The document discusses the autonomic nervous system and pharmacology of its sympathetic and parasympathetic divisions. It describes the pre- and post-ganglionic fibers, neurotransmitters, and receptors involved. Catecholamines, adrenergic receptors, and drugs that target the sympathetic system like agonists, antagonists, and their effects are summarized. Parasympathetic muscarinic and nicotinic receptors, cholinergic drugs like direct and indirect agonists, and anticholinergic drugs are also outlined.

1. Introduction to Pharmacology
February 2015
Diogo José Capela Oliveira
João Daniel Soares Almeida
AUTONOMIC NERVOUS SYSTEM
Pharmacology of the

2. Functions of the autonomic nervous
system:
- Maintaining homeostasis of the
organism
- Coordinate the body’s response to
exercise, stress or injury

3. Sympathetic
Nervous System
Parasympathetic
Nervous System
PRE-GANGLIONIC FIBER SHORT LONG
POST-GANGLIONIC FIBER LONG SHORT

4. Sympathetic Nervous
System
Parasympathetic
Nervous System
Pre-ganglionic Neuron ● Acetylcholine ● Acetylcholine
Post-ganglionic Neuron
● Nicotinic Receptors ● Nicotinic Receptors
● Norepinephrine ● Acetylcholine
● Acetylcholine
● Dopamine
Tissue Receptor
● Adrenergic Receptors ● Muscarinic Receptors
● Muscarinic Receptors
● Dopamine Receptors
Exceptions of the Sympathetic Nervous System
Adrenal Medulla Releases norepinephrine
Sweat Glands Releases acetylcholine
Renal Vasculature Releases dopamine

5. Catecholamines Receptors:
- α1 Receptors
- α2 Receptors
- β1 Receptors
- β2 Receptors
- Dopamine Receptors
Catecholamines:
- Epinephrine
- Norepinephrine
- Dopamine
DRUG
AGONIST ANTAGONIST

6. ADRENERGIC
AGONIST
ADRENERGIC
RECEPTOR
ADRENERGIC
RECEPTOR
ADRENERGIC
ANTAGONIST
Stimulates a
response through
catecholamines.
Inhibits the action of
catecholamines.

7. Most drugs interact
with more than one
receptor type!
But usually they have
more affinity to one
specific type of
receptor.

8. α1 Agonists
Some of the important effects of α1 agonists:
- Mydriasis
- Raising blood pressure
- Piloerection
- Contraction of bladder sphincters
- Contraction of the spleen capsule

9. α1 Agonists
Phenylephrine
- Treat hypotensive states
- Mainly stimulates α1 receptors
Norepinephrine
- Treatment of shock
- Great capacity in stimulating both α1 and β1 receptors
Epinephrine
- Support blood pressure during anaphylaxis
These agents are sometimes used
with local anesthetics

10. α1 Antagonists
Some of the important effects of α1 antagonists:
- Negates de responses of the α1 receptor
- Reduces the blood pressure
Some of the α1 antagonist agents:
- Phentolamine
- Phenoxybenzamine
- Prazosin

11. α1 Antagonists
Phentolamine
- Competitive, short-acting
- Help diagnose pheochromocytoma
- Side effects:
- Cardiac stimulation
- Abdominal cramping (chronic use)
- Ulcer exacerbation (chronic use)
- Diarrhea (chronic use)
Phenoxybenzamine
- Non-competitive, long-acting
- Managment of pheochromocytoma
Prazosin
- Treatment of hypertention
- Treatment of congestive heart failure
- Side effects:
- “Prazosin syncope”

12. α2 Agonists
Some of the uses of α2 agonists:
- Antihypertensive
- Sedative
- Treatment of opiate dependence
- Treatment of alcohol withdrawal symptoms
Clonidine is used as a treatment for:
- High blood pressure
- Attention-deficits / Hyperactivity
- Anxiety disorders
- Migraine
- Menopausal flushing
- Diarrhea
- Side effects:
- Hypotension
- Dry mouth

13. α2 Antagonists
Yohimbine:
- Treatment of erectile dysfunction
- Aphrodisiac effects
- Treatment of dry mouth
- Treatment of sexual dysfunction

14. β Agonists
Isoproterenol
- Stimulates both β1 and β2 receptors
- Bronchioles are relaxed (β2)
- Gravid uterus is relaxed (β2)
- Increased contractiity and heart rate (β1)
Dobutamine
- Stimulates selectively β1 receptors
- Increased contractiity and heart rate

15. β Antagonists
Propranolol
- Inhibits both β1 and β2 receptors
- Reduces heart rate, contractility and blood pressure
- Increases bronchiolar tone
- Side effects:
- Hearth failure
- Reduced AV conduction
- Worsened COPD
Metoprolol
- Inhibits selectively β1 receptors

16. Acetylcholine Receptors
• Acetylcholine Postganglionic neurotransmitter in the PNS
Preganglionic neurostranmitter for both SNS and PNS
• Cholinergic receptor Muscarinic receptor (M)
Nicotinic receptor (N)

17. Muscarinic receptors location
• Tissues innervated by postganglionic parasympathetic
neurons
• Presynaptic noradrenergic and cholinergic nerve terminals
• Non-innervated sites in vascular endothelium
• Central nervous system

18. Muscarinic receptors subtypes
• There are 5 subtypes of muscarinic receptors: M1, M2, M3,
M4, and M5
• They mediate their effects through:
• G proteins coupled to -
• Phospholipase C (M1,3,5),
• Potassium channels (M2,4)

19. Nicotinic receptor location
• Sympathetic and parasympathetic ganglia
• Adrenal medulla
• Neuromuscular junction of the skeletal muscle
• Central nervous system

20. Nicotinic receptor subtypes
• There are two subtypes of nicotinic receptors NM and NN
Nicotinic receptor Action
NM Mediates skelital muscle stimutalion
NN Mediates stimulation of the ganglia of the ANS

21. Cholinergic drugs

22. Direct-acting muscarinic agonists
The direct-acting agents include:
• Achetylcoline and choline derivates
(longer duration and more selective)
• Pilocarpine

23. Autonomic effects of muscarinic agonists
Local of action Effect
Iris sphincter muscle Miosis
Ciliary muscle Contraction
Sinoatrial node Bradycardia
Atrioventricular node Reduced conduction velocity
Atrium Reduced contractility
Bronchial muscle Contraction
Gastrointestional tract Increased motility and secretion
Bladder (detrusor) Contraction
Bladder (trigone, sphincter) Relaxation
Salivary and lacrimal glands Secretion
Sweat glands Secretion

24. Nicotinic Agonists
• Nicotin is the most commonly encountered nicotinic agonist
• Stimulates both symphatetic and parasympathetic ANS.
• 1 mg: blood pressure by 10 mmHg and heart rate 15bpm
peripheral vascular resistance, cardiac output, heart work
High doses: Bradycardia, hypotension, nausea tremors and
convulsions

25. Direct acting cholinergic drugs
Bethanechol is used in:
• Urinaty retention ( not obstructed )
• Xerostomia ( Sjogren’s syndrome, traumatic or
radiation injury )
• Gastroparesis
• Impaired gastric absorption
Side effects:
• Hypotension and bradycardia
• Myocardial ischemia ( high doses )

26. Direct acting cholinergic drugs
Pilocarpine used in:
• Xerostomia ( more commonly than bethanechol)
• Open-angle glaucoma.
Side effects:
• Sweating
• Asthma worsening
• Nausea
• Hypotension
• Bradycardia
• Hiccups

27. Indirect-acting cholinergic drugs
“Cholinesterase inhibitors”

28. Reversible cholinosterase inhibitors
Inhibitor Duration Main site of action Clinical use Adverse
effects
Edrophonium Short (10m) Neuromuscular juntion Diagnosis of myasthenia
gravis
Cramps
Physostigmine Medium (0,5-5h) Postganglionic
parasympathetic
Glaucoma (eye drops)
Anticholinergic
syndrome
Nausea,
sweating,
bradycardia
Neostigmine Medium (1-2h) Neuromuscular juntion Nonobstructive paralytic
ileus.
Myasthenia gravis
(orally)

29. Irreversible cholinesterase inhibitors
• Long acting
• Organophosphates
• Insecticides
• War gases
Include:
• Parathion
• Malathion
• Sarin

30. Irreversible cholinesterase inhibitors
intoxication
Muscarinic Nicotinic CNS
Salivation Fasciculations Anxiety
Lacrimation Weakness Confusion
Urination Adrenomedullary discharge Tremors
Defecation
Gastrointertinal spasms
Emesis (vomiting)
Miosis
Bradycardia
Hypotension
Dyspnea
Therapy:
Pralidoxime + Atropine
(Anticholinergic drugs)

31. Anticholinergic drugs

32. Muscarinic Antagonists
( Atropa belladonna)
Classicly derived from plantsLocal of action Effect
Iris sphincter muscle Mydriasis
Ciliary muscle Cycloplegia
Sinoatrial node Thachycardia
Exocrin glands Decreased secretions
Bladder Urinary retention
Salivary and lacrimal glands Xerostomia and decreased
lacrimation
Sweat glands Hypohidrosis
Ex: Atropine (non-selective muscarinic antagonist)
Pirenzipine (M1 selective muscarinic antagonist)

33. Nicotinic Antagonists – Neuromuscular
blockers
Neuromuscular
blockers
Nondepolarizing
agents
Tubocurarine
Depolarizing
agents
Succinylcholine

34. THE END