5. CATECHOLAMINES
• These are compounds containing a catechol
moiety
(a benzene ring with two adjacent hydroxyl
groups and an amine side chain.)
6. Dopamine :
• It is the metabolic precursor of noradrenaline
and adrenaline.
• Main neurotransmitter in the Brain.
7. • Noradrenaline (norepinephrine) : a
transmitter released by sympathetic nerve
terminals.
• Adrenaline (epinephrine): a hormone
secreted by the adrenal medulla
8.
9.
10. Synthesis, Storage, Release, and
Removal of Norepinephrine
In Noradrenergic Neuron
• It starts with the amino acid tyrosine (from
diet)
• It enters the Noradrenergic neuron by active
transport.
In the neuronal cytosol….
• Tyrosine is converted by the enzyme tyrosine
hydroxylase to dihydroxyphenylalanine (dopa).
11. -------------------------------
Drug :
• Tyrosine hydroxylase enzyme inhibitor :
“α-Methyl-p-tyrosine”
• Can be Used to control the discharge of NE and E
in surgical removal of adrenal tumor.
------------------------------------
12. • DOPA is converted to dopamine by the
enzyme L–amino acid decarboxylase or DOPA
decarboxylase
• The dopamine is actively transported into
storage vesicles.
In storage vesicles…..
• It is in here, Dopamine, is converted to
Norepinephrine by dopamine –beta-hydroxylase
(exclusively present in synaptic
vesicles)
13. In the adrenal medulla..
• The synthesis is carried one step further.
• The enzyme phenyl-ethanolamine N-methyltransferase
converts norepinephrine to
epinephrine.
• The human adrenal medulla contains
approximately 80% epinephrine and 20%
norepinephrine.
14. • NE is stored in the synaptic vesicles.
• Noradrenergic transmitter is released during
action potentials through exocytosis.
Action Potential causes : Na+, Ca2+ and Cl- enter
while K+ efflux…
Ca2+ entry causes disruption of Vesicles to
release NE
15. Drugs :
• Release of NE is inhibited by bretylium and
guanethidene.
• Can be used in HTN (now obsolete)
16. • So.. after Action Potential and effect…..
• There is removal of norepinephrine from
Synapse.
Three processes contribute :
1. Transport back into the noradrenergic neuron
(uptake1)
• For vesicular storage or enzymatic inactivation
by mitochondrial MAO.
17. ------------------------------------------------
About , Monoamine Oxidase (MAO) and
Catecholamine-O-Methyltransferase (COMT) :
• Both enzymes inactivates NE and E.
• Both are widely distributed (Liver, Intestine,
Kidney, Brain)
• However, COMT is absent In ADRENERGIC Neuron.
• So it is only MAO which metabolises NE,
intraneuronally…
--------------------------------------------
18. 2.Diffusion from the synapse into the
circulation
For ultimate enzymatic destruction in the liver
( by COMT and MAO ) and renal excretion
3. Active transport of the released transmitter
into effector cells (extraneuronal uptake or
uptake2)
followed by enzymatic Inactivation by COMT
19. Drugs :
• Neuronal reuptake (uptake1) inhibitors :
Cocaine and Tricyclic antidepressants.
-potentiates effect of NE and E
• Vesicular reuptake inhibitors : Reserpine
(used in HTN, obsolete)
20. • Inhibitors of MAO-A (present in Adrenergic
neuron, intestine, liver, Kidney and Placenta) :
Clorgyline and Meclobemide ( rarely used in
depression)
• Inhibitors of MAO-B (present in Dopaminergic
neuron, brain, Platelets and Iiver) :
Selegeline ( used in parkinson’s disease)
23. Adrenergic Receptors
• The liberated NE at Synaptic junction
stimulates postsynaptic adrenoreceptors---
Alpha1, Alpha2. Beta1, Beta2, Beta3
to elicit end organ response.
So what are the end organ responses of each
receptor ????
24. • All belong to the superfamily of G-protein-coupled
receptors
• α1 receptors activate phospholipase C, producing
inositol trisphosphate and diacylglycerol as
second messengers
• α2 receptors inhibit adenylyl cyclase, decreasing
cAMP formation
• All types of β receptor stimulate adenylyl cyclase
25. • All receptors Are mostly present Postsynaptically
except α2 which is in Presynaptic region.
26. α1 Receptors
• When activated produces Excitatory effects on
in most organs.
• E.g, Vascular smooth muscle, Salivary glands,
Bronchi, Uterus, Radial muscle of iris etc.
• Except in intestine where they produce
Relaxation.
27. α2 Receptors
• Present Presynaptically in Post ganglionic
Adrenergic and Cholinergic (gut) Neuron.
• When activated by NE in synaptic cleft-
it inhibits further release of NE from
presynaptic Adrenergic neuron.
28. They also inhibit Ach in cholinergic neuron (in gut)
• They are also present Postsynaptically in blood
vessels etc. where it behaves like α 1
(vasoconstriction)
In Brain, whether Pre or Post synaptically present
it decreases sympathetic outflow.
29. β1 receptors
• located Postsynaptically.
• found in heart.
- Produce Positive ionotropic and
Chronotropic effects.
• found in Kidney
- Promotes Renin release.
30. β2 Receptors
• Their action causes smooth muscle relaxation
(Except in Myocardium)
• It is present in Bronchi, Blood vessels
supplying Skeletal Muscles, coronary artery,
uterus , GIT, Heart smooth muscle.
• There are also some presynaptic β2. these
facilitates NE release unlike α2.
31.
32.
33.
34.
35.
36. • Uterus
Non pregnant Contraction α1
Pregnant Relaxation β2
40. • Indirect-acting drugs are those increase the
availability of norepinephrine (NE) or
epinephrine to stimulate adrenergic receptors.
By releasing or displacing NE from vesicles of
sympathetic nerve varicosities
41. or by blocking the transport of NE into
sympathetic neurons
or by blocking the metabolizing enzymes,
(MAO ,COMT)
42.
43. Epinehrine or Adrenaline
• Acts on β2 > β1= α1= α2, and weak β3 action
• Cardiac Effects : β1, β2 effects
• Final effect : increase in SBP
44. Vascular Effects :
• Constricton of arterioles in skin,mucous
membrane, viscera and renal beds-- α1 effect
• Dilation predominates in skeletal muscle, liver
and coronaries– β2 effect. Decrease in
peripheral vascular resistance
• So the cumulative effect decease in DBP
45.
46. • What happens when adrenaline is given after
pretreatment of α Blocker ?
ANS : Hypotension
( Dale’s vasomotor reversal phenomenon )
predominant β2 effect.
• What happens when adrenaline is given after
pretreatment of β Blocker ?
ANS : Accentuated Hypertensive effect.
47. • Effects on smooth muscle :
• Bronchial :
bronchodilation- β2 effect.
Decrease in bronchial secretion α1 effect
• GIT :
• Constriction on sphincters α1 effect
• Gut relaxation α2 and β effect
48. Uses of Adrenaline
Anaphylactic Shock :
• Relieves Bronchospasm and Angioneurotic
edema of larynx
• Prevents release of histamine from mast cell.
• Dose : 0.3 – 0.5 ml IM. 1: 1000 solution IM or SC
49. • Bronchial Asthama : Rarely used.
• Cardiac resusitation : Intracardiac route to
reverse sudden cardiac arrest in drowning and
electrocution
(Absolute Containdication in Ventricular
Fibrillation)
• To prolong duration of loacal Anaesthetic agents.
• To control Epistaxis : Rarely
52. Noradrenaline
• Acts on α1=α2>β1, β3.
• Poor β2 action.
Cardiovascular effects :
• Raises both SBP and DBP. (because β1-SBP,
α1-DBP )
53.
54.
55. Uses
• Cardiogenic Shock
• Hypotensive states in Surgical shock and MI (
it increases peripheral vascular resistance)
• Dose : 0.5 to 1 ml per minute. IV infusion.
56. Facts :
• Should be careful of renal shut down. So
Dopamine is preferred.
• As it is a powerful vasoconstrictor, if given
undiluted via SC or IM causes, Necrosis.
57. Dopamine
• Acts on D1, D2, β1, little α action
• No β2 and β3 action.
• Does not enter the BBB when given
Parentrally.
• Effects :
It is dose dependent.
58.
59. Uses
• Cardiogenic Shock
• CCF, liver and renal failure
• Hypotensive states (after correcting
hypovolemia)
• Dose is 5mcg-10mcg/kg/min IV
61. Dobutamine
• Synthetic Catecholamie.
• Racemic Mixture of -
L-form (α1 agonist )
D- form (α1 antagonist and β1 agonist)
• So it is relatively selective β1 agonist.
62. Effects :
• More selective ionotropic and chronotropic
effects.
Uses :
• Heart failure : it increases CO and stroke Volume
without increasing Heart rate.
Adverse effects :
• Sharp rise in BP in HTN patients
• Angina can be aggravated
63. Dopexamine
• Synthetic Catecholamie.
• Acts on D1, D2, and β2 receptors
• Effects : Peripheral Vasodilation, increase Cardiac
output and increased renal blood flow.
• Uses : To provide Haemodynamic suppport in CCF and
Shock
Adverse Effects :
• Tachycardia and Hypotension
64. Fenoldapam
• Synthetic. Selective D1 agonist
Effects :
• vasodilation in peripheral arteriole, coronary,
Renal and Mesentric vessels
Uses :
• Short term management of Severe Hypertension
in Patients with severe Renal impairement.
• Adverse Effects : Reflex Tachycardia, Headache.
65. “ α1 Selective agonists ”
Phenylephrine
• Non Catecholamine
• So not metabolized by MAO or COMT
• Effects : α1 stimulation increases Peripheral
vascular resistance and BP ( associated with
reflex Bradycardia)
Uses :
• Nasal decongestant
• Mydriatic
• Hypotension (rarely)
66. Other similar drugs are :
• Oxymetaxoline
• Xylometazoline
• Midodrine
• Naphazoline
67. α 2 Selective Agonist
Clonidine
Uses with MOA :
1) Moderate Hypertension
Mechanism : Not properly elucidated.
• stimulates central α 2 receptors to decrease
sympathetic outflow.
68. • Stimulates presynaptic α2 on postganglionic
sympathetic neuron to supress NE release.
----------------------------------
• When given I.V there is transient rise in BP
( post syaptic α2 effect which causes
vasoconstriction) and then Decrease.
• However when given oral, there is only
hypotensive effects
• 100 % bioavailability.
69. • Dose :100-300 mcg BD.
• Also available as Transdermal Patch.
• Major limitation is Rebound Hypertension.
2) In the Prophylaxis of migraine
• It reduces cerebral blood flow
3) Management of opiate, alcohol and Nicotine
Withdrawl
• It reduces sympathetic effects associated with
withdrawl
70. 4) Preanaesthetic Medication:
• For its slightly sedative, anxiolytic and
analgesic effect
5)Menopausal Hot flushes :
• For counteracting symptoms
71. 6) To control diarrhoea in diabetic patients with
autonomic neuropathy
α2 in GIT decreases sodium,water retention
and reduces motility by inhibiting Ach
73. Newer congeners of clonidine
• Moxonidine
• Rilmenidine
In these rebound hypertension is less frequent
longer acting than Clonidine
----------------------------------
74. • Apraclonidine
• Brimonidine
Used in Glaucoma (reduces Aqueous Humor
by α2 action in cilliary muscles)
75. β2 selective Agonists
Salbutamol
Effect : Produce relaxant effect on bronchi,
uterus.
• Has minimal cardiac stimulant property.
• Half life : 4hr
Uses :
• Immediate relief of Asthama
76. • Dose : 100mcg in Metered dose inhaler
• or 2-4 mg PO TDS
• To arrest uncomplicated premature labour
(inbetween 24 to 34 weks of gestation) by
slow IV injection
Adverse effects :
• Tremors in hands, Palpitations, hypokalemia
77. • Terbutaline
• Salmetrol and Formetrol ( longer acting 12hr)
• Pirbuterol
• Clenbuterol ( anabolic strength on skeletal
muscle, illicit use in sports)
78. Indirectly acting drugs
Tyramine
• Not used clinically
• It is found in cheese, beef, wine, beer, yoghurt
yeast.
• Metabolized by MAO.
• Significance : If patient on MAO inhibitor, it
can trigger hypertensive crisis
79. Amphetamine
• Powerful CNS stimulant .
CNS effects :
Stimulation of
• cortical region
• Reticular activating system.
• Medullary respiratory centre.
Causes
• Wakefullness
• Alertness
80. • Decreased sense of fatigue
• The performance of simple task increases but
errors increase
• Physical performance improves
81. CVS effects :
• Increases SBP and DBP
• Tachycardia followed by bradycardia
Other effects
• Suppression of appetite by depressing lateral
hypothalamic centre
82. Uses :
• Narcolepsy : prevents attacks of daytime time
sleep
• ADHD (excitability, impulsiveness, difficulty in
sustaining attention) : Paradoxically improves
with low dose
• Weight reduction
83. Other Analogues…
• Methylphenidate : more prominent action on
mental function.
• Methamphetamine : High potential of abuse
• Pemoline : minimal CVS effects and longer
plasma half life. Used in ADHD
84. Mixed Action drugs
Ephedrine
• Non catecholamine alkaloid
• Has direct action on α and β. Also enhance NE
release.
• CNS : powerful stimulant
• CVS: increase in BP, CO, HR.
• RS : Bronchodilation.
89. Phenoxybenzamine
• Irreversible, nonselective, Non competitive
Antagonist at α1,α2
• Also inhibits reuptake of NE by adrenergic
nerve terminal.
• Crosses BBB.
Effects :
• Vasodilation
• Decrease Peripheral vascular Resistance
90. • Hypotension ( this triggers baroreceptors
causing sympathetic discharge)
• Tachycardia (sympathetic discharge action on
β 1 )
91. Uses :
Treatment Phaeochromocytoma :
• Controls episodes of severe hypertension
during surgical manipulation .
• Dose : 1mg /kg , slow IV infusion
In Raynaud’s syndrome and
Frostbite.
Dose 10mg TDS PO
92. Adverse effects :
• Marked Postural Hypotension with initial doses.
• Tolerance develops later.
• Inhibition of ejaculation
• Salt and water retention
• Sedation
• Fatigue
• Nausea
93. Phentolamine and Tolazoline
• Competitive, Reversible antagonist of α1, α2.
Effects :
• Vasodilation
• Decrease Peripheral vascular Resistance
94. • Hypotension ( this triggers baroreceptors
causing sympathetic discharge)
• Tachycardia (sympathetic discharge action on
β 1 )
95. Other effects
• Nasal stufiness
• Miosis (loss of tone of radial muscles)
• Failure of ejaculation
• Nausea vomitting diarrhoea
( inhibition of inhibitory sympathetic influence
of GIT and agonist action on H2 receptors,
Tolazoline)
96. Uses
• Treatment Phaeochromocytoma.
• In peripheral vascular disease
• To prevent dermal necrosis ( after incidental
extravasation of NE after IV infusion)
• To treat hypertensive crisis
97. α1 selective blockers
Prazosin
Effects :
• Peripheral vasodilation
• Fall in arterial pressure
• Lesser tachycardia
Because of lack α 2 blocking no promotion
of NE release, so no β1 stimulation.
98. Also partly because it decreases sympathetic
outflow from CNS
It decreases cardiac preload
• It is also potent phosphodiesterase inhibitor
this leads to rise in cAMP in smooth muscle
So vasodilating effect.
• It relaxes smooth muscle - in bladder neck
Prostate capsule
Prostatic urethra
99. • So improves urine outflow in BPH
• Uses :
• In Hypertension : oral dose is 1mg bed time to
avoid postural hypotension
• In BPH : 1-5 mg BD PO, however newer ones
are preferred.
• In raynaud’s disease : rarely, because CCB are
preferred.
101. Terazosin and doxazosin
• Longer duration of action
• Terazosin : 12 hr
• Doxazosin : 20hr..
• So OD dosing in HTN and BPH
102. Bunazosin and Alfuzosin
• Similar to Prazosin profile
• Alfuxosin : to be cautiously used in hepatic
impairement as it is metabolized there.
• Bunazosin : longer acting but no favourable
profile than Prazosin
103. Tamsulosin and Silodosin
They are α 1A antagonist .
• α 1A is located on bladder neck and urethra
• α 1B is located in blood vessels
• It is more efficacious in BPH with little effect on
BP unlike non-selective ones.
104. • Better bioavailability
• Plasma Half life 8hr
Dose :
Tamsulosin 0.2 to 0.4mg OD, PO
Silodosin(longer acting analogue of Tamsulosin)
4-8mg , PO
105. Adverse effects :
• Abnormal ejaculation
• Floppy iris syndrome – which creates problem
in cataract surgery.
106. Alpha2 Antagonists
Yohimbine
• Natural alkaloid from Pausinystalia Yohimbe
• Other than Alpha2 blocking action, has 5HT
antagonist action.
Uses are unestablished
• To teat male sexual dysfunction
• To treat diabetic neuropathy
107.
108. Propranolol
• Nonselective, Competitive blocker . acts on
beta1 and beta2.
• It is prototype drug in the group
( all features are characteristic except that its
not used in glaucoma even though it does
reduces IOP)
109. • Cardiovascular effects :
The blockade of β1 causes
decrease of
heart rate,
myocardial contractility
conduction velocity
cardiac output
Automaticity ( suppression of SA Node)
This causes reduced myocardial oxygen demand
Consequent to all these BP falls
110. Blockade of β 2
• Peripheral vascular resistance rises, because α1
adrenoreceptor is no longer opposed by β 2
• This reflex vasoconstriction is maintained.
So Postural hypotension is least troublesome.
• Patient show a gradual fall in BP after chronic
use.
111. Other minor mechanism to lower BP
• β1 blockade decrease release of renin.
(however pindolol which has no effect in renin is
also effective antihypertensive)
• Blockade of facilitatory effect of presynaptic β 2
receptor on NE release.
• Chronic decrease in Cardiac output
112. Other effects on circulation :
• Plasma lipid profile is worsened in long term
intake.
• Total TG, LDL increase and HDL level falls.
113. Respiratory effects
• Least affected in normal individuals
• In Asthmatic patients, it causes severe
bronchoconstriction because of β 2 effect
114. • Metabolic effects
• In normal persons , minimal effects on basal
glucose level.
• Normally ,
In stress-induced hypoglycemia and insulin
induced hypoglycemia in diabetics, there is
protective adrenaline induced glycogenolysis
( β 2 effect in liver )
115. This is protective mechanism to overcome
hypoglycemia
Therefore Patients on Propranolol
blocking β 2 has adverse delay on recovery of
hypoglycemia.
• Also it blocks sympathetic manifestations like
palpitations and sweating
116. CNS effects
• It is lipid soluble . Enters BBB.
• Upto some extent decreases sympathetic
outflow
• Produces sedation, lethargy and disturbances in
sleep.
117. • It supresses performance anxiety ( more of
peripheral action rather central)
• At higher doses it has Antipsychotic effects
118. Ocular effects
• It decreases formation of Aqueous Humor in
glaucoma patients.
• But seldom used - low potency, Local
Anesthetic action on cornea which is not
desired
119. Miscellaneous effects :
• It prevents platelet aggregation and promotes
fibrinolysis
• It reduces portal vein pressure in cirrhotic
patients
• increases synthesis and release of PGs
120. Pharmacokinetics :
• Low bioavailability, extensively metabolized in
liver.
• Plasma T ½ is 4-6 hrs.
• It has L and D forms.
• L is 100 times potent than D form
• D form has more membrane stabilizing
property ,quinidine like effects.
• Commercial available is racemic mixture.
121. Uses :
Essential Hypertension :
• Used alone or with a diuretic
• Dose : 20-40 mg TDS PO
or 80mg sustained release single dose.
122. Congestive cardiac failure :
• It can worsen the condition.
• However now its established that it is
beneficial in mild to moderate HF
• To be started with low dose and increased
gradually.
123. • It is said to retard progression of condition
and prolong life
How ?
• In CCF, there is damaging hyperactivity of β1
which causes remodeling of myocardium
• So these prevent the hyperactivity, the
remodeling.
124. Angina Pectoris
• Used only in stable or effort-induced angina
• It decreases cardiac workload
• Decreases myocardial oxygen demand
• But absolute contraindicated in Prinzmetal’s
angina
Because beta blocking will unmask Alpha
receptor to cause coronary vasoconstriction
125. Cardiac arrhythmias :
• It is effective in all supra ventricular
arrhythmias.
• Effect is mainly due to increase in refractory
period at AV node
126. Myocardial infarction
• It will decrease the incidence , recurrence and
mortality on long term use
• Prevent platelet aggregation
• Promotion of fibrinolysis
• Prevents ventricular fibrillation in the 2nd
attack of MI
127. • Non cardiovascular uses :
Migraine
• Used in prophylaxis
• Mechanism is uncertain
• Dose : 10 to 20 mg BD or TDS
128. Anxiety provoking situation
• It only blocks peripheral manifestation
(palpitations, tremors and sweating)
• Dose : 10-20 mg TDS
no action in Parkinson’s tremors
129. Hyperthyroidism
• Reduces sympathetic over activity
• It also inhibits conversion of T4 to T3
( independent of beta action)
• Dose : 20mg BD
130. Phaeochromocytoma
• Given in combination with alpha blockers to
antagonize beta1 effects of catecholamines
during surgery
• Dose : 20 mg TDS, 3 days before surgery
132. Esophageal varices and Portal hypertension
• It induces splanchnic vasoconstriction (beta2
blocking and unopposed alpha1 action)
• This reduces bleeding and reduces portal
pressure by 40%
133. Adverse effects :
• Bronchoconstriction
• Bradycardia
• Cold extremities
(loss of beta2,loss of cutaneous vasodilation)
• Hypoglycemia
• Fatigue , sleep disturbances.
• Rebound hypertension on withdrawal
( upregulation of beta receptors)
• Adverse lipid profile
134. Other non selective 1st Gen
• Timolol
Main use :
wide angle glaucoma as eye drops 0.25%
135. Sotalol
• Uses and side effects are similar to
propranolol (less lipid soluble, less CNS side
effects)
• It has additional K+ blocking property and this
makes it class III anti arrhythmic drug
• Dose : 80- 320mg BD PO
136. Nadolol
• Uses and side effects are similar to
propranolol ( does not cross BBB)
• Longer plasma half life- 20 hrs
• Least first pass metabolism
137. β1 selective blockers
• At high doses it can even block beta2
Advantages
• Safer in Asthmatics
• Safer in hypoglycemic conditions ( glucose
release is not inhibited )
• Safer in PVD ( no beta2 blockade)
• Less deleterious effect on lipid profile.
138. Metoprolol :
• Uses are similar to Propranolol
• Dose : extended release 50-100 mg .
Atenolol :
• Uses are similar…
• Do not cross BBB
• Dose : 25-50 mg once daily
139. • Nebivolol
• Highly selective antagonist
• Additional action : enhances NO production
and release . Used in effective reduction of BP
• Dose : 5-10 mg OD
140. Esmolol
• Ultra short acting selective antagonist
• Plasma half life 8-10min.
Uses :
• Only in emergency conditions/ during surgery/
critically ill patients as IV preparations
To treat SVT, AF etc
141. Non selective β blocker with intrinsic
sympathomometic Activity
Beneficial properties are
• Lesser bradycardia, myocardial depression
• Rebound hypertension after withdrawal is less
likely. Because β agonist property of this group
prevents upregulation of receptors
• Lipid profile is less worsened.
142. • Disadvantages
• Cannot be used in migraine- intrinsic Beta2
agonistic action causes further dilation of
cerebral vessels
• Less suitable for secondary prophylaxis MI
143. Acebutolol :
• It is a prodrug , converted to ‘Diacetolol’
• T1/2 10-12 hrs
• Dose : 400 mg OD
Celiprolol :
• It has partial agonist action on β 2 as well
• Also causes direct vasodilation by releasing
NO.
• Preferred in HTN+ bronchial asthma patients
• Dose : 200-400 mg OD
144. • Drugs are : Pindolol and Oxprenolol
• Dose : Pindolol 10 mg OD
Oxyprenolol 20 mg BD or TID
145. selective β1 blocker with intrinsic
sympathomimetic Activity
• They offer all the advantages of “ non
selective β1 blocker with intrinsic
sympathomometic Activity “ group
with
• Membrane stabilizing Action ( however its of
no clinical use as it appears to significant at
higher doses)
• Drugs are : Acebutolol and Celiprolol
146. Mixed(α+ β ) antagonist
• Labetolol and Carvedilol
• Labetolol
• It is racemic mixture of 4 diastereomers.
• Racemic mixture exhibits
selective blockade of α1 , β1
Partial agonist action on β2
147. Effects :
• Fall in BP (α1 , β1 blockade)
• Also peripheral vasodilation and bronchodilation
(β2 agonistic)
Main Uses :
• Hypertension in pregnant women
• In pheochromocytoma
• Rebound hypertension in clonidine withdrawl
Adverse effects :
• Postural hypotension, hepatotoxicity
148. Carvedilol :
Actions :
• Has prominent β1 β 2 blockade , lesser α1
blockade.
• Inhibits free radical induced lipid peroxidation.
• Inhibits smooth muscle mitogenesis.
• It blocks L-type voltage gated Ca2+ channels.
• All these prove to be cardio protective In CCF
