Beta Blockers and Other Sympatholytic Agents
Beta Blockers and Other Sympatholytic Agents
Beta Blockers and Other Sympatholytic Agents
SYMPATHOLYTIC AGENTS
CENTRAL
NERVOU
S
SYSTEM
SOMATIC
PERIPHE SENSO
RAL RY
AUTONO SYMPATHETIC
MIC
MOTOR
PARASYMPATH
ETIC
AUTONOMIC NERVOUS SYSTEM
(ANS)
Largely independent from direct conscious control
Integrated and controlled at many levels from the
CNS
Sensory inputs modify autonomic output through
reflex arcs
CHOLINERGIC
SYMPATHETIC
NORADRENERGIC
SYMPATHETIC
DOPAMINERGIC
SYMPATHETIC
MODIFIED
SYMPATHETIC
Katzungetal,BasicandClinicalPharmacology12thedition
Generally the parasympathetic and the
sympathetic system innervate the same
visceral organs,
but determining opposite effects
REST FIGHT
AND OR
DIGEST FLIGHT
RATE-
LIMITI
NG
STEP
1A 1B 1C 2A 2B 2C 1 2 3
D1like D2
Gs protein like
Gi protein
coupled coupled
D1 D5 D2 D3 D4
Katzungetal,BasicandClinicalPharmacology12 thedition
Katzungetal,BasicandClinicalPharmacology12 thedition
SYMPATHETIC ACTIVATION
It prepares the body to cope with physiological stressors,
such as exercise, excitement, and danger
HYPOTHALAMUS
AMYGDALA
HYPPOCAMPUS
LOCUS COERULEUS
CEREBELLUM
SPINAL CORD
NORADRENERGIC PATHWAYS IN
CNS
Regulation of blood pressure
Vasomotor centre within the medulla is involved
in the postural baroreflex
1. BETA BLOCKERS
Propranolol, Pindolol, Atenolol, Bisoprolol, Labetalol,
Carvedilol
2. ALPHA1 ANTAGONISTS
Prazosin, Doxazosin, Terazosin
3. ALPHA2 AGONISTS
Clonidine, Alpha metildopa, Guanfacine, Guanabenz
4. ADRENERGIC NEURON BLOCKERS
Guanethidine, Guanadrel, Reserpine
5. SYMPATHETIC GANGLION BLOCKERS
Trimetaphan
SYMPATHOLY
TICS: SITES 3
OF ACTION
2
1
Katzungetal,BasicandClinicalPharmacology12thedition
BETA BLOCKERS
MILESTONES blocker, is developed
useful beta
the frst clinically
Propranolol,
1964
1954
Isoproterenol
hydrochloride
induces relaxation in
vitro of tracheal tissue
1958 - 1962
James Black recognizes that a
therapeutic strategy against angina
would be to antagonize the beta
adrenergic receptors to which the
stress hormones CA bind, thereby
1847 increasing the workload and oxygen
Nitroglycerin reduces the demand of the heart
pain of angina by dilating the
cardiac blood vessels, thereby
increasing the supply of
MEDICINE NOBEL PRICE 1988
Propranolol Metoprolol
Pindolol Timolol
Labetalol Atenolol
Nebivolol
Katzungetal,BasicandClinicalPharmacology12thedition
PHARMACODYNAMIC PROPERTIES
No pharmacological activity
in the absence of sympathetic activation
Non Selective
Blockade of beta1 and beta2 receptors in the presence
of high CA concentrations (competitive antagonism)
heart rate
conduction
release glycogenesis
lipolysis of insulin glycogenolys and
is glycogenolysis
ModifiedfromRossiCuomo,MinervaMedica
PHARMACOKINETICS
Max Min
LIPOPHILIC
GI absorption
IDROPHILIC
Short half-life
Propran hepatic
olol metabolism
drug-protein
Alprenol bond
Oxpreno
ol Nadolol
Transfer into GI absorption
lol Celiprol
CNS Long half-life ol
Metopro hepatic Sotalol
lol metabolism
Atenolo
drug-protein
l
bond
Min Max
Renal elimination
CARDIOVASCULAR INDICATIONS
Hypertension
Stable and acute coronary artery disease
Heart failure
Cardiac arrhythmias
Hypertrophic cardiomyopathy
COMPLEX ANTIHYPERTENSIVE
EFFECT
First haemodynamic response
Decrease of cardiac output
Reflex peripheral vasoconstriction
Beta-blocker-initiated therapy is
duration of
diastolic
heart rate
perfusion
contractility
O2 DEMAND vs O2 endocardic
SUPPLY blood flow
A-V conduction
vascular
spontaneous firing of
resistance in non-
ectopic pacemakers
ischaemic areas
systolic blood pressure
ventricular size
STABLE CORONARY ARTERY
DISEASE (SCAD)
STABLE ANGINA MANAGEMENT
VASOSPASTIC ANGINA
Calcium antagonists and nitrates should be
considered
Beta blockers must be avoided, as they might
favour spasm by leaving alpha mediated
vasoconstriction unopposed by beta mediated
ACUTE CORONARY ARTERY
DISEASE
CRITICAL OCCLUSION OF A CORONARY ARTERY,
DUE TO THE RUPTURE/EROSION OF AN ATHEROMATOUS
PLAQUE AND TO THE FOLLOWING THROMBOSIS
UA NSTEMI STEMI
Unstable Angina Non ST Segment ST Segment
Elevation Elevation
Myocardial Myocardial
PharmacologicalInfarction
therapy Reperfusion (PCI) or
Infarction
Fibrinolysis
First choice in all the patients First choices
Reperfusion (PCI O CABG) Pharmacological therapy
In medium-high risk patients of
Eur Heart J. 2012; Eur Heart J.
2015
ACUTE CORONARY ARTERY
DISEASE
Early oral treatment with beta-blockers is
recommended in all NSTEMI patients with ongoing
ischaemic symptoms and should be considered as
ancillary in STEMI patients during hospital
Prophylaxis of migraine
Essential tremor
Glaucoma
In hyperthyroidism and anxiety, control of
somatic symptoms, such as tremor,
tachycardia
Infantile hemangioma
Bleeding of oesophageal varices
associated with portal hypertension
European Federation of Neurological
Societies 2009
MIGRAINE
PREVENTION
Raynauds phenomenon
Worsening of severe peripheral vascular
BETA disease
2 In type-I diabetes, mask of warning
symptoms of hypoglycaemia, such as
tremor and tachycardia
Bronchospasm in asthma/COPD
Reduced capability to exercise
LIPOPHILIC Impotence and loss of libido
MOLECULES
Central effects, such as fatigue,
headache, insomnia and vivid dreams,
ALPHA1 ANTAGONISTS
PRAZOSIN, DOXAZOSIN,
TERAZOSIN
Prazosin (short-acting)
Doxazosin and Terazosin (long-acting)