Hypertension

1
Hypertension

• Presented by
• Maha Islami
• Pharm.D.candidate
• Supervised by
• Prof.Osama M .Ibrahim
• Professor of clinical pharmacy

2
outlines

• Definition .
• Classification .
• Etiology .
• Complication .
• Diagnosis .
• Treatment .

3
What is blood pressure?

• Arterial BP co x PVR
• co HR x SV (blood out flow after-load
  systolic BP) .
• pVR resistance of arterioles
  resistance to blood flow pre-load
  diastolic BP.

4
Classification of BP
DBP mmHg SBP mmHg category
lt80 lt120 Normal
Or 80 - 89 120 - 139 prehypertension
Or 90 -99 140 -159 Stage 1 HTN
Or gt100 gt160 Stage 2 HTN
5
Isolated systolic HTN

• a systolic BP of gt 140 mm Hg and diastolic BP lt
  90 mm Hg and staged .
• Ex BP 170/82 mmHg is stage 2 isolated systolic
  HTN.
• Treatment chlorthalidone .

6
Classification of HTN
Secondary HTN Primary (essential) HTN
There is specific cause No specific cause
Accounts for about 5 of cases of HTN Accounts for about 95 of cases of HTN
Usually develops between the ages of 30 and 50 years old Usually develops at the age of 35 years old
curable chronic
7
Etiology of primary HTN

• Primary HTN may be affected by number of
  factors
• Age .
• Genetics .
• Body weight .
• Stress (mental and physical stress causes
  transient increase in BP ) .
• Smoking .
• Sodium intake .
• Sympathetic NS hyper-reactivity .
• Renin-angiotensin system hyper-reactivity .

8
Etiology of secondary HTN

• Renal diseases
• Renal artery stenosis.
• Pyelonephritis.
• Polycystic kidneys.
• 2) Endocrinal disease
• Cushings disease.
• Pheochromocytoma.
• Conns disease.
• Hyperthyrodism.

9
Etiology of secondary HTN cont.

• 3) Drug induced
• a)Oral contraceptives.
• b)corticosteroids.
• c)NSAIDs.
• d)cyclosporine.
• e) erythropoietin.
• f) venlafaxine.
• 4) pregnancy
• Preclampsia(the development of HTN,albuminuria
  and edema between the 20th week of pregnancy and
  the end of the first week postpartum).

10
Complications

• Cardiovascular complication
• 1- angina. 2-heart failure. 3-aneurysms.
• b) Cerebral complicaions
• 1-cerebral hemorrhage.
• 2- hypertensive encephalopathy.
• c) Renal failure due to arteriolar
  nephrosclerosis.
• d) Retinal hemorrhage.

11
Diagnostic studies

• 1-urin analysis
• Increase Urinary excretion of catecholamines or
  its metabolites (VMA) confirms pheochromocytoma.
• Presence of hematuria , proteinuria and casts
  suggests primary renal disease.
• 2- blood analysis
• Increase BUN and creatinine suggest renal
  disease.
• Hypokalemia suggests primary hyperaldosteronism
  or cushings syndrome.
• Increase serum cortisol confirms cushings
  syndrome.

12
Diagnostic studies cont.

• 3- ECG
• may reveal left ventricular hypertrophy or
  ischemia .
• 4- CT scane or MRI
• may be done to confirm the diagnosis of
  secondary or complicated HTN .

13
Treatment

• BP GOAL lt140/90 mm Hg .
• lt130/80 mm Hg if DM or renal
  disease.
• More than 2/3 of hypertensive patients cant be
  controlled on one drug and will require 2 or more
  agents from different classes.

14
Algorithm for Treatment of Hypertension
Lifestyle Modifications
Not at Goal Blood Pressure (lt140/90 mmHg)
(lt130/80 mmHg for those with diabetes or chronic
kidney disease)
Initial Drug Choices
15
Lifestyle modification
Average BP reduction range modification
5-20 mm Hg /10 kg Weight reduction
8-14 mm Hg DASH diet
2-8 mm Hg Na restriction
4-9 mm Hg Physical activity
16
Ischemic heart disease

• BBs are DOC due to ? HR ( ? of MO2).
• If BBs are contraindicated such as high degree AV
  blook , sick sinus syndrome give CCB .
• Treatment include smoking cessation , ttt DM ,
  Lipid lowering , antiplatlets , wt reduction.
• If BP is not controlled with BB alone, add CCB
  (dihydropyridine is preferred for combination )
  DHP CCB ? total peripheral resistance but NDHP
  CCB will also ? HR more if added to BB sever
  bradycardia or heart blook may occur.
• If BP is still not controlled on BB CCB , add
  nitrate.

17
Heart failure
treatment stages
ACEI (? Mortality ) and thiazide diuretics have been suggested to prevent dz progression Stage A High risk , no symptoms or LV dysfunction
ACEI BB are recommended Stage B Reduced LV function , EFlt 40 but asymptomatic
ACEI , BB , aldosterone antagonist loop diuretics digoxin. Stage C Manifest LV dysfunction , overt symptoms
Pacemaker , mechanical assist devices or transplantation in addition to ttt included in stage C Stage D Critically ill pts
18
Diabetes /HTN

• The coexistence of HTN in diabetes is
  particularly pernicious b/c of the strong linkage
  of the two condition with all ( CVD , Stroke ,
  renal dz ,and retinopathy).
• American Diabetics Association(ADA) state that BP
  goal in DM is 130/80 mm Hg or lower.
• Treatment many agent are used (ACEI , BB , CCB ,
  Diuretics)difficult to specify one b/c most
  diabetic pts require 2 or more drugs.
• ACEI is important component to control BP in
  diabetic pts can be used alone or combined with
  other agents esp.diuretic.

19
....Diabetes /HTN cont

• The ADA has recommended ACEI for diabetics pts
  gt55 years at high risk for CVD and BBs for those
  with known CAD.
• The ADA recommended both ACEI and ARB for use in
  type 2 diabetic pts with CKD b/c these agents
  delay the deterioration in GFR and worsening of
  albuminuria.

20
Chronic kidney disease

• Many studies found that ACEI or ARB are more
  effective in slowing progression of CKD.
• Goal BP lt130/80 mm Hg .
• ACEIdiuretic (loop is better)
• or ARB loop diuretic.
• central alpha -2 agonists as clonidine appear
  to the safest in dialysis population.
• Transdermal clonidine up to 1.2 mg/day as
  monotherapy in one short term study was
  successful .

21
stroke

• The management of BP during an acute stroke
  remain controversial b/c BP is high immediately
  post stroke period as a compensatory physiologic
  response to improve cerebral perfusion . If you
  reduce BP may lead to neurologic deterioration .
• American Stroke Association has a guideline
  SBPgt220 mm Hg or DBP gt120-140 mmHg ? BP by approx
  10-15 and monitor for neurologic deterioration.
• If DBPgt140 mm Hg give IV nitropusid carefully to
  ? BP by 10-15 .
• BP affect the use of thrombolytic agents in
  ischemic stroke .SBPgt185mm Hg or DBPgt110 mm Hg
  is contraindication to use tPA within first 3h of
  attack, should ?BP first to prevent intracerebral
  bleeding.

22
Black people

• HTN is more common , more severe , develop at
  earlier age .
• The pathogenesis of HTN in different racial
  subgroups may be due to contribution factors such
  as salt , stress , cv reactivity , hormonal
  system and socioeconomic condition .
• CCB or thiazide is effective in these people.

23
Left ventricular hypertrophy

• Most antihypertensive agents produces LVH
  regression .
• New trend
• the most consistent reduction in LV mass was
  achieved with ACEI.
• the intermediate benefits with diuretics and CCB
  .
• the least reduction with BB .
• Significant LV mass reduction was also achieved
  with Losartan .

24
HTN in older people

• With age SBP continue to rise , DBP rises until
  age of 55 then it decreases due to central
  arterial stiffness.(ISH).
• Increase in age ------- postural hypotension .
• Geriatric gt 65 yo the preferred agent is CCB .

25
Orthostatic hypotension

• Present when there is a supine to standing BP ?gt
  20 mm Hg systolic or gt 10 mm Hg diastolic.
• Causes
• Sever volume depletion , baroreflex dysfunction ,
  autonomic insufficiency.
• venodilator such as alpha blockers , alpha-beta
  blockers , and nitrates may further aggravate
  orthostatic hypotension .

26
Urinary Outflow Obstruction (BPH)

• Use alpha 1 blockers such as terazosin ,
  doxazosin , or prazosin .
• They indirectly dilate prostatic and urinary
  sphincter smooth muscle and also lower BP .
• Precautions
• 1- first dose phenmenon (a syncopal epiaode
  occur 30-90 min of the first dose .
• 2- palpitation sweating to minimize this effect
  the first dose should be limited to 1 mg of each
  agent given at bedtime.

27
treatment of chronic HTN in pregnancy
comments agents
Preferred based on long term follow-up studied supporting safety methyldopa
Reports of intrauterine growth retardation (atenolol) Generally safe BBs
Increasingly preferred to methyldopa due to reduced SE labetalol
Limited data clonidine
Limited data CCB
Not first line agents (probably safe ) Diuretics
Contraindicated (reported fetal toxicity and death) ACEIs , ARBs
28
HTN during lactation

• All antihypertensive agents are excreted into
  human milk.
• In mother with stage 1 HTN who wish to breast
  feed for a few months , it might be prudent to
  withhold antihypertensive with close monitoring
  of BP .resume drug after d/c of breast feeding .
• No short term SE have been reported from exposure
  to methyldopa .
• Propranolol Labetalol are preferred if BB is
  indicated .
• Avoided ACEI ARB .
• Diuretic may ? milk volume .

29
Renal transplantation

• HTN is a relatively common occurence in organ
  transplantation.
• In kidney allograft HTN prevalence approx 65.
• Mechanism
• vasoconstriction and long term vascular
  structural changes caused by chronic
  immunosuppressive such as cyclosporine ,
  Tacrolimus and corticosteroid .
• the high risk of graft occlusion and CV events
  has suggested that BP should be lowered to 130/80
  mm Hg or less.
• No particular class is superior , combination
  agent is necessary.
• Monitor K and Src particularly when ACEI or ARB
  are used.

30
Renal transplantation cont.

• In practice I see CCB is effective in HTN in
  transplant.
• National kidney foundation Guidelines
• most transplant centers use dihydropyridine CCB
  for initial therapy , since these agents dilate
  the afferent arteriole, therapy ameliorating
  vasoconstricton afferent arteriole induced by
  calcineurin inhibitors (cyclosporin and
  tacrolimus).
• a recent randomized study comparing nifedipine
  and lisinopril demonstrated improved kidney
  outcomes (lower creatinine and improved GFR at 2
  years ) with use of nifedipine.

31
Hypertensive emergency

• Characterized by sever elevation in BP gt180/120
  mm Hg complicated by evidence of impending or
  progressive target organ damage .
• Target organ damage
• Heart LVH , angina or MI , HF .
• Brain stroke or TIA , retinopathy .
• Kidney GFR , chronic kidney disease.
• Pts must be admitted to ICU for BP monitoring and
  administration IV antihypertensive agent .

32
Hypertensive emergency cont.

• Initial goal is to reduce BP no more than 25
  within minutes to 1 hr, then if stable, to
  160/110 mm Hg within the next 2-6 hrs(avoid
  excessive fall in BP ---to avoid precipitation of
  renal , cerebral or coronary ischemia. If the pts
  tolerated this BP and clinically stable , further
  gradual reduction toward a normal BP within the
  next 24-48 hrs .

33
Parental drugs for treatment of hypertensive
emerencies
33
Special indication Onset of action Dose Drug
Most use Caution with high ICP or azotemia vasodilators
Most use Caution with high ICP or azotemia immediate o.25-10 µg/kg/min as IV infusion Na nitroprusside
Coronary ischemia 2-5 min 5-100 µg/min as IV infusion nitroglycerin
eclampsia 10-20 min IV 20-30 min IM 10-20 mg IV 10-40 mg IM Hydralazine hydrochloride
Adrenergic inhibitor
Most use except acute HF 5-10 min 20-80 mg IV bolus every 10 min 0.5-2 mg/min IV infusion Labetalol hydrochloride
Aortic dissection, Perioperative 1-2 min 250-500 µ/kg/min IV bolus then 50-100 µg/kg min by infusion Esmolol hydrochloride
Catecholamine excess 1-2 min 5-15 mg IV bolus phentolamine
34
Hypertensive urgency

• Severe elevation of BP without target organ
  damage . E.g., upper level of stage 2 HTN with
  severe headache , SOB , epistaxis or severe
  anxiety.
• Either non compliant or inadequately treatment .
• Treatment
• oral , short acting agents such as captopril ,
  labetalol , or clonidine followed by several hrs
  of observation at ED. If stable , reinstitute
  previous medications , combination .

35
Diuretics

• 1 K sparing diuretics
• weak when used alone , combined with Thiaz/ loop
  to prevent ? K .
• Avoided in ARF .
• 2-thiaz diuretics
• initial therapy is more effective than loop .
• Efficacy _at_ Cr CL gt 30 ml/min .
• Low dose 12.5 mg HCTZ , not gt 50 mg .
• 3- loop diuretics
• Indicated loss of THIAZ effect Cr CL lt 30
  ml/min.
• Expensive than THIAZ.

36
BBs

• Three pharmacodynamic diffrences
• 1- cardioselectivity affinity for B1 than B2
  (Atenolol , metoprolol , bisoprolol acebutolol)
  dose dependent phenomenon , effect is lost at
  higher doses .
• 2- intrinsic sympathomimetic activity (ISA)
  these agents release catecholamines to maintains
  normal basal sympathetic tone . Not safer to use
  in HF , sinus bradycardia . (acebutolol ,
  carteolol , penbutolol , pindolol ) .

37
BBs cont.

• 3- membrane-stabilizing action (MSA) (or
  quinidine like effect ) on cardiac cell if large
  enough doses are given (antidysrhythmic effect )
  ,the dose exceeds that used in HTN.
• all BBs share this property .
• Only (propranolol , sotolol , acebutolol )
  indicated for arrythmias.
• Precautions
• no BB is totally safe in pts with bronchospasm .
• abrupt cessation may produce unstable angina ,
  MI , taper dose over 14 days before d/c the drug .

38
conclusion

• HTN is not a disease but an important risk factor
  for CV and cerebrovascular disease.
• Education of the pt is necessary on longterm
  importance of treatment and lifestyle changes.
• There is no ideal antihypertensive drug that
  reduces BP without causing SE .
• It is imortant to match the antihypertensive to
  the patients other coexisting disease states to
  gain the most benefit .

39
references

• Daniel H.cooper. The Washington Manual Of Medical
  Therapeutics. Lippincolt Williams and Wilkins ,
  Baltimore , MD . 32nd ED , 2008 chapter 4 ,
  page 72-91 .
• http//www.emedicinehealth.com/high_blood_pressure
  /article_em.htm.
• Richard A Helms PharmD, BCNSP David J Quan
  PharmD. Text Book of Therapeutics. Disease and
  Drug Management. LWW,
• 8th Edition ( 2005 ), Chapter 20,
  hypertension pg 565 - 485.