The autonomic nervous system has two main divisions - the sympathetic and parasympathetic nervous systems. The sympathetic nervous system is responsible for the "fight or flight" response and activates processes like increased heart rate and dilation of bronchioles. The parasympathetic nervous system is responsible for "rest and digest" functions like decreased heart rate and activation of gastrointestinal and genitourinary functions. Both systems use neurohumoral transmission using acetylcholine and norepinephrine as neurotransmitters which act on nicotinic and muscarinic receptors. There are many drugs that can selectively target components of the autonomic nervous system including parasympathomimetics, parasympatholytics, sympathomimetics, and sympathol

1. AUTONOMIC NERVOUS SYSTEM
• Autonomic Nervous System
• Somatic & Autonomic Nervous System
• Parasympathatic & Sympathatic nervous system
• Neurohumoral Transmission
•
• Receptors
-Cholinoceptors
-Adrenergic receptors
• Drugs affecting parasympathetic NS
• Drugs affecting sympathetic NS

2. Organization of The Nervous
System
Central Nervous System
“Brain and spinal cord”
Peripheral Nervous System
Somatic Nervous System
(voluntary)
Autonomic Nervous
System (involuntary)
Sympathetic
“thoracolumbar”
Parasympathetic
“craniosacral”
Efferent Division
Afferent Division

3. Efferent division of the peripheral nervous
system

4. In the nervous system, chemical transmission
occurs between nerve cells and between nerve
cells and their effector cells
Chemical transmission takes place through the
release of small amounts of transmitter
substances from the nerve terminals into the
synaptic cleft
The transmitter crosses the cleft by diffusion
and activates or inhibits the postsynaptic cell by
binding to a specialized receptor molecule

5. Neurohumoral Transmission
• It should be present in the presynaptic neurone
(usually along with enzyme synthesizing it)
• It should be released in the medium following nerve
stimulation
• Its application should produce responses identical
to those produced by nerve stimulation
• Its effects should be antagonized or potentiated by
other substance which similarly alter effects of nerve
stimulation

6. • Almost all autonomic nerves
(Syp+Parasaymp) have relay centre in
between called as ganglion
Which lies outside the CNS
Preganglionic Neuron
Postganlionic neuron

7. Efferent neurons
of the autonomic
system
Brainstem
or spinal cord
Cell body
Ganglionic transmitter
Neuroeffector transmitter
Preganglionic
neuron
Postganglionic
neuron
1
2
Effector
organ

8. The Synapse
 A functional connection between surfaces
 Signal transmission zone
 Synapse – synaptic cleft, presynaptic cell, and
postsynaptic cell
 Synaptic cleft – space in between the presynaptic and
postsynaptic cell
 Postsynaptic cell – neurons, muscles, and endocrine
glands
 Neuromuscular junction – synapse between a motor
neuron and a muscle

9. Comparison of Somatic and Autonomic Systems

11. Steps in neurohumoral transmission
• Impulse conduction
• Transmitter release
• Transmitter action on postjunctional membrane
-EPSP
-IPSP
• Post-junctional activity
• Termination of transmitter action

12. • Presynaptically releases neurotrnsmitter
is regulated by
By homotropic receptor ineraction
By heterotropic receptor ineraction

13. Sympathetic Responses
to Fight-or-Flight
Pupils should dilate
HR and contractility increase
Bronchials should dilate
GI tract should shut down
Bladder should be shut down
Blood should be shunted from GI tract and
skin to muscles
Metabolism should increase supply of
glucose

14. Parasympathetic Nervous
System
assimilation of food,
conservation of energy

15. Preganglionic neurons
• Long
• Synapse with postganglionic neurons at or near organ
• Release acetylcholine (ACh) to activate nicotinic receptors on postganglionic
neurons
Postganglionic neurons
• Short
• Synapse on the target organ
• Release ACh to activate muscarinic receptors on the target organ
Cholinergic fibers: i.e., act by releasing acetylcholine.
• Include:
– all preganglionic efferent autonomic fibers
– the somatic (non-autonomic) motor fibers to skeletal muscle
– most parasympathetic postganglionic and a few sympathetic postganglionic
fibers
Parasympathetic Neurons & Synapses

16. Presynaptic autoinhibitory receptors
• Presynaptic release of NT
• Homotropic receptors interaction
• Heterotropic receptors interaction

17. Cholinergic System & Drugs
Synthesis Store & estruction Ach

18. Cholinestrase: Two types
• True Acetylcholinestrase:
• Location: neuronal membrane, RBC, Placenta
• Plasma Cholinestrase (pseudocholinestrase,
Butyrylcholine-estrase):
Succinylcholine, Butyrylcholine, Ingested esters

19. • Muscarinic receptors: parasympathetic neuroeffector junction
• M1 Sympathetic ganglia, gastric glands, cerebral cortex
• M2 Myocardium, presynaptic terminal of peripheral & central
neurones
• M3 Glandular & visceral smooth muscle
• M4
• M5
• Nicotinic receptors
• NM : Skeletal muscle end plate
• NN: Ganglionic cells(SP &PSP), Adrenal medulla

20. Cholinoceptors
• Muscarinic
• AGONIST: Muscarine
• ANTAGONIST: Atropine
• M1:
• Autonomic ganglia
• Gastric glands: histamine release
• CNS: learning,memories, motor function
• Agonist : Oxotremorine
• Antagonist: pirenzepine , telenzepine

21. • M2: SA Node Rate of impulse generation
• AV Node  Velocity of conduction
• ATRIUM  Contractility
• VENTRICLE  Contractility (SLIGHT)
• Visceral smooth muscle :Contraction
• Agonist : Methacholine
• Antagonist: Methoctramine,

22. • M3: Visceral SM: Contraction
• IRIS: Constriction
• CILIARY MUSCLE: Contraction
• EXOCRINE GLANDS: Secretion
• Vascular endothelium: EDRF (NO)
Vasodilatation
Agonist : Bethanechole
Antagonist: Hexahydrosiladifenidiol, Darifenacin

23. NICOTINIC RECEPTORS
• NM
• AGONIST PTMA, NICOTINE
• ANTAGONIST TUBOCURARINE
• NN
AUTONOMIC GANGLIA
AGONIST DMPP, NICOTINE
ANTAGONIST HEXAMETHONIUM

24. The main effects of the autonomic nervous system
ORGAN SYMPATHETIC
EFFECT
ADRENERGIC
RECEPTOR
TYPE
PARASYMPATHETIC
EFFECT
CHOLINERGIC
RECEPTOR TYPE
Heart
Sinoatrial node
Atrial muscle
Atrioventricular
node
Ventricular muscle
Rate 
Force 
Automaticity 
Automaticity 
Force 
b1
b1
b1
b1
Rate 
Force 
Conduction velocity

No effect
M2
M2
M2
M2
Blood vessels
Arterioles
Coronary
Muscle
Viscera
Skin
Brain
Erectile tissue
Salivary gland
Veins
Constriction
Dilatation
Constriction
Constriction
Constriction
Constriction
Constriction
Dilatation
a
b2
a
a
a
a
a
b2
No effect
No effect
No effect
No effect
Dilatation
Dilatation
No effect
No effect
? M3
? M3
Viscera
Bronchi
Smooth muscle
Glands
Gastrointestinal
tract
Smooth muscle
Sphincters
Glands
Uterus
Pregnant
No sympathetic innervation, but
dilated by circu-lating
adrenaline
No effect
Motility 
Constriction
No effect
Contraction
b2
a1, a2, b2
a2, b2
a
b2
Constriction
Secretion
Motility 
Dilatation
Secretion
Gastric acid
secretion
Variable
M3
M3
M3
M3
M3
M1

25. ORGAN SYMPATHETIC
EFFECT
ADRENERGIC
RECEPTOR
TYPE
PARASYMPA-
THETIC EFFECT
CHOLINERGIC
RECEPTOR TYPE
Male sex organs Ejaculation a Erection ?M3
Eye
Pupil
Ciliary muscle
Dilatation
Relaxation (slight)
a
b
Constriction
Contraction
M3
M3
Skin
Sweat glands
Pilomotor
Secretion (mainly
cholinergic)
Piloerection
a
a
No effect
No effect
Salivary glands Secretion a, b Secretion M3
Lacrimal glands No effect Secretion M3
Kidney Renin secretion b2 No effect
Liver Glycogenolysis
Gluconeogenesis
a, b2 No effect

26. • Heart M2
Atria -ve chronotropic
-ve ionotropic
Decrease in conduction velocity
RP (increase)
Ventricular:
Sweat glands: M3 receptors
Innervation sympathetic but cholinergic in nature

27. Classification of drugs affecting the ANS
• Parasympathetic nervous system
Mimic acetylcholine = cholinergic = muscarinic
agonists = parasympathomimetic
Block acetylcholine = anticholinergic = muscarinic
antagonist = parasympatholytic
• Sympathetic nervous system
Mimic norepinephrine = adrenergic = adrenergic
agonist =Adrenoceptors= sympathomimetic
Block norepinephrine = antiadrenergic = adrenergic
antagonist = sympatholytic

28. CHOLINERGIC AGONISTS
CHOLINESTERS
• Acetylcholine
• Methacholine
• Carbachol
• Bethanechol
• ALKALOIDS
• Muscarine
• Pilocarpine
• Arecoline

29. ACTIONS (of ACh as prototype)
• Heart
• Smooth muscle
• Blood vessels
• Glands: Secretion from all parasympathetically
innervated
• Eye

30. Nicotinic: Autonomic gangliaBoth sympathetic
and parasympathetic ganglia are stimulated
• This effects manifested at higher doses
Skeletal muscles
• Iontophoretic application of ACh to muscle
endplate causes contraction of the fibres
• High dose can cause twitching and
fasciculations,buti.v. injection
• CNS

31. Uses
• Pilocarpine
• Acetylcholine
• Bethanechol
• Carbachol
• Methacholine

32. ANTICHOLINESTERASES
• Reversible
• Carbnmates
• Physostigmine(Eserine)
• Neostigmine
• Pyridostigmine
• Edrophonium
• Rivastigmine, Donepezil
• Galantamine
lrreversible lrreversible
• Organophosphates
• Dyflos (DFP)
• Echothiophate
• Parathion
• Acridine
• Tacrine
Carbamates
• Carbaryl
• Propoxur

33. • Uses
• In glaucoma
• Myasthenia gravis
• Postoperative paralytic ileus/urinary retention
• Postoperative decurarization
• Belladona poisoning
• Alzheimer's disease

34. •ANTICHOLINERGIC DRUGS
•(Muscarinic Receptor Antagonist, Parasympatholytics,
•Atropine-like Drugs)
Atropine, the prototype drug of this class

35. Natural alkaloids: Atropine, Hyoscine (Scopolamine),
Semisynthetic derivatives
• Homatropine, Hyoscine butyl bromide, Ipratropium bromide,
• Tiotropium bromide
Synthetic compounds
• (A) Mydriatics: Cyclopentolate, tropicamide
• (B) Antisecretory-antispasmodics:
• Quaternary compounds: Oxyphenonium, clidinium, glycopyrrolate
• Tertiary amines: dicyclomine, pirenzipine
• (C) Vesicoselective: oxybutynine, flavoxate, tolterodine
• (D) Antiparkinsonian (central Anticholinergics):
Biperiden, Trihexyphenidyl(benzhexol)
•ANTICHOLINERGIC DRUGS

36. •CNS An overall stimulant action but not appreciable at low doses which
•produce peripheral effects because of restricted entry
•Hyoscine produces central depressant effects even at low doses
•Atropine stimulates many medullar centers –
• vagal, respiratory, and vasоmotor
• Basalganglia, it suppresses tremor and rigidity in parkinsonism
•High doses cause cortical excitation, rest-
• lessness, disorientation, hallucinations, and delirium
• followed by respiratory depression and coma.

37. CVS
• Atropine causes tachycardia, due to blockade of
•M2-receptors on SA node
•Tachycardia is more marked in young adults than in children and the
elderly.
•Atropine shortens the refractory period of AV conduction,
•Atropine does not influence BP

38. Eye
• Topical instillation of atropine (0.1%) causes
mydriasis, abolition of light reflex, and
cycloplegia, lasting 7–10 days.
• Results in photophobia and blurring of near
vision.
• Intraocular tension?
• Specially in narrow angle glaucoma

39. •Smooth muscles.
•All visceral smooth muscles with parasympathetic innervation are relaxed (M3-
blokade).
•Tone and amplitude of GIT are reduced.
•Spasm may be reduced, constipation may occur.
•Peristalsis is only incompletely
•Atropine causes bronchodilation and reduced airway. Inflammatory
•mediators (histamine, PGs, and kinins) increase vagal
•activity in addition to their direct action on bronchial
•muscle and glands. Atropine attenuates their action
•by antagonizing the reflex vagal component.It has a
•relaxant action on urinary bladder
•Urinary retention can occur in older men with prostatic hyperplasia.

40. Glands
•Atropine decreases sweat, salivary, tracheo-bronchial, and
lacrimal secretion (M3-blockade)
•Eyesdry, talking, and swallowingdifficult.
•Atropine decreases less the secretion of acid and pepsin and
more of the mucus in the stomach.
Body temperature
•Rise in body temperature occurs at higher doses, and is due to
both inhibition of sweating as well as stimulation of the temperature
regulating centre in the hypothalamus.
•Children are highly susceptible.

41. •Local anaesthetic action. Atropine has a mild
anaesthetic action on the cornea.
•The sensitivity of different organs and tissues
•to atropine varies and can be graded as
•saliva, sweat, bronchial secretion > eye >
•bronchial muscles > heart > intestinal and
•bladder smooth muscles > gastric glands
•and gastric smooth muscles

42. •Pharmacokinetics
•Atropine and hyoscine are rapidly absorbed from
•GIT. Applied to the eyes they penetrate the cornea.
•Passage across BBB is somewhat restricted. 50%
•of atropine is metabolized in the liver and excreted
•unchanged in urine. It has t1/2 3–4 h. Hyoscine is
•more completely metabolized and has better BBB
•penetration. Some rabbits have a specific atropine
•esterase which degrades atropine very rapidly.

43. Unwanted effects
•Dry mouth, difficulty in swallowing and talking;
•Dry and hot skin (especially over the face and neck);
•fever difficulty in micturition;
•Photophobia , blurring of near vision;
•Palpitation
•Contraindication:

44. Atropine (atropine sulphate 0.6mg) i.v./i.m. ointment/eye drop)
Homatropine (Homide 1%, 2%)
Hyoscine butylbromide
(tab buscopan 10mg/inj 20 mg),
Ipratropium bromide (IPRAVENT 40 microgram)
Tiotropium bromide (TIOVA 18 Microgram)
•ANTICHOLINERGIC DRUGS
•Atropine
•Homatropine
•Cyclopentolate
•Tropicamide
•Tropac-p

45. Clidinium (NORMAXIN 2.5 mg, dicyclomine 10 mg, chlordiazepoxide)
Glycopyrrolate (Pyroalte 0.2 mg/ml, 10 ml vial)
Tertiary amines: Dicyclomine (colimex drops 10 mg/ml with dimethicone)
Pirenzipine
Drotavarine (tab drotakind-M)
VESICOSELECTIVE oxybutynine, flavoxate, tolterodine

46. USES
• Preanaesthetic medication
• Peptic ulcer
• Pulmonary embolism???
• COPD & Bronchial asthma
• As mydriatic agent for diagnosis refraction errors,
• Iridocycltis
• Adhesions between iris and lense
• Bradycardia
• Parkinsonism
• Motion sickness
• Lie detector test
• Relieve urinary frequency
• Dysmenorrhoea

47. CATECHOLAMINE
 STORAGE OF CA
 NA+ATP(4:1 ) IS ABSORBED ON A
CHROMOGRANIN
 IN ADRENAL MEDULLA: NA DIFFUSES OUT
OFCYTOPLASMMETHYLATED TO ADR
 CYTOPLSM POOL OF CA IS KEPT LOWBY
MAO

48.  RELEASE OF CAS ALONG WITH NA OR ADR+ATP+DOPAMINE
HYDROXYLASE+CHROMAGRANIN
 UPTAKE OF CAS
 AXONAL UPTAKE : ACTIVE AMINE PUMP NETTRANSPORT NA BY
A Na+ coupled mechanismcocain,desipramine can block this pump
 VESICULAR UPTAKE: VMAT (VESICULAR MONOAMINE
TRANSPORTER) RESERPINE can block this pump
 METABOLISM CAS:
 MAO IN CYTOPLASM
 COMT (CATECHOLE-O-METHYL TRANSFERSE) LIVER & OTHER
 VMA (VANILLYLMANDELIC ACID), 3-METHOXY-4-HYDROXY
PHENYLETHYLENE GLYCOL,
NORMETANEPHRINE,
 3,4 DIHYDROXY MANDELLIC ACIDCONJUGATIONEXCRETION
IN URINE

49. Classification of drugs affecting the
ANS
 Parasympathetic nervous system
Mimic acetylcholine = cholinergic = muscarinic
agonists = parasympathomimetic
Block acetylcholine = anticholinergic =
muscarinic antagonist = parasympatholytic
Sympathetic nervous system
Mimic norepinephrine = adrenergic = adrenergic
agonist =Adrenoceptors= sympathomimetic
Block norepinephrine = antiadrenergic =
adrenergic antagonist = sympatholytic

50. ADRENALINE
• HEART: increases HR by increasing slope
of slow diastolic depolarization of cells in
the SA node
• Activates latent pacemaker in AV node
• Cardiac contraction incraesed

51. • BLOOD VESSELS: vasoconstriction &
vasodilation can occur depending on drug,
dose, vascular beds
• Cutaneous,mucus membrane,renal beds
• Dose
• Skeletal muscle
•

52. • BP:

53. • RESPIRATION
• ADR
• NA
• ISPRENALINE

54. EYE
• a1 vasoconstriction of ciliary musclereduced
aqueous fprmation
• a2 reduced secretary activity of ciliary
epithelium
• b2 enhanced secretary activity of cilliary
epithelium

55. GIT
• Relaxation: a & b
• Bladder: Detruser relaxes b &
• Trigone constricted a1
• Uterus:
• Human: contractionnonpreg
• relaxation:pregnant
• Skeletal muscle: neuromuscular transmission
facilitated
• CNS:
• METABOLIC:

56. • Adrenaline
• For systemic action, 0.2-0.5 mg s.c., i.m., action lasts 1/2 to 2 hrs.
• ADRENALINE 1mg/ml inj.
• As local vasoconstrictor, 1 in 200,000 to 1 in 100,000 added to
lidocaine; in xylocaine with Adrenaline: lidocaine 21.3 mg +
adrenaline O.005mg/ ml .
• Noradrenaline (levarterenol)
• 2-4 ug/min I.V.. infusion; local tissue necrosis occurs if the
solution extravasates;
• do not mix with NaHCO3 same bottle (rapid oxidation occurs);
• Action starts declining within 5 min of discontinuing infusion.
adrenor 2 mg (base)/2 ml amp.
• Isoprenaline (Isoproterenol) 20 mg sublingual, 1-2 mg i.m., 5-10
ug/min i.v. infusion; action lasts 1-3 hrs.
• It is occasionally used to maintain idioventricular rate till
pacemaker is implanted. For bronchial asthma

57. • Adverse effects and contraindications:
• Marked rise in BPcerebral haemorrhage, ventricular
tachycardia/fibrillation, angina, MI doses
• Adr is contraindicated in hypertensive, hyper-thyroid
• AP patients. Adr not be given during anaesthesia
halothane (risk of arrhythmias)
• In patients receiving beta blockers (markecd rise in BP
can occur due to unopposed action).

58. • THERAPEUTIC CLASSIFICATION OF ADRENERGIC DRUGS
• Pressor agents
• Noradrenaline
• Phenylephrine
• Ephedrine, Methoxamine
• Dopamjne, Mephentermine
• Cardiac stimulants
• Adrenaline, Dobutamine, Isoprenaline
• Bronchodilarors
• Salbutamol (Albuterol), Isoprenaline Terbutaline Salmeterol, Formoterol,
Bambuterol
• Nasal decongestants
• Phenylephrine Naphazoline
Xylometazoline Pseudoephedrine
Oxymetazoline Phenyl propanolamine
• CNS stimulants
Amphetamine
Dexamphetamine
• Anorectics
• Fenfluramine, Sibutramine Dexfenfluramine
• Uterine relaxant and vasodilators
Ritodrine, Salbutamol , Isoxsuprine,Terbutaline
• .
•

59. • Dopamine: (Dl and D2) as well as adrenergic a & b1 agonist.
• D1  b1 a1 action
• Low dose of DA : Dl in renal & mesenteric BV are the most
sensitive
• Moderately doses : positive inotropic (direct b1 & Dl action + that
due to NA release) & little chronotropic effect on heart.
• Large doses infused: a1 action
• At doses normally employed, it raises cardiac output and systolic
BP with little effect on diastolic BP.
• Does not penetrate BBBCNS effects.
• DA : cardiogenic or septic shock and severe CHF to increase BP
& urine outflow
• i.v. infusion (0.2-1 mg/min): DOPAMINE, 200 mg in 5 ml amp

60. • Dobutamine: not a Dl or D2 receptor agonist.
• b1 (prominent action) + a
• At 2-8ug/kg/ min i.v. infusion: increased force of cardiac
contraction and output, without significant change in heart
rate, peripheral resistance
• Dobutamine is b1 selctive agonist
• Ephedrine:
• Mainly acts indirectly but has some direct action on alpha
and beta receptors also.
• Repeated injections Tachyphylaxis
• Resistant to MAO orally.

61. • Amphetamines
• Central effects: alertness, jncreased concentration & attention span,
euphoria, talkativeness, increased work capacity. Fatigue is allayed.
Athletic performance is improved temporarily followed by
deterioration
• 'dope test' for athletes.
• Reticular activating system is stimulated resulting in wakefulness
and postponement of sleep deprivation
• But short-lived & may be accompanied by anxiety, restlessness,
tremor, dysphoria and agitation
• Use in examinations can only be condemned
• Potentiate antiepileptics, analgesics and anti motion-sickness drugs.
Peripheral effects on heart and BP are not significant at the usual
doses
• Amphetamines are drugs of abuse & capable of producing marked
psychological but little or no physical dependence

62. • Phenysephrine:selective a1 agonist, has negligible
beta action
• raises BP by causing vasoconstriction little cardiac
actionreflex bradycardia.
Topical nasal decongestant
Producing mydriasis when cycloplegia is not required.
Phenylephrine tends to reduce IOT by constricting ciliary
body blood vessels
Orally administered nasal decongestant preparations.
Central effects are not seen with usual clinical doses
DECOLD PLUS 5 mg with paracetamol 400 mg +
chlorpheniramine 2 mg + caffeine 15 mg
DROSYN EYE DROPS 10%

63. • Methoxamine : a1 agonist
• Mephentermine a & b+NA release
• Not substrate for MAO &COMT

64. • SELECTIVE BETA-2 STIMULANTS
• Salbutamol, Terbutaline, Salmeterol,
Formoterol & Ritodrine
• As uterine relaxant to delay premature labour
(Ritodrine, Isoxsuprine)
• In hyperkalemic familial periodic paralysis—
BETA-2 agonists benefit by enhancing K+ uptake
into muscles  lowering plasma K+ levels
• The most important side effect is muscle tremor;
tachycardia

65. • Nasal decongestants
• Phenylephrine Naphazoline
Xylometazoline Pseudoephedrine
Oxymetazoline PhenylPropanolamine
• Anorectics
• Non adrenergic appetite centre
• Phenylpropanolamine
• Serotonergic satiety centre
• Fenfluramine, Dexfenfluramine
• Non adrenergic/Serotonergic : Sibutramine

66. Therapeutic uses
• Hypotension
• Along with local anaesthetic agent
• As an styptics
• Nasal decongestant
• Cardiac arrest
• AV block: Isoprenaline
• CHF
• Bronchial asthma
• Mydriatic
• Hyperkinetic children
• Narcolepsy
• Obesity
• Uterine relaxant
• Insulin hypoglycemia
• Nocturnal enuresis in children

67. a-ADRENERGIC BLOCKING DRUGS
• adrenergic neurone blocking agents
• a- adrenergic blocking Drugs

68. • CLASSIFICATION
• Nonequilibrium type (non-competitive)
• Phenoxybenzamine
• Equilibrium type (competitive)
• A. Nonselective
Ergot alkaloids: Ergotamine, Ergotoxine
Hydrogenated ergot alkalolds: Dihydroergotamine, Dihydroergotoxine
Imidazolines: Tolazoline, Phentolamine
• B. a1 selective: Prazosin, Terazosin, Doxazosin,
Tamsulosin
• C. a2 selective: Yohimbine

69. • GENERAL EFFECTS OF a BLOCKERS
• Blockade of a1TPR & VENOUS RETURN DECREASED &
CO………..BP??? POSTURAL HYPOTENSION
• Reflex tachycardia
• Nasal stuffiness & miosis
• Intestinal motility is increased
• Hypotension  reduce renal blood flow & g.f.r more complete
reabsorption of Na & water increase in blood volume
• Tone of s.m. in bladder trigone, sphincter & prostate is
reduced(a1 blockade) improvement in BPH patients
•
• Contractions of vas deferensEjaculation(a response)

70. • Phenoxybenzamine
•
• Venodilatation is more prominent than arteriolar dilatation
• In recumbent subjects cardiac output and blood flow to many organs are
increased due to reduction in peripheral resistance & increased venous return
• It tends to shift fluid from extravascular to vascular compartment.
• Phenoxybenzamine is lipid soluble, penetrates brain and can produce CNS
stimulation, nausea and vomiting on rapid i.v. injection
• Oral doses produce, depression, tiredness and lethargy. postural hypotensiory ,
palpitation, nasal blockage, miosis, inhibition of ejaculation

71. • Phentolamine
• Rapidly acting a blocker with short duration of action (in minutes).
• a1 & a2 equally blockade
• NA release increased and venodilatation predominates over arteriolar
dilatation
• Diagnosis & intraoperative management of Pheochromocytoma
• and for control of hypertension due to clonidine withdrawal, cheese
• Reaction
• It is the most suitable a blocker for local infiltration to counteract
vasoconstriction due to extravasated NA/DA

72. Prazosin
• Highl selective a1: a2 100o:1
• Only mild tachycardia; NA released is not increased due to
absence of a2 blockade
• Prazosin dilates arterioles more than veinPostural
hypotension is less marked
• ‘first dose effect can be minimized by:
• Starting with a low doses
• Taking it at bedtime.
• Prazosin is effective orally (bioavailab -
• -60%), highly bound to plasma proteins
• Antihypertensive
• BPH

73. • Tamsulosin
• This uroselectivec a1A /a1D
• a1B BLOOD VESSEL
• Tamsulosin : URIMAX,

74. • Pheochromocytoma & Phentolamine test
• Hypertension
• Clonidine withdrawal & Cheese reaction
• Benign hypertrophy of prastate (EHP)
• Secondary shock Shock due to blood or fluid loss is
accompamed by reflex vasoconstriction
• Peripheral vascular disease
• Papaverine & Phentolamine induced penile erection
therapy for impotence (inj corpus cavernosum )
• Cangestive heart fatlure (CHF)???
USES OF a BLOCKERS

75. CLASSIFICATION b ADRENERGTCB LOCKTNGD RUGS
• Nonselective (b1 & b2)
• Without intrinsic sympathomimetic activity
• Propranolol, Sotalol, Timolol.
• With intrinsic sympathomimetic activity
• Pindolol
• With additional a blocking property
• Labetalol, Carvedilol
• Cardioselective (b1 )
• Metoprolol, Atenolol, Acebutolol, Bisoprolol
• Esmolol, Betaxolol, Celiprolol, Nebivolol

76. PHARMACOLOGICAL ACTIONS
• Heart Propranolol decreases HR, FC (at relatively higher
doses) & C.O.
• Effects on a normal resting subject are mild, but become
prominent under sympathetic over-activity (exercise, emotion).
• Cardiac work & oxygen consumption are reduced
• Coronary flow is reduced but this is largely restricted to the
subepicardial region.
• Overall effect in angina patients is improvement exercise
tolerance is increased
• The A-V conduction is delayed.

77. • Blood vessels Propranolol blocks vasodilatation
• On prolonged administration BP gradually falls in hypertensive subjects
but not in normotensive
• Total peripheral resistance (t.p r.) is increased
• With continued treatment, resistance vessels graduallv adapt to chronically
reduced c.o. so that t.p.r. decreases-both systolic and diastolic BP fall
•
• Reduced NA release from sympathetic terminals due to blockade of
presynaptic beta -receptor mediated facilitation of the release process
• Decreased renin release from kidney
• Central action reducing sympathetic outflow.

78. • Respiratory tract: B2
• CNS: anxiety & migrain
• Metabolic: Hypglycemia, HDL/LDL: (B2)
• Skeletal muscle: B2
• Eye:
• Tremors: B2
• PHARMACOKINETICS

79. • Uses
• Hypertension
• AP
• Cardiac arrhythmias
• MI
• By preventing reinfarction
• By preventing sudden ventricular fibrillation at the second attack of MI
• Myocardial salvage during evolution of MI
• CHF
• THYROTOXICISIS
• MIGRAINE
• ESSENTIAL TREMORS BETA-2 action
• GLAUCOMA
• Anxiety
• Pheochromocytoma
• ADRs & contraindications