This document summarizes the sympathomimetic system. It describes the synthesis, storage, release, reuptake and metabolism of catecholamines like norepinephrine and dopamine. It also discusses the pharmacological actions and therapeutic uses of endogenous catecholamines like epinephrine and norepinephrine. Additionally, it covers various classes of sympathomimetic drugs like alpha and beta agonists, their mechanisms and clinical applications.

1. SYMPATHOMIMETIC SYSTEM
Nehal V. Trambadiya
Asst. Professor
Smt. N. M. Padalia Pharmacy College

2. CATECHOLAMINES
• Norepinephrine and dopamine
are synthesized in axonal
terminals
• Epinephrine is released by the
adrenal medulla

3. CATECHOLAMINES SYNTHESIS
• Transmitter synthesis involves the following
steps:
– L-tyrosine is converted to dopa by tyrosine hydroxylase
(rate limiting step). Tyrosine hydroxylase occurs only in
catecholaminergic neurons.
– Dopa is converted to dopamine by dopa decarboxylase.
– Dopamine is converted to noradrenaline by dopamine
β-hydroxylase (DBH), located in synaptic vesicles
– In the adrenal medulla, noradrenaline is converted
to adrenaline by phenylethanolamine N-methyltransferase

4. Storage of Catecholamines:
• NA is stored in a synaptic vesicle or ‘granules’ within adrenergic
nerve terminal.
• Vesicular membrane activally take up Dopamine from
cytoplasm and final step of synthesis of NA take place inside
the vesicle.
• NA is stored as a complex with ATP
• In adrenal medulla the NA formed within chromaffin granules
diffuse out into cytoplasm and methylated thus adrenaline is
formed.

5. Release of Catecholamine:
• Release of catecholamine take place by exocytosis and all the
vesicular content are poured out.
• Indirect acting sympathomimetic amines for example tyramine
also induce the release of NA.

6. Uptake of Catecholamines:
• NA release from nerve terminal is recapture.
• Axonal uptake:
• Active amine pump (NET) is present at the neuronal membrane
which transport NA by Na+ coupled mechanism.
• Take up NA at a higher rate than adrenaline and known as
uptake 1.
• This uptake is important for terminating post junctional action of
NA.
• This pump is inhibited by cocaine, desipramine.

7. • Vesicular uptake:
• The membrane of intracellular vesicles has another amine
pump Vesicular monoamine transporter (VMAT-2) transports
CAs from cytoplasm to storage vesicle.
• Transport monoamine by exchanging with H+ ion.
• Vesicular NA is constantly leaking out into axoplasm and is
recapture by this mechanism.
• This carrier also take Dopamine for further synthesis to NA.
• Important in maintaining NA content of the neuron.
• This uptake is inhibited by reserpine.

8. • Extraneuronal uptake:
• Carried out by extraneuronal amine transpoter
• In contrast to NET ,this uptake transport adrenaline at a higher
rate than NA.
• Is not Na+ dependent and is not inhibited by cocaine.
• Inhibited by corticosterone

9. • Metabolism of CAs:
• Adrenaline is metabolised by MAO to formed 3,4 Dihydroxy
mandelic acid which is converted into 3-methoxy 4 hydroxy
mandelic acid and further excreted by glucuronide or sulfate
conjugation
OR
• Adrenaline is converted to metanephrine by COMT and further
excreted by glucuronide or sulfate conjugation.

10. • Adrenergic receptor :
• G protein couple receptor,
• Increase or decrease cAMP or IP3 / DAG.
• Adrenergic receptor are of two type α and 
• An α receptor again classified into α1 and α2.
•  receptor again classified into 1 , 2, , 3

13. SYMPATHOMIMETICS
• Sympathomimetics are the drugs that produce action similar to
that of sympathetic nerve stimulation.
• CLASSIFICATION:
• They classified in different way:
• (a) According to structure:
 Catecholamines: Adrenaline, nor adrenaline, isoprenaline.
 Non Catecholamines: Amphetamine, ephedrine, tyramine

14. • (b) According to clinical uses
 Pressor agent : Noradrenaline, Ephedrine,
methoxamine, dopamine, mephentermine, phenylephrine
 Cardiac stimulant : Adrenaline , Isoprenaline , Dobutamine
 Bronchodilator : Isoprenaline, Salmeterol, Formeterol,
Terbutaline, salmeterol, bambuterol

15.  Nasal decongestant : Naphazoline, Phenyl propanolamine,
Xylometazoline, oxymetazoline, pseudoephedrine,
phenylephrine
 CNS stimulant : Amphetamine, Dexamphetamine,
methamphetamine
 Anorectics: Fenfluramine, dexfenfluramine, sibutramine
 Uterine relaxant and vasodilators: Ritodrine, Salbutamol,
Terbutaline, isoxsuprine

16. • (c) According to mechanism of action :
• 1 Directly acting :
 Specific α adrenoceptor agonist : Noraderaline, Phenylephrine
 Specific  adrenoceptor agonist : Isoprenaline
 Mixed agonist : Adrenaline
 α1 agonist : Mithoxamine, Phenylephrine
 α2 agonist : Clonidine, Guanabenz
 1 agonist : Dobutamine, xamoterol
 2 agonist : Salbutamol, Terbutaline, salmeterol
 3 agonist : BRL – 37344, AD - 9677

17. • 2 Indirectly acting :
• These drugs do not act directly on the receptors but affect
adrenergic transmission to produce noradrenaline at the site or
increase availability of noradrenaline at the site of action.
I. Drugs that release the transmitter : tyramine, Amphetamine,
Methamphetamine, Methyphenidate, Pemoline
II. Uptake blockers : cocaine, desipramine (blocking uptake 1 )
corticosteroid (blocking uptake 2)
Reserpine (blocking granular uptake)
III.Enzyme inhibitors : tranylcypromine (MAOI)
tolcapone and entacapone (COMTI)

19. • Directly acting Endogenous Catecholamines
• PHARMACOLOGICAL ACTION
• CVS :
Heart :
• Increase in heart rate and force of contraction
• Followed by reflex bradycardia.
• Increase cardiac output.
blood vessels :
• Adrenaline constricts artery due to alpha effect
• Dilation due to 2 action
• Beta receptor more sensitive than alpha receptor.

20. • Blood pressure :
• NA increase systolic ,diastolic and mean BP

21. • Respiratory System:
• Adrenaline and isoprenaline produce a powerful relaxation of
smooth muscle of bronchi, through stimulation of 2
adrenoceptors.
• Adrenaline produce transient apnoea due to inhibition of
respiratory centre.
• High dose of Adrenaline cause pulmonary edema by shifting
blood from systemic to pulmonary circuit.
• Noradrenaline does not produce any significant action.
• GIT:
• Both α and  adrenoceptor are inhibitory in nature.
• Produce relaxation of smooth muscle.
• Thus decrease in tone and motility.

22. • Eye:
• Mydriasis occur due to contraction of radial muscle of iris (α1).
• This effect is minimum after topical application because
Adrenaline penetrate cornea poorly.
• Intraocular tension tends to fall in wide angle glaucoma

23. • Urinary Bladder:
• Detrusor muscle is relaxed and trigone is constricted.
• Cause retention of urine.
• Uterus:
• Response of uterus is dependant on state of uterus.
• Human uterus is constricted by adr. and noradr., if it is non
pregnant.
• This action is mediated through α adrenoceptor.
• Pregnant uterus is again constricted in first two trimester by
adrenaline.
• In last trimester, particularly in last month of pregnancy, it is
relaxed.
• This action is mediated through  adrenoceptor.

24. • CNS:
• Does not produce any CNS effect, because It is poorly
penetrated in brain.
• Directly injected into brain, it produce excitation followed by
depression.
• Metabolic:
• Produce hyperglycemia by enhancing glycogenolysis.
• Increase blood lactate.
• Lipolysis.
• Hyperkalaemia
• Stimulation of α receptor inhibit and stimulation of  receptor
activate insulin secretion.

25. PHARMACOKINETICS
• Adrenaline, Noradrenaline, isoprenaline are not absorbed from
GIT.
• So, it is not given orally.
• Isoprenaline sometimes given by sublingual route, I.V.
• Metabolized by MAO or COMT.
• Final product is 3-methoxy 4-hydroxy mandelic acid which is
excreted in urine.

26. Contraindication
• Not given during anaesthesia with halothane because risk of
arrythmias.
• Not given patient receiving  blocker because increase in blood
pressure.
• Adrenaline is contraindicated in hypertensive, hyperthyroid,
angina patient.

27. Therapeutic uses
1. Vascular uses
Hypotensive state
Along with local anaesthetics, action prolonged
Control of local bleeding (hemostatic)
. Nasal decongestant
2 Cardiac uses
Cardiac arrest (Cardiac resuscitation)
Partial or complete A-V block
CCF
3. Bronchial asthma

28. 4. Allergic disorder
5. Mydriatic
6. Insulin hypoglycemia
7. Uterine relaxant
8. Obesity
9. ADHD
10. Narcolepsy
11. Nocturnal enuresis eg. In children. Amphetamine. By its
central action and increases tone of vesical sphincter.

29. ADVERSE EFFECT
• Palpitation
• Tremor
• Anxiety
• Headache
• Ventricular arrhythmias

30. • Synthetic Catecholamines
• Dobutamine :
• Act on 1 adrenoceptor in the heart.
• Little or no action on 2 or alpha receptor.
• Does not release noradrenaline.
• Increase the contractile force of the heart raising the stroke
volume and cardiac output.
• Without increase in heart rate.
• Increase oxygen demand to the heart to a lesser extent.
• Produce vasodilation of renal and mesenteric vessels.
• Systemic vascular resistance is decreased
• Has short duration of action.

31. THERAPEUTIC USES
• Management of acute cardiac decompensation due depressed
contractility resulting from organic heart disease on cardiac
surgery.
• Cardiac shock
Adverse effect and contraindication :
• Premature ventricular beat
• Less frequently headache, palpitation , nausea, anginal pain.
• Contraindication include idiopathic hypertrophic subaortic
stenosis, pre existing hypertension, cardiac valvular disease.

32. Non-catecholamines 1 agonists
• Phenylephrine
1 agonist
Increases BP and peripheral resistance
uses:- nasal decongestant, mydriatic,
hypotension or shock.
• Naphazoline, Oxymetazoline,
Xylometazoline
nasal decongestants in rhinorrhoea, in epistaxis

33. 2 agonists
Clonidine
• Presynaptic 2 agonist,
• Uses:- Hypertension, controls diarrrhoea in diabetic
patients with autonomic neuropathy, prophylaxis of
migraine, management of nicotine, alcohol and opiate
withdrawal, preanesthetic medication( for its sedative,
anxiolytic, analgesic, anti-stress effects),Menopausal hot
flushes, for diagnosis of pheochromocytoma, for pain
relief
• Adv effects:- rebound hypertension, nasal stuffiness,
impotence, constipation

34. Alpha methyldopa
• Centrally acting antihypertensive
• Uses:- Hypertension with renal insufficiency, reduces
ventricular hypertrophy, safe to be used in hypertension
during pregnancy, safe for mother and foetus.
• Adv,effects:- sedation, dry mouth, reduction in libido,
increases prolactin secretion (gynecomastia,
galactorrhea), severe hepatotoxicy, cause hemolytic
anemia.

35. Non-catecholamines beta2 agonists
Salbutamol, Pirbuterol
• Beta2 agonist
• Relaxes Bronchi, uterus, minimal cardiac
effects
• Being non-catecholamines, not degraded
by COMT, thus longer action
• Uses:- asthma, to arrest premature labour
• S/e:- tremors in hands, palpitations
• Pirbuterol – same as salbutamol

36. Terbutaline
• Beta2 selective bronchodilator
• Not metabolised by COMT, longer acting
• Relieves bronchospasm
• Also in COPD, premature labour,
urticaria(used along with ketotifen)
• Inhaled powder may harm tooth enamel,
cause tooth erosion

37. Non – catecholamine beta3 agonists
BRL-37344 and AD-9677
• Beta3 agonist
• Anti obesity drugs

38. Indirectly acting sympathomimetics
Tyramine
• Not used clinically
• Alarming food-drug interactions with MAO
inhibitors
• Tyramine found in cheese, beef, wine,
beer, banana, yeast and yoghurt

39. Amphetamine
• Powerful CNS stimulant, has peripheral effects
also
• Wakefulness, alertness, removes fatigue
• Improves physical performance
• Increases BP, HR
• Appetite supressant by action on hypothalamic
feeding centre
• Dependence and tolerance seen
• Uses:- Narcolepsy, Attention deficit hyperacive
disorder, Weight reduction

40. Sympathomimetics having mixed actions
Ephedrine
• Non-catecholamine alkaloid obtd from Ephedra Vulgaris
• Directly acts on receptors and releases NE from neurns.
Not destroyed by MAO and COMT< therefore longer
acting than E and NE
• Crosses BBB, powerful CNS stimulant action
• Used to treat hypotension that may occur with spinal
anesthesia.
• S/e:- Hypertension, insomnia, tachycardia
• Pseudoephedrine is stereo isomer of ephedrine, used
as nasal decongestant in oral formulations

41. • Orlistat :
• Pancreatic and gastric lipase inhibitor.
• Inhibit digestion and absorption of triglycerides.
• Absorption of cholesterol, fat soluble vitamin is impaired.
• Weight loss seen in clinical trial.
• Use in management of obesity and type II diabetes
• Contraindication include chronic malabsorption syndrome,
pregnancy, breast-feeding.
• Side effect include nasal congestion , headache, abdominal
pain, fluid motions, steatorrhoea, vitamin deficiency

42. Sibutramine
• Inhibits reuptake of NE and 5-HT at
hypothalamic sites that regulate food
intake.
• Reduces food intake
• Cause dose-dependant weight loss.
• Increases thermogenesis mediated by
sympathetic nervous system.
• S/e:- drug interactions, CVR effects.

43.  adrenergic blocking drugs
• These drugs inhibits adrenergic responses mediated through
the  receptor.
• All are competitive antagonist.
• CLASSIFICATION :
• NONSELECTIVE (beta 1 and beta2)
 Without intrinsic sympathomimetic activity : Propranolol,
Sotalol, Timolol
 With intrinsic sympathomimetic activity : Pindolol
 With additional α blocking property : Labetalol, carvedilol

44. • CARDIOSELECTIVE (beta1)
Metoprolol, Atenolol, Betaxolol, Esmolol, Nebivolol,
Acebutolol,Bisoprolol, Celiprolol
• According to generation :
1. First generation (nonselective beta1 plus beta2)
propranolol, timolol, sotalol, pindolol, Nadolol, Oxyprenolol
2. Second generation (1 selective )
metoprolol, atenolol, acebutolol, bisoprolol, esmolol, celiprolol
Selective Beta2 blockers eg. Butoxamine, ICI 118551
3. Third generation (with additional alpha blocking and/or
vasodilator property )
labetalol, carvedilol, celiprolol, nebivolol
Mixed alpha and beta Blockers eg. Labetolol, Carvedilol

45. Pharmacological action
Propanolol
• Cardiovascular system :
Cause decrease in heart rate, myocardial contractility,
conduction velocity and cardiac output
• Because of decrease in workload by heart , so decrease in
oxygen demand.
• Automaticity of heart is suppressed because of inhibition of
latent pacemaker.
• Produce fall in BP.
• Postural hypotension is least troublesome as is seen with α
blocker.

46. 2. Respiratory system :
• Propranolol increase bronchial resistance by blocking 2
receptor.
• Hence it is contraindicated in asthmatic patient.
• Specific 1 adrenoceptor blockers are prefer in patient
with bronchial asthma in the treatment of hypertensinon
3. Local anesthetics :
• Is potent local anesthetics as lignocaine.
• It is not use because of its irritant property.

47. 4. Eye :
• Reduce formation of aqueous humour.
• Thus reduce intraocular pressure in patient with glaucoma.
5. Uterus :
• Relaxation of uterus by 2 agonist is blocked by propranolol.
• Normal uterus activity is not altered.
6. CNS :
• Produce sedation , disturbing in sleep after long term use.
• Propranolol supress anxiety in short term stressful states.

48. 7. Metabolic :
• Propranolol block lipolysis and increase plasma free fatty acid
level.
• Inhibit glycogenolysis.
8. Miscellaneous :
• Prevent platelet aggregation.
• Propranolol increase synthesis of prostaglandin.
• Reduces portal vein pressure in cirrhosis
• On skeletal muscle- Inhibits adrenergically provoked tremors.

49. PHARMACOKINETICS
• It is completely absorbed orally but has low bioavailability.
• It is metabolised in liver.
• It is highly lighly lipid soluble and cross BBB.
• Plasma half life is short.
• Exist in two isomeric form, l-propranolol is 80-100 times more
potent than d-propranolol in blocking beta receptor.
• d-propranolol has more membrane stabilising property.

50. Interaction :
1. Due to Pharmacokinetic reasons :
• Al3+ salt, cholestyramine, cholestipol decrease the absorption
of  blocker.
• Enzyme inducer decrease its plasma concentration.
• Cimetidine and hydralazine may increase its bioavailability.
•  – blocker impair the clearance of lignocaine and thus
increase its bioavailability.

51. 2. Due to pharmacodynamic reasons :
• Digitalis and verapamil cause additive depression of SA
node, AV conduction and lead to cardiac arrest.
• Indomethacin and aspirin can oppose the antihypertensive
effect of  blocker.

52. • Adverse effect and contraindication ;
• Bronchoconstriction
• Cardiac failure
• Hypoglycemia
• Bradycardia
• Cold extremities
• Rebound hypertension and anginal attacks after sudden
withdrawal
• Adverse serum lipid profile
• CNS effect such as fatigue, depression

53. • Therapeutic uses :
• Essential hypertension
• Ischaemic heart disease (angina)
• Myocardial infarction
• CCF
• Cardiac arrhythmias
• Hyperthyroidism
• Pheochromocytoma
• Migraine
• Anxiety
• Glaucoma
• Oesophageal Variceal bleeding and hepatic portal hypertension
• Alcohol withdrawal
• Essential tremor
• Hypertrophic obstructive cardiomyopathy

54. • Timolol:- Used in wide angle glaucoma
• Sotalol:- Low lipid solubility, uses same as
propranolol, Has additional K+ channel
blocking and class III antiarrythmic
property independent of beta blocking
activity

55. Pindolol and Oxyprenolol
• Possess inherent intrinsic sympathomimetic activity on
beta1 and beta2 receptors.
• Benefits of this property are:-
1. Lesser bradycardia and myocardial depression. Can be
used in patients prone to bradycardia and in those with
low cardiac reserve as in CHF. Because of beta
agonistic action, less troublesome to asthamatics.
2. Less likely rebound hypertension. Beta action prevents
supersensitivity of upregulated beta receptors.
3. Lipid profile less worsened, compared to propranolol

56. • Disadvantage of intrinsic sympathomimetic activity
• Can not be used in migraine as intrinsic 2 agonist activity dilate
cerebral blood vessel.
• Less suitable for secondary prophylaxis of MI.
• Membrane stabilising activity in Propranolol, oxprenolol,
acebutolol contributes to antiarrhythmic action
• Lipid insolubility ( atenolol, sotalol)
• Less likely to produce central effects.
• Are incompletely absorbed orally.

57. • Selective Beta1 blockers( cardioselective beta blockers)
• Metaprolol, Atenolol, Esmolol, Betaxolol
Advantage of cardioselective 1 blocker over non selective :
• Safe in asthmatic patient.
• Safe in diabetes , cause less inhibition of glycogenolysis during
hypoglycaemia.
Safe in patient with peripheral vascular disease.
• Less deleterious effect on lipid profile.
Disadvantage of cardioselective :
• Rebound hypertension after abrupt withdrawal.
• Ineffective in controlling essential tremors.

58. • Selective 1 blocker with intrinsuc Sympathomimetic action :
• Acebutalol and Celiprolol :
• Have combine advantage of pindolol group and atenolol group.
• Have membrane stabilising action.
• Acebutalol
• well absorbed,
• During first pass metabolism in liver it is converted into active
metabolite, Diacetolol which has a half life 10 -12 hr.

59. • Celiprolol :
• Bioavailability is 75%
• Partial agonist action at 2 receptor
• Also cause some direct vasodilation, non- adrenoceptor
mediated vasodilatation probably due to NO production adds to
its antihypertensive action.
• Prefer for hypertensive patient having asthma.
• half life 4-5 hr.

60. • Nebivolol:- highly selective beta1 blocker
plus NO donor, produces vasodilatation
and has a potential to improve endothelial
function which may delay atherosclerosis
• Has rapid hypotensive action. Used in
Hypertension and CHF.

61. Selective B2- blocker
• Butoxamine and ICI-118551
• Experimental tools

62. Mixed alpha beta blocker
eg. Labetalol, Carvedilol
• Labetalol blocks 1, 1, 2, partial agonist
at 2 ( causes peripheral vasodilatation
and bronchodilation), inhibits NE uptake,
has vasodilator capacity, cause fall in BP,
s/e:- postural hypotension , hepatotoxicity
Uses:- hypertension in elderly,
pheochromocytoma, to control rebound
hypertension after clonidine withdrawal.

63. • Carvedilol orally effective, blocks 1, 2
and 1. 1, 2 blockade more prominent
than 1 blockade.
• Inhibits free radicals induced lipid
peroxidation, inhibits vascular smooth
muscle mitogenesis. Thus cardioprotective
in CHF patients
• Also used in essential hypertension.

64. Alpha adrenoceptor antagonist
• These drugs inhibits adrenergic responses mediated through
the α receptor.
CLASSIFICATION :
1. Non selective :
• Reversible : Phentolamine, Tolazoline
• Irreversible : Phenoxybenzamine
2. Selective :
• α1 blocker : Prazocin, terazocine, Doxazocine,Tamsulosin,
Alfuzocine
• α2 blocker : Yohimbine
3. Miscellaneous : Ergot alkaloid

65. Reversible non selective a blockers :
• Phentolamine and Tolazoline
• Similar affinity for α1 as well as α2 receptor.
• Pharmacological effect :
1. CVS :
• Produce vasodilation, decrease in peripheral vascular
resistance.
• Resultant fall in BP stimulate baroreceptor reflex causing
sympathetic discharge.
• Block presynaptic α2 receptor which promote neuronal
release of NE to produce more tachycardia and palpitation.
• Pretreatment with α1 blocker prevent pressor response of
adrenaline.

66. 2. Other effect :
• Miosis means loss of tone of radial muscle of iris
• Nasal stuffiness due to vasodilation and congestion of nasal
mucosa.
• Improve urine flow rate due to smooth muscle relaxation of
bladder neck and prostate.
• Failure of ejaculation due to inhibition of contraction of vas
deference and ejaculation duct.

67. • Therapeutic uses :
• For diagnosis and management of Pheochromocytoma
• For peripheral vascular disease.
• Prevent dermal necrosis
• Treatment of hypertension

68. • Phentolamine:
• Potent alpha blocker.
• Used for diagnosis of pheochromocytoma.
• Also used as an antidote to the pressor effect of overdose of a
agonist , and treatment of hypertension due to interaction of
sympathomimetic with MAOI.

69. • Diagnostic tests for pheochromocytoma :
1. Phentolamine test :
• Done when hypertension is sustained.
• Phentolamine 5 mg is given i.v.
• Fall of arterial pressure within 2 minutes by at least 35 mm Hg
systolic and 25 mmHg diastolic .
• Fall is not observed in patient suffering from other type of
hypertension.
2. Histamine test :
• Done when hypertension is intermittent.
• 0.05 mg is given i.v.
• Directly stimulate tumour, and blood pressure shoots up, often
preced by a fall.

70. • Adverse effect
• Orthostatic hypotention,
• Tachycardia
• Nasal stuffiness
• Contraindicated in CAD and angina pectoris.

71. • Thymoxamine (opilon)
• Competitive alpha adrenoceptor antagonist
• Has weak antihistaminic property.
• Use to treat peripheral vasospastic disorders like
ACROCYANOSIS and RAYNAUD’S DISEASE.
• Given orally or intravenously.
• Overdose cause palpitation, hypotension, headache.

72. Irreversible Non-selective :
• Phenoxybenzamine bind covalently to α1 and α2 receptor
causing irreversible blockage of this receptor.
• Pharmacological action :
• Cause vasodilation, decrease in peripheral resistance and
tachycardia.
• Causing marked postural hypotension.
• Therapeutic uses :
• Treatment of pheochromocytoma
• Treatment of benign prostatic hyperplasia
• Treat haemorrhagic and endotoxic shock
• To control manifestations of autonomic hyperreflexia in patients
with spinal cord transection.

73. Reversible, selective α1 adrenergic blockers :
• Prazosin
• Pharmacological action :
• Cause peripheral vasodilation and a fall in arterial pressure with
lesser tachycardia as compared to non selective α- blockers
because of following reason :
1. It lack α2 receptor blocking action and hence does not promote
NE release from sympathetic nerve terminals.
2. Decrease cardiac preload
Observe rise in concentration of HDL. And decrease in
concentration of LDL and triglycerides.
• Relax smooth muscle of bladder neck, prostate capsule and
prostatic urethra, reduces obstruction, increases urine flow rate
and causes complete bladder emptying and hence improve flow
of urine in BPH.

74. • Therapeutics uses :
• Treatment of hypertension
• Treatment of benign prostatic hypertrophy
• In the patient of Raynaud’s disease
• In patients with mitral and aortic valvular insufficiency
• Adverse effect :
• Postural hypotension
• Impotence
• Nasal congestion
• Na+ and water retention

75. • Terazosin and Doxazosin have longer
duration of action.
• Used in Hypertension and BPH( Terazosin
more effective than Finasteride- drug
which inhibits conversion of testosterone
to dihydrotestosterone, arrests growth and
reduce size of prostrate gland)

76. • Tamsulosin:
• Uroselective α1A and α1D blocker.
• Does not cause significant change in BP or HR. No CVR s/e
• Dizziness and retrograde ejaculation (failure of ejaculation) are
side effects.
• Plasma half life is 6-9 hr.

77. α2 adrenergic blockers :
• Yohimbine , Mianserine and Idazoxan
• Yohimbine can cross BBB.
• Also has 5-HT antagonist action.
• Use to treat autonomic insufficiency (by blocking α2 presynaptic
receptors), Sexual dysfunction, diabetic neuropathy and
postural hypotension
• Reverses action of Clonidine
• Idazoxan has membrane stabilising action
• Mianserine used as antidepressant

78. Miscellaneous Non- selective
α adrenergic blockers
• Ergot alkaloids eg. Ergotamine and
dihydroergotamine
• Block both α1 and α2 , partial agonist at α
receptors and 5 HT2 receptors.
• Used as oxytocics and dopamine receptor
agonists and in migraine.

79. • Drugs for glaucoma:
• Characterised by a progressive form of optic nerve damage.
• Associated with rise intraocular tension ( > 21 mmHg ).
• Therapeutic measure is to lower i.o.t. By reducing secretion of
aqueous humor or by promoting its dranage.
(A)Open angle glaucoma :
• Genetically predisposed degenerative disease affecting
trabecular meshwork
• i.o.t rises progresively.
• Following drugs are used :
1. Beta blocker :
• Lower i.o.t. by reducing aqueous formation
• Down regulation of adenylylcyclase due to 2 receptor
blockage.
• Timolol, betaxolol, levobunolol,

80. 2. Alpha adrenergic agonist :
• Adrenaline, dipivefrine, apraclonidine, brimonidine
3. Prostaglandin analogues :
• PGF2 lower i.o.t without inducing ocular inflammation.
• Increase out flow of aqueous humor .
• For eg. Latanoprost
• Needs only once dosing, has replaced beta blocker.
4. Carbonic anhydrous inhibitor :
• Reducing aqueous formation by generation of bicarbonate ion
in the ciliary epithelium.
• For eg. Dorzolamide, acetazolamide
5. Miotics :
• Topical pilocarpine and/or antiChEs
• Lower i.o.t by increasing ciliary muscle tone.

81. • Levobunolol:- Used for open angle
glaucoma.
• Introduced as once daily alternative to
Timolol . Ocular and systemic effects are
similar, only duration of action is longer.

82. (B) Angle closure (narrow angle, acute congestive ) glaucoma :
• Occur with narrow iridocorneal angle and shallow anterior
chamber.
• i.o.t remain normal until an attack is precipitated.
• i.o.t rises to very high value (40-60 mmHg)
• Following drugs may be used :
1. Hypertonic mannitol (20%) or glycerol (10%)
2. Acetazolamide
3. Miotic
4. Topical beta blocker
5. Apraclonidine
• Drugs only terminate the attack of angle closure glaucoma.
• Definitive treatment is surgical or laser iridotomy.

83. FUTURE PROSPECTS
• Carvedilol, a vasodilating  antagonist with antioxidant
properties which reduce mortality in patient with CCF.
• Further work in this area can lead to the development of novel
drug having such cardioprotective action.
• New  blocker eg. BWA 575c with unique combination of
properties ( blocker + ACE inhibitor ) for more effective
antihypertensive effects are under the process of development.
• Anti haemorrhagic property of alpha blockers is studied. They
increase survival in uncontrolled haemorrhage by decreasing
spontaneous blood loss.
• Rilmenidine has sympatholytic activity , clinical studies found
prevention of mental stress, prevention of orthostatic
sympathetic responses and prevention of adrenergic secretion.

84. • Indoramine and Urapidil are alpha
blockers chemically distinct from Prazosin,
used as antihypertensive in some
countries

85. References
• Essential of medical pharmacology by KD TRIPATHI
• Principles of pharmacology by HL sharma, KK Sharma
• Essential of pharmacotherapeutics by F.S.K. BAROR
• Pharmacology by G. M. Brenner, C. W. stevens