Anti-hypertensive Drugs II

Calcium Channel blockers CCBs)

CCBs: in Hypertension

CCBs: in Hypertension

Amlodipine, Felodipine, lercanidippine & SR of others
preferred for mild to moderate HT
Monotherapy or in combination
Long acting, Well tolerated, Fewer drug interaction
• Isolated systolic, elderly ∙ Stroke prevention
• Second to ACEI/ARBs in nephropathy protection
Avoid in MI
• Imm release nifedipine & short acting DHP not used for HT

Verapamil & diltiazem
short half life
more cardiac side effects
high drug interaction potential (> verapamil- CYP3A4 inhibitor)
Not first line anti-HT
• Clevidipine intravenous formulation only
t1/2 = 2 min rapid onset and offset
Metabolised by plasma esterases
Used in severe or peri-operative hypertension

• No triggering of compensatory mechanisms
• CO, HR is not increased
• No CNS effect- no sedation
• Can be used in patients with asthma, angina, PVD
• No effect on electrolytes, lipid, uric acid levels
• Do not impair renal perfusion- Used in nephropathy,
used in renal impairment ( metabolised in liver)
• No adverse effect on foetus

Arteriolar Dilators Arteriovenous Dilators
Hydralazine Sodium nitroprusside
Minoxidil
Diazoxide

Baroreceptor stimulation : Combined with diuretic And β1 blockers

Arterial Vasodilators

Hydralazine

SNS activation – baroreceptor mediated,
increased plasma renin : Tachycardia, fluid
retention -> Tolerance
Combined with diuretic and β1 blockers
• ‘Acetylation’ – slow and fast acetylators
palpitations, flushing, tremors, psychosis, SLE
• Causes coronary “ Steal” phenomenon in IHD

NOT used in HT with coronary artery disease,
in elderly
No longer a first-line drug in the treatment of HT
􀀀 Some utility in severe or resistant HT
Safe in pregnancy, useful in the treatment of
hypertensive emergencies in pregnant women

Minoxidil- minoxidil N-O sulfate

• Most potent Prodrug, orally acting
• Not Preferred for HT
• KATP activation in hair follicle
Hypertrichosis : Face, back, arm, legs
Used for Male pattern baldnesstopically
lotion, spray(2%)

Diazoxide

Used in past only intravenously during
emergencies only if Sodium nitroprusside can
not be given
▪ BP reduction in 3-5 minutes only if used rapidly
as large bolus dose
▪ Can cause drastic fall in BP causing stroke or MI
• Hyperglycemia due to insulin inhibition
Orally to treat hypoglycemia, in pts with insulinoma

Sodium nitroprusside

• Arterial and venous dilator
Nitric oxide → activates cyclic GMP
Improved myocardial function
• Rapid onset, short duration (3 min),
continuous variable rate IV infusion in 5% dextrose
Hypotension, Thiocyanate toxicity

Precautions

  • Decomposes in light; only fresh solutions used
  • Bottle covered with an opaque wrapping.
  • Administered as a controlled continuous infusion
  • Patient closely monitored.

Sodium nitroprusside : uses

􀀀 HT emergencies
􀀀 Acute aortic Dissection
􀀀 HT with Myocardial infarction
􀀀 CHF with pulmonary edema
􀀀 Controlled hypotension during surgery

Adrenergic receptor
blockers

Alpha, beta and mixed blockers

Prazosin

Selective α1 blocker : PR, venous return
Symptomatic orthostatic hypotension with first dose
Retention of salt and water
Reduces total, LDL-cholesterol and TGs; Increases HDL
Status as antihypertensive: as adjunct to other drugs
􀀀 Other uses: Benign Prostatic Hyperplasia, Peripheral vascular disease

β1 blockers ( atenolol,
metoprolol)

• Rationale for anti HT effect
Cardiac, renal, central
• Delayed fall in PR- due to reduced Angio II
• Loss of selectivity at high dose
• Avoid if bradycardia, AV nodal dysfunction
Nonselective to be avoided in asthma, DM

β1 blockers: in Hypertension

Not as first line drug

􀀀 Used when other compelling indications (patients with angina,
post MI, stable heart failure)
􀀀 4th -5th line for combination in resistant hypertension
no postural hypotension, no tachycardia
Well tolerated, Cardioprotective,
Tab. Atenolol 25 to 50 mg once a day Not to withdraw abruptly.

Mixed adrenergic receptor
blockers ( Labetalol, carvedilol)

Vasodilatory beta blockers: carvedilol, labetalol,
celiprolol, nebivolol
Ca++ blockade, β 2 agonist, NO release, K+ channel openers,
antioxidants
Labetalol α1 and β blocker , partial agonist at β 2
Used IV in emergencies, orally in resistant HT
Safe in pregnancy
Carvedilol α1 and β blocker , antioxidant, Antiproliferative
Used in HT and CCF

Central sympatholytics Clonodine

Clonidine: imidazoline
Central α2A agonist, postsynaptic in vasomotor center
Moxonidine, rilmendine –selective imidazole receptor
(IR1) agonists
CO and PR decreases
Postural hypotension: less common
Dryness of mouth, nose, eyes,
sedation, parotid pain, vertigo
Bradycardia, AV block
Retention of salt and water : Tolerance

SHOULD NEVER BE ABRUPTLY WITHDRAWN
Overshoot of B.P.
Sodium nitroprusside, mixed α+β blocker
Other uses
Opioid, alcohol and nicotine withdrawal
Menopausal hot flushes Diagnosis of GH deficiency
Glaucoma – apraclonidine
0.3-1.5 mg/d twice a day, Transdermal patch

Methyldopa

( α-methyl-3,4-dihydroxy-L-phenylalanine)
• Prodrug, α- methylnorepinephrine
• Not deaminated by MAO
• Central α2 agonist, inhibit central sympathetic
outflow
• Retention of salt and water – Tolerance
• Baroreceptor reflex intact

Dryness of mouth, sedation,
parkinsonian signs, hyperprolactinemia,galactorrhoea,
Bradycardia
Hemolytic anemia (1-5% after 1 year)
Hepatotoxicity rare
250 mg/d twice a day
• Current use -HT in pregnancy

Ganglion blockers

Hexamethonium,

Trimethaphan

Ganglion Blocking Agents
( Hexamethonium, Trimethaphan)
Direct action on ganglia
Baroreceptors inhibited – orthostatic hypotension
Tolerance, High incidence of adverse effects
Controlled hypotension during Surgery
HT emergency due to aortic dissection

Adrenergic neuron blockers

Reserpine

Central and peripheral action
Alkaloid from root of Rauwolfia serpentina
(Sarpagandha): Sen and Bose ( 1931) reported its uses
Popular anti HT of 1950s and 60s
Cheapest anti HT
Binds tightly to storage vesicles of norepinephrine,
dopamine,serotonin : ‘Hit and run drug’

Salt and water retention
ADRS – sedation, depression
secondary to parasympathetic predominance
Delayed onset of anti-HT action
0.25 mg once a day
Status as antihypertensive – not preferred

Adrenergic neuron blockers

Guanethidine

• Triphasic action on BP: fall, followed by increase in B.
P.on IV adm.
• Taken up and stored as substitute neurotransmitter
norepinephrine is depleted, postsynaptic receptors
upregulated
• Postural hypotension , Diarrhoea, failure to ejaculate,
Fluid retention
Status as antihypertensive – not used

Principles of drug therapy of hypertension

AHA/ACC -2017 Guidelines on the prevention,
detection, evaluation, and management of high
blood pressure (BP) in adults

BP (mm of Hg) Category
<120 /< 80 Normal
120–129 < 80 Elevated
130–139/80–89 Stage 1
140-180/90-120 Stage 2
180/ > 120 Hypertensive crisis
Target BP to be achieved- <130/80

Approaches to Treatment
(ACC/AHA-2017)

Target BP <130/80

  • 130–139/80–89 Stage 1 (Monotherapy)
    • (Drugs if, h/o MI, Stroke, DM, CKD, High risk for ASCVD >10%)
  • 140-180/90-120 Stage 2 (combination with different mechanisms)
  • 180 / > 120 Hypertensive crisis
    • (Prompt treatment)
    • (Hospitalize if signs of organ damage)

Principles of Treatment

• Diagnosis : Repeated independent
measurements
• Rule out secondary Hypertension
if present, correct the cause
• Initiate lifestyle modifications
• Drug treatment

Drugs if no compelling indications

Choice of drug is driven by the likely benefit in an
individual patient, taking into account
✔ concomitant diseases,
✔ adverse effects of specific drugs
✔ Cost
Monotherapy : ACEI/ARBs
Thiazides
CCBs
START LOW, GO SLOW
Assess compliance

Combination therapy

□ Renin
Increased with diuretics/ vasodilators/ CCB/ ACE
Decreased with β blockers/ clonidine/ methyldopa
□ Fluid retention
sympatholytic/ vasodilator + diuretic
□ Tachycardia
CCBs/ Hydralazine +β blockers
□ Potassium
ACEI/ARB/Spironolatone + Thiazide

Hypertension with comorbidities (Associated disease
conditions)

Heart Failure

• ACE- I
• ARBs
• Beta blockers – only in stable HF
• Aldosterone antagonist
• Thiazides / loop diuretic

High Coronary disease risk
(Stable angina and silent ischemia)

□ Beta blockers
□ ACEI / ARBs
□ Diuretics

Post-myocardial Infarction

□ ACE-I
□ ARB
□ Aldosterone antagonist
□ Beta blockers

Chronic Renal Disease

□ ACEI / ARBs
□ Loop diuretic
□ Calcium channel blockers
Thiazides do not work if GFR too low
Beta blockers decrease renal blood flow

Diabetes mellitus

□ ACE – I , ARBs
□ CCBs
Nonselective Beta blockers – mask signs of
hypoglycemia
Diuretics cause hyperglycemia

Asthma/ COPD/ Peripheral vascular Disease
□ CCBs , Alpha blocker
Hyperlipidemia
□ ACEI/ ARBs, Alpha blocker
BPH
□ Alpha blocker

Other Antihypertensives

□ Centrally acting drug, Arterial Vasodilators
not preferred as 1st line agents
□ Reserved for resistant cases and for specific
indications

Hypertensive Crisis :
Emergency and Urgency

□ Hypertensive emergency : A severe
elevation in BP (>180/120 mm of Hg) with
evidence of active organ damage
□ Hypertensive urgency : A severe elevation in
BP without signs of end organ damage

Hypertensive Emergency

Controlled reduction of BP over minutes or hours is required to counter
threat to organ function in:
• Hypertensive Encephalopathy
• CVA – haemorrhage
• Acute Aortic Dissection
• Acute LVF with Pulmonary Edema
• Acute MI / Unstable Angina
• Acute Renal Failure
• Eclampsia
• Hypertensive episodes – Pheochromocytoma, cheese reaction

Hypertensive crisis

• ICU- BP reduced by 25% over minutes to hours,
gradually to not lower than 160/100 why?
• IV Nicardipine/ labetolol/ clevidipine/ esmolol/ glyceryl
trinitrate/ enalaprilat/ fenoldopam, furosemide
IV – Na nitroprusside
Oral- Labetalol, Amlodipine
Close monitoring required

Hypertension in Pregnancy

□ ≥140 / 90 mm of Hg
□ pre-existing HT or pregnancy related?
□ Toxaemia of pregnancy, Risks for mother and child
□ Drugs Safe in Pregnancy
􀀀 Labetalol : First line, Preferred
􀀀 Methyldopa
􀀀 Dihydropyridine – Nifedipine sustained release
􀀀 Hydralazine
Hypertensive Moms Love Nifedipine

171 thoughts on “Anti-hypertensive Drugs II”

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  93. An impressive share! I’ve just forwarded this onto a colleague who had been doing a little homework on this. And he in fact bought me breakfast due to the fact that I stumbled upon it for him… lol. So allow me to reword this…. Thanks for the meal!! But yeah, thanks for spending some time to discuss this matter here on your web site.

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