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Lecture 6: Autonomic Nervous System

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: System Nervous Autonomic

Nervous System

1. Peripheral NS 2. Central NS

Peripheral Nervous System can be classified according to:*

Cranial (12 pairs). :Origin 1.

Spinal (31 pairs).

Afferent (sensory) :Function 2.

Efferent (motor) which can be divided into:

2. Somatic NS (Voluntary) 1. Autonomic NS (Involuntary)

*One neuron system.

*Affects activities of somatic

muscles.

*Two neurons system.

*Enteric→ innervates GIT, Pancreas, gall bladder

It is divided into:* b. Parasympathetic NS a. Sympathetic NS

shortpreganglionic & 1. Long

postganglionic.

preganglionic & 1. Short

postganglionic. long

2. Never discharge as

complete system→ discrete

effects.

2. Often discharge as

complete system

3. Arise from cranium III.

& rd, 3ndVII. IX,X & sacral 2

th4

3. Arise from thoracic &

lumbar

4. Essential for life 4. Not essential for life

5. Rest & digest response. 5. Fight or flight response

:exceptN.B. All organs receive dual innervations *

1. Adrenal Medulla.

2. Kidney.

3. Pilomotor muscle.

4. Sweat glands.

*Difference between actions of Sympathetic &

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:Parasympathetic systems on different body organs

:system Parasympathetic affecting Drugs A.

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*Neurotransmission at Cholinergic Neuron:

*Cholinergic receptors:

receptors: Muscarinic A.

M

4

2M 5M 3M 1M

Inhibit cellular excitability Leads to cellular excitation

Found on cardiac cells & smooth

muscles

Found on bladder, smooth

muscle & exocrine glands

Found on gastric parietal

cells

receptor→ 2Activation of M

conformational change→ interaction

with Gs protein→ inhibition of adenyl

conductance→↓ rate & + cyclase →↑ K

force of contraction of heart muscle.

Activation of M1&M3 receptors→ conformational

change of the receptor→ interaction with Gq

protein→ Activation of phospholipase C→ hydrolysis

of Phosphatidylinositol 4,5-bisphosphate (PIP2)→

Diacylglycerol (IP3)→ ↑ intracellular Ca2+

receptors: Nicotinic B.

*Composed of five subunits.

*Function as ligand- gated channel: binding of 2 ACh molecules→ Conformational

entry→ depolarization. +change→ Na

*Nicotine or ACh initially stimulates then blocks receptor.

located at neuromuscular junction, : nicotinic R mN Nicotinic receptors may be: *

Tubucurarine.selectively with inhibited

, other receptors located at the ganglia :nN

Hexamethoniumblocked by

*1. Cholinergic Agonists:

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Indirect Acting: Direct Acting:

Irreversible Reversible choline1. Acetyl

2. Direct Acting M alkaloids:

a. Pilocarpine.

b. Cevimeline.

3. Choline esters:

a. Bethanechol

b. Carbachol

1. Ecothiophate

-Organo 2. Isoflurophate

phosphates 3. Parathion & Malathion

4. Sarine

Metrifonate.5.

1. Neostigmine.

2. Physiostigmine

3. Pyridostigmine

4. Galantamine

5. Ambenomium.

6. Edrophonium

7. Demecarium

8. Donepzil

9. Tacrine

10. Ribavamine.

ttt by ACh Esterase

reactivation

By Oximes:

1.Parlidoximes (2 PAM)

2.Diacetyl monoximes (DAM)

acting: Direct A.

1. Acetyl

Choline:

2. Choline esters:

1. Muscarinic agonist (no action on nicotinic receptors)

: a) Urologic ttt→↑ contraction of bladder wall & relaxation of sphincter M.in Used 2.

↑ urine flow→ for post operative non obst. urinary retention.

b) Neurogenic atony & Mega colon.

1. Bronchospasm 2. Sweating effects: Adverse 3.

3. Diarrhea 4. ↓ Bp

:a. Bethanechol

1. Non selective agonist (acts on both nicotinic & muscarinic receptors)

2. Used in: eye preparation→ Miotic effect→↓ IOP Used in ttt of Glaucoma

3. No S.E when used topically in ophthalmic preparations.

b. Carbachol:

3. Muscarinic alkaloids or synthetics

1. like Bethanechol partial agonist.

2. Causes Miosis & contraction of ciliary muscle.

3. Uses: a) D.O.C in emergency cases of open angle & narrow angle glaucoma.

b) ↑ salivation in patients with Xerostomia

c) Sjogren's Syndrome (dry mouth & lack of tears)

a. Pilocarpine:

selective agonist. 31. Synthetic M

2. Used in Sjogren's syndrome.

b. Cevimeline:

choline esterase inhibitors which inhibit Acting: Indirect B.

degradation of Ach by acetyl choline esterase→ prolonging its effect.

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a. Reversible:

1. Acts on M & N receptors in ANS & also on N receptors in NMJ.

intestinal motility & bladder motility ) ↑1 Uses: 2.

2) Topically (↓ IOP)

3) ttt of overdose of drugs having antimuscarinic action (Atropine,

TCAs).

: 1) Bradycardia & ↓ C.O.PS.E 3.

2) ↑ Ach at NMJ→ paralysis of skeletal muscle.

3) Convulsions→ crosses CNS

1. Physiostigmine:

natural alkaloid

amine ry3

enters CNS

1) ↑ GIT & bladder motility→ post operative, Neurogenic ileus & Uses: .1

urinary retention.

2) Antidote for Tubucurarine (neuromuscular blocker).

3) ↓ symptoms of Myasthenia gravis. N.B. It is not used for ttt of antimuscarinic drug toxicity

( not for Atropine).

S.E.No CNS As Physiostigmine but doesn't cross CNS→ :S.E .2

2. Neostigmine:

Oral & parentral

amine ry4

not enter CNS

6 hrs)> -ttt of Myasthenia gravis with ↑ duration of action (4 in Used .1

Neostigmine.

Similar to Neostigmine. :S.E .2

3. Pyridostigmine &

Ambenomium:

*Used in: 1) Chronic open angle Glaucoma

→ Diagnosis & ttt of Accommodative esotropia (2 العين حول 4. Demecarium:

* Used in diagnosis of Myasthenia gravis

*Atropine is used as antidote.

5. Edrophonium:

Alcohol

Short acting

*Used in ttt of Alzheimer's disease.

*S.E: GIT distress.

*Tacrine→ hepatotoxic

6. Tacrine, Donepzil,

Rivastigmine &

Galantamine:

b. Irreversible: Insecticides.

War gas

Anti- bilharzias.

Binds irreversibly with Ach esterase causing paralysis & convulsions.

*Used topically for ttt of chronic open angle glaucoma.

1. Parathion & Malathion

2. Sarine (nerve gas)

3. Metrifonate

4. Ecothiophate &Isoflurophate

sterase reactivators→ parlidoxime → Choline eOximestoxicity by ttt of

(2 PAM) & Diacetyl monoxime (DAM).

*Can reactivate Ach esterase before aging (loss of alkyl gp).

*Unable to penetrate CNS.

Nicotinic Agonists:**

m.& N n*Agonist on both N

*Activates autonomic postganglionic neurons (sympathetic & parasympathetic) &

skeletal muscle neuromuscular end plates.

receptors n* Enters CNS & Activates N

smoking cessation 1) Medicinal use:: Uses*

: insecticide & smoking2) Non medicinal use

th CNS stimulants.Additive effect wi Interactions:*

1) Nicotine:

*Selective partial agonist at nicotinic receptors

*Exclusive for smoking cessation

2) Varenicline:

®)(Champix

2. Cholinergic Antagonists: (imp)

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c. Ganglion

blockers:

b. Antimuscarinics: a. Neuromuscular

blockers:

Mecamyl amine

Nicotine

Trimethaphane.

Atropine A

Cyclopentolate C

Ipratropium I

Scopolamine S

Tropicamide T

Oxybutyrine O

+O ACIST

Mivacurium M

Rocuronium R

Vencuronium V

Pancuronium P

Metocurine M

Succinyl Choline S

Tubucurarine T

Cisatracurium C

Atracurium A

Doxacurium D

CAD يتعلم لازم VP مستر

blocks Muscarinic receptors )• ( A. Antimuscarinics:

Mydriasis & cycloplegia (loss of accommodation for near vision)1) Eye: Actions:*

↓ motility. 2)GIT:

hypermotility of the bladder.: ↓ 3) Urinary bladder

: low doses→ ↓ HR.4) CVS

↓ Salivation & sweating.5) Secretions:

mydriatic & cycloplegic.1) Ophthalmic preparations: Uses:*

agonist (phenyl ephrine) for mydriatic effect only.

Tropicamide & Cyclopentolate are also used.

2) Antispasmodic

(for ttt of Organophosphorous cpds). 3) Antidote for Ach esterase toxicity

2) Dry mouth n (sandy eyes).: 1) blurred visioeffects *Adverse

3) Constipation

Atropine cause hemodynamic alteration as it causes initial bradycardia then 4)

Tachycardia

1. Atropine:

*Used in motion sickness (most effective/ prophylaxis not ttt).

*Have amnesic action→ used as adjunct therapy in anesthesia.

*It blocks short term memory.

**May produce Euphoria→ may be abused.

*In low doses→ sedation *In high doses→ excitement.

2. Scopolamine:

*belladonna alkaloid.

*Enters CNS

*Competitive blocker

*Uses: 1) As inhalation for patients with asthma unable to take 2 agonists

2) ttt of chronic obstructive pulmonary disease (COPD). 3. Ipratropium:

*As Atropine in ophthalmic preparations. 4. Tropicamide &

Cyclopentolate:

*For nocturnal enuresis & antispasmodic. 5. Oxybutyrine:

: blockers Ganglionic B.

Q) Although Ganglionic agents are very potent antihypertensives, they aren't extensively used as

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antihypertensive agents→ why?

because they interfere with action of acetyl choline at both: a)Sympathetic→ anti HTN

b) Parasympathetic ganglia→ S.E dry mouth,..

*Small doses→ activation, large doses→ blocking

*Used to ↓ nicotine cravings in smoking cessation. 1. Nicotine:

*Used to ttt moderate- severe HTN. *May be taken orally 2.

Mecamylamine:

*IV infusion for emergency lowering of BP

WHY?Na nitroprusside is preferred in emergency ttt of HTN→ *

Due to No tolerance.

3. Trimethaphane:

: blockers Neuromuscular C.

*Difference between neuromuscular B & Central muscle relaxants:

Central muscle relaxants: neuromuscular B

Used to: control spastic muscle tone *Used in surgery to maintain muscle

relaxation &↓ dose of anaesethia.

*Diazepam & Baclofen→ binds to GABA receptors in CNS.

from sarcoplasmic 2+→ directly acting by ↓ CaDantrolene*

reticulum.

They are divided into:*

: Depolarizing B.

Succinyl Choline

(Competitive): Depolarizing Non A.

Atracurium, :1. Benzylisoquinolone cpdsCisatracurium, Doxacurium, Mivacurium,

Tubucurarine & Metocurine.

Rocuronium, steroid cpds: -2. AminoVencuronium, pipercuronium & Pancuronium.

Binds to nicotinic receptors→ transient

depolarization (Phase I) →Repolarization

& desensitization of receptors→ Flaccid

paralysis (Phase II).

receptors in NMJ -→ blocks Na) Low doses

*Blocked by Ach esterase inhibitors.

block ion channels of the end plate →b) High doses

*Ach esterase can't block this action.

1. M.O.A:

cross BBB don't& IV*All are given

(Isomer of Atracurium) replaced Cisatracurium*

Atracurium due to release of histamine

2.

Pharmaco-

kinetics:

1) When rapid endotracheal intubation is

required.

electroconvulsive shock ttt.2) Used in

1) Adjunct therapy with Anesthesia to↓ dose.

2) Facilitated intubation.

3. Uses:

when :) Malignant Hyperthermia1 S.E:

taken with halothane

ttt by cooling patient + Dantrolene.

in pts who are genetically 2) Apnea:deficient in plasma choline esterase.

so dangerous with burn :3) Hypokalemiapts or with tissue damage.

s ) Choline esterase inhibitorD.I.: 1

NMB of action ↓(Physiostigmine, Neostigmine..)→

Halogenated anesthetics2)

of action ↑e.g. Halothane

NMB Aminoglycosides AB3)

(Gentamycin or Tobramycin)

ch. blockers 2+Ca4)

4.

Important

notes:

*Important Notes:

*Short duration of action→ used for short surgical procedures 1)Mivacurium:

*Useful in mechanical ventilation of critically ill patients.

*It is the ONLY NMB that can be used in Renal failure.

2)Cisatracurium:

Rapid onset→ used for tracheal intubation with gastric content 3) Rocuronium

↑ HR 4)

Pancuronium:

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System: Sympathetic affecting Drugs B.

*Neurotransmission at Adrenergic neurons:

*Adrenergic Receptors:

Beta receptors () Alpha receptors ( )

*Isoprotrenol- *Epinephrine- *Nor Epinephrine

High affinity Low affinity

*Epinephrine- *Nor Epinephrine- * Isoprotrenol

High affinity Low

affinity

*Activation of Adenyl cyclase→ ↑ cAMP

*V.D (skeletal vascular bed) →↓P.R

*Bronchodilation.

*Relaxed uterine smooth muscle.

*↑ Glucagon release.

*↑ liver & muscle glucogenolysis.

* ↑ Myocardial

contractility & T.C

*↑ Lipolysis

*↑ Renin release

*(-) NE release.

*(-) Insulin release.

sent onpre . N.B

cells of the

pancrease

*V.C (skin & abdominal

viscera) → ↑ P.R→↑ B.P.

*Mydriasis

*↑Closure of internal

sphincter of the bladder.

is divided into (A, B, C, D) n.b.

is divided into (A, B, C, D)

antagonists. A *Tamsulosine Selective

for ttt of benign prostate hypertrophy.

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is found primarily in the urinary tract.A

Agonists: Adrenergic 1.

Adrenergic agonists:*Characteristics of

.Contains 3,4 dihydroxybenzene group Catecholamines: A.

*Norepinephrine *Ephedrine *Phenylephrine

*Dopamine. *Isoprotrenol Epinephrine*

) or 1) High potency activating ( :*Characters

) Poor CNS penetration

3) Rapid inactivation → why?

Because they are metabolized by:

a) COMT postsynaptically.

b) MAO intraneuronally.

c) COMT in gut wall. Given parenterally

d) MAO in liver & GUT Wall.

Amphetamine. Catecholamines: Non B.

1. Long duration →why?

a) Aren't inactivated by COMT.

b) Poor substrates for MAO.

2. High CNS penetration.

:nitrogen amine on Substitution C.

Isoprotrenol > Epinephrine > Nor epinephrine as B-Agonists why?

affinity to B-receptor by increasing size of group on amine N

Put (T) or (F):**

1) COMT doesn't metabolize isoprenaline (F).

2) Slow IV adrenaline → ↑ diastolic BP (F).

It increases cardiac output with slight decrease in diastolic BP.

3) Stimulation of Sympathetic nerve causes contraction of vascular smooth muscle (T).

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of Adrenergic agonists:M.O.A *

→ drugs directly activates receptor.:Direct Acting agonists1.

→ drugs enhance release of NE from vesicles. :Indirect Acting agonists. 2

→ direct & indirect. Mixed Acting:3.

Mixed Indirect Acting: Direct Acting:

Ephedrine.

Pseudoephedrine.

Amphetamine.

Cocaine.

Tyramine.

*Epinephrine. *Isoprotrenol.

*Nor epinephrine. *Metaprotrenol.

*Phenylephrine. *Methoxamine.

*Dopamine. *Salmetrol.

*Dobutamine *Formetrol

Clonidine *Pirbuterol*

*Terbutaline. *Albuterol

1. Direct Acting Adrenergic agonists:

Uses: Action: Receptor

specificity

Drug:

ttt of Open angle a)

glaucoma → How?

1-2% solution→ vasoconstriction of

ciliary body blood vessels→

) ↓production of aqueous humor.a

↑ outflow of Aqueous humor. b)

*Duration of action of this

1% epinephrine: 1-2 hrs.

: b) Anaphylactic shock

D.O.C in ttt of Type I

hypersensitivity Rx.

CIV or S. c) Acute asthma:

receptor: )Stimulation of a

relaxation of bronchial muscle.

receptor: b) Stimulation of

constriction of bronchial vessels→ ↓

congestion & edema.

: anestheticd) With local

1:100,000 solution→ why?

V.C at injection site→ ↑ duration of

action.

a)Cardiovascular:

Strengthen contractility *: 1a)

(+ve inotropic)

*↑ rate of contraction

(+ve chronotropic).

demand by Myocardium. 2O ↑

vasoconstriction :1b)

(skin, mm, viscera)

vasodilation (sk. muscles). c)

↓ renal blood flow.d)

: Overalle)

(↑ systolic, slight↓ diastolic)

b)Respiratory:

bronchodilation. *

c)Hyperglycemia:

↓ insulin. :2*

glucagon & glucogenolysis. ↑

d) Lipolysis:

Lipolysis. *

Epinephrine:1.

*If taken orally→ inactive so taken parentrally or by inhalation

→ dose must be reduced→ Why?a) Hyperthyroidism: D.I*

Due to ↑ adrenergic receptors on vasculature of hyperthyroid individual.

→ it inhibits reuptake of catecholamines by adrenergic neuron→ Exaggerated C.V. action.b) Cocaine

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(also Atropine & Homotropine) → why? Narrow angle glaucomac)

stimulation so if propranolol taken→ no reverse of the 1due to Mydriasis (produced by epinephrine due to

effect of Mydriasis but block other B receptor mediated effects.

ttt of shock (cardiogenic)*

→ why?

↑ B.P.

is favored coz it Metaraminiol N.B.

doesn't reduce blood flow to the

kidney as N.E.

*Never used for asthma→ why?

effect. weak

Cardiovascular:

V.C→ ↑ Systolic & diastolic *

B.P→ baroreceptors→ ↑vagal

activity→ reflex bradycardia (but

with no effect on + ve inotropic

effect).

N.B. If atropine (which blocks

vagal effect) given before N.E→

N.E stimulation of heart is

tachycardia.evident as

2.

Norepinephrine:

a) As cardiac stimulant:

in ttt of atrioventricular block or

cardiac arrest.

: by inhalation Asthmab) Acute

but now rarely used.

a) Cardiovascular:

↑ force & rate of contraction *

V.D→ ↓ P.R: *

*Overall ↑ systolic & ↓ diastolic

markedly.

3. Isoprotrenol

= Isoprenaline:

**Stable to MAO but

inactivated by COMT.

→ why?ttt of shocka)

as it ↑ B.P.

Why?→ *Preferred over N.E

because N.E ↓ blood flow to

kidney→ renal shut down.

ttt of C.H.F*

→:+ve inotropic 1Low dose→ *

& chronotropic.

→ V.C →↑ B.PHigh dose→ *

→ V.D→ ↑ blood flow to 1& D 2*D

kidney.

*dopa-

minergic.

*

4. Dopamine:

**D.O.C for ttt of

cardiogenic shock

*ttt of C.H.F

doesn't → *It ↑ C.O with little change on cardiac rate

demand of myocardium.2 significantly ↑ O

It is used with caution in patients with atrial fibrillation→ N.B.

conduction→ lead to Coz it increases atrioventricular → why?

ventricular fibrillation which is fatal

5. Dobutamine:

1. Nasal decongestant.

2. Ophthalmic solution→ mydriasis.

3. ttt of supraventricular tachycardia→ How?

V.C→ ↑ B.P→ reflex bradycardia. →

) (

6.

Phenylephrine:

*Used locally in nose & eye as vasoconstrictors to ↓ congestion.

with long term use.Rebound congestion S.E:*

7.

:Oxymetazoline

by vagal stimulation. 1) ttt of supraventricular tachycardia→

.halothaneinvolving during surgery Overcome hypotension 2)

doesn't trigger cardiac *N.B. It is the only adrenergic drug that

.general anestheticsthese bywhich is sensitized arrhythmia

) (

8. Methoxamine:

1. ttt of HTN

2. Minimize opiate & Benzodiazepine withdrawal symptoms. 9. Clonidine:

*ttt of bronchospasm & asthma.

* not catecholamine→ may be taken orally 10.

Metaprotrenol:

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*ttt of bronchospasm → short duration < 3hrs,

*onset of action: 5 min→ ttt of acute asthmatic attack. 11. Terbutaline,

Albuterol &

Pirbuterol:

= 12 hours.1/2*ttt of bronchospasm→ long acting → t

*Used in nocturnal asthma.

N.B. Not recommended for use as monotherapy→ combination with

corticosteroids.

12. Salmetrol &

Formetrol:

s:adrenergic agonist -2. Indirect Acting

, attention deficit syndrome*Used as CNS stimulant in ttt of children with

control.appetite & narcolepsy

C.I. in pregnancy.

a. Amphetamine:

CNS

*Found in fermented foods such as ripe cheese & wine.

*It is normal byproduct of Tyrosine metabolism.

*Normally it is oxidized by MAO but if patient is taking MAO Inhibitors→

Hypertensive crisis.

b. Tyramine:

*Inhibits uptake of N.E c. Cocaine:

3. Mixed Action adrenergic agonists:

Long action duration & excellent oral absorption→ why?*

(not degraded by MAO & COMT).Catecholamine -Because it is Non

→ why?for prophylaxis not ttt)Chronic ttt of asthma not acute ( 1) *uses:

Due to slow action.

→ ttt of Myasthenia gravis.2) With Anticholinestrases

.↑ athletic performance3) Stimulates CNS→↑ alertness, ↓ fatigue&

synergistic toxicity.→ Ephedrine + Theophylline C.I:

Ephedrine:1.

CNS

& eustachian tube congestion. ttt of Nasal congestion*for 2.

Pseudoephedrine:

effects of Adrenergic agonists:Adverse *

Arrythmia Hyper-activity Insomnia

Tremors(dose limiting

toxicity)Nausea Headache

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Antagonists: Adrenergic 2.

:Adrenergic blocking agents A)

blockers: 1) Non selective b) Phentolamine: a) Phenoxybenzamine:

.blockers Non selectivei)

hrs.duration = 4 with Competitive blocker*

.blockers Non selectivei)

durationwith Non competitive irreversible *

→ why?= 24 hrs

→ Time to synthesize new adreno-receptors.

Action: ii)

→ prevents peripheral V.C by endogenous catecholamines→↓ P.R 1) Blocks

→ Orthostatic hypotension Reflex tachycardia

2) Blocks

3)Sexual dysfunction in males→ why?

adrenergic activation. sexual function is mediated through Because

4) Nasal stuffiness.

:Isoprotrenol & N.E E, on them of Effect iii)

*Reverse action (↓ B.P.)→ WHY?

→ V.C→ Interrupted. ↓ B.P1

→ V.D→ not blocked

a) Epinephrine:

Not reversed but diminished. b) Norepinephrine:

No effect→ why? coz it is pure B agonist. c) Isoprotrenol:

.

uses: Therapeutic iv)

(Catecholamine secreting tumor of cells derived pheochromocytomaused in ttt of Phenoxybenzamine:1)

from adrenal medulla).

ttt of Raynaud's disease. Phenoxybenzamine or Phentolamine:2)

→ why? → Due to tachycardia.In patients with decreased coronary perfusion C.I: v)

, Terazosin, Prazosin 2) Selective Competitive blockers:

.Tamsulosine& Doxazosin

*Therapeutic Uses:

dose of this drug produce exaggerated st: 11) ttt of HTN (All except Tamsulosine)

overcome? to Howhypotensive response that can result in syncope (fainting)→

dose to 1/3 or 1/4 of the normal dose & by giving drug at bed time. stby adjusting 1

e.g. Dose of Prazosin: 1mg X 3/d, then can be slowly increased to 10mg X 2/d.

2) ttt of prostate hypertrophy.

*Notes:

in feces. except Doxazosin1) Metabolites excreted in urine

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longest acting of these drugs. :DOXAZOSIN2)

& fluids→ +due to tendency to retain Na ITH DIURETIC) PRAZOSIN IS USED W3

risk of CHF if used as monotherapy.

4) Same S.E of non selective blockers but with less degree.

Adrenergic blocking agents: -) B

receptors remain functional. Coz → why?**Never produce postural hypotension

): 2& 1 antagonists (blocks Selective-1) Non

Actions: i)

2effects so cardiac work & Ove inotropic & chronotropic –) 1→ *blocks

consumption ↓ → useful in ttt of Angina

O retention so used with diuretic.2& H +→ Na↓ renal perfusion .→2) ↓ B.P

→ why?peripheral vasoconstriction→1) :blocks *

mediated V.D is blocked. -

block→ ↓ B.P→ reflex V.C -

→ C.I. in pts with asthma.2) Bronchoconstriction

→ ↓ glycogenolysis & ↓ Glucagon.→ why? 3) Hypoglycemia

Careful monitoring of blood sugar in insulin dependent patient.

unknown mechanism. :Sexual impairment*

Q) What is effect on E, N.E & Isoprotrenol?

Blocking of its action *Isoprotrenol:

No longer lowers diastolic B.P or stimulates the heart but

its Vasoconstrictive action is unimpaired.

*Epinephrine:

Unaffected coz its action mediated mainly by receptors. *N.E:

uses: Therapeutic ii)

.Hypertension. 1

→ how?Glaucoma2.

*↓ secretion of aqueous humor by ciliary body→ ↓ IOP.

*For chronic ttt but acute→ Pilocarpine is D.O.C

in brain.by blocking of catecholamine induced V.D :Migraine (chronic ttt). 34. Hyperthyroidism:

a) protects against cardiac arrhythmia.

"Active form". 3to T 4b) Prevents conversion of T

↑ intolerance to moderate exercise but :)t5. Angina pectoris (chronic tt

not severe exercise as tennis.

6. Myocardial infarction:

attack. nda) For prophylaxis against 2

b) Immediately following infarction (↓ infarct size & hasten recovery)→↓ morbidity

& mortality.

why? →blockers must never be stopped quickly Q) ttt with

Due to upregulation of receptors.

propranolol: of S.E common Mostiii)

1) Cold extremities 2) Lipophilic→ crosses BBB causing nightmares.

a) Propranolol :

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: Propranolol causes tremors (F).Q) Put (T) or (F)

Only B agonists cause tremors.

interactions: Drug iv)

*inhibit metabolism (Cimetidine, Furosemide & chlorpromazine).

*Stimulate metabolism (barbiturates, phenytoin & Rifampin).

More potent than propranolol. *

*Nadolol: very long duration of action.

*Timolol: Chronic ttt of open angle glaucoma.

b) Timolol &

Nadolol :

,Atenolol, Acebutolol :Antagonists1 2. Selective

.Esmolol.& Metoprolol

:in especially*ttt of Hypertension

1) Patients with asthma. 2) Diabetic patients.

which is common with → less frequent coldness of extremities*Less effect on vascular

−blockers therapy.

or diagnostic (10 min) → so it is given IV during surgery or f 1/2: very short t*Esmolol

procedures e.g. cystoscopy.

& lolAcebuto 3. Antagonists with Partial Agonist activity:

.Pindolol

→ are said to have receptor Have ability to weakly stimulate*

intrinsic sympathomimetic activity (ISA).

blockers -cardiac rate & Cardiac output compared to Diminished effect on *

without ISA.

especially: : ttt of hypertension*Uses

1) Patients with moderate bradycardia.

2) Diabetic patients.

:receptors c) Antagonists of both

:Carvedilol) :(Labetalol

peripheral vasodilation→ orthostatic hypotension.→ 1. Block

2. Don't alter serum lipid or blood glucose.

↓ Lipid peroxidation & vascular wall

thickening→ ttt of CHF.

ttt of elderly or block hypertensive

patients in whom increased peripheral

vascular resistance is undesirable.

D) Drugs affecting neurotransmitter release or uptake:

*Dopamine + preformed N.E Amine transporter vesicles.

/ ATP+Mg

(-)

Reserpine

degraded by MAO in cytoplasm → N.E→ Gradual ↓ in B.P & Heart rate.

ine:1.Reserp

17

*block release of stored N.E→ gradual ↓in B.P & Heart rate.

*It also displaces N.E from storage vesicles→ transient ↑ in B.P.

*Overall: depletion of N.E except in CNS.

Hypertensive crisis in patients with pheochromocytoma→ *It may cause

→ Due to depletion of N.E→ Supersensitivity to N.E why?

diarrhea.&inhibition of ejaculation Orthostatic hypotension, S.E:*

why? →Q) Diarrhea is common during ttt with Guanethidine

because it blocks sympathetic outflow so parasympathetic tone predominates→ diarrhea.

→ why? → because they block uptake of Guanethidine into 1) TCAs Guanethidine: of *D.I

adrenergic neuron→ so inhibit its antihypertensive effect.

2) MAOIs.

2.

Guanethidine:

ATPase→ accumulation of N.E in synaptic gap→ enhancement of +/ k+*Inhibits Na

sympathetic activity→ so small dose of Catecholamines produce greater effects in

individual taking cocaine than others who aren't e.g. Epinephrine.

3. Cocaine: