ANS - Doc Rasha

3.  It regulates the involuntary functions which are not
consciously controlled including:
 Cardiac output, blood pressure and blood flow to various
organs.
 Respiration. Peristalsis of the GIT.
 Tone of smooth muscles (gall and urinary bladders ,
ureter and uterus.
 Glandular secretions (sweat ,saliva and GI
secretions,…….)
 It regulates other important functions such as cellular
metabolism.

4. SYMPATHETIC DIVISION (thoraco lumber outflow):
a) Origin: the preganglionic nerves originate in lateral
horn cells of all thoracic and upper 3 lumber segments
of the spinal cord .
b) The pre ganglionic nerve fiber is short and the post
is long.
c) The synapse between the pre- and post- is located in
the sympathetic chain.

5. PARASYMPATHTIC DIVISION (Cranio sacral outflow):
a) Origin : originates from cranial nuclei III, VII, IX
and X.
› b) Sacral outflow originates from the 2nd, 3rd and
4th sacral segments of the spinal cord.
› c) The pre ganglionic is long ,while the post is
short,
› d) The ganglia being close or even embedded in
the effector organ.
›

8. 1- Both are physiologically antagonists.
2- Activation of one gives the same effect as inactivation of the
other.
3- Each involuntary organ receives a dual nerve supply ( except
body of the uterus “sympathetic”.
4- The level of activity is the algebraic sum of the two
components.
5- Parasympathetic “trophotropic” leads to growth and concerned
with restoration and conservation of energy.
6- Sympathetic “ergotrophic” prepares the individual for fight and
flight and leads to energy expenditure.

12. Based on the chemical mediators released ,the ANS can be
divided into:
A) Cholinergic division:
Acetylcholine is the neurotransmitter and the cholinergic
neurons are:
1- All of the preganglionic neurons.
2- The parasympathetic postganglionic neurons.
3- The sympathetic postganglionic neurons that innervate
sweat glands.
4- The parasympathetic neurons to the skeletal blood
vessels.
5-The sympathetic neurons innervating the adrenal
medulla.

13. Norepinephrine is the neurotransmitter , and
the adrenergic neurons are :
The remaining postganglionic sympathetic
neurons are noradrenergic and secret
norepinephrine.
The adrenal medulla is a sympathetic
ganglion that secrets norepinephrine (20%),
epinephrine (80%) and some dopamine
directly into the blood stream.

15. Chemical transmitters in sympathetic nervous
system :
A) Norepinephrine. B) Epinephrine.
C) Dopamine.
Steps of adrenergic neurotransmission:
1)Synthesis.
2) Storage.
3) Release.
4) Binding with receptors.
5) Uptake and metabolism.

17. 1- Synthesis:
a) L-tyrosine ------>L-DOPA by tyrosine hydroxylase
b) L-DOPA --- dopamine by alanine decarboxylase
c) Dopamine is actively transported into synaptic
vesicles.
d) Dopamine--- norepinephrine by dopamine beta
hydroxylase.
e) Norepinephrine--epinephrine by N-
methyltransferase
.

18. Norepinephrine is also synthesized in and
released from the adrenal medulla.
Chromaffine cells of the adrenal medulla are
innervated by sympathetic preganglionic
cholinergic neurons and release catecholamines
into blood stream.

19. 2- Storage:
NE is bound to ATP and stored within the vesicles until
released.
3- Release :
I – When the action potential arrives Ca++ channels open
allowing Ca++ to enter into the neuron.
II- NE –containing vesicles fuse with the neuronal
membrane and expel their contents to the synapses to
allow NE binding with receptors.
.

20.  4- Metabolism:
 After binding to the receptors NE is removed
by one or more of the following
 a) High Affinity uptake system (uptake I ):the
major mechanism of removal
 NE is transported back into the neuron Where
it is stored in the synaptic vesicles (uptake III)
for further re-release.
 Uptake III is blocked by reserpine

21. Neuronal uptake I is inhibited by cocaine ,
guanethedine, phenylpropanolamine and TCA
(imipramine).
b) Oxidative deamination by MAO:
MAO is located in the cytoplasm of the neuron .
It metabolizes un stored NE and the metabolite is
excreted in urine.
c) Non neuronal uptake (uptake II system)
Occurs in the post junctional cells . NE is O-
methylated by COMT.
Uptake II is blocked by phenoxybenzamine.

22. ADRENERGIC RECEPTORS
A) α-Adrenergic receptors:
i- α1 ii- α2
B) β adrenergic receptors :
i- β1. ii- β2 iii-β3
A) α1- Receptors :Present on the postsynaptic
membrane of the effector organ.
Mechanism:
Receptor stimulation----G protein activates
phospholipase-C
--- IP3 + DAG from phosphatidyl inositol---
release of intracellular Ca++ from endoplasmic
reticulum.

23. ACTIONS of α1- RECEPTORS
1- Active mydriasis.
2-Generalized vasoconstrictionperipheral
resistanceBlP
3- Spasm of GIT and Urinary bladder sphincters.
4- Uterus: contracts pregnant and relaxes non-pregnant.
5- Ejaculation.
6- Contraction of pilomotor muscle--hair erection.
Selective Agonists :Phenylephrine and Methoxamine
Selective Antagonists : Prazosin and Tolazoline.
.

25. B) α2- Receptors:
Located in the pre synaptic membrane of the ad.
nerve terminals and in CNS,
Also In the β-cells of pancreas .
They are inhibitory in function cause feedback
inhibition of ongoing release of NE.
MECHANISM:
↓ adenylyl cyclase ----- cAMP ---- of
further release of NE.
.

26.  1-  sympathetic outflow from CNS.
 2-  release of NE & Ach from nerve terminal.
 3-  of insulin release.
 4-  lipolysis in fat cells
 Selective agonists: α methyl noradrenaline
,clonidine , and guanabenz.
 Selective antagonists: Yohimbine, tolazoline
and phentolamine

27. C) β-Receptors:
β1 receptors are found mainly in the heart.
β2 receptors are located mainly on bronchial and
vascular smooth muscle.
β2 receptors are located presynaptic to increase NE
release.
β3 located in the adipose tissue to increase free fatty
acids.
MECHANISM
adenylyl cyclase --- cAMP ---  intracellular Ca++

28. Actions of β1-Receptors
Cardiac stimulation : tachycardia and increase in
myocardial contractility.
Selective agonists: dobutamine and prenalterol.
Selective antagonists: atenolol ,acebutolol , and
metoprolol.
.

29. Actions of β2-Receptors
 1- Vasodilation in skeletal blood vessels.
 2- Bronchodilation.
 3- muscle and liver glycogenolysis.
 4- Relaxation of GIT and urinary bladder walls.
 5- Relaxation of uterine muscle.
 Selective Agonists : Salbutamol and albuterol.
 Selective Antagonists : Butoxamine

30. SYMPATHOMIMETICS (ADRENERGIC AGONISTS)
Chatecholamines present in A-cells of adrenal
medulla
According to mechanism of action classified into
1- Direct acting agonists e.g.Ep , NE, isoproterenol
and phenylephrine.
2- Indirectly acting : e.g. amphetamine
,methamphetamine and tyramine.
3- Mixed action agonists :ephedrine & metaraminol.

31. Direct Acting Agonists
1-EPINEPHRINE (ADRENALINE )
Not administered orally due to
Poor absorption from the GIT.
Rapid destruction by the intestinal juice.
Rapid metabolism by liver enzymes.
All CAs. Do not pass bbb.
Administration : S.C. ,I.C ,inhalation , eye drops.
Metabolites excreted in urine.
Acts on α1, α2 , β1, β2 ,β3 - receptors
General Features:

32. PHARMACOLOGICAL ACTIONS of EPINEPHRINE
1- Cardiovascular System:
a)↑ heart rate (+ve chronotropic action), b)↑ force of
contraction (+ve inotropic)[β1].
c)↑ Arterial blood pressure (mainly inc. systolic with slight
dec. in diastolic).
d) ↓ in renal blood flow.
2- Respiratory System:
a) Bronchodilatation and ↑ in tidal volume (β2).
b) Relieves dyspnea and acute symptoms of asthma.

33.  3- GIT:
 A)↓ Tone and motility. B)↓ secretions.
c) Constriction of the sphincters.
 4-Urinary Bladder:
 Urine retention due to constriction of
trigone muscle and internal sphincter.

34. 5- Eye:
a) Topically vasoconstriction of conjunctiva blood
vessels (so used as decongestant).
b) Vasoconstriction of ciliary body blood vessels , so
reduces the production of aqueous humor (used in
open angle glaucoma).
c) Systemic EN causes decongestion and active
mydriasis.

35.  a) Inhibition of insulin secretion (α2 receptors
) and stimulation of glucagon secretion (β2-
receptors).
 b) Increased circulating concentration of :
 GLUCOSE , LACTIC ACID hyperglycemia ,
brief K+ K+
 c) Increased lipolysis (β effect ).

36. EFEECT on LYPOLYSIS
Stimulation of β3-receptors of adipose tissue
Adenylyl cyclase- cAMP   lipase enzyme 
 hydrolysis of TGs to FFas + glycerol.
7- Anti-Allergic Effect:
The release of histamine ( physiological
antagonist ).
8- Effect on
Hormones:
 of hypothalamus---> of ant. Pituitary- ACTH--
 adr. Cortex -  cortisone.

37. 4- Cardiac resuscitation in cardiac arrest.
5- Acute bronchial asthma.
6- Acute insulin hypoglycemia
7- Allergy, urticaria , angioedema and anaphylactic
shock.
THERPEUTIC USES:
1- S.C. inj. With local anesthetics, vasoconstriction
 absorption-> duration and  toxicity ,and
decreases bleeding.
2- Nasal pack in epostaxis.
3- Eye drops in open angle glaucoma.

38. CONTRA-INDICATIONS
1- Coronary diseases. 2- Hyperthyroidism.
3- Hypertension. 4- Gangrene.
5- Hemorrhagic shock. 6- Arrhythmia.
7- Pulmonary embolism.

39.  A- Alpha effects: a) Gangrene if injected around the
finger or toe.
 b) Hypertension ,may lead to cerebral
hemorrhage.
 B- β1-Effect: a) Tachycardia ,palpitation and angina.
 b) Arrhythmia specially in pts, receiving
digitalis or halothane.
 C- β2- Effects: Skeletal muscle tremors.
 D- Eye troubles after local application.
 E- CNS: Anxiety and headache.

40. DRUG INTERACTION:
1- Digitalis.
2- General anesthetics: halothane and
cyclopropane.
3- Adrenergic neuron blockers e.g. guanethidine
and reserpine.
4- Ganglion blockers.
5- MAO inhibitors.

41. It is nonselective α1 ,α2 ,β1 ,β3 agonist.
PHARMACOLOGICAL EFFECTS
1- CVS: a) Blood vessels : Generalized vasoconstriction
(except coronaries)  peripheral resistance blood
pressure.
b) both systolic and diastolic bl.p.
c) Heart rate :reflex bradycardia due to reflex vagal
/baroreceptor stimulation (antagonized by atropine).
If atropine then NE  tachycardia.
d) Positive inotropic effect due to inc contractility (β1
effect ) The cardiac output is not affected.

42. 2- GIT: Relaxes walls and contracts sphincters.
3- Metabolism : Hyperglycemia and hyperlipidaemia.
4- Uterus; contracts pregnant uterus.
5) CNS : mild stimulation.
THERAPEUTIC USES:
1- Acute hypotension ;
2- Treats shock due to decreased bl p. but dopamine
is better.
CONTRAINDICATIONS: similar to EN

43. Direct acting synthetic NONSELECTIVELY STIMULATES β1,β2-
receptos.
Pharmacological Actions:
1- CVS:a) Force of contraction ,HR ,Cardiac output and
A-V conduction so used in cardiac arrest.
b)  excitability and automaticity.
c) Generalized arteriolar vasodilatation specially in sk. Bl
vessels  in per. resistance.
d) Systolic pressure slightly increase ( due to intense cardiac
stimulation) with reduced mean and diastolic pressure .
2- PULMONARY : Rapid and profound bronchodilation.

44. 3-Smooth Muscles : GIT ,Urinary bladder relaxation.
4- CNS : mild stimulation.
5- Uterine: relaxation.
6- Metabolism : hyperglycemia and increased lipolysis.
THERAPEUTIC USES:
1- Heart Block (sublingual )
2- Rarely used in acute bronchial asthma.
ADVERSE EFFECTS and CONTRAINDICATIONS: Similar to
EN

45. Natural sympathetic CA ,Chemical transmitter
in CNS, ganglia, and periphery.
It acts on α , β1, D1, D2- receptors.
D2 are found presynaptic in adrenergic nerve
terminals where it Interferes with NE release
and responsible for most of the central
actions.
Not absorbed orally.
Not pass bbb.
Given by i.v. infusion.

46. a) Peripheral Actions:
1- Low dose :
D1 renal vasodilatation renal bl.
Flow urine outflow.
This effect is blocked by haloperidol.
It dilates the mesenteric ,coronary and cerebral
bl. vs. per.resis
2- Moderate Dose:
β1and D1-receptors selective +ve inotropic
+minimal tachycardia
3- Large Dose:  α1-receptors
vasoconstriction periph. Resis.

47. Dopamine precursor L-DOPA can pass bbb and and
converts to dopamine by dopadecarboxylase enzyme.
1- In limbic system dopamine causes euphoria and
psychosis.
2- In basal ganglia ( negro-striatal) DA has anti-
Parkinsonism.
3- In hypothalamus : hyperpyrexia ,decreased appetite
and PL.
4- DA  CTZ  nausea and vomiting.
THERAPEUTIC USES:
1- Shock : Cardiogenic, haemorrhagic and endo toxic as
it inc. urine output, improves microcirculation of vital
organs and causes +ve inotropic effect and inc.
Systolic bl.P.

48.  ADVERSE EFFCTS:
 1-Tachycardia and arrhythmia.
 2- Nausea and vomiting.
 3- DA is contra-indicated in Pts on
MAOI’s

49. Synthetic sympathomimtic CA
Selective β1- agonist some α activity.
Selective +ve inotropic effect with minimal effect on
heart rate.
THERAPEUTIC USES :
Cardiogenic shock , resistant heart failure and heart
block.
6- PHENYLEPHRINE
Synthetic ,selective α1- adrenoceptor agonist.
Not CA so not substrate to COMT
 Both systolic and diastolic bl.P reflex bradycardia.
USES : topically as nasal decongestant and as
mydriatic.

50. Selective α2 adrenergic agonist.
Used to lower bl.p. due to its central actions
(suppresses sympathetic vasomotor
center).
8- Metaproterenol, Albuterol & Terbutaline
Selective β2 agonists , not substrate to
COMT
Given mainly by inhalation to control acute
asthma.
Salmeterol is long acting β2 agonist.

51. 1- Amphetamine:
It is synthetic sympathomimtic Non CA.
Given orally and parenterally.
Pass bbb and has central effects.
bl.p.(α1 effect ) , HR (β1 effect )  reflex
bradycardia abolished by atropine.
Has CNS effects : so used in the treatment of
depression, narcolepsy and Hyperactivity in
children(ADHD).

52.  Found in aged cheese and red wine.
 Normal by-product of tyrosine metabolism.
 Normally oxidized by MAO but if the pt.
uses MAOI it causes hypertensive crises.

53. 1- EPHEDRINE
Sympathomimtic non CA not metabolized by
COMT or MAO ,
Can pass bbb, absorbed orally , and parentrally.
It acts by both releasing CA’s and by direct
stimulation of α and β- receptors.
It is a potent CNS stimulant but weaker than
amphetamine.
PHARMACOLOGICAL ACTIONS
Similar to those of epinephrine.
IT facilitates neuromuscular transmission.

54. 1- As analeptic in toxicity with CNS depressants.
2- Mydriatic eye drops.
3- Nasal decongestant.
4- Prophylactic in bronchial asthma (due to slow onset )
5- Hypotension may be used before spinal anesthesia.
6- Myasthenia gravis.
ADVERS E EFFECS
1- CNS : insomnia, anxiety , tremors , convulsions.
2-CVS: hypertension ,tachycardia, palpitation , and
arrhythmia.
3-Urinary retention in old pts. 4- Tolerance and
tachyphylaxis , no addiction.

55.  An acute (sudden) decrease in the response to a drug
after its administration. It can occur after an initial dose
or after a series of small doses.
 Increasing the dose of the drug may be able to restore
the original response. This can sometimes be caused by
1-depletion or marked reduction of the amount of
neurotransmitter responsible for creating the drug's
effect,
 or 2-by the depletion of receptors available to which
the drug or neurotransmitter can bind.
 This depletion is caused by the cells reducing the
number of receptors in response to their saturation.

56. According to their site of action
A) Adrenergic Receptor Blockers
B) Adrenergic Neuron Blockers
C) Drugs that Reduce Central Sympathetic
Outflow

57. Have a profound effect on blood pressure (due to
reduced vascular resistance). ↓ bl.P. reflex
tachycardia.
According to their interaction to the receptors they are
classified into:
i- Irreversible Alpha- Blockers :
They bind covalently to α –receptors e.g.
phenoxybenzamine.
1- PHENOXYBENZAMINE
It produces irreversible noncompetitive block of α1 and α2
adrenergic receptors.
Its effect lasts for 24 hrs. the time required to synthesize
new rec.

58. It is inactive and biotransformed to active
form so has slow onset.
Pharmacological Actions:
1- Reduces bl.p. ( α1 receptors ) BUT it
does not block the vasodilator effect of EN
on skeletal bl vessels.
Phenoxybenzamine before EN-  blp. i.e.
EN reversal.
2- It increases cardiac output due to
inhibition of α2rec.(EN )

59. 1- Treatment of pheochromocytoma chronically
or prior to surgery.
2- Phentolamine or phenoxybenzamine is used
to control symptoms of Raynaud’s disease
(peripheral vasoconstriction in the extremities
especially in response to cold).

60. Block α1,α2-rec.
They cause vasodilatation by blocking
sympathetic tone to bl vessels. This results
in orthostatic hypotension.
A reflex tachycardia may result. This may be
also due to blocking α2 rec. which
increases the release of NE. Which
stimulates cardiac β1-rec.
They are contra-indicated in peptic ulcer pts.

61. Selective competitive α1-rec. antagonists
Cause less tachycardia than nonselective
blockers.
Decrease peripheral vascular resistance and lower
arterial blp.
Therapeutic Uses:
1- Control acute hypertensive episodes.
2- In the treatment of Raynaud’s disease.
3- Treating urine retention in pts. with benign
prostate hypertrophy (block of α-rec. dec tone
in smooth muscles of bladder neck and improve
renal flow).(TAMSULOSIN)

62. 1- Postural hypotension.
2- Reflex tachycardia.
3- Nasal congestion.
4-Additive antihypertensive effects when
prazocine + β- blockers or diuretics.
5- Mild sexual dysfunction in males.

63. They are classified into
Non selective β-blockers Selective β1-blockers α & β
Propranolol Metoprolol Labetalol
Nadolol Atenolol
Timolol Esmolol
Pindolol Acebutolol

64. Pharmacological Actions:
1-Dec. H.R. and cardiac contractility red. Cardiac
output and A-V conduction.
2-Broncho-constriction due to block of β2 rec.
3-Peripheral vasoconstriction due to block of β2 –
mediated vasodilatation.
Reduction of bl.p. due to
a- Red. of cardiac output. No postural hypotension.
b- Reduced renin release.
c- Decreased sympathetic outflow from the CNS.

65. 1-Treatment of hypertension.
2- Prophylactic in angina pectoris and
infarction (it reduces cardiac work and
oxygen consumption).
3- Prophylactic in cardiac arrhythmia
specially in hyperthyroidism.
4- Migraine : it blocks CA –induced
vasodilation in brain.

66.  1- Heart failure sp in pts with disturbed
myocardial function.
 2- It must be used with caution in asthmatic pts.
 3- It must be used with caution in diabetic pts (it
masks the warning sign of hypoglycemic coma).
 4- Decreases glycogenolysis and decreases
glucagon secretion.
 5-Cold extremities due to block of β2 rec. and
the effect of α- rec. is unopposed.
 6- Sexual impairment in male.

68. It is reversible antagonist of α1 ,β1,β2 adrenergic
rec.
Its effect is similar to combination of propranolol
and prazocine.
It is effective in the treatment of pheochromocytoma
and hypertensive Pts with increased peripheral
resistance.
Other non-selective β-blockers:
Timolol , Nadolol and Pindolol
Nadolol has long duration of action.
Timolol  the production of aqueous humor so used
in chronic open angle glaucoma.

69. Atenolol , Metoprolol , Esmolol , and Acebutolol
Used in the treatment of cardiac disorders &
hypertension in pts. with bronchial asthma.
Used in diabetic hypertensive pts.
Pindolol & Acebutolol are antagonist with partial
agonist activity so weakly stim. bothβ1 ,β2-rec. i.e.
have intrinsic sympathomimetic activity ISA.
Minimize bradycardia and disturbance in lipid and
carbohydrate metabolism.

70. Drugs affecting neurotransmitter release and
uptake:
1- Guanethidine:
It inhibits the release of neurotransmitter from
peripheral adr. neurons.
It is taken up by the neuron to replace NE .Thus
depleting the neuron.
Chronic administration of guanethidine reduce
sympathetic tone to all organs.

71.  Therapeutic Use
 Potent ,long acting antihypertensive. But
rarely used due to side effects.
 Adverse effects
 1- Postural hypotension and nasal
stiffness.
 2-GIT disorders

72. It produces CA depletion.
It inhibits the uptake of NE into vesicles , thus
allowing its breakdown by MAO.
Therapeutic uses:
Rarely used in the treatment of hypertension.
Adverse effects:
Sedation ,peptic ulcer , psychic depression, and
diarrhea.

73. It blocks the Na+-K+- activated ATP-ase
required for cellular uptake Of NE.
So NE accumulates in the synaptic space 
sympathetic activity.
It is CNS stimulant. Considered as a drug of
abuse.

74. 1- Clonidine:
It can penetrate the BBB.
IT activates α2- rec. in the hypothalamus
and medullaof Sympathetic outflow of
impulses to the peripheral sympathetic
neurons.
It causes no postural hypotension.
.

75. IT is transported to adr. Neurons where it is
converted to
-α-methyl NE that partially displaces NE in
synaptic vesicles,
Upon stim. it will be released as a false
neurotransmitter of no sympathetic activity.
It also activates α2-rec. It  blp. ,little effect
on HR & CO.No postural hypotension.

77. Types of cholinergic recptors:
A- Muscarinic Receptors (M):
Stimulated by acetyl choline and muscarine
There are M1 ,M2,M3 ,M4 ,&M5 receptors subtype.
Activity M1 Rec. M2 Rec. M3 Rec
1-location Gastric parietal Myocardium, Smooth muscles,
cells and CNS &smooth muscles Exocrine glands
2-Agonists Ach , Methacholine & and Carbachol
3-Antagonists Atropine Atropine Atropine &
& Pirenzepine & Gallamine Hexahydro-
siladifenidol

78. When M1 or M3 are activated  conformational
changesinteracts with G-proteine
↑ phospholipase –C hydrolysis of
phosphatidylinositol  DAG+ IP3↑ iCa++
iCa++ can stimulate or inhibit enzymes or cause
hyperpolarization , secretion or contraction.
Activation of M2-rec. on the cardiac muscle ↑ G-
proteine↓ adenylyl cyclase↑ K+Conductance,
↓ HR & force of contraction.

79. They are found in the CNS , autonomic ganglia
(Ng), adrenal medulla (Ng) and in the skeletal
muscles (Nm) ( neuromuscular junction NMJ )
Stimulated by Ach. & very low concentration of
nicotine.
Nicotine initially stimulates then blocks the
receptors.
Ng are selectively blocked by hexamethonium
,tetraethylamonium &pentamethonium & high
concentration of nicotine.
Nm are blocked by D-tubocurarine

80. They stimulate muscarinic receptors ( peripheral
cholinergic) & mimic the action of acetylcholine.
A) Direct Parasympathomimtic:
1- Synthetic Choline Esters: Methacholine, carbachol,&
bethanechol.
2- Cholinomimetic Alkaloids: Pilocarpine ,muscarine &
arecholine.
B) Indirect Parasympathomimtic ( anticholinesterases):
Cholinesterase (true & pseudo- )enzyme hydrolyzes Ach .
These drugs cause accumulation of endogenous Ach--↑ of
both M &N rec they are miotic & used to reduce the IOP in
case of glaucoma.

82. a) Quaternary Alcohol : Edrophonium.
b) Carbamate Derivatives (substrate for the
enzyme) : Physostigmine, Neostigmine ,
Pyridostigmine.
2- Irreversible Anticholinesterases
(Organophsphorus compounds
They produce noncompetitive irreversible
inhibition of CE.
e.g. a) Echothiofate.
b) Insecticides.;parathione and malathion.
c) War gases : sarin , tabun & soman.
d) Metrifonate: antibelharzial.

83. 1- Acetylcholine:
Natural direct parasympathomimtic.
Synthesis , Storage, Release and Fate of Ach.:
1- Active uptake 0f choline by cholinergic neuron(rate
limiting step).
Himicholinium inhibits neuronal uptake of choline.
2-In the mitochondria of cholinergic nerve terminal :
Acetate + CoA+ ATP  Acetyl CoA + ADP
3- In the cytoplasm of cholinergic nerve ending :
Choline + Acetyl Co A Acetylcholine + Co A

84. 4- Storage in vesicles.
5- Release by exocytosis.
N.B. Ach release is blocked by Mg++,
botulinum toxin and procaine.
6- FATE : hydrolyzed by choliesterase
enzymes:
a)Acetylcholinesterase enzyme (true):
inactivates endogenous Ach.
b) Butryl cholinesterase (pseudo-) : of
unknown role.

86. Acetylcholine esterase
(true CE)
Butrylcholinesterase
( pseudo CE}
Present in all ch sites,
RBC’s &CNS
It takes 3-6 months
to regenerate.
It acts on endogenous
Ach., methacholine.
Present in liver &
plasma
It takes 2-3 weeks to
regenerate . .
It acts on exogenous
Ach. ,butyryl choline
,succinyl choline &
procaine

87. 1- Muscarinic Actions:
I Cardiovascular System:
Heart: -ve chronotropic effect through inhibition
of SA –node ↓HR (bradycardia)
-ve inotropic effect(↓ force of contraction )
-Ve dromotropic ( ↓ A-V conduction )  ↓
cardiac output.

88. Blood Vessels(M3rec.): they are not innervated by
parasympathetic supply .
,but Ach. Injection causes ↑ the release of
endothelium derived relaxing factor(EDRF ,nitric
oxide) ↑ cGMP vasodilation of peripheral
and systemic bl vs
↓ of arterial bl.p. ↓ of periph.vas. resis. ↓
of bl. Flow to some organs e.g. kidney & liver.

89. Decrease in blood pressure: Injection of ACh causes
vasodilation and lowering of blood pressure by an
indirect mechanism of action.
 ACh activates M3 receptors found on endothelial cells
lining the smooth muscles of blood vessels.
This results in the production of nitric oxide from
arginine as endothelium derived relaxing factor NO then
diffuses to vascular smooth muscle cells to stimulate
protein kinase G production, leading to hyperpolarization
and smooth muscle relaxation .
In the absence of administered cholinergic agents, the
vascular receptors have no known function, because ACh
is never released into the blood in any significant
quantities.
Atropine blocks these muscarinic receptors and prevents
ACh from producing vasodilation.

90. 2- GIT: a) ↑ motility b)↑ secretions.
c) Relaxation of sphincters.
3-Urinary Bladder:
a) Contraction of detrusor muscle urination.
b) Relaxation of sphincter urination.
4- Eye: a) Circular m. contraction miosis.
b) Ciliary m contraction to see near objects.
5- Glands: Stimulation and increase secretion of
sweat , salivary and lachrymal glands.
6-Lung:a) Bronchoconstriction.
b) Stimulation of bronchial gland secretion.

91. Organ Receptor Action
Eye
Circular muscle
of the iris
M3 Contracts
Ciliary muscle M3 Contracts
Heart
Sino-atrial node M2 Slows
Myocardium M2 Negative inotropic action (more in
atria) and negative chronotropic
action
Blood vessels Endothelium M3 Vasodilatation
Bronchioles M3 Contraction
GIT
Smooth muscle
walls
M3 Contraction
Sphincters M3 Relax
Glands M3 Secretion
Urinary bladder
Wall M3 Contracts
Sphincter M3 Relax
Pregnant uterus M3 Contracts
Glands M3 Secretion 9

92. II- Nicotinic Actions:
1- Stimulation of autonomic ganglia & adrenal
medulla:
Ach ↑ autonomic ganglia the release of NE from
sympathetic nerve endings, this effect is blocked
by ganglion blocker e.g. hexamethonium.
Ach at low conc. After atropine hypertension
(Ach reversal action) because:
a) Ach ↑ the parasympathetic ganglia release of
postsynaptic Ach ↑ M rec. ↓ bl.p. , this
effect is blocked by atropine.

93. b) Ach ↑ sympathetic ganglia ↑ postganglionic
endogenous NE hypertension.
c) Ach ↑ adrenal medulla ↑ the release of
adrenaline hypertension.
This hypertension may be:
-Abolished by ganglion blockers
- Reversed by α – blockers.
2- Neuromuscular Junction:
Ach causes muscle twitching. This effect is
blocked by decamethonium or flaxedil

94. 2- Synthetic Cholinomimetic Esters
General Properties:
1- All are quaternary ammonium compounds.
2-More specific in action & effective orally (compared to
Ach).
3-Less metabolized by CE , so longer duration.
4-Not given parenterally due to high incidence of toxicity
(can be controlled by atropine).
5-Contraindicated in : a) Bronchial asthma.
b) Peptic ulcer.
c) Angina pectoris
d) Thyrotoxicosis since they cause
arrhythmia (atrial fibrillation)

95. Activity Ach Metacholine Carbachol Bethanechol
1-Oral abs. NO Irregular Complete Complete
2-Metab. True & pseudo true only Not Not
3-M Effects +++ +++ +++ +++
4- N Effects +++ + +++ NO
5—Selectivity NO CVS EYE ,GIT & UB NO
6-Adminis. IV oral& S.C. Oral ,SC &eye drops oral ,SC

96. A) Methacholine
It has longer duration of action than Ach.
Therapeutic Uses:
1- Used in the treatment of peripheral vascular
diseases.
2-To relief the attacks of paroxysmal atrial
tachycardia.
B) Carbachol:
It has longer duration of action than Ach.
Therapeutic uses:
1- In the treatment of glaucoma. 2- In case of
urine retention.

97. C) Bethanechol (Urecholine):
Similar to carbachol but does not have
nicotinic action.
Therapeutic uses:
1- Postoperative urine retention.
2- Glaucoma.
3- Following bilateral vagotomy for peptic
ulcer to relieve gastric retention.

99. Pilocarpine: Natural alkaloid of plant origin.
Direct , tertiary amine , stable to CE. far less
potent than Ach.
Pharmacological Actions:
1- Direct M-rec. agonist with very weak N rec. effects.
2- Locally on the eye  rapid miosis + contraction of
ciliary muscle.
The eye undergoes spasm of accommodation & vision is
fixed at particular distance.
3- Potent stimulant of sweat , tears & saliva sec.
4- Well abs. orally ,& excreted in urine.
5-Not metabolized by CE , so has long duration of action

102. Therapeutic Uses of Pilocarpine
1- In the form of eye drops to treat glaucoma. It
produces miosis better drainage of aqueous
humor ↓ in IOP in both close and wide angle
glaucoma.
2- Counteracts mydriasis after eye fundus
examination.
3- Acts as sialagogue to treat dry mouth.
4-Diaphoretic (↑ sweating) nonspecific treatment
of fever. 5- To promote hair growth.
Adverse Effects:
1- Can pass bbb and causes CNS disturbance
( so avoid in Parkinsonism).
2- Stimulates salivation & sweat.

103. They inhibit both true and pseudo CE enzymes
resulting in accumulation of endogenous Ach.
In the synaptic space inducing both muscarinic
& nicotinic actions in the ANS &
neuromuscular junction and the brain.
According to the extent of enzyme inhibition
they may be used either as therapeutic or life
threatening agents.
Reversible Anti-cholinesterases:
They weakly inhibit CE by reversible association with
the anionic site & hinder access to Ach .

104. A- Carbamate Derivatives:
Physostigmine , Neostigmine ,
Pyridostigmine.
a)They attach to both sites of the
enzyme .
b) They are substrates for CE ,and then
will be hydrolyzed slower than Ach.

105. Physostigmine(Eserine) Neostigmine(Prostigmine))
Natural (calabar beans) ,tertiary
amine.
1- Well abs. orally.
2- Pass bbb.
3-Rapid metabolism by CE.
4- Short
duration
--Stimulates M & N receptors
-- Specific on eye
--CNS stimulant.
-Uses:1- Eye drops:
-a) Glaucoma.
-b) To counter act mydriatics.
Synthetic ,quaternary amm.
comp.
1-Irregular oral abs.
2- Does not pass bbb.
3-Slow metabolism by CE.
4- Long duration.
-Stimulates M & N receptors
-Specific on GIT & UB
-Direct skeletal muscle
stimulant.
-Uses:1- Myesthenia gravis
-Diagnosis (0.5-1 mg IM)
Treatment (15-75 mg oral)

106. Physostigmine Neostigmine
Uses:2- I.V. in atropine
poisoning.
3- Alzheimer disease.
Toxicity :
-Exaggerated Ach-like
actions.
- CNS convulsions.
Managed by atropine+
anticonvulsant.
2- Curare poisoning.
3- Paralytic ilius. 4- Urine
retention.
Toxicity:
-Exaggerated Ach –like
actions.
-No convulsions in CNS.
-Managed by atropine only.

107. Pyridostigmine is similar to neostigmine but
with longer duration of action .
used in chronic management of myasthenia
gravis.

109. Edrophonium:
Similar to neostigmine BUT more rapidly absorbed and
has short duration of action.
It is not hydrolyzed by CE ,excreted in urine
unchanged.
Used in the diagnosis of myasthenia gravis.

110. a) Muscarinic side Effects:
1-↑ Salivary and bronchial secretions.
2- ↑ GI activities &nausea , vomiting and
diarrhea , &colic.
3-Bradycardia & hypotension . These side
effects can be antagonized by atropine.
b) Nicotinc side effects:
1- Stimulation of autonomic ganglia.
2-Neuromuscular junction: m. twitching &
spasm

112. They bind covalently to CE long lasting
increase in Ach at all sites.
Many of them are very toxic and were developed
by military as nerve agents.
Parathion is an insecticide.
Isoflurophate: (diisopropylfluorophosphate DFP):
It permanently inactivates the enzyme ,
Restoration of the enzyme requires 3weeks for
the pseudo & 3 months for the true enzyme

113. Pharmacological Actions:
1- Generalize Ch stimulation.
2- Paralysis of motor functions (breath
difficulties & convulsions ).
3-Intense miosis so has a therapeutic
application.

114. Atropine in high doses can reverse many
of the peripheral and central effects.
Therapeutic Use:
1- For chronic treatment of open angle
glaucoma (Topically as ointment).
The effect lasts for one week after a
single dose.
Echothiophate is similar to isoflurophate.
.

115. By the use of a synthetic enzyme reactivator
pralidoxime (PAM)
IT has a charged group & approaches the anionic site on
the enzyme so displaces the organophosphate and
regenerate the enzyme.
It is effective only before enzyme aging.
Enzyme Aging :
Organophosphorous comp. + enzyme
phosphorylated enzyme this complex loses an
isopropyl group (Aging) this makes it impossible for
PAM to break the bond bet. the drug and the enzyme

117. Impairment in the neuromuscular transmission
in the skeletal muscle.
CCC by inability to control voluntary movements
and muscle in-coordination.
Etiology:
1- Defect rate in Ach synthesis .
2- Excessive CE enzyme at the neuromuscular
junction.
3- An autoimmune disease  destruction of
cholinergic rec. at NMJ.

118. Symptoms:
-Ptosis
- Diplopia
-Difficulty in chewing & swallowing.
--Respiratory failure.
Diagnosis:
1- Edrophonium: (2-8 mg iv rapid inc. in m
strength & improvement in 1 min.
2-Neostigmine : (0.5 mg im) + atropine
0.5mg.

119. Treatment:
1-Neostigmine ( 15 mg/6hrs.) also
pyridostigmine.
2- Atropine to counteract the side effects of
neostigmine.
3- Ephedrine and caffeine to improve
neuromuscular transmission.
4- Immune –suppressant e.g. prednisolone &
antimetabolite e.g. azathioprine.

120. An eye disorder charachtarized by increased
intraocular pressure (IOP) due to defective
drainage of aqueous humaur through the canal
of Schlemm.
TYPES:
1- Chronic Open-Angle Glaucoma ( simple
chronic):
- Gradual painless rise in IOP with progressive
loss of vision due to pressure on the optic nerve.
--Commonly bilateral .mostly in pts. over 40
years of age.
-- The etiology is not known.
-

122. - Common in people over 60 years & usually
affects one eye.
- The lens gradually increases in size by age 
pushing the iris forward.
- When the pupil dilates during the dark the
relaxed iris may come in contact with the
cornea and closes the canal of Schlemm ↑ IOP.

123.  The angle between the iris and the cornea
is gradually reduced and the canal of
Schlemm is occluded following repeated
moderate or severe attacks  chronic
closed –angle glaucoma.

124. The strategy of treatment is:
1- To facilitate the drainage of aqueous humor .
2- To decrease the production of aqueous humor.
Miotic agents pull the iris away from the filtration angle
opening of the canal↓IOP
- Treatment of narrow –angle glaucoma:
- A) Drainage of aq. Humour :
- Pilocarpine (1-2%) + physostigmine(0.5%)
B) Reduction in the Synthesis of aq. Humour :
- Acetazolamide ( carbonic anhydrase inhibitor)
- Mannitol iv infusion, glycerine orally (osmotic agents) .

125. 1- Miotic eye drops : pilocarpine +
physostigmine.
2- Carbonic anhydrase inhibitor :
acetazolamide.
3- Sympathomimetic eye drops:
a) Adrenaline 1-2%.
b) Phenylephrine 10%.
4- ß- blockers: timolol 0.25- 0.5 % eye
drops.(NO Change IN PUPIL SIZE)

126. They are classified to:
A- Anti-muscarinic agents.
Selectively block peripheral muscarinic
receptors↓ of muscarinic action of Ach.
B-Ganglion Blockers:
They block both sympathetic &
parasympathetic ganglia.
C- Neuromuscular Blockers:
They block nicotinic receptors at the
neuromuscular junction.

128. 1- Atropine:
Pharmacological actions:
It blocks peripheral & central M1 , M2 , M3
– receptors.
a) Cardiovascular System
- Actions on the heart (M2-rec.):
- Bradycardia Tachycardia.
- The initial bradycardia is due to block of the
inhibitory M1- (presynaptic rec.)↑release
of endogenous Ach.
At higher doses the cardiac rec.(M2 )on the
SA-node are blocked tachycardia.

130. Therapeutic doses do not affect the vessel tone &
not affect arterial bl.p.
b) GIT: ↓ tone & motility  antispasmodic effect.
No significant effect on gastric acid secretion.
Pirenzepine is a selective M1 – blocker used to
control peptic ulcer.
c) Urinary Tract:
Relaxation of the smooth m. of the ureter (
antispasmodic ) & urinary bladder urinary
retention.
d) Bronchioles: Dilatation and reduced bronchial
secretions.

131. e) Exocrine Glands:
Atropine↓ salivary ,lachrymal, sweat & bronchial
secretions.
f) Eye:
1- It causes passive mydriasis ( paralysis of circular
muscles ).
2- Loss of accommodation for near objects
(cycloplegia ) due to relaxation of ciliary muscle.
3-loss of light reflex.
Mydriasis  closure of canal of Schlemm in closed –
angle glaucoma (so contra-indicated).

133. 1- As pre-anaesthetic medication to:
a) Decrease both salivary and bronchial
secretions.
b) Protect the heart from excessive vagal tone.
c) Counteract the inhibitory effect of morphine
on the respiratory center.
2- As antispasmodic .
3- Mydriatic and cycloplegic.
4- Treatment of sever bradycardia.
5- As an antidote for organophosphorous
compounds poisoning.

134. a) Fever.
b) Glaucoma.
c) Tachycardia.
d) Constipation & paralytic ileus.
e) Senile hypertrophy of prostate
f) After neostigmine severe bradycardia.
G) Allergy to atropine.

136. Scopolamine:
=atropine but with more CNS-effects , longer
duration of action.
Mainly used for motion sickness.
Homatropine:
Used in ophthalmology as rapidly –acting
mydriatic with short duration.
Propantheline:
Synthetic used as antispasmodic.
Ipratropium: Given by inhalation for obstructive
pulmonary disease & asthma.

137.  A) Ganglionic Stimulants
 Stimulate cholinergic receptor sites on
autonomic ganglia.
 1- Nicotine:
 Natural tertiary amine alkaloid of tobacco ,
it does not have any clinical applications.
 Absorbed from all sites , pass bbb &
placental barrier metabolized in liver & lung
, excreted in urine & milk .

138.  1- CNS stimulation →anxiety , hyperreflexia ,
tremors convulsions and coma.
 2- Stimulates the respiratory center.
 3- Stimulates the VMC , CTZ and ADH secretion.
 4- Stimulation of autonomic ganglia →+ve
inotropic ,+ve chronotropic &↑CO
 ↑ cardiac work→↑O2 need may →angina.
 - Increase automaticity so may cause
arrhythmia.
 - Increase peripheral resistance so may cause
hypertension .

139.  5- GIT ↑ parasympathetic activity →↑ gastric
acidity →peptic ulcer.
 - increased motility →colic , stimulation of CTZ
→ nausea. - depress appetite.
 Therapeutic Uses: limited to smoking cessation
programs as skin patches or chewing gum.
 B- Ganglion blockers
 They interfere with the transmission of the
nerve impulses from preganglionic nerve
terminals to the cell bodies of of postganglionic
neurons.
 The end organ response may show a
predominant adrenergic or cholinergic effect.


140.  The degree of enervation by the adrenergic and
 cholinergic nervous system and the extent of
adrenergic and cholinergic dominance in a
given organ may not be equivalent leading to a
response that is characteristic of the less
dominant component.
 e.g. in the heart the cholinergic system
dominates over the adrenergic component
 ,so the administration of a ganglion blocker will
have the greatest effect on the cholinergic
component leading to adrenergic effect.

141.  There are two types of ganglion blockers
 1- Depolarizing Ganglion Blockers
 They initially stimulate the ganglia by acetyl
choline –like action and then block them due
to a persistent depolarization e.g. nicotine.
 Prolonged application of nicotine results in
desensitization of cholinergic receptors sites
and continued block e.g. nicotine in high
concentration.

142.  2- Competitive Ganglion Blockers
 They do not cause prior ganglion
stimulation , they impair transmission
by:
 - Competing with Ach. for ganglion
receptor sites e.g. tetraethylamonium
and trimethphan.
 OR- Blocking the ion channel when it
is open e.g. hexamethonium , and
pentamethonium

143.  1- Blocking of Sympathetic Ganglia
 - Hypotension , orthostatic hypotension ,
inhibition of sweat secretion, supersensitivity
to exogenous sympathomimetics.

144.  2- Blocking of Parasympathetic Ganglia
(atropine – like action)
 - Eye : passive mydriasis cycloplegia.
 -GIT : dry mouth distension and constipation .
 - UB : urine retention .
 - blocking of both ganglia → impotence.
 Most side effects are due to blocking of
parasympathetic ganglia.
 Norepinephrine or ephedrine is used to correct
hypotension.
 Piolcarpine or neostigmine is used to correct
the atropine –like actions.

146.  Rarely used due to side effects.
 Trimethaphane has short duration of
action so used to produce
 hypotension during surgery and
 in the treatment of hypertensive crises.

147.  They act by interrupting transmission at the
junction between skeletal muscle fibers and
somatic nerve.
 They can produce skeletal muscle relaxation
and are classified into
 A) Neuromuscular blockers B) Spasmolytic
agents.
 A) Neuromuscular Blockers:
 Based on their mechanism:
 a) Competitive Neuromuscular Blockers.
 b) Depolarizing Neuromuscular Blockers .

148.  e.g. Tubocurarine , Gallamine , Pancuronium
 They inhibit Ach competitively at receptor
sites , they combine with the nicotinic
receptors at the motor end plate but do not
activate them.
 The released Ach is unable to stimulate the
already occupied receptors and it will be
immediately hydrolyzed by cholinesterase
enzyme leading to skeletal muscle paralysis.

149.  e.g. Succinylcholine, decamethonium , and
suxamethonium
 They cause sustained depolarization of the motor end
plate
 Like Ach they react with the nicotinic receptors leading
to depolarization of the muscle fiber followed by receptor
 desensitization and muscle relaxation.
 They are given parentrally
 Succinylcholine has rapid onset and very short duration
(3-7 min.) it is hydrolyzed rapidly by
pseudochollinesterase enzyme.
Tubocurarine and pancuronium have longer duration of
action (40-120 min )

150.  1- Facilitate operative manipulation.
 2- maintaning controlled ventilation during
surgery.
 3- Facilitate the endotrachial intubation (
laryngoscopy ,bronchoscopy, oesophagscopy
), ( succinylcholine single iv dose )
 4- D-tubocurarine is used for the
symptomatic treatment of tetanus and other
convulsive states.
 5- Diagnosis of Myasthenia gravis.
 6- With electro convulsent shock therapy.

151.  Adverse Effects:
 1- Prolonged apnea.
 2-Muscle pain with depolarizing
blockers.

152.  1- Competitive Blockers.
 Can be antagonized by cholineesterase inhibitors e.g.
neostigmine . The unwanted actions of Ach. Can be
blocked by atropine.
 2- Depolarizing Blockers:
 No antagonist ,but artificial respiration until recovery
occurs.
 If an anticholinesterase is given, muscle paralysis will
 be increased.

153.  They produce skeletal muscle relaxation either
by
 a) Central mechanism e.g. Diazepam and
baclofen.
 b) Direct effect outside the CNS e.g.
dantrolene.
 Diazepam:
 IT facilitates the action of GABA in the CNS.
 Its spasmolytic action is partly in the spinal
cord.

154.  Baclofen:
 It reduces the release of excitatory
neurotransmitters in the brain and the S.C.
 It may also inhibit the release of substance P
in the S.C.
 Dantroline: It interferes with excitation
contraction coupling in the m fiber.
 It interferes with the release of activator
Ca++ from the sarcoplasmic reticulum.