BETA BLOCKERS

PRESETED BY :GROUP 10
➢ QAMAR IQBAL (06331913064)
➢ MUHIB ULLAH (06331913067)
➢ ZAHID ALI (06331913066)
➢ MADIHA HAFIZ (06331913065)
➢ SHEEMA FAZAL (06331913063)
➢ HIRA ALI (06331913068)
Beta blockers
(introduction and
pharmacokinetics)

Presented by : QAMAR IQBAL

ROLL NO : 06331913064
INTRODUCTION TO BETA
BLOCKERS
▪ Beta blockers are competitive antagonists that block the receptor sites
for the endogenous catecholamines epinephrine (adrenaline)
and norepinephrine (noradrenaline) on adrenergic beta receptors, of
the sympathetic nervous system, which mediates the fight-or-flight
response.
▪ Some block activation of all types of β-adrenergic receptors and others
are selective for one of the three known types of beta receptors,
designated β1, β2 and β3 receptors.
▪ Beta receptors are found on cells of the heart muscles, smooth muscles,
airways, arteries, kidneys, and other tissues that are part of the
sympathetic nervous system and lead to stress responses, especially
when they are stimulated by epinephrine (adrenaline). Beta-blockers
interfere with the binding to the receptor of epinephrine and other stress
hormones and weaken the effects of stress hormones.
CONTINUE..
➢ Nonselective beta blockers (e.g., pindolol, propranolol) inhibit all β
receptors and may cause bronchoconstriction, peripheral
vasoconstriction and metabolic imbalances (e.g., hypoglycemia
and hyperglycemia, hypertriglyceridemia) in addition to cardiac
effects.
➢ Cardio-selective beta blockers have a lower side-effect profile and
are preferred in the management of coronary heart disease,
compensated heart failure, acute coronary syndrome and certain
types of arrhythmias.
➢ Propranolol a nonselective beta blocker, is the first-line drug in the
management of essential tremor, portal hypertension, migraine
prophylaxis, and thyroid storm
CLASSIFICATION OF BETA
BLOCKERS
PHARMACOKINETICS OF BETA
BLOCKERS
Absorption:
▪ Most of the drugs are well absorbed after oral administration.
▪ Peak concentrations occur 1-3 hours after ingestion.
▪ Propranolol and metoprolol are also available in sustained release.

BIOAVAILABILITY:
➢Propranolol undergoes extensive first pass effect so its bioavailability
is relatively low.
➢As the first pass effect varies among individuals so there is great
individual variability in plasma concentration achieved after oral
administration of propranolol.
➢So, the bioavailability is limited except, pindolol, sotalol, betaxolol and
penbutolol.
 PHARMACOKINETICS
DISTRIBUTION AND CLEARANCE:
➢the beta antagonists are rapidly distributed and thus have
large volume of distribution .
➢Most beta antagonists have half lives In the range 3-10
hours.
➢EXCEPTION : emolol have half life of approx 10 min .
➢Propranolol and penbutolol are quite lipophilic so they can
cross BBC(blood brain barrier).
➢Propranolol and metoprolol are extensively metabolized in
liver little unchanged drug appears in urine.
➢Atenolol, celiprolol and pindolol are less completely
metabolized.
Continue…
▪ Nadolol: have extensive high life among all. It is
excreted unchanged in urine.
▪ Shortest- Esmolol
▪ Ultra short acting blocker
▪ Inactivated by esterases in blood
▪ Plasma t1/2 < 10 min
▪ Rapid onset, short lasting effect
▪ Intravenous in emergency
THANK YOU ALL…..

ANY QUESTIONS?
Pharmacodynamics of Beta Blockers

Muhib Ullah
06331913067
Group 10
Pharmacodynamics
The study of the biochemical and physiologic
effects of drugs.
Beta Blocker Drugs
Are beta receptor antagonists which occupy or block
the beta1 and beta2 receptors.
Some actions may be due to other effects, including
partial agonist activity at beta receptors and local anesthetic
action.
EFFECTS
▪ Effects of Beta Blockers are discussed below on following.
➢HEART
▪ BBD acts B1 receptor present on conduction system and
ventricular myocardium.
▪ Decreases Heart rate and contractility.
▪ Decreases BP which is desired in patients with Hypertension.
▪ Decrease in BP decreases actual conduction effect in
arrhythmic patients.
➢Kidney
▪ BBD acts on B1 receptor of JG cells resulting in low renin
production.
▪ Hence production of Angiotensin I and Angiotensin II also
decreases.
▪ Which results in the reduction of BP by inhibiting
vasoconstrictive mechanism and inhibiting aldosterone and
ADH production. In this way reabsorption of sodium and
water is decreased.
➢Lungs
▪ Beta blockers acts on B2 cells present in bronchial smooth
muscles particularly, causes bronchoconstriction or
bronchospasm.
▪ Hence causing airway resistance.
▪ These drugs should be avoided in patients having asthma while
COPD patients may tolerate these drugs quite well.
➢Eye
▪ Beta Blocker Drugs acts on B2 receptors of Ciliary muscles
of eye.
▪ Results in decreased production of aqueous humor which
entails low intraocular pressure.
▪ These Drugs have significant value for patients having
Glaucoma.
➢Metabolic effects
▪ When BBD acts on B2 receptors pancreatic cells, reduction
in glucagon production also affects glucose production.
▪ Effect in liver is also same when these drugs binds with B1
receptors.
▪ These drugs are important in conditions like hypoglycemia.
▪ When these drugs binds with B2 receptors on gastric
smooth muscle.
▪ This decreases GI motility which may impair secretion
and cause mild diarrhoea.
▪VASCULAR SYSTEM
▪ Acts on B2 receptor present on vascular smooth muscles,
resulting in mild vasoconstriction leading to minor drop in
blood flow to muscle tissue.
▪ Also decreases the expression of lipoprotein lipase by
blocking capillary endothelium results in increase of
triglycerides.
Specific agents
Presented by: ZAHID ali
06331913066
Specific agents:
Following are the beta blocker (B-receptor antagonist)

classification
First generation:(non selective)
 Propranolol
 Timolol
 Sotalol
 Pindolol
 Nadolol
Second generation (Beta 1 selective)
 Metoprolol
 Atenolol
 Acebutolol
 Bisoprolol
 Esmolol

Third generation(additional alpha1blocking)

 Labitalol
 Carvedilol
 Celiprolol
 Nebivolol
Propranolol:
 It is non selective prototypical B- blocking drug
 It has low and dose dependent bioavailability
 No partial agonist activity
 Half life is 3.5 to 6 hr
 It has also local anesthetic action

Timolol:
 Non selective beta blocker
 No partial agonist activity
 It has no local anesthetic action
 Half life is 4 to 5 hr
Sotalol:
 Non selective beta blocking
 No partial agonist activity
 No membrane stabilizing action
 Low lipid solublity
 Half life is 12 hr

Acebutolol:
 Selectiv beta 1blocking drug
 It has partial agonist activity
 It has local anesthetic action
 Low lipid soluble

Atenolol:
 Beta 1 selective blocking drug and no partial agonist activity
 No membrane stabilizing action
 Lipid solublity is low
 Half life is 6 to 9 hr
 Metoprolol:
 Selective beta 1 blocking drug
 No partial agonist activity
 And has membrane stabilizing action
 Moderate lipid solublity
 Half life is 3 to 4 hr

Labetalol:
 Non selective beta blocking drug with additional alpha blocking activity
 Partial agonist activity
 It has membrane stabilizing action
 Half life is 5 hr
Carvedilol:

 Non selective beta blocking drug with additional vasodilatio

property
 No partial agonist activity
 No membrane stabilizing action
 Moderate lipid solublity
 Half life is 7 to 10 hr
Thank you
CLINICAL PHARMACOLOGY
OF THE BETA-RECEPTOR-
BLOCKING DRUGS
Presented by:
Madiha Hafiz
06331913065
1: Hypertension:
› The β-blocking drugs have proved to be effective and well tolerated in
hypertension.
› Although many hypertensive patients respond to a β blocker used alone,
the drug is often used with either a diuretic or a vasodilator.
› β blockers effective in lowering blood pressure are:
Propranolol:
• The first β blocker shown to be effective in hypertension.
• Non selective β blocker
• Decreases Cardiac Output and hence B.P
• Inhibits stimulation of renin
• Depressing the renin-angiotensin-aldosterone system which ultimately
decreases systemic vascular resistance and hence B.P
• In mild to moderate hypertension, it produces a significant reduction in
B.P without prominent postural hypotension.
Metoprolol & Atenolol
› Cardioselective
› most widely used
› Metoprolol is almost equipotent to propranolol in inhibiting stimulation of β1
adrenoceptors
› But it is 50-100 fold less potent than propranolol in blocking β2 receptors
[relative selectivity for β1 receptor]
› Cardioselectivity is of advantage in hypertensive patients also suffering from
asthma, diabetes, or peripheral vascular disease.
› metoprolol causes less bronchial constriction than propranolol.
Labetalol, Carvedilol
› These drugs have both β-blocking and vasodilating effects.
› Labetalol has a 3:1 ratio of β:α antagonism after oral dosing. It is useful in
treating the hypertension of pheochromocytoma and hypertensive
emergencies.
› B.P is lowered by reduction of systemic vascular resistance without significant
alteration in heart rate or cardiac output.
› Carvedilol reduces mortality in patients with heart failure.
Esmolol
› β1 -selective blocker
› Esmolol is used for management of intraoperative and postoperative
hypertension, and sometimes for hypertensive emergencies, particularly
when hypertension is associated with tachycardia.
Pindolol, Acebutolol, & Penbutolol
› These are partial agonists, i.e., β blockers with intrinsic sympathomimetic
activity
› They lower B.P by decreasing vascular resistance and appear to depress
cardiac output or heart rate less than other β blockers
› perhaps because of significantly greater agonist than antagonist effects
at β2 receptors.
› This may be particularly beneficial for patients with bradyarrhythmias or
peripheral vascular disease.
2: Ischemic Heart Disease:
› β blockers reduces the frequency of anginal episodes and improves
exercise tolerance in many patients with angina.
› M.O.A: These actions relate to the blockade of cardiac β receptors
resulting in decreased heart rate, decreased blood pressure, and
contractility which ultimately decrease myocardial oxygen requirements
at rest and during exercise
› Beta blockers may also be valuable in treating silent or ambulatory
ischemia.
› Beta-blocking agents like timolol, propranolol or metoprolol decrease
mortality of patients with heart failure or recent myocardial infarction
and improve survival and prevent stroke in patients with hypertension.
› In addition, β blockers are strongly indicated in the acute phase of a
myocardial infarction.
› CONTAINDICATIONS include bradycardia, hypotension, moderate or
severe left ventricular failure, shock, heart block, and active airways
disease.
3: Cardiac Arrhythmias
› β antagonists are often effective in the treatment of both supraventricular and
ventricular arrhythmias
› By increasing the atrioventricular nodal refractory period, β antagonists slow
ventricular response rates in atrial flutter and fibrillation.
› These drugs can also reduce ventricular ectopic beats, particularly if the ectopic
activity has been precipitated by catecholamines.
› Propranolol and similar drugs have antiarrhythmic properties by virtue of their
β-receptor-blocking action and direct membrane effects
› Although β blockers are fairly well tolerated, their efficacy for suppression of
ventricular ectopic depolarization is lower than that of sodium channel blockers
› These agents can prevent recurrent infarction and sudden death in patients
recovering from acute myocardial infarction
› Esmolol is a short-acting β blocker used primarily as an antiarrhythmic drug for
intraoperative and other acute arrhythmias
› Sotalol is a nonselective β-blocking drug that prolongs the action potential
involving ion channel blockade in addition to its β-blocking action.
4: Heart Failure
› Three β antagonists— metoprolol, bisoprolol, and carvedilol—are
effective in reducing mortality in selected patients with chronic heart
failure
› Although administration of these drugs may worsen acute congestive
heart failure, cautious long-term use with gradual dose increments in
patients who tolerate them may prolong life.
Other Cardiovascular Disorders
› β antagonists have been found to increase stroke volume in some
patients with obstructive cardiomyopathy.
› This effect is thought to result from the slowing of ventricular ejection
and decreased outflow resistance.
› Beta antagonists are useful in dissecting aortic aneurysm to decrease the
rate of development of systolic pressure.
› Beta antagonists are also useful in selected at-risk patients in the
prevention of adverse cardiovascular outcomes resulting from non-
cardiac surgery.
In a world full of HYPERTENSION… be someone's
beta-blocker…
CLINICAL USE OF BETA BLOCKERS
Presented by : SHEEMA FAZAL
( 0633191063)
■ Glaucoma
■ Glaucoma is a group of eye conditions that damage the optic
nerve,. This damage is often caused by an abnormally high
pressure in eye.
■ Beta – 2 receptors in Ciliary epithelium increase aqueous humor
secretion. Which increase intraocular pressure.
■ Beta blockers reduce this intraocular pressure in glaucoma
patients by reducing the aqueous humor production .
■ MECHANISM
■ Topical beta-blockers reduce the intraocular pressure (IOP) by
blockade of sympathetic nerve endings in the ciliary epithelium
causing a fall in aqueous humour production.
■ Timolol and related beta antagonists are suitable for local use in the
eye because lack anesthestic properties.
■ Betaxolol, carteolol and netipranolol are also approved for treatment
of glaucoma.
As these beta blockers are effective in reducing intraocular pressure by
decreasing aqueous humor production by ciliary bodies which is
physiological activated by cAMP.
■ HYPOGLYCEMIA UNAWARENESS
■ Normally Adrenaline activate beta 2 receptor in liver and pancreas alpha cell,
which glucose production by gluconegenis and glycogenolysis, inhibit
glucagon production leading hypoglycemia.
■ Beta blockers block the beta receptor in liver, no Adrenaline bind, inhibit
glucose production through gluconegenis and glycogenolysis so there is
decrease in glucose level which is important in diabetic patients.
■ HYPERTHYROIDISM
■ In many tissues, hyperthyroidism is associated with an increased
number of beta-adrenergic receptors.The ensuing increase in beta-
adrenergic activity is responsible for many of the symptoms associated
with this disorder.
■ Beta blockers effects Adrenoeptors activity results in decrease receptor
sensitivity, inhibition of peripheral conversion of thyroxine to triiodothyronine,
By decrease thyroid hormone secretion.
■ Propranolol has been use extensively in pateint with thyroid storm.
. Propranolol will not only help control the symptomatic tachycardia and tremors
associated with thyroid storm, but shows propranolol may also known to inhibit
the monodeiodinase type I enzyme responsible for conversion of T4 to the more
biologically potent T3 hormone.This reduction in T4's metabolism, via the
inhibition of monodeiodinase type I, may cause the T4 to then be shunted through
the enzyme monodeiodinase type Iil resulting in the production of 3,3',5'-
triiodothyronine Reverse T3 is known to be metabolically inactive.
NEUROLOGICAL DISEASES
■ Migraine Headache
■ Migraine Headache is regulated by blood flow to brain due to blood vessels dilation.
■ Beta-blockers reduce blood vessel dilation, which is known to contribute to migraine.
Restrict blood flow in the brain.by vasoconstriction of vessels.
■ TREMOR
■ BETA 2 in muscles spindles cause contraction due to epinephrine or norepinephrine
binding, increase action potential through these sensory receptor and therefore
increase potential through motor fiber causing TREMOR.
■ Beta blocker block these receptors, no TREMOR produced.
■ Anxiety
■ Sympathetic activity Cause anxiety i.e., shortness of breath, palpitations.
■ Beta blockers inhibit sympathetic activity to control physical symptoms.
■ Propranolol reduce the frequency and intensity of migraine headache.
■ Other beta receptor antagonists metaprolol and also atenolol timolol
is use.
TOXICITY AND
CONTRAINDICATIONS
OF BETA BLOCKERS

PRESENTED BY: HIRA ALI

ROLL NO : 06331913068
CONTRAINDICATIONS
1) Asthma, COPD (chronic obstructive
pulmonary disease )
2) Prinzmetals angina
3) Bradycardia Heart Block
4) Decompensated heart failure
5) Peripheral Vascular disease
6) Bradycardia.
7) Diabetes mellitus
ADVERSE EFFECTS (NON SELECTIVE
AND CARDIOSELECTIVE BETA BLOCKERS )
CARDIAC:
▪ Bradycardia
▪ Bradyarrythmia
▪ Ventricular tachyarrythmia.
▪ Worsened heart failure.
▪ Orthostatic hypotension.
CNS:
➢Fatigue
➢Sleep disorders ,night mares
➢Depression, hallucination
➢Seizure
ADVERSE EFFECT (non-selective
beta blocker (beta 2 antagonist))
PULMONARY:
➢Bronchoconstriction
• Dyspenea
• Bronchospasm
• Exacerbation of asthma and COPD.
PERIPHERAL VASCULATURE :
➢Peripheral vasoconstriction
• Erectile dysfunction
• Secondary Raynaud phenomenon
• Cold extremeties
Continue…..
METABOLIC:
➢Hypertriglyceridemia, low HDL with beta blockers without ISA.
➢Hyperglycemia and new-onset diabetes.
➢Hypoglycemia: they can mask the sympathetic effect of
hypoglycemia (e.g. tachycardia, sweating) leading to dangerous
silent hypoglycemia.
➢Weight gain.
Note:
➢A number of beta blockers (e.g., metoprolol, carvedilol) are
metabolized by CYP2D6. Genetic polymorphisms of CYP2D6
(e.g., ultra-rapid metabolization, poor metabolization) can influence
adverse effects and tolerated doses.
BETA BLOCKER OVERDOSE
➢CLINICAL FEATURES
▪ Bradycardia/bradyarrhythmia
▪ Cardiogenic shock (hypotension cold, clammy extremities)
▪ Hypoglycemia
▪ Hyperkalemia
▪ Wheezing (bronchoconstriction)
▪ Neurological symptoms (seizure, delirium, coma)
TREATMENT FOR THE TOXICITY OF
BETA BLOCKERS
▪ Secure the airways.
▪ Correct cardiovascular decompensation (hypotension, bradycardia and
cardiogenic shock) via IV access:
▪ Fluids (saline) and vasopressors(e.g., epinephrine)
▪ Atropine: to correct bradycardia
▪ Glucagon: antidote for beta-blocker poisoning
▪ Calcium salts: to improve cardiac contractility
▪ High-dose insulin with glucose: If cardiovascular decompensation is
refractory to all of the above-mentioned agents, high-dose insulin is
given for its positive inotropic effect.
▪ Prevent further absorption of beta blocker: activated charcoal/gastric
lavage , IV lipid emulsions (esp. useful in lipophilic beta-blocker
overdose).
▪ Poisoning with hydrophilic beta blockers (e.g., atenolol, nadolol) may
require hemodialysis for removal of the drug from circulation. [27]
WITHDRAWAL OF BETA
BLOCKERS
▪ Beta blockers should be introduced gradually with slow increases in
dosage and slowly tapered off when no longer needed.
▪ Beta-blocker withdrawal.Caused by the sudden termination of beta
blockers

Clinical features
▪ Tachycardia, tachyarrhythmia
▪ Hypertension
▪ Acute coronary syndrome, sudden cardiac death
Prevention:
▪ Taper dose over 7–10 days before discontinuing. [29]
 “I Wish I had my
beta-blockers handy”
-James Black-

On being told that he had won the

Nobel Prize, referring to the drug he
discovered for the treatment of heart
disease.
Thank you
Any Question?