Chapter 5: Adrenoceptor Blockers increase in blood pressure because of

its vasoconstrictive effects on alpha receptors

I. Introduction and its positive inotropic and chronotropic
• These are agents that blocks adrenergic effects (increasing heart rate and contractility)
receptors on beta receptors. However, if a patient is pre-
• Selective and non-selective type treated with an alpha-blocker (like
• A-blockers (non-selective): used in phenoxybenzamine or phentolamine), the
Pheochromocytoma following can happen:
• a-1 receptor blockers: management of
hypertension and benign prostatic hyperplasia • Alpha-blockade: This blocks the
• B-blockers (non-selective): used in the vasoconstrictive effects of epinephrine
treatment of HPTN, ischemic heart disease, on alpha receptors, leading to vasodilation
arrythmia, endocrinologic and neurologic instead. Without the usual alpha-mediated
disorder and glaucoma vasoconstriction, epinephrine's effects on
beta- adrenergic receptors become more
II. BASIC PHARMACOLOGY OF THE ALPHA- pronounced.
RECEPTOR CLOCKERS
• Beta effects: With the alpha receptors
a. Mode of Action blocked, the beta-mediated vasodilatory
• Reversible Antagonist: dissociate from effects on the blood vessels can dominate.
receptors that blocks it and it is influenced by This leads to a decrease in peripheral
high concentration of the blocker. resistance and, consequently, a reduction in
(Phentolamine and Prazosin) blood pressure, rather than the expected
increase.
• Irreversible: do not dissociate
(Phenoxybenzamine) CLINICAL IMPLICATIONS

THE REVERSIBILITY OF THE DRUG IS ALWAYS • Epinephrine reversal has important

BASED ON ITS HALF-LIFE. clinical implications, especially in emergency
situations and surgeries. If a patient is on
b. Pharmacologic effects alpha-blockers or has taken them for medical
reasons (like treating hypertension or
1. CARDIOVASCULAR EFFECTS pheochromocytoma), administering
epinephrine might lead to unexpected
• The alpha-receptor blockers LOWERS hypotension instead of the expected
peripheral vascular resistance--- lowering of hypertensive response.
BP.
• A-receptor blockers causes orthostatic • This is why healthcare providers should be
hypotension and reflex tachycardia aware of a patient's medication history and
• Explained by the phenomena of potential interactions when considering the
EPINEPHRINE REVERSAL use of epinephrine or similar agent

THE EPINEPHRINE REVERSAL 2. OTHER EFFECTS

• Miosis and nasal stuffiness
• Also known as Epinephrine paradox or • A1blockage: decrease resistance of the flow
Epinephrine antagonism of URINE (tx for urinary retention due to
• unexpected effects of epinephrine are prostatic hyperplasia)
reversed due to specific circumstances,
often involving the administration of
alpha-blockers or alpha-adrenergic
antagonists.
• Epinephrine typically causes an
C. SPECIFIC AGENTS 3) PRAZOSIN
• PIPERAZNYL QUINAZOLINE effective fr the
(1) PHENOXYBENZAMINE
management of HYPERTESION
• Irreversible blockage, a1 antagonist with • A1 selective antagonist
long duration of action • No tachycardia seen on its effects;
• Inh. NE reuptakes relaxes both arterial and venous
• Blocks H1, acetylcholine and serotonin vascular smooth muscle in
receptors prostate
• Attenuates cathecholamine-induced • Half-life: 3 hours
vasoconstriction
• Used in the tx of PHEICHROMOCYTOMA 4) TERAZOSIN
• SE: Orthostatic hypotension and tachycardia,
• Reversible a-selective antagonist used for
nasal stuffiness, inh. Of ejaculation, fatigue, HPTN
sedation and nausea. • Used in men with urinary symptoms (BPH)
• Half life: 9-12 hours

5.) DOXAZOSIN
• Tx to HPTN and BPH
•Longer half-life At 22 hrs

2) PHENTOLAMINE

• Competitive a1 and a2 antagonist

• Reduces peripheral resistance
• Stimulates cardiac activity through D. OTHER ALPHA ANTAGONIST
antagonism of q2 receptors with minor
(1) AFLUZOSIN-a1 selective quinazoline
inhibitory effects at serotonin receptors and
derivative for BPH; inc. risk of QT prolongation
agonist effects at muscarinic H2 and H2
receptors. (2) SILODOSIN-ressembles tamsulosin in
• AE: severe tachycardia, arrythmia and blocking a1A in the treatment of BPH
myocardial ischemia
• Treatment to pheochromocytoma (3) INDORAMIN-a1 selective antagonist used
• Reverses local anesthetic effects in in HPTN

(4) URAPIDIL-a1 antagonist with a2 and 5-

HT1A agonist action that is used in HPTN and
BPH
(5) LABETALOL-a1 and B antagonistic effects; operative pheochromocytoma in the
for HPTN management of hypertension

(6) CHLORPROMAZINE AND HALOPERIDOL- • Dose 10mg/d that can be increased at

alpha and dopamine receptor antagonist as intervals for several days until HPTN is
neuroleptic drugs that causes HYPOTENSION controlled; given 1-3weeks before surgery
• Other physician DO NOT CONSIDER using
7) TRAZODONE- a1 blocker used as an
this agent instead they use LOCAL ANESTHTIC
antidepressant to control BP
8) ERGOTAMINE and DIHYDROERGOTAMINE- • Useful in CHRONIC TREATMENT OF
INOPERABLE/METASTATIC
ergot-derivative
PHEOCHROMOCYTOMA
9) YOHIMBINE-a2 receptor blocker • Other agents used in combination with
Phenoxybenzamine: calcium channel
• Indole alkaloid blockers and B-receptor blockers
• Tx to orthostatic hypotension • ALPHA BLOCKERS AFTER B-BLOCKERS
• Used as an erectile dysfunction but replaced TO REVERSE CARDIAC EFFECTS
by SILDENAFIL (a phosphodiesterase-5- (VASOCONSTRICTION)
inhibitory)
• SE: inc. BP to px receiving medication, Treatment:
reverses CLONIDINE; used in veterinary to
reverse anesthesia using XYLAZINE • METYROSINE-(a-metyrosine, a-
methyl analog of tyrosine)
III. CLINICAL PHARMACOLOGY OF A-
• For sympatomatic with inoperable or
RECEPTOR BLOCKERS metastatic pheochromocytoma
a. PHEOCHROMOCYTOMA • SE: Extrapyramydal effects because of
dec. in DOPAMINE
• Tumor of the adrenal medulla/sympathetic
ganglion cells.
b. HYPERTENSIVE EMERGENCIES
• Identified through imaging with increased
• Agents used: LABETALOL
plasma and urinary NE, and Epinephrine and
other metabolites (normetanepinephrine and • Above 180/120 mmHg
metanepinephrine)
• Presence of severe hypertension and
Signs and Symptoms: hypertension induced acute end- organ
damage
• Catecholamine Excess
• Intermittent and Sustained HPTN (c )Chronic Hypertension
• Headaches
• Palpitations • Also known as Gestational Hypertension
• Inc. Sweating
• Hypertension during pregnancy
• Localization Technique: Computed • A-blockers are useful in the tx of mild-
Tonography, MRI and Scans to I-meta- moderate hypertension but are NOT
iodobenzylguanadine. RECOMMENDED for monotherapy for HPTN

• Treatment: • Adverse Effects: Orthostatic

• A-Blockers: NITROPRUSSIDE- useful in Hypertension(should be monitored)
post-operative management
• Prazosin causes dizziness
• PHENOXYBENZAMINE- used in post-
(d) Peripheral Vascular Disease

• The accumulation of fats and cholesterol in I. PHARMACOKINETICS

the arteries in your legs/arms.
• Absorption
• Prazosin and Phenoxybenzamine
o Most are absorbed in oral
• Ca-channel blockers could be used. administration
(e) Urinary Obstruction o Peak concentration : 1-3 hours after
ingestion
• Benign Prostatic Hyperplasia o Sustained release: Metoprolol and
• Agents: Prazosin, Doxasozin, Terazosin and Propranolol
Tamsulosin • Bioavailability
• Used to improve urine flow involving partial o Propranolol: low bioavailability with
reversal of smooth muscle contraction in the extensive hepatic metabolism
enlarged prostate thatmhelps improve
symptoms of BPH • Distribution

• All of the agents are used to manage BPH o Large volume of distribution
and Hypertension except for Tamsulosin. (Propranolol and Penbutolol are
lipophilic that it crosses the BBB
(f) Erectile Dysfunction o Half life: 3-10 hours to almost al B-
• Agents used: Phentolamine with non- blockers except esmolol with 10
specific smooth muscle relaxant PAPVERINE minutes half life.

• Injected directly in the penis

• May cause erection in men

• SE: Long-term: Fibrotic reactions,

Orthostatic hypotension and Priapism

• Priapism can be treated with phenylephrine

• Other agents: prostaglandins, sildenafil and

CGMP inhibitors

III. BASIC PHARMACOLOGY OF BETA-

RECEPTOR ANTAGONIST DRUGS

• Competitive and Irreversible block

• Epinephrine and Isoproterenol partially
block B-receptors.
• Classified based ion its affinities
• The selectivity is based on the dose of the
drug
• Has a local anesthetic effect.
 o the metabolic process through which
triacylglycerols
II. PHARMACODYNAMICS
o (TAGs) break down via hydrolysis into
a. Effects on the CARDIOVASCULAR SYSTEM their constituent molecules: glycerol
and free fatty acids (FFAs).
• Used in the management of Hypertension
o Used to mobilize stored lipids for
with no event of Orthostatic hypotension
energy during fasting and exercise
• Used in the treatment of Angina and Chronic
• Effect in Glycogenolysis through B2
Heart Failure following Myocardial infarction,
Inhibition is not clear though this inhibition is
has an effect in the PR interval that may
partially inhibited.
influence vasodilation
o Used in caution by diabetic patients
• Selective B1 receptor blockers antagonizes
(IDDM) and in patents that undergoes
the release of RENIN caused by sympathetic
pancreatectomized
activation.
o Safer to type-2 diabetic patients
• Chronic drug administration may lead to fall
• Chronic use maybe associated with
in peripheral resistance in patients with
increased plasma concentration of VLDL with
hypertension.
declined HDL
b. Effects in the Respiratory Tract
o Unfavorable to patients with
• B2 blockers: increase airway resistance or cardiovascular problem
bronchodilation; effective to Asthmatic
e. Effects not related to Beta-Blockade
patients
• Applies to partially anatagonistic B blocker:
• B1 receptor antagonist (metoprolol and
contraindicated to asthmatic and COPD
atenolol) is advantageous over non selective B
patients; could also cause excessive
receptor blockers when B1 receptor in the
bradycardia.
heart is desired and b2 blocker is undesired.
• However, B-blockers are also used clinically
o Hypertensive and Asthmatic
t0 produce Bradycardia and
o On the other hand, patients with
Bronchoconstriction
COPD can tolerate a nonselective B
blockers. • It also has Local anesthetic action or
membrane- stabilizing action of several B-
c. Effects on the eye
blockers
• Used in Glaucoma to reduce IOP.
o Attributed to its ability to block
• MOA: Decreases aqueous humo
sodium channels
o Not used in the EYE because it is
UNDESIRABLE

• ONLY SOTALOL do not have a local

anestheticeffect
d. Metabolic and Endocrine Effects
• Partial antagonistic B-blockers are effective
• Agent: PROPRANOLOL-inhibits sympathetic as antihypertensive agents in managing
nervous system through stimulation of hypertension and Angina
LIPOLYSIS
 • Betaxolol- B1 selective antagonist with slight
local anesthetic action

Indication: used in the treatments to

III. Specific Agents
open-angle glaucoma
• Propranolol: Non-selective Beta blocker; no
partial agonistic activity with Local anesthetic • Carteolol- none-selective beta blocker with
action. partial agonistic action

o Has effects both in a and muscarinic -Indication: used in the managements of

receptors but blocks the serotonin hypertension and treatment of glaucoma
levels of the brain
Labetalol-reversible adrenoceptor ntagonist
o Indication: B-blockers as
available as racemic mixture
antihypertensive agent, tx symptoms
of anxiety (tachycardia) and prevent -(S,S) and (R,S) are INACTIVE
migraines.
-(S,R) potent a-blocker and (R,R) isomer is a
• Metoprolol and Atenolol: Beta-1 selective potent B-blocker
antagonist without partial agonistic effect.
-Indication: used in the management of
o Metoprolol has a local anesthetic hypertension during pregnancy
action
• Carvedilol- non-selective B-blockers that
o Indication: Used to manage
blocks a1-adrenergic effects
Hypertension; beneficial to patients
with asthma, COPD and Diabetic -Has greater B-blocking effects than a1-
patients blocking effects
• Nebivolol-B1-selective antagonist without -Half life: 6-8 hours
local anesthetic action
-Indications: used in the management of
o Elicits vasodilation due to its action in chronic heart failure
endothelial nitric oxide production
Esmolol-
o Indication: Used as antihypertensive
agent especially to patients with MI • Ultra-short acting B-blocker
• 10 minutes
• Nadolol-non-selective B-blockers with very
• Considered safer than long-acting b-
long duration of action. blockers
o Used to manage hypertension and • Indications: used to manage arrythmias
associated with thyrotoxicosis, perioperative
Angina pectoris
hypertension and myocardial ischemia.
• Timolol-non-selective B-blockers with no
local anesthetic activity
IV. CLINICAL PHARMACOLOGY OF BETA-
Indication: used in the treatment and BLOCKING DRUGS
management of open-angle glaucoma and
(a) Hypertension
ocular hypertension.
• Beta-blockers are usually combined with
• Levobunolol- non-selective B- blockers diuretics or vasodilator
Indication: used in the treatment to open- • Prescribed once or twice daily
angle glaucoma • (Chapter 6)
 • Beta blockers are used to treat dissecting
aortic aneurysm

(b) Ischemic Heart Disease

(e) Glaucoma
• Also known as Coronary Heart Disease • B-blockers are used in glaucoma as it is
(CHD) involved in the reduction of aqueous humor
• Blocked / narrowed coronary arteries due to
production.
fat deposits.
• Manifested with Angina pectoris • B-blockers used should have no anesthetic
• B-receptors reduces frequency of anginal effect because it is contraindicated.
episodes and improve exercise tolerance in
many patients with angina. • Agent: Timolol (for glaucoma: 1mg)
-Blockade of Cardiac B receptors, resulting in
• This agent is also used in HPTN in 10- 60mg
decreased cardiac work and reduction in
oxygen demand. • Other agents: Bataxolol, Carteolol,
Levobunolol, and Metipranolol
• Indicated to patients with myocardial
infarction and acute coronary syndrome • B1 selective antagonist
• Common agents: Timolol, Propranolol and
Metoprolol • AE: worsening of pulmonary symptoms
• Contraindicated to: Patients with
bradycardia, hypotension, moderate or severe
left ventricular failure, shock, heart block and (f) Hyperthyroidism
active airways disease
• Caused by excessive catecholamine action
(c) Cardiac Arrythmias (especially in the heart)

• MOA: prevents the action or conversion

• Treatment to supraventricular and
thyroxine to triiodothyronine.
ventricular arrythmias; prescribed to patients
with Myocardial Infarction • Agent: Propranolol( used to address thyroid
• These drugs can also reduce ventricular storm); reduces supraventricular tachycardias
ectopic beats, particularly if the ectopic that often precipitate to heart failure.
activity has been precipitated by (g) Neurologic Disorders
catecholamines.
• Sotalol has antiarrhythmic effects involving • Reduces frequency of headache/migraine
ion channel blockade in addition to its β- • Agents: metoprolol, atenolol, timolol and
blocking Action nadolol

• Also used in controlling tremors

(d) Heart Failure and Other Cardiovascular
disorders • Agent: low dose propranolol
• Agents in heart failure: Metoprolol,
• Propranolol are also used prophylactically in
Bisoprolol and Carvedilol
performance anxiety (stage fright)
• Beta blockers are used to treat
Cardiomyopathy (h) Miscellaneous
• Inability of the heart to pump properly
(muscle weakness)
• B-receptors found to diminish portal vein -B1 adrenoceptor blockers are more
pressure in patients with cirrhosis suggested considering the recovery to
hypoglycemia in diabetic patients.
• Agents: Propranolol and Nadolol

• Sclerotherapy in prevention of rebleeding in

patients with

esophageal varices

• Agents: Nadolol + Isosorbide mononitrate

• Other treatment: Variceal band ligation with

B-blockers.

V. CHOICE OF A BETA- ADRENOCEPTOR

ANTAGONIST DRUG

• Propranolol- Newer B-antagonist drug that

is widely used because of its safer and more
effective effects; used as prophylaxis in
Myocardial Infarction

VI. CLINICAL TOXICITY OF BETA- RECEPTOR

ANTAGONIST

• Most common: Bradycardia

• Other AE: coldness of hands and feet CNS

effects (sedation, vivid dreams and
depression)

• Major effects: worsening of asthma and

COPD especially in non-selective B-blockers

• Depression of myocardial contractility and

excitability (counteracted with isoproterenol
or glucagon)

• CI: Calcium antagonist (hypotension.

Bradycardia, heart failure, cardiac conduction
abnormalities. –also applies upon using an
ophthalmic beta blocker and an oral
verapamil.

• Sudden discontinuation of B blocker may

worsen Ischemic Heart Disease or
renovascular hypertension

-Tapering is advised especially in Propranolol

and Metoprolol

• B blockers in diabetic patient could cause

HYPOGLYCEMIA.