Pharmacology Lecture Slides on Antihypertensives- Beta Blockers by Sanjaya Mani Dixit Assistant Professor of Pharmacology at Kathmandu Medical College

1. Beta Blockers
(Antihypertensive Agents)
Sanjaya Mani Dixit
Assistant Prof of Pharmacology

2. Contents
• Anti-adrenergic drugs
• B receptor details
• Beta blockers
• Classification
• Mechanism of Action
• Effects
• Uses
• Adverse Effects
• Specific Drugs
• Differences

3. Anti-adrenergics
• Sympatholytic
• Block or decrease the effects of sympathetic
nerve stimulation, endogenous
catecholamines and adrenergic drugs
• Adrenergic receptor antagonists inhibit the
interaction of NE, Epi and other
sympathomimetic drugs with alpha and beta
receptors.

4. Anti-adrenergics
1. Drugs that induce depletion of catecholamines
from various body tissues
Eg. Reserpine
2. Drugs interfering with the synthesis of adrenergic
transmitter either in adrenergic neurone or in the
adrenal medulla.
Eg. Methyl tyrosine
3. Drugs that interfere with the transmission of
impulses
Eg. Guanethidine
4. Drugs that block the adrenergic receptors directly
Eg. Aplha and beta adrenergic blocking agents

8. Adrenergic receptors

10. Beta adrenergic blockers
Classification
• Mixed Alpha & Beta blocker—Labetalol, Carvedilol
• Cardioselective beta 1 blockers
Acebutolol, atenolol, metoprolol
• Non-selective b1 and b2 blockers
Propranolol -- membrane stabilizer (ms)
Pindolol --ms & intrinsic
sympathomimetic
Timolol --selective beta blockers

11. Beta adrenergic blockers-Generations
There are 3 currently available generations of beta-
blockers:
• 1st generation is non-selective (propranolol,
sotalol, etc),
• 2nd is beta1-selective (“cardioselective”)
(metoprolol, bisoprolol, atenolol, etc),
• 3rd shows additional vasodilating effects
(carvedilol, nebivolol, etc), most effective in the
decrease of blood pressure.

12. Beta adrenergic blockers- MoA
Competitive beta-adrenoceptor blockade
• Bind to beta-adrenoceptors and thereby block
the binding of norepinephrine and
epinephrine
• This inhibits normal sympathetic effects that
act through these receptors.
• Therefore, beta-blockers are sympatholytic
drugs.
• Act selectively and competitively on beta
adrenoceptors.
• Inhibit cell membrane adenylyl cyclase and
decrease the production of cAMP.

13. Beta adrenergic blockers- MoA
Intrinsic sympathomimetic activity (ISA)-Pindolol
• Some beta-blockers, partially activate the receptor
while preventing NE from binding to the receptor.
• These partial agonists therefore provide some
"background" of sympathetic activity while preventing
normal and enhanced sympathetic activity. Such beta-
blockers (partial agonists) are said to possess ISA.
Membrane stabilizing activity (MSA)-Propranolol
• Some beta-blockers also possess membrane stabilizing
activity. This effect is similar to the membrane
stabilizing activity of sodium-channels blockers that
represent Class I anti-arrhythmics.

14. Beta adrenergic blockers- MoA

15. Beta blockers
• Propranolol is prototype
• Useful in treatment of hypertension, dysrhythmias, angina pectoris,
MI
• Useful in pheochromocytoma in conjunction with alpha blockers
(counter catecholamine release)
• Migraines
• In cirrhosis, Propranolol may decrease the incidence of bleeding
esophageal varices
• Used to be contraindicated in heart failure, now are standard
• Known to reduce sudden death in MI
• Often given with ACEIs
• Indications include: HTN, angina, prevention of MI

16. b-adrenergic receptor antagonists
Pharmacological effects
 Decreased CO & HR
 Reduced renin release
 Increase VLDL, Decrease HDL
 Inhibit lipolysis
 Inhibit compensatory
glycogenolysis and glucose
release in response to
hypoglycemia
 Increase bronchial airway
resistance
Propranolol
(Inderal)

17. Effects of beta blocking drugs
• Negatively inotropic, chronotropic, & dromotropic
• Decreased oxygen demand (anti-angina)
• Decreased CO and BP in hypertensive patients.
• Decreased automaticity of ectopic pacemakers
• Decreased renin secretion from kidneys
• Broncho-constriction, increased air way resistance
• Less effective metabolism of glucose. May result
in more pronounced hypoglycemia
• Decreased production of aqueous humor in eye
• May increase VLDL and decrease HDL
• Diminished portal pressure in clients with cirrhosis

18. Beta blocking medications
• Mainly for cardiovascular disorders (angina,
dysarhythmias, hypertension, MI and glaucoma)
• In angina, beta blockers decrease myocardial oxygen
consumption by decreasing rate, BP and contractility.
Slows conduction both in SA node and AV node.
• In glaucoma, reduce intraocular pressure by binding to
beta-adrenergic receptors in ciliary body, thus
decrease formation of aqueous humor
• May worsen condition of heart failure as are negative
inotropes
• May reduce risk of “sudden death” following MI

19. Advantages of selective beta-1 antagonists
• No bronchospasm
• No peripheral vasoconstriction: peripheral
vascular diseases
• No metabolic effects: useful in diabetes
mellitus

20. Therapeutic uses for b-
adrenergic receptor antagonists:
• Hypertension
• Angina
• Cardiac arrhythmias
• Migraine
• Stage fright
• Thyrotoxicosis
• Glaucoma
• Congestive heart failure (types II and III)

21. Side effects
I. CVS:
– Induce CCF,
– Decrease in blood flow (cold extremities),
– Exacerbate angina & MI
– Rebound hypertension
2. Life threatening increase in airway resistance in
bronchial asthma
3. Hypersensitivity: rash, fever, TCP
4. CNS: insomnia, nightmare, depression and
hallucination
5. Muscle cramps, lethargy and fatigue: less blood flow
via muscles

22. Propranolol
• Propranolol interacts with b1 and b2 receptors with equal affinity, lacks
intrinsic sympathomimetic activity, and does not block a receptors.
• Propranolol is highly lipophilic, almost completely absorbed after oral
administration.
• Undergoes first pass metabolism to a high extent., only about 25%
reaching the systemic circulation.
• Individual variation in hepatic clearance contributes to variability in
plasma concentrations (∼20×) PO
• Hepatic extraction is saturable, thus the extracted fraction declines as
the dose is increased.
• The bioavailability of propranolol may be increased by the concomitant
ingestion of food and during long-term administration of the drug.
• Propranolol readily enters the CNS.

23. Propranolol--Therapeutic Uses
• HTN and Angina
Initial dose of 40-80mg/d titrated until desired response is obtained
at <320mg/day.
• Various arrhythmias-T/o inappropriate sinus tachycardia, atrial and
nodal extra systoles provoked by emotion and exercise.
• PVST (Adenosine & verapamil more efficient)
• Myocardial infarction
• Congestive heart failure
• Pheochromocytoma
• Migraine (prophylactically)
• Stage fright
• Akathisia (restless leg syndrome) induced by antipsychotic drugs

24. Propranolol--A/E
Worsens COPD, C/I in asthmatics.
Bradycardia--Resting HR is reduced.
Exacerbates variant angina due to unopposed alpha mediated coronary
constriction.
Carbohydrate tolerance may decrease in prediabetics.
May precipitate CHF, edema especially during cardiovascular stress.
C/I in partial and complete heart block.
Tiredness and reduced exercise capacity, cold hands and feet
Others- GI upset, lack of sex-drive, nightmares, rarely hallucinations.
Withdrawal following chronic use should be gradual so as to avoid
rebound HTN and worsening of angina, even death may occur.

25. Timolol
• It is the prototype of ocular B blockers.
• A potent, non-subtype-selective b receptor
antagonist, without any local anaesthetic or intrinsic
sympathomimetic activity.
• IOP decreases by 20-35%, decreased IOP persists for
2-3 weeks following discontinuation. Hence gives a
high level of clinical safety, with no concern over
missed dosages for open-angle glaucoma.
• Orally it is a potent B blocker---has been used in HTN,
angina and prophylaxis of myocardial infarction.
• It is also used for CHF, migraine prophylaxis, and
intraocular hypertension.

26. Atenolol
• It is a b1 selective antagonist.
• The drug is excreted largely unchanged in
the urine; thus, atenolol accumulates in
patients with renal failure, and dosage
should be reduced when creatinine
clearance is <35 ml/min.
• The initial dose of atenolol for the
treatment of hypertension usually is 50
mg/day, given once daily.
• Atenolol has been shown to be efficacious,
in combination with a diuretic, in elderly
patients with isolated systolic hypertension.

27. Metoprolol
• It is a b1-selective antagonist lacking intrinsic
sympathomimetic activity and membrane-stabilizing
activity.
• High 1st pass effect; low bioavailability.
• Plasma concentrations vary widely, which may relate
to genetically determined differences in hepatic
CYP2D6 activity.
• HTN usual dose 100mg/d increasing weekly till
optimum response is met.
• Metoprolol generally is used in two divided doses for
the treatment of stable angina.
• IV for acute MI. C/I when HR < 45 beats/min.

28. Labetolol [AlPHa & beta blocker]
• With intrinsic beta-2 activity (Beta blockade >
Alpha blockade)
• Adrenergic neuron blocking activity (Some)
• Labetalol causes Orthostatic hypotension &
dizziness due to alpha-1 blockade
• Carvedilol: a newer drug

29. Labetolol ---Uses
1. Hypertension:
• Essential & rebound hypertension,
• Hypertensive emergency,
2. Preoperative treatment in patient with
Pheochromocytoma
3. Correcting uncontrolled high BP prior to general
anesthesia
4. Counteracting acute HTN responses during laryngoscope
& various surgical procedure
5. An alternative to hydralazine in the treatment of PIH

33. Antihypertensive
drugs

34. That’s All
ENJOY
34

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