Pharmacotherapy of hypertension

1
Pharmacotherapy of hypertension
2
Hypertension
according to WHO and Joint National
Committee, hypertension is defined as SBPgt140 and
DBPgt90
3
Blood pressure

• Its the lateral pressure exerted by the flowing
  column of blood
• On the vessel walls.
• Normal value 120/80 mmHg

HYPERTENSION IS NOT A DISEASE, BUT ITS AN
IMPORTANT RISK FACTOR FOR MANY UNDERLYING DISEASES
4
Types of hypertension

• Essential hypertension ( primary )
• -patients with arterial hypertension no
  definable cause
• Secondary hypertension
• -Individuals in whom a specific structural
  organ or a genetic defect is responsible for
  hypertension

5
Essential hypertension

• Factors causing are
• 1.Genetic factors
• 2.Foetal factors
• 3.Environmental factors
• (Risk factors)
• -Smoking
• -Alcohol consumption
• -Na intake
• -Stress
• Obesity leads to
• Insulin resistance
• -Hyper insulinemia causes vaso
  constriction
• -Modified ion transport mechanisms

6
Secondary hypertension

• Causes-
• 80 of the cases are renal
• -Diabetic nephropathy
• -Chronic glomerulonephritis
• -Renovascular disease
• Endocrine causes
  -cushings syndrome
• -Pheochromocytoma
• -Acromegaly
• -Cohns syndrome

7

• CVS
• -Coarctation of aorta
• Drug effects
• -oral contraceptive pills
• -Steroids
  -vasopressins
  
  -MAO- inhibitor

8
CLINICAL ASPECTS OF HYPERTENSION
APPROACH TO THE PATIENT
When hypertension is suspected , BP should be
Measured at least twice during two separate
Examinations after initial screening
9

CATOGORY
SBP
DBP
OPTMAL lt120 lt80
NORMAL lt130 lt85
HIGH NORMAL 130-139 85-89
HYPERTENSION STAGE 1 140-159 90-99
HYPERTENSION STAGE 2 160-179 100-109
HYPERTENSION STAGE 3 gt180 gt110
ISOLATED HYPERTENSION gt140 lt90
10
Signs symptoms

• Most patients have no signs symptoms .
• When symptoms are present they fall into three
  categories
• 1 . symptoms related to elevated BP
• 2 . symptoms related to hypertensive vascular
  disease
• 3 . symptoms related to underlying disease,
  in the case of secondary hypertension

11
1. Symptoms related to elevated BP

• Headache localised to occipital region
• Dizziness
• Easy fatigability
• Palpitations

12
2 . symptoms related to vascular disease

• Epistaxis
• Blurring of vision
• Episodes of dizziness
• Angina pectoris
• Dyspnoea due to cardiac failure

13
3 . symptoms related to underlying disease

• Polyuria, polydypsia, muscle weeknes - in
  patients with primary aldosteronism
• Weight gain in patients with Cushings syndrome
• Episodic headache, palpitations, postural
  dizziness in patients with pheochromocytoma

14
Physical examination

• General appearance
• Fundoscopic findings
• Examination of heart
• Abdominal examination
• Compare BP and pulse in two upper extremeties and
  in supine and standing positions

15
Management

• I- non pharmacological therapy
• If SBP lt 140 mmhg
• DBP lt 90 mm hg
• It includes
• wt reduction , BMI lt25 kg /m2
• Low fat saturated fat diet
• Low sodium diet lt 6 gms daily
• Limited alcohol consumption
• Dynamic exercise
• Increased fruit vegetable consumption
• Decreased smoking
• II- drug therapy

16

Lifestyle Modifications

• Reduce weight to normal BMI (lt25kg/m2) 5-20
  mmHg/10kg loss
• DASH eating plan 8-14 mmHg
• Dietary sodium reduction 2-8 mmHg
• Increase physical activity 4-9 mmHg
• Reduce alcohol consumption 2- 4 mmHg

17

DASH Diet
Dietary Approaches to Stop Hypertension

• Fruits,
• vegetables, low fat dairy
• foods, and reduced
• sodium intake
• Includes whole grains,
• poultry, fish, nuts
• Reduced amounts of red
• meat, sugar, total and
• saturated fat, and
• cholesterol

18
Anti hypertensive drugs
19

• Diuretics
• Thiazides
• Hydrochlorothiazide, chlorthalidone
• Indapamide
• High ceiling diuretics
• Furosemide
• K sparing diuretics
• Spironolactone, amiloride
• ACE inhibitors
• Captopril , enalapril, ramipril , lisinopril,
  perindopril , fosinopril
• Angiotensin receptor blockers
• ( at 1 blockers )
• losartan , valsartan , irbesartan , telmisartan

20

• 4. Calcium channel blockers
• Verapamil , diltiazem , nifedipine , amlodipine
  , felodipine , nitrendipine
• 5. ?ß adrenergic blockers
• Labetelol , carvedilol
• 6. ? adrenergic blockers
• Prazosin , terazosin , doxazosin , phentolamine ,
  phenoxybenzamine
• 7. Central sympatholytics
• Clonidine , methyl dopa
• 8. Vasodilators
• Arteriolar
• Hydralazine , minoxidil , diazoxide
• Arteriolar plus venous
• Sodium nitroprusside

21

22
DIURETICS

23
Classification

• 1. Thiazide diuretics
• - Hydrochlorthiazide
• -Chlorthalidone
• -Indapamide
• 2. High ceiling diuretics
• -Furosemide
• 3. K sparing
• -spironolactone
• -Amiloride

24
(No Transcript)
25
Diuretics (water pills)

• Diuretics are the drugs that have the ability to
  increase urinary excretion of salt and water by
  acting over different parts of nephron.
• Alcohol, caffeine, digoxin, theophylline water
  intake increase urine output. But these are not
  classical diuretics, they are called
  physiological diuretics.
• Getting rid of excess salt and fluid helps lower
  blood pressure and can make it easier for your
  heart to pump.
• Diuretics may be used to treat a number of
  heart-related conditions, including high blood
  pressure, heart failure, kidney and liver
  problems, and glaucoma.

26
Classification of diuretics according to
efficacy/potency

• High efficacy/high ceiling diuretics
• Prevents 15-25 reabsorption of salt water,
  e.g Loop diuretics
• Moderate efficacy diuretics
• Prevents 5-10 reabsorption of salt water, e.g
  Thiazide diuretics
• Low efficacy diuretics
• Prevents 5 (maximum) reabsorption of salt
  water, e.g K sparing diuretics, Osmotic
  diuretics, Carbonic anhydrase inhibitors.

27
?. Thiazide diuretics

• Thiazides are the most widely used of the
  diuretic drugs. They are called celling
  diuretics because increasing the dose above
  normal does not promote a further diuretic
  response.
• Mechanism of action of thiazide In the distal
  convoluted tubule thiazides cause secretion of
  water?Decrease blood volume? Decrease BP.
• In prolonged use may
• cause vasodilation ?
• Decrease peripheral
• resistance ?
• Decrease BP

28
(No Transcript)
29
Thiazides - Pharmacokinetics

• All thiazides are secreted by the organic acid
  secretory system in the proximal tubule and
  compete with the secretion of uric acid by that
  system. As a result, thiazide use may decrease
  uric acid secretion and elevate serum uric acid
  level.
• Not effective at low glomerular filtration rates.
• - Although hydrochlorothiazide is the most widely
  used diuretic for hypertension,
  chlorthalidone may be more effective because of
  its much longer half-life.

30
Clinical Indications of thiazide

• Hpertension They reduce blood pressure and
  associated risk of CVA/stroke and MI in
  hypertension
• - They should be considered first-line therapy in
  hypertension (effective, safe and cheap)
• Heart failure
• Nephrolithiasis due to idiopathic hypercalciuria
• - Condition characterized by recurrent stone
  formation in the kidneys due to excess calcium
  excretion
• - Thiazide diuretics used to prevent calcium loss
  and protect the kidneys
• Nephrogenic diabetes insipidus.
• Thiazides allow increased solute excretion in the
  urine, breaking the Polydipsia-Polyuria cycle.

31
ADVERSE EFFECTS OF THIAZIDES

• HYPOKALEMIA
• HYPONATREMIA
• DEHYDRATION (particularly in the elderly) leading
  to POSTURAL HYPOTENSION
• HYPERCALCEMIA
• HYPERGLYCEMIA possibly because of impaired
  insulin release secondary to hypokalemia.
• HYPERURICEMIA
• HYPERLIPIDEMIA
• HYPERSENSITIVITY - may manifest as interstitial
  nephritis, pancreatitis, rashes, blood dyscriasis
  (all very rare)
• METABOLIC ALKALOSIS due to increased sodium load
  at the distal convoluted tubule which stimulates
  the sodium/hydrogen exchanger to reabsorb sodium
  and excrete hydrogen
• IMPOTENCE

32
Dosage of thiazide
Contraindications Excessive use of any diuretic
is dangerous in patients with hepatic cirrhosis,
borderline renal failure, or heart failure
33
??. Loop diuretics

• furosemide and ethacrynic acid. bumetanide and
  torsemide are sulfonamide loop diuretics. They
  are called high celling diuretics
• The loop diuretics acts promptly, even among
  patients who have poor renal function or have not
  responded to thiazides or other diuretics.
• Mechanism of action
• Loop diuretics inhibit Sodium-Potassium-Chloride
  Transporter 2 (NKCC2), in the thick ascending
  limb of Henles loop.
• By inhibiting this transporter, the loop
  diuretics (TAL) reduce the reabsorption of NaCl
• It also diminish the lumen-positive potential
  that comes from K recycling. This positive
  potential normally drives divalent cation
  reabsorption in theTAL and by reducing this
  potential, loop diuretics cause an increase in
  Mg2 and Ca2 excretion.

34
(No Transcript)
35
LOOP DIURETICS - PHARMACOKINETICS

• Rapid GI absorption. Also given i.m. and i.v.
• Extensively protein bound in plasma
• Short half-lives in general

CLINICAL USES OF LOOP DIURETICS

• Edema due to congestive heart failure , nephrotic
  syndrome or cirrhosis
• Acute pulmonary edema Acute hypercalcemia
• Hyperkalemia, acute renal failure, and anion
  overdose.
• ADVERSE EFFECTS OF LOOP DIURETICS
• Hypokalemia, hyponatremia hypocalcemia (in
  contrast to thiazides)
• Dehydration and postural hypotension
• metabolic alkalosis
• hypercholesterolemia, hyperuricemia,
  hyperglycemia,
• Hypersensitivity
• OTOTOXICITY (especially if given by rapid IV
  bolus)

36
Typical dosages of loop diuretics
Contraindications Furosemide, bumetanide, and
torsemide may exhibit allergic cross-reactivity
in patients who are sensitive to other
sulfonamides, but this appears to be very rare
37
???. POTASSIUM-SPARING DIURETICS

• They act in the collecting tubule to inhibit Na
  reabsorption and K excretion.
• The major use of potassium-sparing agents is in
  the treatment of hypertension, most often in
  combination with a thiazide.
• Types
• - Aldosterone antagonist (spironolactone,
  eplerenone)
• - Na channel inhibitor (amiloride,
  triamterene).
• Spironolactone is a weak diuretic because most of
  the filtered Na is reabsorbed before reaching
  the CT.
• Aldosterone normally stimulates the
  Na/K- exchange sites of the collecting tubule

38
(No Transcript)
39
CLINICAL USES OF POTASSIUM- SPARING DIURETICS

• Hyperaldosteronism
• - Primary hypersecretion (Conns syndrome)
• - Secondary hyperaldosteronism (evoked by
  heart failure, hepatic cirrhosis, nephrotic
  syndrome).
• In combination with K loosing diuretics (loop
  thiazide) to prevent K excretion.
• Eplerenone can slow the progression of
  albuminuria in diabetic patients.
• Eplerenone has been found to reduce myocardial
  perfusion defects after myocardial infarction.

ADVERSE EFFECTS OF POTASSIUM-SPARING DIURETICS

1. Hyperkalemia
2. Hyperchloremic Metabolic Acidosis
3. Gynecomastia
4. Acute Renal Failure
5. Kidney Stones

40
Potassium-sparing diuretics and combination
preparations
Contraindications Potassium-sparing agents can
cause severe, even fatal, hyperkalemia in
susceptible patients. Patients with chronic renal
insufficiency are especially vulnerable and
should rarely be treated with these diuretics.
41
?V. Carbonic Anhydrase Inhibitors

• . Acetazolamide
• Mechanism of action
• H HCO3- ? H2CO3 Carbonic anhydrase_gt H2O
  CO2
• Accumulation of H in the lumen which impairs the
  transport action of Na/H exchanger
• The decreased ability to exchange Na for H in
  the presence of acetazolamide results in a mild
  diuresis.
• Additionally, HCO3 is retained in the lumen,
  with marked elevation in urinary pH. The loss of
  HCO3- causes a hyperchloremic metabolic acidosis
  and decreased diuretic efficacy following several
  days of therapy ( set-off).

42
(No Transcript)
43
CLINICAL USES OF CARBONIC ANHYDRASE INHIBITORS

• Glaucoma (most common indication)
• - The reduction of aqueous humor formation
  by carbonic anhydrase inhibitors decreases the
  intraocular pressure.
• Urinary Alkalinization
• Metabolic Alkalosis
• Acute Mountain Sickness Acetazolamide, a mild
  diuretic, works by stimulating the kidneys to
  secrete more bicarbonate in the urine, thereby
  acidifying the blood. This change in pH
  stimulates the respiratory center to increase the
  depth and frequency of respiration, thus speeding
  the natural acclimatization process. An

ADVERSE EFFECTS OF CARBONIC ANHYDRASE INHIBITORS

• Hyperchloremic Metabolic Acidosis
• Renal Stones
• Renal Potassium Wasting

CONTRAINDICATION - Hyperammonemia - Hepatic
encephalopathy in patients with cirrhosis.
44
Carbonic anhydrase inhibitors used orally in the
treatment of glaucoma
Changes in urinary electrolyte patterns and body
pH in response to diuretic drugs
45
V. Osmotic Diuretics (AQUARETICS)

• Hydrophilic chemical substances that are
  filtered through the glomerulus, such as mannitol
  and urea
• .
• Diuresis is due to their ability to carry water
  with them into the tubular fluid.
• M/A
• The presence of a non-reabsorbable solute such as
  mannitol prevents the normal absorption of water.
  As a result, urine volume increases.
• Osmotic diuretics used to maintain urine flow
  save the patient from dialysis e.g treatment for
  patients with increased intracranial
  intraocular pressure or acute renal failure due
  to shock, drug toxicities, and trauma.
• ADVERSE EFFECTS OF OSMOTIC DIURETICS
• - Extracellular Volume Expansion, Dehydration,
  Hyperkalemia, Hypernatremia, and Hyponatremia
  (When used in patients with severe renal
  impairment)

46
(No Transcript)
47
Class Adverse Side Effects Drug Interactions
Thiazide Hypokalemia Metabolic alkalosis Dehydration leading to hypotension Hyponatremia Hyperglycemia in diabetics Hypercholesterolemia hypertriglyceridemia Increased low-density lipoproteins Hyperuricemia (at low doses) Azotemia (in renal disease patients) hypokalemia potentiates digitalis toxicity non-steroidal anti-inflammatory drugs reduced diuretic efficacy beta-blockers potentiate hyperglycemia, hyperlipidemias corticosteroids enhance hypokalemia
Loop Hypokalemia Metabolic alkalosis Hypomagnesemia Hyperuricemia Dehydration leading to hypotension Dose-related hearing loss (ototoxicity) hypokalemia potentiates digitalis toxicity non-steroidal anti-inflammatory drugs reduced diuretic efficacy corticosteroids enhance hypokalemia aminoglycosides enhance ototoxicity, nephrotoxicity
K-sparing Hyperkalemia Metabolic acidosis Gynecomastia (aldosterone antagonists) Gastric problems including peptic ulcer ACE inhibitors potentiate hyperkalemia Non-steroidal anti-inflammatory drugs reduced diuretic efficacy
Carbonic anhydrase inhibitors Hypokalemia Metabolic acidosis
48
Central sympatholytics

• Clonidine
• Moderately potent antihypertensive
• High affinity and intrinsic activity for a2a
  subtype .

49
Mechanism
a2A RECEPTORS
CLONIDINE
IMIDIZOLINE RECEPTORS
50
METHYL DOPA

• Alpha methyl analouge of dopa
• Precursors of dopamine noradrenaline
• Alphamethyl noradrenaline (na) in the brain acts
  on central alpha 2 receptors to decrease efferent
  sympathetic activity
• Methyl dopa inhibits enzyme dopa decarboxylase
  and decreases production of na
• Inhibition of postural reflexes is mild

51
ADVERSE EFFECTS

• Sedation
• Lethargy
• Dryness of mouth
• Nasal stuffiness
• Headache
• Impotence
• Postural hypotension lesser than clonidene

52
Calcium channel blockers
53
MECHANISM OF ACTION
MEMBRANE POTENTIAL -40 mV

• MEMBRANE POTENTIAL DROPS TO -40mv
• Inward movement of ca2
• Depolarisation of smooth muscle
• Smooth muscle contraction
• So ccbs blocks ca2 entry and thus
• Cause smooth muscle relaxation

54
Classification

• Phenyl alkylamine verapamil
• Dihydropyridine nifedipine
• Benzothiazepine diltiazem

55
VERAPAMIL

• HAS SOME a ADRENERGIC BLOCKING ACTIVITY
• Cardiac effects (myocardial depression)
• DOSE 40 -160 mg TDS

56

• Adverse effects
• Nausea , constipation , bradycardia
• Flushing , headache ankle oedema
• Contraindications
• 2nd and 3rd degree heart block
• CHF
• Sick sinus
• Interactions
• Should not be given with ß blockers
• It increases plasma digoxin level
• Should not be used with other cardiac depressants

57
DILTIAZEM

• Less potent vasodilator than nifedipine
  verapamil

58
NIFEDIPINE

• Most potent vasodilator
• Direct depressent effect on heart requires higher
  dose
• It does not depress SA node or Av node condution
  .
• Adverse effects
• Nausea, hypotension ,palpitation , flushing,
  ankle edema , headache and drowsiness

59
uses

• Angina pectoris
• Cardiac arrhythmias
• Hypertrophic cardio-myopathy
• Premature labour

60
ADRENERGIC BLOCKERS IN ANTIHYPERTENSIVE THERAPY
61
MODE OF ACTION

• ?1 ACTIVATION CAUSES CARDIAC STIMULATION ,
  INCREASED HEART RATE , INCREASED FORCE
  INCREASED CONDUCTION VELOCITY . INCREASED RENIN
  RELEASE ALSO OCCURS gt ? BP
• Thus ß1 blockers produce an opposing action,
  there by reducing bp.
• ?lpha1 a2 causes constriction of blood vessels.
• And thus a blockers produces an opposing
  action ,thereby reducing the bp.

62
ß ADRENERGIC BLOCKERS

• MILD ANTI HYPERTENSIVES
• NON SELECTIVE
• PROPRANOLOL
• MECHANISM OF ACTION
• HEART - ? HEART RATE , FORCE OF CONTRACTION CO
• BLOOD VESSEL - TPR ?
• ? RENIN
• ? SYMPATHETIC OUTFLOW
• DRAWBACKS
• REBOUND HYPERTENSION, PRECIPITATES CHF ,
  BRADYCARDIA , WORSENS COPD

63
OTHER NON SELECTIVE DRUGS

• Pindolol
• Labetalol
• Carvedilol
• Pindolol has more bioavailabily than propranalol
  .

64
USES

• Angina pectoris
• M i
• Chf
• Thyrotoxicosis
• Pheochromocytoma
• Migraine

65
ß a BLOCKERS

• LABETALOL
• PHARMACOLOGICAL ACTION
• ?1 ß 2 a1
• ? SBP ? DBP
• DRAWBACK
• POSTURAL HYPOTENSION
• OTHER DRUG - CARVEDILOL

66
ACE-inhibitors
67
a ADRENERGIC BLOCKERS

• Selective - prazosin
• Pharmacological action
• Vasodilatation
• Drawbacks
• First dose effects may lead to Orthostatic
  hypotension , syncope (start with small dose)
• Nasal congestion
• Headache , palpitation, blurred vision
• Other drugs
• Terazosin
• Doxazosin

68

• Angiotensin converting enzyme inhibitors

69
Captopril

• Sulphydryl containig dipeptide
• Orally active
• Mechanism
• Competitive inhibition of ACE
• Decreased metabolism of bradykinin

70
(No Transcript)
71
Adverse effects

• Hypotension
• Hyperkalemia
• Cough
• Rashes , urticaria
• Acute renal failure
• Angio-oedema , feto- pathic
• Headache , dizziness and GI- problems

72
uses of ACE inhibitors

• CHF
• MI
• Diabetic nephropathy

73
Angiotensin antagonists(AT1 receptor
blockers)LosartanValsartanCandesartanIrbesart
anTelmisartan
74
Mechanism of action

• Competative antagonist of AT1
• Blockade of AT1 receptors
• Vasodilation
• Reduce secretion of vasopressin
• Reduce production secretion of aldosterone
• Leads to reduction of blood pressure

75
Advantages

• Alternative to ACE- inhibitors
• No cough no angioedema
• effective in portal hypertension due to
  cirrhosis

76
Vasodilators
77

• Arteriolar
• hydralazine / dihydralazine,
  minoxidil,diazoxide
• Arteriolarvenous
• - sodium nitroprusside

78
HYDRALAZINE / DIHYDRALAZINE

• First orally active antihypertensive drug to be
  marketed.
• Directly acting arteriolar vasodilator.
• Decrease total peripheral resistance (t.P.R),
  decreases
• Diastolic (dbp) than systolic (sbp)

79
(Mode of Action (MOA
? Ca 2

• Cause fall in intracellular calcium conc.
• Direct relaxation of arteriolar smooth muscle
  
• Arteriolar vasodilation.
• Partly endothelium dependent and involve
  generation of NO and cGMP.
• No action on coronary arteries.
• Hydralazine induced hypotension evokes reflex
  compensatory mechanisms (Sympathetic
  stimulation), so given with diuretics and beta
  blockers.

NO , cGMP
80
PHARMACOLOGICAL EFFECTS

• Decrease in B.P.
• No postural hypotension.
• Reduces B.P equally in supine and up right
  positions.

81
ADVERSE EFFECTS

• 2 types of adv effects-
• Extension of pharmocological effects of drug.
• Headache ,nausea, flushing, palpitation,
  tachycardia ,nasal stuffiness.
• Angina and ischaemia may be ppted.
• Due to immunological reaction.
• Drug induced systemic lupus erythematosis
  (SLE)-syndrome on prolonged use-common in females
  and slow acetylators.
• Serum sickness , hemolytic anaemia , vasculitis,
  rapidly progressive glomerulonephritis.

82
THERAPUTIC USES

• Not a 1st line drug in treatment of hypertension.
• Usually given in low doses along with other
  drugs.
• Oral dosage25-100mg twice daily.
• Used in patients with renal involvement.
• Used in pregnancy.
• Used parenterally in hypertensive emergencies.

83
MINOXIDIL K CHANNEL OPENERS

• Used for severe and drug resistant forms of
  hypertension.
• Moa
• Its a prodrug.
• Hepatic sulfotransferase
• Minoxidil ---------? minoxidil n-o sulfate
• Minoxidil sulfate activates the ATP modulated k
  channel ? k efflux in smooth muscles ?
  hyperpolarisation and smooth muscle relaxation

84
PHARMACOLOGICAL EFFECTS

• Arteriolar vasodilation.
• Blood flow to skin, skeletal muscles, GIT, heart,
  more than to CNS.
• Myocardial contractility (adrenergically
  mediated) and CO.

85
ADVERSE EFFECTS

• Fluid and salt retention.
• Cardiovascular effects.
• Hypertrichosis

86
THERAPEUTIC USES

• Treatment of severe hypertension (htn) , esp in
  patients with renal insufficiency.
• Use in alopecia topical application.

87
SODIUM NITROPRUSSIDE

• Rapidly and constantly acting vasodilator,used in
  short term control.
• Moa
• Its a nitrovasodilator.
• Release NO?activates guanylylcyclase cGMP
  pathway? vasodilation

NO
88
PHARMACOLOGICAL EFFECTS

• Arteriolar venous dilation.
• Myocardial work is reduced,
• ? oxygen demand, no ischaemia.
• 3. Its a non selective vasodilator , so
  regional distribution of blood flow affected. But
  renal blood flow (R.B.F) maintained.
• 4. Only moderate increase in heart rate.

89
PHARMACOKINETICS

• Iv route effective.
• Rapid onset of action-30 sec.
• Duration of action less.
• Decomposes in alkaline pH and exposure to light.

90
ADVERSE EFFECTS

• TOXICITY
• NITROPRUSSIDE ? CYANIDE/THIOCYANATE
• LEADS TO LACTIC ACIDOSIS.
• SIDE EFFECTS DUE TO VASODILATOR
  ACTION-PALPITATION, NERVOUSNESS,PERSPIRATION,PAIN
  IN ABDOMEN,WEAKNESS,DISORIENTATION.

91
THERAPEUTIC USES

• Used in hypertensive emergencies.
• To lower B.P in acute aortic dissection.
• To improve CO in CHF,in hypertensive patients.
• To induce controlled hypotension during
  anaesthesia.

92
Hypertension in pregenecy

• A sustained BP reading over 140/90 mmHg during
  pregnancy.
• 2 types-
• Pregnant woman with preexisting htn.
• Pregnancy induced htn-preeclampsia, eclampsia
  etc.

140 / 90 mmHg
93
Drugs unsafe in pregnancy

• Diuretics, ACE inhibitors, AT1 antagonists,
  reserpine,non selective ß blocker, sodium
  nitroprusside.

DRUGS SAFE IN PREGNANCY

• hydralazine, methyldopa, dihydropyridine CCBs,
  cardioselective ß blocker, prazosin clonidine.

94
Hypertensive emergencies and urgencies

• Emergency controlled reduction of bp over
  minutes.
• Urgency over hours.
• Indications-
• Hypertensive encephalopathy.
• Hypertensive acute LVF pulmonary edema.
• Unstable angina or MI with raised BP.
• Dissecting aortic aneurysm.
• Eclampsia.
• Hyprtensive episodes in pheochromocytoma, cheese
  reaction clonidine withdrawal.

95
Drugs used

• Parenteral drugs with controllable action used.
• Mean BP should be lowered by no more than 25
  over min or few hrs then gradually to not lower
  than 160/100 mmhg.
• Sodium nitroprusside-drug of choice.
• Need infusion pump constant monitoring.
• Glyceryl trinitrate-iv route,venodilator action.
• Esmolol-given as bolus followed by slow iv inj.
• Phentolamine-drug of choice for hyperadrenergic
  states.
• Diazoxide
• Hydralazine
• Labetalol
• Furosemide

96

• Hypertension in diabetics
• The presence of hypertension doubles the
  already elevated risk of heart disease in
  diabetics
• Increases the risk for strokes, retinal damage,
  and peripheral vascular disease
• Accelerates the progression of kidney disease
  in diabetics.
• At an early stage these problems can be treated
  by following diet, exercising, and taking
  medications as directed.
• At a later stage treatment it is often more
  difficult. For example, end-stage kidney disease
  may require dialysis, or heart disease may
  require bypass surgery.

97

• Current recommendations are to maintain a
  pressure below 130/90 in diabetics
• Treatment is also recommended if any signs of
  kidney damage are present
• If the blood pressure is elevated from the
  patients previous readings. For example, if the
  blood pressure has generally been 100/70 and then
  consistently becomes 120/80, treatment should be
  started
• Medications should be started to protect the
  kidneys in diabetics if microalbuminuria is found
  to be present

98

• Choosing medications
• ACE inhibitors are effective at the amount of
  microalbumin in urine and appears to be the most
  effective at reducing the progression of kidney
  disease.
• These drugs can also improve sensitivity to
  insulin and improve blood sugar and cholesterol
  levels.
• They also protect the heart from changes that
  cause congestive heart failure, another
  complication of hypertension.
• It is necessary to monitor blood work frequently
  for possible side effects of these medications.
• Some (but not all) calcium of channel blockers
  may also reduce microalbuminuria

99

• Another choice is the use alpha blockers.
• These also improve sensitivity to insulin with
  improvements in blood sugar and cholesterol.
• They reduce the size of the prostate, reducing
  the need for prostate surgery in men.
• It is necessary to increase the dosage of these
  medications slowly, otherwise dizziness is
  common.
• Caution , they may cause postural hypotension
  in diabetics who are already at risk of this due
  to autonomic neuropathy.
• Taking these medications at bed time.
• Diuretics (water pills) can increase sugar
  and cholesterol. These side effects can be
  reduced by using lower doses

100

• Beta-blockers can also increase blood sugar and
  cholesterol . another side-effect is that they
  can mask some of the earliest symptoms of a
  hypoglycemic reaction, increasing the risk of
  more serious reactions. Because of these
  problems, beta-blockers were avoided in the past
  for diabetics.
• Beta-blockers are now used more commonly  in
  diabetics due to their benefits in reducing the
  risk of heart attacks. They are generally used in
  people who have had a heart attack to reduce the
  risk of subsequent heart attacks.
• As both hypertension and diabetes increase the
  risk of heart disease, it is necessary to control
  other risk factors as well as possible. This
  includes avoiding tobacco and controlling
  cholesterol to maintain the LDL portion of the
  cholesterol below 100.