP β also reduction in venomotor
tone and pooling of blood β reduction in CO
ο Does not produce tachycardia as presynaptic auto (alpha-2)
receptors are not inhibited β autoregulation of NA release
remains intact
38
39. ο Adverse effects:
ο Prazosin causes postural hypotension β start 0.5 mg at bed time with
increasing dose and upto 10 mg daily
ο Fluid retention in monotherapy
ο Headache, dry mouth, weakness, dry mouth, blurred vision, rash,
drowsiness and failure of ejaculation in males
ο Current status:
ο Several advantages β improvement of carbohydrate metabolism β
diabetics, lowers LDL and increases HDL, symptomatic improvement in
BHP
ο But not used as first line agent, used in addition with other conventional
drugs which are failing β diuretic or beta blocker
ο Doses: Available as 0.5 mg, 1 mg, 2.5 mg, 5 mg etc. dose:1-4 mg thrice
daily (Minipress/Prazopress)
39
41. ο Three types Ca+ channels in smooth muscles β Voltage sensitive, receptor
operated and leak channel
ο Voltage sensitive are again 3 types β L-Type, T-Type and N-Type
ο Normally, L-Type of channels admit Ca+ and causes depolarization β
excitation-contraction coupling through phosphorylation of myosin light
chain β contraction of vascular smooth muscle β elevation of BP
ο CCBs block L-Type channel:
ο Smooth Muscle relaxation
ο Negative chronotropic, ionotropic and chronotropic effects in heart
ο DHPs have highest smooth muscle relaxation and vasodilator action
followed by verapamil and diltiazem
ο Other actions: DHPs have diuretic action
41
42. ο Advantages:
ο Unlike diuretics no adverse metabolic effects but mild
adverse effects like β dizziness, fatigue etc.
ο Do not compromise haemodynamics β no impairment of
work capacity
ο No sedation or CNS effect
ο Can be given to asthma, angina and PVD patients
ο No renal and male sexual function impairment
ο No adverse fetal effects and can be given in pregnancy
ο Minimal effect on quality of life
42
43. ο As per JNC 7 CCBs are not 1st
line of antihypertensive unless
indicated β ACEI/diuretics/beta blockers
ο However its been used as 1st
line by many because of excellent
tolerability and high efficacy
ο Preferred in elderly and prevents stroke
ο CCBs are effective in low Renin hypertension
ο They are next to ACE inhibitors in inhibition of albuminuria and
prevention of diabetic nephropathy
ο Immediate acting Nifedipine is not encouraged anymore
43
44. ο Contraindications:
ο Unstable angina
ο Heart failure
ο Hypotension
ο Post infarct cases
ο Severe aortic stenosis
ο Preparation and dosage:
ο Amlodipine β 2.5, 5 and 10 mg tablets (5-10 mg OD) β
Stamlo, Amlopres, Amlopin etc.
ο Nimodipine β 30 mg tab and 10 mg/50 ml injection β
Vasotop, Nimodip, Nimotide etc.
44
45. ο Directly acting vasodilator
ο MOA: hydralazine molecules combine with receptors in the endothelium of arterioles
β NO release β relaxation of vascular smooth muscle β fall in BP
ο Subsequenly fall in BP β stimulation of adrenergic system leading to
ο Cardiac stimulation producing palpitation and rise in CO even in IHD and
patients β anginal attack
ο Tachycardia
ο Increased Renin secretion β Na+ retention
ο These effects are countered by administration of beta blockers and diuretics
ο However many do not agree to this theory
ο Uses: 1) Moderate hypertension when 1st
line fails β with beta-blockers and diuretics
2) Hypertension in Pregnancy, Dose 25-50 mg OD
45
46. ο Powerful vasodilator, mainly 2 major uses β antihypertensive and alopecia
ο Prodrug and converted to an active metabolite which acts by
hyperpolarization of smooth muscles and thereby relaxation of SM β leading
to hydralazine like effects
ο Rarely indicated in hypertension especially in life threatening ones
ο More often in alopecia to promote hair growth
ο Orally not used any more
ο Topically as 2-5% lotion/gel and takes months to get effects
ο MOA of hair growth:
ο Enhanced microcirculation around hair follicles and also by direct stimulation of
follicles
ο Alteration of androgen effect of hair follicles
46
47. ο Rapidly and consistently acting vasodilator
ο Relaxes both resistance and capacitance vessels and reduces t.p.r and CO
(decrease in venous return)
ο Unlike hydralazine it produces decrease in cardiac work and no reflex
tachycardia.
ο Improves ventricular function in heart failure by reducing preload
ο MOA: RBCs convert nitroprusside to NO β relaxation also by non-
enzymatically to NO by glutathione
ο Uses: Hypertensive Emergencies, 50 mg is added to 500 ml of
saline/glucose and infused slowly with 0.02 mg/min initially and later on
titrated with response (wrap with black paper)
ο Adverse effects: All are due release of cyanides (thiocyanate) β palpitation,
pain abdomen, disorientation, psychosis, weakness and lactic acidosis.
47
48. ο Alpha-Methyldopa: a prodrug
ο Precursor of Dopamine and NA
ο MOA: Converted to alpha methyl noradrenaline which acts on alpha-2
receptors in brain and causes inhibition of adrenergic discharge in
medulla β fall in PVR and fall in BP
ο Various adverse effects β cognitive impairement, postural hypotension,
positive coomb`s test etc. β Not used therapeutically now except in
Hypertension during pregnancy
ο Clonidine: Imidazoline derivative, partial agonist of central alpha-2 receptor
ο Not frequently used now because of tolerance and withdrawal
hypertension
ο Read it yourself
48
50. CATEGORIES RISK FACTORS
BP Systolic Diastolic
Normal >120 <80
Prehypertension 120-139 80-89
Stage1 149-159 90-99
Stage2 >160 >100
1. Age above 55 and 65 in
Men and Woman
respectively
2. Family History
3. Smoking
4. DM and Dyslipidemia
5. Hypertension
6. Obesity
7. Microalbuminuria
50
53. ο Stage I:
ο Start with a single most appropriate drug with a low dose.
Preferably start with Thiazides. Others like beta-blockers, CCBs,
ARBs and ACE inhibitors may also be considered. CCB β in case of
elderly and stroke prevention. If required increase the dose
moderately
ο Partial response or no response β add from another group of
drug, but remember it should be a low dose combination
ο If not controlled β change to another low dose combination
ο In case of side effects lower the dose or substitute with other
group
ο Stage 2: Start with 2 drug combination β one should be diuretic
53
54. ο In clinical practice a large number of patients require
combination therapy β the combination should be rational and
from different patterns of haemodynamic effects
ο Sympathetic inhibitors (not beta-blockers) and vasodilators +
diuretics
ο Diuretics, CCBs, ACE inhibitors and vasodilators + beta blockers
(blocks renin release)
ο Hydralazine and CCBs + beta-blockers (tachycardia countered)
ο ACE inhibitors + diuretics
ο 3 (three) Drug combinations: CCB+ACE/ARB+diuretic;
CCB+Beta blocker+ diuretic; ACEI/ARB+ beta blocker+diuretic
54
55. ο Never combine:
ο Alpha or beta blocker and clonidine - antagonism
ο Nifedepine and diuretic synergism
ο Hydralazine with DHP or prazosin β same type of action
ο Diltiazem and verapamil with beta blocker β bradycardia
ο Methyldopa and clonidine
ο Hypertension and pregnancy:
ο No drug is safe in pregnancy
ο Avoid diuretics, propranolol, ACE inhibitors, Sodium nitroprusside
etc
ο Safer drugs: Hydralazine, Methyldopa, cardioselective beta
blockers and prazosin
55
56. ο Cerebrovascular accident or head injury with high BP
ο Left ventricular failure with pulmonary edema due to hypertension
ο Hypertensive encephalopathy
ο Angina or MI with raised BP
ο Acute renal failure with high BP
ο Eclampsia
ο Pheochromocytoma, cheese reaction and clonidine withdrawal
ο Drugs:
ο Sodium Nitroprusside (20-300 mcg/min) β dose titration and monitoring
ο GTN (5-20 mcg/min) β cardiac surgery, LVF, MI and angina
ο Esmolol (0.5 mg/kg bolus) and 50-200mcg/kg/min - useful in reducing cardiac
work
ο Phentolamine β pheochromocytoma, cheese reaction nd clonidine withdrawal
(5-10 mg IV)
56
Baroreflexes are responsible for minute to minute regulation of BP. Central sympathetic neurones in vasomotor area are tonically active. When there is stretch in the vessel wall brought about by rise in pressure, baroreceptor stimulation occurs and inhibits sympathetic discharge. On the other hand reduction in stretch, increases baroreceptor activity. Therefore, there will be increase in PVR (constriction of arterioles), and increase in CO (increase in venous return due to constriction of capacitance venules and direct stimulation of heart β thereby restoring normal blood pressure. Acts in vasodilators and shock.
Inhibition of insulin release due to K+ depletion β ppt of diabetes
a type of ventricular tachycardia with a spiral-like appearance (&quot;twisting of the points&quot;) and complexes that at first look positive and then negative on an electrocardiogram. It is precipitated by a long Q-T interval, which often is induced by drugs (quinidine, procainamide, or disopyramide) but which may be the result of hypokalemia, hypomagnesemia, or profound bradycardia. The first line of treatment is IV magnesium sulfate, as well as defibrillation if the patient is unstable
RAS is important in case of normal physiological maintainance of homeostasis. RAS plays an important role in development of hypertension. In most of the cases of hypertension PRA is seen to be raised. The long term effects of persistenly active PRA leads to cardiac hypertrophy (ventricular) and remodelling and also coronary artery hypertrophy and remodelling. Therefore by blocking of the hypertension can be controlled by blocking of ACE practically in most of the hypertensive cases.
ACE inhibitors have many indications apart from the hypertension which will be talked when particular diseases are talked, For you now you have to remember is that what are the they are the first line of agent now in most of the cases of hypertension specially in young person and persons with ventricular hypertrophy. In practice they are used as first line of agent as monotherapy or in combination with diuretics and beta-blockers. The advantages of ACEIs are
itogen-activated protein (MAP) kinases(ECΒ 2.7.11.24) areΒ serine/threonine-specific protein kinasesΒ that respond to extracellular stimuli (mitogens,Β osmotic stress,Β heat shockandΒ proinflammatory cytokines) and regulate various cellular activities, such asΒ gene expression,Β mitosis,Β differentiation, proliferation, and cell survival/apoptosis.[1