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The nervous system is divided into 2 anatomical divisions, the CNS
which is composed of brain and spinal cord and the peripheral nervous
system, which includes neurones located outside the CNS.
The peripheral nervous system can be further subdivided into 3 major
divisions:
1- Sensory neurones which involved in carrying various types of
sensations to CNS.
2- Somatic neurones which involved in control of voluntary functions
e.g. skeletal muscle contraction.
3- Autonomic neurones which involved in control of involuntary
functions e.g. smooth mucles, cardiac muscle and exocrine gland
functions.
From physiological point of view ANS is subdevided into
Sympathetic
* Heart:
. H.R.
. Ventricular
contraction
* Smooth muscles:
. Eye
. Bronchi
. GIT
Tachycardia (1)
Increase (1)
Mydriasis
Bronchodilatation (2)
Relax wall & contract
sphinters ( )
. Urinary bladder Urine retention ( )
. Blood vessels
Vasoconstriction ()and
* Secretions:
dilatation ()
. Salivary
. Sweat
Thick viscid
Increase
Parasympathetic
Bradycardia
No effect
Miosis
Bronchospasm
(M)
Contract wall & relax
sphinters
Urination
No effect
Profuse watery
No effect
-Usually each organ has double nerve supply except sweat glands and
ventricle have sympathetic supply only, while constrictor pupillae muscle
and ciliary muscle have parasympathetic supply only.
-The parasympathetic tone is usually predominating.
CHEMICAL TRANSMITTERS
Two chemical transmitters are identified in autonomic nerves
namely Acetylcholine & Norepinephrine.
I- Adrenergic Receptors: receptors for norepinephrine.
 Adrenergic Receptors
1 Receptors:
-Activation leads to (Actions).
*Smooth Muscles:
1-Eye: Contraction of dilator pupillae  Active Mydriasis
2-GIT:  motility.
3-Urinary bladder: Contract the sphincter.
4-Bl.Vs: Vasoconstriction (especially of skin and mm) peripheral
resistence  Hypertension.
 Adrenergic Receptors
1 receptors
-Activation leads to (Actions):
*Heart:  Contractility (+ve Inotropic)
 HR (+ ve Chronotropic)
 all cardiac properties
 AV conduction (+ve Dromotropic)
Atrial and ventricular conduction
*Smooth Muscles: GIT motility.
*Others:  Renin release
2 receptors
-Activation leads to (Actions):
*Heart: Coronary dilatation.
*Smooth Muscles:
-Bronchi: Bronchodilatation.
-GlT: Motility
-Urinary bladder: relax wall.
-Bl.Vs: Vasodilatatation of skeletal muscle Bl Vs   peripheral
resistence  Hypotension.
*Others - Glycogenolysis
- Relax wall of pregnant uterus.
3 adrenoceptors (adipose tissue(
 lipolysis  Free fatty acids.
Sympathomimitics
Definition: Drugs, which stimulate the adrenergic receptors.
Classification:
*According to chemistry: (contain catechole nucleus):
1.Catecholamines
-Natural: Epinephrine, Norepinephrine and Dopamine.
-Synthetic: Isoprenaline, dobutamine and hexoprenaline.
2.Non catecholamines: Ephedrine and amphetamine.
*According to mechanism of action:
1.Directly acting: Most of them.
2.Indirectly acting amphetamine and tyramine.
3.Dual (mixed) acting: Ephedrine.
Epinephrine(Adrenaline)
*Actions: Given S.C. and acts on both  and  adrenergic receptors.
*Systemic actions:
1)CVS: - Heart: all cardiac properties (1 effect) CO.
-Blood vessels.
 V.C.of skin and mucous membrane vessels (1 
PRBP
 V.D. of skeletal muscle blood vessels (2)  PR
BP
-Blood pressure: is  due to predominence of 1 effect while  in
small doses due to predominence of 2 effect.
2)Respiratory system:
-Bronchodilatation (2)
-Decongestion of bronchial mucosa (1) due to VC of broncial blood
vessels.
3)Eye:
-Active Mydriasisi (1)
- I.O.P: due to  aqueous formation (VC of ciliary body blood vessels)
especially in open angle glaucoma.
4)G.I.T:  motility (+).
5) Urinary Bladder: Urine retention due to relaxation of wall(2) and
contraction of the sphincter (1)
6)Uterus: relaxes the pregnant uterus (2).
*Anti-allergic action: It is the physiological antagonist of histamine, it
produces VC while histamine produces VD but both act on 2 different
sites.
*Metabolic Actions:
1)Hyperglycemia due to:
- hepatic gluconeogenesis and glycogenolysis (2).
- insulin secretion (2)
2)lipolysis (3).
*Therapeutic uses:
1. Allergy: anaphylactic shock and angioneurotic oedema.
2. Intracardiac in CPR (Cardio-Pulmonary Resuscitation).
3. Hemostatic in epistaxis (bleeding per nose).
4. With local anesthetics to - absorption -Prolong duration- toxicity
– Hemostatic.
*Adverse effects;
1.Tachycardia, palpitation and anginal pains.
2.Hypertension and cerebral hemorrhage.
3.Gangrene if injected with local anesthetics around fingers, toes and in
circumcision.
4.Skeletal muscle tremors.
*Contraindications:
1.Angina pectoris.
2.Hypertension.
3.Hyperthyroidism as thyroid hormone sensitizes the heart to
catecholamines arrhythmia.
4.With Halothane (inhalation anesthetic)  arrhythmia.
Norepinephrine (Noradnenaline)
*Actions: Directly acting sympathomimitic with predominant  and 1.
*CVS:
-Heart:all cardiac properties (1)CO, but the tachycardia is masked
by reflex bradycardia mediated via parasympathetic system.
-BP: generalized VC of skin & mm PR blood pressure
stimulation of baroreceptors in carotid bodies parasympathetic tone to
 reflex bradycardia.
*Other actions: As adrenaline but with predominant  actions
*.Uses: As hypertensive agent in hypotensive states as in hypovelemic
shock with correction of hypovolemia.
Isoprenaline
*Actions: Directly acting sympathomimitic on both 1 and 2
adrenoceptors.
*Uses:
-Acute Bronchial asthma (Inhalation).
-Heart block.
Dopamine
*Actions: Directly acting sympathomimitic on , 1 and specific
dopaminergic receptors (in renal, mesenteric, coronary and intracerebral
blood vessels).
*Uses: Cardiogenic, endotoxic and hypovolaemic shock (with correction
of hypovolemia).
Dobutamine
*Actions: Directly acting selective 1 adrenergic sympathomimitc.
*Uses: Cardiogenic shock due to acute myocardial infarction.
Ephedrine
*Actions:
-Dual acting sympathomimitic on both  and  adrenoceptors, but
mainly indirect repeated administration  tachyphylaxis.
1)Sytemic actions: as Epinenephrine but weaker, slower in onset and
longer.
2)CNS actions: Stronger CNS stimulant effect than Epinephrine but
weaker than amphetamine. It stimulate the cortex, medullary centers and
reticular activating System “responsible for aurosal state”  Insomnia.
*Theraputic uses:
1-Nasal decongestant.
2-Narcolepsy (hypersomnia).
3-Bronchial asthma.
Amphetamine
- *Actions: Indirectly acting sympathomimitic i.e. agonist on both 
and 1 adrenrgic receptors  repeated administration 
tachyphylaxis.
- Its actions are similar to Norepinephrine but weaker, slower and
longer.
- It has a prominent CNS action much stronger than ephedrine,
manifested by:
1-Psychic action: euphoria and increase mental activity.
2-Anti-fatigue action:  ability for work.
3-Anorexigenic action:  the appetite.
- Tolerance  addiction usually occurs on prolonged use.
*Theraputic Uses:
1-Obesity.
2-Narcolepsy.
Other Sympathomimitics
(1) Selective 1 adrenrgic agonists:
Phenylephrine and Methoxamine : used as nasal decongestant, Mydriatic in
glaucoma, in hypotensive. Midodrine is methoxamine derivative used
orally in chronic hypotension.
Naphazoline, xylometazoline, oxymetazoline and tetrahydrozoline: used as nasal
decongestant.
Pseudoepherdine : OTC oral nasal decongestant.
All selective 1 agonists are containdicated in hypertention and angina
pectoris.
(2) Selective 2 adrenergic agonists:
I- Bronchodilators: short acting (Salbutamol and terbutaline), long acting
(fermoterol and salmetrol). Used in acute attack (short acting) and
prophylaxis of bronchial asthma (long acting).
II- Uterine Relaxants: Ritodrine. Used in contraction ring uterus and
premature labor.
III- Vasodilators: isoxuprine. Used in peripheral vascular diseases.
All selective B2 agonists may produce serious tachycardia in excessive
doses (WHY?)
Sympathetic Depressants
 Blockers
Classification:
1)Non-selective: block both 1 and 2 receptors as Phentolamine.
2)Selective:- block only 1 receptors as Prazocin.
*Uses:
1-Essential hypertension.
2-Resistant heart failure.
3-Prostatic hypertrophy (Terazocin, doxazocin and tamsulosin are much
better).
*Side effects:
-Postural hypotension with first dose (so starts with small dose at bedtime
and increases it gradually)
 Blockers
-They are competitve antagonists at 1 and/or 2 adrenergic receptors.
Classification:
 Non-selective: block both 1 and 2 receptors e.g. Propranolol and
Timolol.
 Selective: block 1 receptors e.g. Atenolol and Meteprolol.
 Combined  and  blocker: Labetalol
Actions
1) CVS:* Heart: all cardiac properties   CO.
*Blood vessels: Vasoconstriction may occur initially (due to
unopposed 1 action)  PR initial of BP. This may  blood
flow to all organs except the brain.
*Blood pressure: Antihypertensive effect on prolonged use in
hypertensive patients due to:
-CO and PR.
- renin release.
2) Bronchi: Block of 2 receptors in bronchi may increase airway
resistance in asthmatic patients.
3)Eye:  IOP, most probably due to  aqueous formation but have no
effect on pupil size or accommodation.
4)Metabolic Actions: Prevent the glycogenolytic effect of catecholamines
(2 effect) hypoglycaemia
5)CNS actions:
-Anti-anxiety and tremors.
-Propranolol is used in prophylaxis of migraine headache.
6) Other actions: Some blockers have ISA e.g. Pindolol.
*Therapeutic uses:
1)Cardiovascular uses:
 Prophylaxis of Angina Pectoris.
 Essential hypertension.
 Tachycardia.
 Thyrotoxicosis to control adrenergic manifestations of T 3 and T4
(thyroid hormones increase the sensitivity of adrenergic receptors
to endogenous catecholamines). Drugs without ISA e.g.
propranolol are only used (WHY?).
2)Non - cardiovascular uses:
 CNS:
-Control anxiety and tremors (Propranolol.(
-Prophylaxis of migraine headache (Propranolol(
 Eye: Open angle glaucoma (Timolol eye drops).
*Side effects:
1. Heart failure.
2. Hypotension.
3.  The hypoglycemic effect of insulin without appearance of
manifestations of hypoglycemia except sweating (WHY?)
4. Bradycardia.
5. Bronchospasm particularly with non-selective  blockers in
asthmatic patients.
6. Fatigue, depression and sleep disturbances.
7. Sudden cessation of therapy after prolonged use  Rebound
phenomenon (sympathetic overactivity manifested by angina
pectoris, myocardial infarction or arrhythmia. So it is
advised to stop treatment gradually.
*Contraindication:
1. Heart failure.
2. Heart block.
3. hypotension.
4.Peripheral vascular diseases.
2. Bronchial asthma (2 blockers). 6.Diabetes Mellitus.