Antihypertensive Therapy
Drug Name/Infos
Thiazide Diuretics
1. Hydrochlorothiazide
Diuretics
Mechanism of Action
1. Inhibits the NaCl cotransporter at Distal
tubule
2. ↑Na and water excretion
3. ↓effective circulating volume
a. ↓stroke volume
b. ↓cardiac output
c. ↓Blood pressure
Therapeutic
Uses
1. Mild to
moderate
hypertension
Adverse Effects
1. Hyperuriceamia
a. Compete for
organic transporter
with uric acid at the
proximal tubule
2. Hyponatreamia
3. Hypokalaemia
a. Due to ↑Na in
tubular fluid at the
collecting duct for
exchange to K
4. Hyperglyceamia
a. Due to
Hypokalaemia (K
needed to activate
insulin)
5. Hyperlipideamia
6. Allergic reaction
a. Thiazide is one type
of Sulfonamide
Drug Name/Infos
Nonselective Alpha
Blocker
1. Irreversible blocker
(isnt been used in
clinical setting )
a. Phenoxybenzamine
2. Reversible blocker
a. Phentolamine
Selective Alpha Blocker
1. Prazocin
Alpha Blockers
Mechanism of Action
1. Blocks both a1 and a2 receptors
2. Blockage of receptors lead to
a. Vasodilation of
i. Coronary arteries
ii. Skin
iii. GIT
iv. Kidney (↑GFR ↑diuresis)
v. Veins
b. Therefore leads to ↓Total Peripheral
Resistance
i. ↓Blood pressure
Blocks only a1
Mechanism of action same to that of
non-selective
Therapeutic Uses
Phentolamine
1. Pheochromocytoma
(cancer of the
adrenal gland)
2. Hypertensive
emergency
1. Mild to moderate
hypertension
Adverse Effects
1. Postural
hypertension
2. Refelx
tachycardia
Drugs
Name/Infos
Beta Blockers
Mechanism of Action
Non selective Beta 1. Blocking:
4. Kidney
Blocker
a. Beta 1
a. ↓in Bp may:
1. Propranolol
b. Beta 2
i. ↓renal prefusion
Contraindicated in 2. Actions:
ii. ↓in:
1. Asthma
a. Cardiovascular system
1. Na+ retention
2. COPD
i. (-) in :
2. Plasma volume
3. Heart block
1. Inotropic
5. Disturbance in glucose
4. Peripheral
2. Chronotropic
metabolism:
vascular disease
ii. Causing in:
a. ↓in:
1. ↓cardiac output
i. Glucogenolysis
2. ↓cardiac work
1. Glucagon
3. ↓oxygen
secretion
consumption
b. May lead to
3. Respiratory system
hypoglycemia in
a. Blocking the Beta 2
i. Insulin dependent
receptor will:
diabetic patient
i. Deteriorated the
Careful monitoring is
respiratory disease in
required
COPD patient
ii. Therefore
contraindicated for
COPD and Asthma pts
Same to that of propanolol just it doesn’t block B2  no
Selective Beta
Blocker
bronchospams
1. Atenolol
Therapeutic
Uses
Adverse Effects
Propanolol
1. Hypertension
2. Angina
pectoris (IHD)
1. AV block
2. Masked
hypoglyceamia
a. If pts in insulin
tx with
blockers can
both get
hypo ADR
(dizziness)
Atenolol
1. Hypertensive
pts with
a. Asthma
b. Diabetes
mellitus
c. Peripheral
vascular
disease
1. Risk of rebound
hypertension if
drug withdrawn
abruptly
Drug Name/Infos
1st generation
1. Clonidine (Direct
agonist)
2. a-methyldopa
(Prodrug)
2nd generation
1. Moxonidine
Alpha 2 Agonist
Centrally Acting Antihypertensive
Mechanism of Action
Therapeutic
Uses
Clonidine
1. Direct alpha2 agonist
a-methyldopa
1. Converted into Methylepinephrine
(false neurotransmitter)
Therefore both will stimulate Alpha 2
receptor
1. ↓norepinehrine release from the CNS
2. Lead to peripheral vasodilation
3. ↓Total Peripheral Resistance
4. ↓ blood pressure
Acts on Imidazoline receptor (Ii) at the
medula oblongata
1. ↓sympathetic outflow
2. ↓blood pressure
1. Chronic
outpatient
management
of hypertension
1. Mild to
moderate
hypertension
Adverse Effects
1. Edema
a. Due to peripheral
vasodilation
2. Sedation
a. Acts centrally
3. Orthostatic hypotension
4. Bradycardia
a. ↑vagal outflow
b. ↓symp outflow
5. Dry mouth
6. Rebound hypertension
(Clonidine)
a. If stop suddenly
Calcium Channel Blocker
Contraindication
1. Sinus bradycardia
2. AV conduction defect
Drug Name/
Infos
3. Severe cardiac failure
Drug interaction
1. Cimetadine (CYP450 inhibitor)
Mechanism of Action
Dihydropyridines
1. Nifedipine
More on arteriole
not heart
1. Primary action is at the smooth muscles of arterioles not vein
2. Vasodilation due to blockage of calcium channel, no
contraction of smoth muscle cells
3. ↓after load but not preload
4. ↓Total Peripheral Resistance
5. ↓Blood pressure
Benzothiazepine
1. Diltiazem
Both arteriole and
heart
(intermediate)
1. Acts on both cardiomyocytes and smooth muscle cells of
arterioles
2. At the heart
a. ↓slow pacemaker activity
i. ↓heart rate
b. ↓impulse conduction between atria and ventricle
i. ↓strength of contraction
ii. ↓stroke volume
c. Therefore ↓ blood pressure
1. At the heart
d. ↓slow pacemaker activity
i. ↓heart rate
e. ↓impulse conduction between atria and ventricle
i. ↓strength of contraction
ii. ↓stroke volume
f. Therefore ↓ blood pressure
Phenylalkylamines
1. Verapamil
Only acts on heart
Therapeutic
Uses
Adverse
Effects
1. Hypertension
2. Angina
pectoris
1. Edema
2. Headache
3. Reflex
tachycardia
a. Less for
verapamil
and
diltiazem
4. ↑sympatheti
c outflow
Drug Name/Infos
Anti Angiotensin II Drugs
Mechanism of Action
Therapeutic Uses
Angiotension Converting 1. Inhibit activity of ACE, therefore inhibit
Enzyme (kininase)
conversion of Ang I to Ang II
Inhibitor (ACE inhibitor)
a. Leads to vasodilation
st
1 line
b. ↓ Total Peripheral Resistance
1. Captopril
c. ↓ aldosterone release
Contraindication
i. ↓ Na and water retention
1. Pregnancy; due to
ii. ↑ K retention
a. Fetal hypotension
b. Fetal renal failure
c. Fetal malformation
d. Fetal death
Angiotensin Receptor
1. Blocks AT1 receptors; therefore leads to
nd
(AT1) Blocker (2 line)
a. Vasodilation
1. Losartan
b. ↓ADH and Aldosterone release
Contraindication
i. ↓Na and water retention
1. Pregnancy
ii. ↑K retention
2. Angioedema due to 2. No effects on bradykinin metabolism
ACE inhibitor (prev tx)
a. No dry cough; preferable compared
to ACE inhibitor if pts couldn’t
tolerate dry cough
Direct Renin Inhibitor
1. Block cleavage of Angiotensinogen to
1. Aliskiren
Ang 1
Limitation of usage
2. ↓Ang II formation
1. Further increase renin 3. ↓blood pressure
release cause
product (Ang II)
inhibitory mechanism
is inhibited
Adverse Effects
1. Hypertension
2. Congestive Heart
Failure
a. Prevent
inappropriate
cardiac remodelling
(nonheamodynamic
benefit)
3. Renal insufficiency
a. Stabilize renal
function
b. ↓ proteinuria
1. Dry cough (ACE
inhibitor)
a. Bradykinin
metabolism is
inhibited
b. Bradukinin is local
irritant
2. Angioedema
3. Acute renal failure
a. Pts with renal artery
stenosis
4. Hyperkalaemia
a. ↑with spironolactone
1. Hypertension (less use)
1. ↑renin release
Drug Name/ Infos
Hydralazine
Potassium Channel
Openers
1. Minoxidil
Pharmacokinetics
1. Well absorbed orally
2. Longer duration of
action (it is a prodrug
though)
Direct Vasodilators
(Direct Acting Vascular Smooth Muscle Relaxant)
Mechanism of Action
Therapeutic
Uses
1. ↑cGMP
2. ↓IP3 (second messenger)
3. ↓Ca release from Sarcoplasmic
Reticulum of smooth muscle
4. Involved in the generation of Nitric
Oxide (potent vasodilator)
5. All of these will lead to vasodilation
a. ↓Total Peripheral Resistance
b. ↓ Blood Pressure
6. No action on coronary artery, no
postural hypotension
1. It is a prodrug
a. Minoxidil  minoxidil sulfate (by
sulfotransferase)
2. Minoxidil sulfate activats K+ATPase
a. K+ efflux from smooth muscle cells
b. Leads to smooth muscle relaxation
c. This will lead to arteriolar
vasodilation
Adverse Effects
1. 1st line drug of
hypertension
a. Given low
dose with
other agents
1.
2.
3.
4.
Flushing (vasodilation)
Reflex tachycardia
Sodium retention
Drug induced systemic lupus
erythematosus
a. Slow acetylators
1. Severe
hypertension
2. Drug resistant
hypertension
3. Alopecia
a. Topical
application
1. Fluid and salt retention
2. Hypertrichosis
3. Reflex tachycardia
Direct Vasodilators
(Direct Acting Vascular Smooth Muscle Relaxant)
Mechanism of Action
Therapeutic
Uses
Drug Name/ Infos
Sodium Nitroprusside
1.
2.
3.
4.
5.
Release Nitric Oxide
Activates Guanylylcylase
↑cGMP pathway
↓PIP3
↓Ca release from Sarcoplasmic
Reticulum
6. Relaxation of smooth muscle cells
a. Vasodilation, ↓TPR, ↓BP
7. Rapid and Constanly acting
vasodilator
a. Arteries and veins
1. Hypertensive
emergencies
2. ↓BP in aortic
dissection
3. Improve CO in
CHF
4. Induce
controlled
hypotension
during
anesthesia
Adverse Effects
1. Lactic acidosis
Nitroprusside
cyanide/thiocyanatelactic
acidosis
2. Reflex tachycardia