Antihypertensive

Drugs

Sympatholytic Direct ACE

Diuretics
agents vasodilators inhibitors
Adrenergic Adrenergic Arterial &
Thiazidess & Loop K- sparing Centrally Ganglionic Arterial - Captopril
neuron receptor venous
related drugs diuretics diuretics acting drugs blockers vasodilators - Enalapril
blockers blockers vasodilator
Furosemide Methyldopa Guanithidine K- channel SodiumNitr
spironolactone β-blockers
Hydrochlorothiazide Reserpine agonists oPrusside
Bumetanide Clonidine Trimethaphan - propanolol
triametrine - Metoprolol -Hydrolazine
chlorothalidone
Ethacrynic Guanfacine - Atenolol - Minoxidil
acid omiloxide - Diazoxide
α-blockers
-Prazosin
Ca- channel
Mixed blockers
blockers - verapamil
-Labetalol - Nifidipine

Hassan Jamal M.Hisham

 Diuretics
Diuretics lower BP primary by depleting body Na+ stores.
Na+ increases BV & PVR by: ↑ vessel stiffness & ↑neural reactivity

Thiazides & related drugs Loop diuretics K- sparing diuretics

1) Initial ↓ in blood volume & COP

2) After chronic administration (6-8 1) More potent than thiazides as
weeks), COP gradually returns to diuretics BUT less potent as
Mechanism normal while PVR declines due to: antihypertensive
a. Loss of Na+ from arterial wall 2) The antihypertensive effect of
b. ↓ sensitivity of vascular or loop diuretics is related ↓ BV
smooth muscle to NE
- Hypertension associated with
reduced glomerular filtration rate
- Mild or moderate hypertension - Avoid excessive K depletion
(↓ GFR) – Renal impairment
(lowering BP by 10-15 mmHg) particularly in patients taking
- Heart failure or liver cirrhosis,
Indicated in cases of - In sever hypertension in digitalis
where Na retention is marked
combination with other - Enhance the natriuretic effects
- Hypertension in which multiple
antihypertensive drugs of other duretics
drugs with Na retaining properties
are used (Contraceptives)
1) Hypokalemia (Except for K- sparing diuretics)
Side effects 2) Impair glucose tolerance, diabetes mellitus and increase serum lipid conc.
3) Impotence loss of libido, diarrhea and gout

Centrally acting drugs
Clonidine
1) Central action
stimulates the central
presynaptic α2-receptors
that are inhibitory to
sympathetic outflow
2) Peripheral action
- Reduces the release of NE
from adrenergic nerve
Mechanism
- Prevents cardiac
responses to
postganglionic adrenergic
nerve stimulation
- Has a weak direct
peripheral vasodilation
action
- Moderate
Therapeutic Hypertension
uses - prophylactic
treatment for margin
- Sedation & dry mouth
- Postural hypotension
- Rebound hypertension if
clonidine is suddenly
Side effects
withdrawn
Guanfacine ~ clonidine
Sympathetic agents
Ganglionic blockers
Adrenergic neuron blockers
( Symp. & para.)
Methyldopa Trimethaphan Guanethidine Reserpine
Converted into α- 1) ↓ sympathetic It inhibits the release - Blocks the ability of
methyl NE (potent α2- vasoconstriction tone of NE that occur when adrenergic
adrenergic agonist) in leading to: a normal action transmitter vesicles
the CNS, this would a. Dilation of the potential reaches to uptake and store
lead to decrease in arterioles sympathetic nerve biogenic amines by
sympathetic outflow b. Dilation of the ending thus tend to interfering with
veins ↓COP by bradycardia uptake mechanism,
(M Dopa  αM NE  and relaxation of resulting in
α2 agonist  ↓NE  2) Produces a direct capacitance vessels - Depletion of NE,
↓Symp.) vasodilation action & Dopamine &
histamine like effect - With chronic serotonin in both
therapy, COP central and
returns to normal peripheral vascular
while PVR ↓ resistance
- In malignant
hypertension
- Acute pulmonary
Little use due to side
moderate & sever edema due to Little use due to its
effects
forms in hypertension hypertensive cardiac side effects
failure
- Hypertensive
encephalopathy
-Sedation on long - Postural hypotension - Postural - Postural
term therapy & Tachycardia hypotension and hypotension
- Impaired mental - Constipation, dry hypotension - Sedation, nightmars
concentration & following exercise and severe mental
mouth, urinary
mental depression - Diarrhea and depression
- Nightmares & retention delayed ejaculation - Diarrhea and
vertigo - Mydriasis increase gastric acid
- Impotence secretion

Propranolol (β)
1- β1 β2 antagonists
2- Depresses renin-angiotensin-
aldosterone system by
inhibition of renin production
Mechanism
(β2 effect)
- Lowers BP in mild & moderate
hypertension
- Prevent reflex tachycardia
Therapeutic uses that often results from
treatment with direct
vasodilators in case of sever
hypertension
- May increase plasma
triglycerides and decrease
HDL-cholesterol
- Nervousness, Nightmares,
Side effects
Mental depression and
increase intensity of angina
- Asthma, peripheral vascular
insufficiency and diabetes
β blockers ↓BP by ↓COP. With continued treatment COP returns to normal but PVR is reset at lower level and thus BP remains low
Ganglionic Blockers (Trimethaphan)
The depolarizing blockers are not used in hypertension as they cause initial stimulation if the ganglia and thus tend to raise BP at first
The competitive blockers suffer from the disadvantage of that they block both sympathetic and parasympathetic ganglia, with the exception of
trimethaphan, so they have been replaced by drugs which have better selective action an sympathetic tone in the prolonged management of
essential hypertension
Adrenergic receptor Blockers
Metoprolol & Atenolol (β) Prazosin (α) Labetalol (Mixed)
β1- selective blockers, both blocking of α 1 receptors in - It blocks α & β receptors
have side effects fewer arterioles and venules , β blocking is
than propranolol predominant
Has a vascular smooth - Reduces the
muscle relaxant effect sympathetic vascular
resistance without
significant alteration in
HR or COP
- reduces plasma renin
activity
For treatment of Treatment of severe - Hypertension of
hypertensive patients who hypertension in pheochromocytoma
suffer from asthma, combination with other (adrenal gland tumors
diabetes or peripheral antihypertensive agents that produce xss
vascular disease adrenalin)
- Hypertensive
emergencies
- Postural hypotension
and tachycardia are
observed with 1st dose
- Angina pectoris & fluid
Similar to non-selective β-
retention
blockers
- Drowsiness, headache,
GIT disturbance,
blurred vision, dry
mouth
 Direct Vasodilators

Arterial & venous

K+ channel agonists
Hydralazine & Minoxidil
Relaxation of smooth
muscle of arterioles,
Mechanism ↓systemic vascular
resistance
K+ out, can’t Ca+2 in, relaxation
Out patient’s therapy of
Therapeutic uses
hypertension
- ↑ HR & stroke volume
due to compensatory
responses mediated by
baroreceptors and
sympathetic NS as well
as renin and
aldosterone leading to
↑ COP and renal blood
Side effects & toxicity fllow
- Tachycardia, palpitation
and angina
- Headache, nausea,
anorexia, sweating and
flushing
Arterial vasodilators
Diazoxide
Effective in long acting
arteriolar dilator
hypertensive emergencies
- Excessive hypotension
with tachycardia and ↑
COP
- Hyperglycemia due to
the inhibition of insulin
release
- Salt & water retention
Ca+ Channel blockers
Verapamil & Nifidipine
Inhibit Ca+ influx in arterial
smooth muscle leading to
dilation of peripheral
arterioles
Mild to moderate
hypertension, Angina or
coronary spasm
Slight tachycardia & in ↑
COP
vasodilator
Na Nitroprusside
Dilates both arterial &
venous vessels, resulting in
↓ PVR and venous return
Hypertensive emergencies
severe cardiac failure
Prolonged therapy leads to
accumulation of: CN- / SCN-
1) Cyanide (metabolic
acidosis, arrhythmias,
excessive hypotension
& death)
2) Thiocyanate
(weakness, psychosis,
muscle spasm &
cconvulsion
Both can be avoided by:
Sodium thiosulfate as a
sulfur donor or hydroxyl
cobolamin
Nausea, vomiting,
sweating, restlessness,
headache and palpitation
 Angiotensin converting enzyme inhibitors
(Captopril – Enalapril)

𝑅𝑒𝑛𝑖𝑛 𝑟𝑒𝑙𝑒𝑎𝑠𝑒𝑑 𝑓𝑟𝑜𝑚 𝑟𝑒𝑛𝑎𝑙 𝑐𝑜𝑟𝑡𝑒𝑥 𝑖𝑛 𝑡ℎ𝑒 𝑙𝑢𝑛𝑔 𝑏𝑦 𝐴𝐶𝐸 𝑖𝑛 𝑡ℎ𝑒 𝑎𝑑𝑟𝑒𝑛𝑎𝑙 𝑔𝑙𝑎𝑛𝑑
Angiotensin �⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯� Angiotensin I �⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯� Angiotensin II �⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯⎯� Angiotensin III
Action by renin-angiotensin – - Angiotensin II has a vasoconstrictor and Na retaining activity
aldosterol system - Booth Angiotensin II & Angiotensin III stimulate aldosterone release, which increase Na and water retention
and thus the blood pressure increase

- Inhibit the ACE and thus inhibit the action of renin- angiotensin- aldosterone system
Mechanism - They stimulate Kallikrein-Kinin system (bradykinin) which has a potent vasodilation effect.
- The hypotensive effect of ACE inhibitor is associated with increasing glomerular filtration rate

Treatment of:
Therapeutics - sever or refractory hypertension -Hypertensive diabetic patients
- Renal insufficiency to increase glomerular filtration rate

Side effects - Proteinuria - Neutropenia or Pancytopenia - Skin rashes, drug fever, taste impairment and dry cough
 Management

Mild & Moderate

Non pharmacological - Thiazides
therapy: - Ca+2
• Contraceptives ( drugs with
- Low Na diet - Clonidine
Na retaining prop.)  Loop Contraindications
- Weight reduction - Propranolol
diuretics Diabetes
- Stop smoking Sever
- Thiazide
- Exercise - ACE inh.
- Propranolol
- Cope with stress • Digitalis ( K depletion)  - Methyl dopa
- Diuretics
Monotherapy therapy: K-sparing diuretics - Prazosin (comb.)
- Diuretics Use propranolol 2 prevent
Asthma / angina
- Sympatholytic reflex tachycardia due 2
• Malignant hypertension – - Β2 blockers (Propranolol,
- Vasodilators & Ca vasodilators
pulmonary edema – labetalol).
channel blockers Emergencies
hypertensive - Prazosin
- ACE inhibitors - Diazoxide
- K+ channel agonists
Combination therapy: encephalopathy  - Sod.Nitroprusside (Hydralazine, Minoxidil,
- Diuretics & β-blockers trimethaphan - Labitolol Diazoxide)
- Diuretics & β-blockers & - Trimethaphan
vasodilators • Pheochromocytoma  (malignant) Causes lipido / impotence
- Ganglionic blocker, loop Diabetic - Diuretics
labetalol
diuretics & vasodilators - ACE inh. - Trimethphan
Emergencies : - Β1 selective blockers - Guanthidine (delayed
- Diuretics • Outpatient  Hydralazine (Metoprolol, Atenolol) ejaculation)
- Vasodilators: Diazoxide & Minoxidil Impaired GFR
- ACE inh. Causes fluid retension
i.v, sod.nitroprossside i.v,
- Prazosin
hydralazine i.m • Sever cardiac failure  - Loop diuretics
- diazoxide
- Lobtalol, trimethaphan, sod.nitroprusside Angina / asthma
reserpine, methyldopa - Ca+2 blockers
- Dialysis - Β1 selective blockers
(Metoprolol, Atenolol)