Propranolol

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Propranolol
Isoproterenol
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Class III antiarrhythmic an alpha-1
blocker also. ISA intrinsic sympathomimetic
activity MSA membrane stabilizing activity.
AM active metabolite. Many other Beta blockers
available.
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Properties of Beta-blockers

• Potency
• Membrane stabilizing activity (quinidine-like)
• Structure-activity relationships L-isomer has
  the Beta-blocking action.
• Cardioselectivity (Beta-1 selectivity)
• Intrinsic sympathomimetic activity (partial
  agonist activity)
• Lipid solubility relation to pharmacokinetics

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Intrinsic Sympathomimetic Activity
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Intrinsic Sympathomimetic Activity
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Beta-Blockers Pharmacokinetics

• Lipid soluble agents (vs. water soluble) tend to
  
• Be better absorbed
• Have more variable bioavailability
• Be metabolized in liver
• Enter the CNS
• Be more widely distributed
• Have shorter elimination half-lives

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Pharmacological Properties Propranolol

• Cardiovascular
• Blood pressure, heart rate, cardiac output,
  peripheral vascular resistance, coronary and
  organ blood flows
• Pulmonary
• Central Nervous System
• Metabolic

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Beta-Blockers Cardiovascular Effects
MAP
HR
PVR
SV
Pindolol (has ISA)
CO
Propranolol (no ISA)
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Effect of Beta-Blockers during Exercise
Heart Rate
Cardiac Index
Stroke Index
Pulm. Pressure
A-V O2 Diff.
Arterial Pressure
O2 Uptake
No Propranolol
Propranolol
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Effect of Beta-Blockers during Exercise
ß-Blocker
ß-Blocker
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Antihypertensive Effect of Beta-Blockers
Mechanisms

• 1. Decreased cardiac output
• 2. Inhibition of renin-angiotensin system
• 3. Decreased central sympathetic outflow
• 4. Resetting of baroreceptor
• 5. Others prejunctional receptors,
  prostaglandins, etc.

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MAP
HR
PVR
SV
Time (h)
CO
Pindolol
Time (h)
Propranolol
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Pharmacological Properties Propranolol

• Cardiovascular
• Blood pressure, heart rate, cardiac output,
  peripheral vascular resistance, coronary and
  organ blood flows
• Pulmonary
• Central nervous System
• Metabolic

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Effect of Beta-Blockers on Recovery from
Hypoglycemia
Insulin
ß-Blocker
Glucose (mmol/L)
Control
Atenolol
Propranolol
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Beta-Blockers - Adverse Effects

• Cardiac (mechanical electrical)
• Vascular (decreased perfusion)
• Pulmonary (bronchocostriction)
• Metabolic (diabetes mellitus)
• Central Nervous System (depression, nightmares,
  etc.)
• Withdrawal Syndrome

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The Withdrawal Syndrome
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The Withdrawal Syndrome
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The Withdrawal Syndrome
CD25
Pindolol
Metoprolol
Propranolol
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Beta-Blockers Therapeutic Uses

• Coronary artery disease
• Hypertension
• Arrhythmias
• Congestive heart failure
• Hypertrophic obstructive cardiomyopathy
• Dissecting aortic aneurysm

• Pheochromocytoma
• Hyperthyroidism
• Migraine -prophylaxis
• Essential tremor
• Anxiety stage fright
• Glaucoma (topical)

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Beta-Blockers in Myocardial Infarction
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Beta-Blockers in Myocardial Infarction
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Beta-Blockers in Heart Failure
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Beta-Blockers in Heart Failure
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Beta-Blockers in Heart Failure
Cumulative Mortality () in patients with
congestive heart failure
Placebo
Metoprolol CR/XL
Risk Reduction 34
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Beta-Blockers in Heart Failure
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Cardioselective Blockers - advantages

• In asthma
• In diabetes mellitus
• In peripheral vascular disease
• In hypertension (?)