Tutorial on AUTONOMIC Nervous System

Effects on body organs

M- Receptors
M1 &

Nicotionic Receptors
Parasympathetic ganglia

Sympathetic ganglia

Suprarenal medulla
Motor end plate

Parasympathomimetics a) Direct
i) Choline esters: 1. Acetyl choline 2. Methacholine 3. Carbachol 4. Bethanechol
Reversible 1. Physostigmine 2. Neostigmine 3. ..

b) Indirect (Anticholinesterases)

ii) Cholinomimetic alkaloids Pilocarpine

Irreversible Organophosphorous poisoning

Therapeutic uses of reversible anticholinestrases

Neostigmine:
1. Myasthenia gravis 2. Antidote to curare 3. Paralytic ileus 4. Post-operative urine retention

Physotigmine

Treatment of atropine poisoning.

Edrophonium
Diagnosis of myasthenia gravis. Differentiation between "myasthenic crisis" & cholinergic crisis

Irreversible Anticholinesterases

[1] Insecticides
[2] Organic Phosphate Poisoning
1. Causes

Eating

Dusting
accidental

R of organic phosphate
poisoning
Atropine IV or IM till Oximes (if patient is seen within 6-8hs) Mechanism of action: 1. Set the enzyme free 2. Bind circulating poison before reaching the enzyme. Anticonvulsants Care of respiration Gastric lavage/ wash skin

Atropine

Mechanism of action

By competing with acetylcholine for M receptors

Pharmacological actions

secretions Bronchodilatation & secretions 1) Heart: If IV, initial bradycardia followed by tachycardia 2) BV and BP:.
1) Passive mydriasis Tone, motility 2) Cycloplegia and secretion 3) IOP (antispasmodic) 4) Loss of light reflex 5) lacrymation Antispasmodic, urine retention

(2) CNS actions

Stimulant actions Therapeutic dose: 1. CIC bradycardia 2. RC Large dose: Cereberal cortex

Depressant actions 1. tremors & rigidity RC

Uses of atropine

Preanaesthetic medication (Why?) Colic Heart block Eye: . Organic phosphate poisoning.

Side effects of atropine

Dryness of mouth, blurred vision and tachycardia. Retention of urine in patients with enlarged
prostate.

Acute glaucoma In children, cutaneous VD with flushing and

elevation of body temperature.

Hyoscine

Preferred over atropine in pre-anaesthetic medication. (Why?) Colic Motion sickness

Synthetic Atropine Substitutes

1. Mydriatics. 2. Antisecretory-antispasmodic 3. Antiparkinsonian. 4. urinary bladder activity. 5. Bronchial asthma.

Mydriatic Atropine Substitutes

Atropine Duration action of 7-10 days

Homatropine Tropicamide 24 hrs. 6 hrs.

Cyclopentolate
24 hrs

Concentration

1%

2%

2-5%

0.5%

Cycloplegia
Antagonism by eserine

+
Not complete

+
Complete

+
Complete

+
Complete

Questions

Atropine is useful in treating poisoning produced by organophosphate insecticides because it:

a) Reactivates inhibited A. cholinesterase.
b) Stimulates nicotinic receptors directly.

c) Stimulates - receptors directly.

d) Inhibits normal ganglionic transmission.

e) Blocks the action of acetylcholine at peripheral

sites.

Characteristics of neostigmine include all of the following EXCEPT:

a) It is a parasympathetic agent.
b) It exerts both nicotinic & muscarinic

effects. c) It inhibits acetylcholinesterases reversibly. d) It has a direct stimulant action on MEP e) It crosses the BBB readily

Which of the following symptoms is not likely to be present in a patient poisoned with organophosphorous compound?

a) Excessive salivation.
b) Abdominal cramps.

c) miosis .
d) Tachycardia.

e) Convulsions.

Which of the following drugs is incorrectly paired with an appropriate use?

Atropine : Urinary retention. Physostigmine: For overdose with atropine-like drug. Neostigmine: antidote to curare

Which of the following drugs are recognized for treatment of raised intraocular pressure?

a) Cyclopentolate.
b) Corticosteroid eye drops. c) Topical timolol eye drops.

d) Both c and e.
e) Dipifevrin.

Glaucoma may occur as a side effect of which of the following drugs?

a) Neostigmine.
b) Pilocarpine

c) Homatropine eye drops.

d) Bethanechol

For these statements, write (T) for true & (F) for false:
1) Neostigmine may cause constipation and

bronchodilation.

2) Accepted therapeutic indications for the use of

anti-muscarinic drugs include: parkinsons disease and motion sickness.

3) Atropine is used in Curare poisoning. 4) Pilocarpine constricts the pupil.

F
T

COMPLETE:

Hyoscine is preferred than atropine in pre-

anaesthetic medication because:

a) More CNS depressant b) Stronger antisecretory c) Stronger antispasmodic

COMPLETE:

Atropine is given before neostigmine in

Myasthenia Gravis to :

block muscarinic SE

THE SYMPATHETIC SYSTEM

The synapse in the sympathetic ganglion

uses Ach as a neurotransmitter.

The post-ganglionic sympathetic neuron

within the target organs uses NE as a neurotransmitter. (there is one exception)

ADRENERGIC RECEPTORS
1. ALPHA RECEPTORS:
1 & 2

2. BETA RECEPTORS:
1, 2 & 3

3. DOPAMINE RECEPTORS:
D1 & D2

Stimulation of alpha-1 receptors results primarily in (Ca2+ ):

Vasoconstriction. Mydriasis. Contraction of the GIT &urethral sphincters.

Alpha-2

receptors are mainly presynaptic & their stimulation results in a decrease of NA release.

Beta-1: (+) inotropic effect ( force), (+) chronotropic effect (rate), (+) dromotropic effect (conduction acceleration) & increase of excitability

Beta-2 :
bronchodilatation, uterus , bladder & GIT relaxation.
Stimulation of glycogenolysis. Skeletal muscle tremors, vasodilatation of b.vs.

Sympathomimetics
a) Direct
Non selective Adrenaline Noradrenaline Dopamine

b) Indirect Selective Phenylephirine

Salbutamol Ritodrine

C) Dual
Cocaine Amphetamine

Ephedrine Dopamine

Catecholamines
Adrenaline alpha1, alpha2 1, 2

Noradrenaline

alpha1, alpha2, 1
D1 (minimal doses) 1 (intermediate dose) alpha1 (high dose)

Dopamine

Non Catecholamines
Phenylephrine Clonidine Salbutamol Direct Ritodrine 2 Direct Direct alpha1 alpha2

Amphetamine
Indirect Cocaine

Ephedrine
Dual

alpha1, alpha2 1, 2

Adrenergic depressants
1- Adrenergic receptor blockers - adrenergic antagonists (- blockers).

- adrenergic antagonists (- blockers).

& blockers.

2- Sympatholytics

I. Pharmacodynamic Classification
Non selective
Propranolol Pindolol

Selective 1

B-blockers

Atenolol Metoprolol

Combined & blocker

labetalol &carvedilol

II. Pharmacokinetic Classification:

B-blockers

Lipophilic

Hydrophilic

Lipophylic
oral absorption Complete

Hydrophilic
Irregular

Liver metabolism
T 1/2

Yes
Short

No
Long

CNS side effects

High

low

Anti-hypertensive
1. COP (1- blocking effect).
2. Block rennin release, so Ag II & aldosterone (1- effect). 3. NE release from Nerve terminals. 4. central sympathetic outflow. 5. Ressetting of baroreceptor

Therapeutic Uses of Propranolol & other beta-blochers:

1. Hypertension. 2. Angina pectoris 3. Cardiac arrhythmia.

4. Mild Myocardial infarction.

5. Prophylaxis of migraine 6. Hyperthyroidism

OTHERS
1. Familial tremors & anxiety.

2. Pheochromocytoma ( must be used

with - blocker)
5. Open angle glaucoma

Side effects of Propranolol

Block of cardiac 1-receptors: CHF / Severe bradycardia in patients with impaired myocardial functions. Hypotension Blockade of 2-(non-selective) Severe bronchospasm ( non-selective) in asthmatics 1 are better. Cold extremities . Hypoglycemia if given with hypoglycemic drugs as insulin
Sudden stoppage will give rise to a withdrawal syndrome:

Rebound angina, arrhythmia, myocardial infarction and hypertension due to up-regulation of -receptors.

Contraindications:
1. Hypotention & heart block.
2. Severe heart failure & massive myocardial

infarction. 3. Peripheral vascular disease (not CI with cardio-selective -blockers). 4. Bronchial asthma (not CI with cardioselective -blockers). 5. Diabetic patients. (Type I)

Drug interactions
Pharmacokinetic Pharmacodynamic Interactions Interactions 1. Hepatic enzyme 1. Anti-diabetic drugs e.g. inhibitors as: cimetidine insulin. & isoniazid 2. Hepatic enzyme inducers 2. Verapamil (calcium as: barbiturates, channel blocker) phenytoin, & rifampin 3. Non-steroidal antiinflammatory drugs

Alpha 1-ANTAGONISTS: Prazosin Terazosin

Peripheral VD of arterial & venous

SMs PR, BP Tachycardia (reflex)

Therapeutic uses:

Hypertension
Alternative to surgery in patients with benign prostatic hyperplasia

Alpha 1-ANTAGONISTS: Prazosin Terazosin

SIDE EFFECTS:
1. Orthostatic hypotension and syncope. 2. Salt and water retention. 3. Failure of ejaculation.

ERGOT ALKALOIDS
Pharmacologic actions
Direct VC -blocking effect Oxytocic action weak weak potent

Ergotamine

Dihydroergotamine
weak Potent ++

Potent Weak

Ergometrine & methylergometrine moderate

weak

CNS

weak

weak

weak

ERGOT ALKALOIDS
Uses
Ergotamine DihydroErgometrine ergotamine & methylergometine
Acute Migraine Acute Migraine Post-partum hemorrhage

Enhance placenta delivery

Pathogenesis of MIGRAINE

Triptans (serotonin receptor agonists) are now preferred in treatment of acute attack of migraine

 -Methyldopa

Mechanism of action

 -Methyldopa Therapeutic use

1. It is the antihypertensive drug of choice in pregnancy.

2. Mild, Moderate or severe

hypertension with impaired renal function.

 -Methyldopa
Side effects
1. Hypersensitivity reactions:
Liver damage Hemolytic anemia

2.

Sedation ( 5-HT)

Questions

Which of the following agents would bring a rapid heart rate (120 beat/min) back to normal:
A. Dopamine B. Atropine C. Propranolol D. Phenylephrine E. Adrenaline

At therpapeutic doses, this drug dilates the bronchioles, increases heart rate and conduction but does not elevate BP: 1. Salbutamol.
2. Adrenaline. 3. Nor-adrenaline. 4. Prazosin.

5. Atropine.

A drug injected I.V. into a dog. Five minutes later, the following signs were observed : bradycardia broncho-constriction a fall in mean blood pressure. The drug most likely evoked these signs is :

A. Atropine B. Ephedrine C. Prazosin D. Propranolol

Which of the following drugs is incorrectly paired with an appropriate use?

A. Epinephrine: anaphylaxis. B. Propranolol: Acute attack of migraine C. Atropine: heart block D. Terbutaline: bronchial asthma

E. Amphetamine: Attention deficit syndrome.

Atenolol differ from propranolol in: 1. 2. 3. 4. Its oral absorption is complete. It does not affect the release of renin. It has more central side effects It has minimal risk of producing bronchospasm. 5. It does not inhibit gluconeogenesis

Epinephrine would cause a decrease in mean arterial blood pressure if it is administered after pre-treatment with :
A. A beta 1 antagonist . B. An alpha 1 antagonist . C. A beta 2 antagonist . D. A non-selective beta antagonist. E. Both alpha 1 and beta 1 antagonist

Dilatation of blood vessels in muscles, constriction of cutaneous vessels, positive inotropic & chronotropic effects are all actions of :
A. Salbutamol . B. Nor-epinephrine. . C. Acetylcholine . D. Epinephrine . E. Isoprenaline .

Propranolol is useful in all of the following except:

A. Hypertension . B. Anxiety C. Tachycardia . D. Angina E. Atrioventricular heart block

Non catecholamine differ from catecholamine in that they :

A. Have a short duration of action B. Not effective orally C. Dont act indirectly, but usually combine directly with 1 and 2 receptors subtypes D. Have greater CNS effects E. Are metabolized at more rapid rate

beta adrenoceptor blockers may lower ABP by the following mechanisms EXCEPT:
A. Decrease sympathetic mediated renin release B. Causing vasodilatation in skeletal muscle C. Action on CNS D. Decrease Norepinephrine release from sympathetic nerve endings E. Reconditioning of baroreceptors to a lower level

Patients taking beta adrenoceptor blockers may experience all of the following EXCEPT:
A. Exacerbation of existing heart block B. Precipitation of heart failure C. Increased capacity to vigorous exercise D. Cold extremity E. Hypoglycemia if they are diabetic

A directly acting sympathomimetic decongestant drug is:

A. Ephedrine. B. Amphetamine. C. Phenylephrine. D. Dopamine

Sympathomimetics may be employed in all of the followings Except :

A. Relief symptoms of hypersensitivity reaction to drugs B. Induction of labor C. Narcolepsy
D. Acute hypotensive states as during

spinal anesthesia
E. Reduction of nasal congestion causing temporary relief

Put True or False:

A. Propranolol can reduce tremors in thyrotoxicosis.
C. Propranolol is used in the treatment of angina T pectoris. D. B-blockers can cause heart block or T bronchospasm in susceptible individuals.

T F

B. B-blockers often cause orthostatic hypotension.

E. Phenylephrine cause dilation of conjuntival F

blood vessels

Complete
Adrenaline acts on 1 2 1 2 -------------- receptors.

1 2 1 receptors. Nor adrenaline acts on ---------------Dopamine acts on ------, ----- & ------ receptors

D1 , 1,

Complete
Nor adrenaline is used in--------------

---

Septic shock & severe hypotension

Atenolol is preferred over propranolol

in treating hypertension because

More B1 selective

A drug useful in treatment of postpartum hemorrhage is:

1. 2. 3. 4.
Dihydroergotamine Methyl ergometrine. Ergotamine. Ritodrine.

Adrenaline elevates the blood sugar level by:

Inhibition of insulin secretion (2) Increase in hepatic glycogenolysis (2)

Increasing release of glucagon (2)

All of the above

Match the drug and clinical effect with correct receptor

Phenylephrine, salbutamol,

epinephrine, clonidine. Bronchial relaxation, nasal decongestion, heart rate and strength, treatment of hypertension.

1 2 1

Receptor

Drug

Clinical effect

1
1

Phenylephrine
Epinephrine

Nasal decongestion
heart rate & strength Bronchial relaxation Treatment of hypertension

2 2

Salbutmol Clonidine

Thank You