Natural Sources of Drugs e.g. from Microorganisms Prepared by Mustafa Kamal Ahmed Khan, Jamia Hamdard, New Delhi.

1. Presentation
ON
Beta Blockers
‫ہمدرد‬ ‫جامعہ‬

2. Prepared By -
Mustafa Kamal Ahmed Khan.
Subject- Basic Principles of Pharmacology.
Second Presentation.
3rd Semester- 2019.
B.Sc.-M.Sc. Integrated Program
Department of Toxicology.
School of Chemical and Life Sciences.
Jamia Hamdard, New Delhi – 110062.

3. What is Beta Blockers:
 Beta-blockers as a class of drugs are primarily used to treat cardiovascular
diseases and other conditions.
 Beta Blockers are competitive antagonists that block the receptor sites
for
the endogenous catecholamines epinephrine (adrenaline)and norepinephri
ne (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. β1-adrenergic receptors are located mainly in the heart and
in the kidneys. β2-adrenergic receptors are located mainly in the lungs,
gastrointestinal tract, liver, uterus, vascular smooth muscle, and skeletal
muscle. β3-adrenergic receptors are located in fat cells. Blockage of these
receptors by beta-blocking medicines are used to treat a broad range of
illnesses. Beta-blockers as a class of medications are essential drugs and
are first-line treatments in many acute and chronic conditions.

4. Contd.
 In 1964, James Black synthesized the first
clinically significant beta blockers—
propranolol and pronethalol; it revolutionized the
medical management of angina pectoris and is
considered by many to be one of the most
important contributions to clinical medicine
and pharmacology of the 20th century.
 For the treatment of primary hypertension, meta-
analyses of studies which mostly
used atenolol have shown that although beta
blockers are more effective than placebo in
preventing stroke and total cardiovascular events,
they are not as effective as diuretics, medications
inhibiting the renin–angiotensin system (e.g., ACE
inhibitors), or calcium channel blockers.

5. Skeletal formula of propranolol, the first clinically successful beta blocker.

6. Medical Uses:
 Beta blockers are indicated and have FDA approval for the treatment
of tachycardia, hypertension, myocardial infarction, congestive heart
failure, cardiac arrhythmias, coronary artery disease,
hyperthyroidism, essential tremor, aortic dissection, portal
hypertension, glaucoma, migraine prophylaxis, and other conditions.
They are also used to treat less common conditions such as long QT
syndrome and hypertrophic obstructive cardiomyopathy. Beta
blockers are available for administration in three main forms: oral,
intravenous, and ophthalmic and the route of administration is often
determined by the acuity of the illness (parenteral use in
arrhythmias), disease type (topical use in glaucoma) and chronicity
of the disease.
 Congestive heart failure patients are treated with beta blockers if
they are in a compensated state. Specifically, the beta blockers
bisoprolol, carvedilol, and metoprolol succinate are the agents
chosen.

7. Contd.
Performance-enhancing use
 Athletes and musicians may use beta blockers for their anxiolytic
effect as well as their inhibitory effects on the sympathetic
nervous system. Because they promote lower heart rates and
reduce tremors, beta blockers have been used in professional
sports where high accuracy is required,
including archery, shooting, golf and snooker. Beta blockers are
banned by the International Olympic Committee. In the 2008
Summer Olympics, 50-metre pistol silver medalist and 10-metre
air pistol bronze medalist Kim Jong-su tested positive
for propranolol and was stripped of his medals.

8. Mechanism of Action:
 The catecholamines, epinephrine, and norepinephrine
bind to B1 receptors and increase cardiac automaticity as
well as conduction velocity. B1 receptors also induce
renin release, and this leads to an increase in blood
pressure. In contrast, binding to B2 receptors causes
relaxation of the smooth muscles along with increased
metabolic effects such as glycogenolysis.
 Beta-blockers vary in their specificity towards different
receptors and accordingly the effects produced are
determined by the type of receptor(s) blocked as well as
the organ system involved. Some beta blockers also bind
to alpha receptors to some degree, allowing them to
induce a different clinical outcome when used in specific
settings.

9. Contd.
 Once beta blockers bind to the B1 and B2 receptors, they inhibit these
effects. Therefore, the chronotropic and inotropic effects on the heart
undergo inhibition, and the heart rate slows down as a result. Beta
blockers also decrease blood pressure via several mechanisms, including
decreased renin and reduced cardiac output. The negative chronotropic
and inotropic effects lead to a decreased oxygen demand; that is how
angina improves after beta-blocker usage. These medications also
prolong the atrial refractory periods and have a potent antiarrhythmic
effect.
 Beta-blockers classify as either non-selective and beta-1 selective.
There are also beta-2, and beta-3 selective drugs; neither has a known
clinical purpose to date. Non-selective agents bind to both beta-1 and
beta-2 receptors and induce antagonizing effects via both receptors.
Examples include propranolol, carvedilol, sotalol, and labetalol. Beta-1
receptor selective blockers like atenolol, bisoprolol, metoprolol, and
esmolol only bind to the beta-1 receptors therefor are cardio-selective.

10. Contd.
 Beta-blockers lower the secretion of melatonin and hence
may cause insomnia and sleep changes in some patients.
 Alpha-1 receptors induce vasoconstriction and increased
cardiac chronotropy; this means agonism at the alpha-1
receptors leads to higher blood pressure and an increased
heart rate. In contrast, antagonism at the alpha-1 receptor
leads to vasodilation and negative chronotropic which leads
to lower blood pressure and decreased heart rate. Some beta
blockers, such as carvedilol, labetalol, and bucindolol, have
additional alpha-1 receptor blockage activity in addition to
their non-selective beta receptor blockage. This property is
clinically useful because beta blockers that also block the
alpha-1 receptor have a more pronounced clinical effect on
treating hypertension.

11. Administration:
 Beta blockers are available in oral, intravenous, or
ophthalmic form and can be also injected
intramuscularly.
 Dosages are available in various ranges, depending
on the specific medication.

12. Adverse Effects:
 Beta receptors are found all over the body and induce a broad
range of physiologic effects. Blockage of these receptors with
beta-blocker medications can lead to many adverse effects.
Bradycardia and hypotension are two adverse effects that
may commonly occur. Fatigue, dizziness, nausea, and
constipation are also widely reported. Some patients report
sexual dysfunction and erectile dysfunction.
 Less commonly, bronchospasm presents in patients on beta
blockers. Asthmatic patients are at a higher risk. Patients with
Raynaud syndrome are also at risk of exacerbation. Beta
blockers can induce both hyper glycemia and mask the
hemodynamic signs usually seen in a hypo glycemic patient,
such as tachycardia.

13. Contd.
 Some patients report insomnia, sleep changes and
nightmares while using beta blockers. This effect is more
pronounced with beta blockers that cross the blood-brain
barrier.
 Carvedilol may increase edema in some patients.
 Sotalol blocks the potassium channels in the heart and
thereby induces QT prolongation. It increases the risk of
torsades de pointes.
 All beta blockers, especially in patients with cardiac risk
factors, carry a risk of heart block.

14. Contra indications:
 Traditionally, beta blockers have been contraindicated
in asthmatic patients. However, recommendations have
aligned for allowing cardio-selective beta blockers, also
known as beta-1 selective, in asthmatics but not non-
selective beta blockers.
 Beta blockers should not be used in patients who have
cocaine-induced coronary vasospasm. There is a
significant risk of unopposed alpha receptor activity
which would worsen the vasospasm. Agonist activity at
the alpha receptor leads to increased vasoconstriction
and increased cardiac chronotropy.

15. Contd.
 Patients who have either acute or chronic
bradycardia and/or hypotension have relatively
contraindication to beta-blocker usage.
 Specific beta blockers are contraindicated depending
on the patient's past medical history. Patients
diagnosed with long QT syndrome or who have had
torsades de pointes in the past should not use the
drug sotalol. Patients with Raynaud phenomenon
should avoid beta blockers due to the risk of
exacerbation.

16. Monitoring:
The patient's heart rate and blood pressure
should be generally monitored while using beta
blockers. When specifically using sotalol, the
QTc interval requires monitoring as sotalol has
QT-prolonging effects.

17. Toxicity:
The antidote for beta-blocker
overdose is glucagon. It is especially
useful in beta-blocker-induced
cardiotoxicity. The second line of
treatment is cardiac pacing if glucagon
fails.

18. Intrinsic sympathomimetic activity:
 Also referred to as intrinsic sympathomimetic effect, this term is used
particularly with beta blockers that can show both agonism and
antagonism at a given beta receptor, depending on the concentration of
the agent (beta blocker) and the concentration of the antagonized agent
(usually an endogenous compound, such as norepinephrine). See partial
agonist for a more general description.
 Some beta blockers
(e.g. oxprenolol, pindolol, penbutolol, labetalol and acebutolol) exhibit
intrinsic sympathomimetic activity (ISA). These agents are capable of
exerting low-level agonist activity at the β-adrenergic receptor while
simultaneously acting as a receptor site antagonist. These agents,
therefore, may be useful in individuals exhibiting
excessive bradycardia with sustained beta blocker therapy.
 Agents with ISA are not used after myocardial infarctions, as they have not
been demonstrated to be beneficial. They may also be less effective than
other beta blockers in the management of angina and tachyarrhythmia.

19. Examples:
Nonselective agents:
 Nonselective beta blockers display both β1 and β2 antagonism.
 Propranolol
 Bucindolol (has additional α1-blocking activity)
 Carteolol
 Carvedilol (has additional α1-blocking activity)
 Labetalol (has additional α1-blocking activity)
 Nadolol
 Oxprenolol (has intrinsic sympathomimetic activity)
 Penbutolol (has intrinsic sympathomimetic activity)
 Pindolol (has intrinsic sympathomimetic activity)
 Sotalol (not considered a "typical beta blocker")
 Timolol

20. β1-selective agents:
β1-selective beta blockers are also known as
cardioselective beta blockers.
 Acebutolol (has intrinsic sympathomimetic activity, ISA)
 Atenolol
 Betaxolol
 Bisoprolol
 Celiprolol (has intrinsic sympathomimetic activity)
 Metoprolol
 Nebivolol
 Esmolol

21. β2-selective agents:
 Butaxamine
 ICI-118,551
β3-selective agents:
 SR 59230A
β1 selective antagonist and β3 agonist agents:
 Nebivolol

22. *Thank You*