1. Autonomic Nervous System

2. Nervous system:
- Central (CNS)
- Peripheral (ANS)
Sympathetic NS (Thoracolumbar)
Parasympathetic NS (Craneosacral)
Cranial nerves III, VII, IX, X (vagus nerve)
NA = Noradrenaline = NE = Norepinephrine
Ad = Adrenaline = EP = Epinephrine
Ach = Acetylcholine

3. Symp C Ach NA
O Ach Ach
Parsymp.
R Ach
Motor
Nerves D

6. Sympathetic receptors:
** α-receptors (2 types) :
- α1- receptors; postsynaptic receptors; NA & AD agonists
Mediate a. Vasoconstriction (skin) → ↑ B.P
b. Dilatation of pupils
- α2- receptors; presynaptic receptors; inhibitory in nature; clonidine agonist

7. α1- blockers; phentolamine; prazosin
** β- receptors (2 types):
- Β1- receptors; postsynaptic; NA, AD, isoprenaline (agonists)
Mediate: - ↑ heart rate (tachycardia)
- ↑ heart contractility
- ↑ cardiac output

8. - β2-receptors; postsynaptic; AD, isoprenaline, salbutamol (albuterol) agonists
Mediate: - broncchodilation
- dilatation of muscle & heart blood vessels
β- blockers:
- Selective; block only β1 receptors (atenelol)
- Nonselective; block β1 & β2 receptors (propranolol)

9. Sympathomimetic drugs
Drugs producing effects similar to sympathetic activity
1. Adrenaline=Epinephrine
Effects: - ↑ heart rate & contractility
- ↑ systolic B.P
- bronchodilatation
- pupil dilatation

10. - ↑ blood sugar level
- ↓ GIT motility
- ↓ salivary secretions
Adrenaline is ineffective orally; given S.C or I.M
I.V injection is contraindicated → fatal cardiac arrhythmias (ventricular fibrillation)

11. AD & NA effects are mainly terminated by a high specific uptake mechanism (inhibited by cocaine & TCA’s)
Also metabolized by monoaminoxidase (MAO) & catecholamine O-methyl transferase enzymes (COMT)
AD clinical uses: - Anaphylactic shock
- Cardiac arrest
- Combined with L.A’s

12. 2. Noradrenaline=Norepinephrine:
Most important effect is widespread vasoconstriction & ↑ in B.P; bradycardia
Mainly used in the management of shock and given in an I.V infusion
3. Isoprenaline (Isoproterenol):
Stimulates β1 & β2 receptors; a good bronchodilator & ↑ heart rate & contractility

13. Isoprenaline clinical uses:
- Bronchial asthma
Given orally or by inhalation
- Shock & cardiac arrest
Given I.V
Isoprenaline side effects:
- Palpitation
- Cardiac arrhythmias

14. 4. Selective β2 agonists:
Salbutamol (albuterol); terbutaline; perbuterol
Salbutamol is the most widely used drug in the management of bronchial asthma and chronic bronchitis
Given by inhalation, orally and I.V
Produces little if any effects on the heart

15. 5. Dopamine (DA):
β1 stimulant used in shock and given in an I.V infusion
6. Amphetamine:
Has marked CNS stimulant effect
It suppresses appetite
↑ B.P
Stimulates respiration

16. Cont. Amphetamine…
↑ mental activity
↑ alertness
Given orally
Clinical uses: - Narcolepsy (frequent deep sleep)
- Hyperkinetic syndrome
Major disadvantage: leads to addiction

17. Adrenergic blockers
- α- blockers (α1)
* Phentolamine :
Given I.V and used in the management of pheochromocytoma (a tumor affecting the adrenal medulla & characterized by high levels of AD & an ↑ in B.P)

18. * Prazosin:
Another α1 blocker given orally in the management of hypertension
B.P = CO × Peripheral resistance
Ht. rate & Bld. Vol Diam. B.V
contractility

19. - β-blockers
* Selective (block only β1-receptors)
Atenolol; bisoprolol; betaxolol…
* Nonselective (block both β1 & β2 receptors)
Propranolol; oxprenol; pindolol; timolol; sotalol; nadolol…
- α & β blockers
Labetalol; carvedilol (block α & β receptors)

20. β- blockers differ in potency, duration of action & route of administration
General effects to β-blockers:
- ↓ Ht. rate, ↓ Ht. contractility, ↓ cardiac output
- ↓ B.P
- ↓ sweating, ↓ tremors, ↓ nervousness (antianxiety or anxiolytic effect)
- Bronchospasm

21. Clinical uses to β-blockers:
- Hypertension
- Angina pectoris
- Cardiac arrhythmias
- Thyrotoxicosis
- Essential tremors, Parkinson’s disease
- Anxiety (stage phobia)

22. Preparations to β-blockers:
Oral and parenteral dosage forms
Side effects to β-blockers:
- Bronchospasm
- Severe drop in CO
Contraindications to β-blockers:
- Bronchial asthma
- Severe heart failure

23. Parasympathomimetic drugs
Cholinergic system
Acetylcholine (Ach)
- Parasympathetic nerve terminal & sweat glands
Muscarinic receptors
- Ganglia & voluntary muscles
Nicotinic receptors
Not used clinically; quickly broken down by cholinesterase enzyme

24. Ach effects:
- ↓ heart rate
- ↑ salivation
- ↑ GIT motility
- ↑ urinary bladder muscle contraction
- Dilates blood vessels
- Contracts bronchi
- Constricts pupils and accommodates for near vision

25. Carbachol & bethanechol:
Synthetic Ach-like drugs. Have similar effects to Ach but not affected by cholinesterase so have more prolonged effect. Given orally & S.C
Clinical uses: - urine retention following surgery or child birth
- Clear bowel gases before x-rays
Side effects: Abdominal pain; diarrhea, ↓ B.P

26. Anticholinesterases
- Physostigmine
↑ Ach effects at all sites. Most important effects:
a. Constriction of pupils
b. ↑ intestinal movement
Clinical uses:
a. Glaucoma
b. Myasthenia gravis
Given orally; S.C; locally to eye

27. - Neostigmine
Has similar effects to physostigmine but has more effect at neuromuscular junction
Given orally; S.C; I.M
Clinical uses:
a. Myasthenia gravis
b. Paralytic ileus
c. Urine retention

28. Many anticholinesterases are not used clinically but used as insecticides or weapons in war (chemical weapons) known as nerve gases, therefore side effects produced by such drugs are important to know
Side effects include: Abdominal pain, diarrhea, sweating, constriction of pupils, salivation, ↓ B.P → death
Rx: - Atropine S.C
- Pralidoxime (cholinesterase reactivator) given I.V

29. Parasympatholytics (inhibitorrs of Ach action)
Anticholinergics
Antimuscarinics
Atropine:
An anticholinergic drug blocks muscarinic receptors at all sites
Origin: plant source Atropa belladona

30. Atropine actions: (anticholinergic effects)
- ↓ intestinal movement (↓ spasm)
- ↑ heart rate
- Dilatation of the pupils; cycloplegia; loss of accommodation to near vision
- ↓ salivary and respiratory secretions
- Dilatation of bronchi
Atropine could be given orally; S.C; I.M & I.V

31. Atropine clinical uses:
- Preoperative medication ( to ↓ salivary and bronchial secretions)
- To dilate pupils for eye examinations
Homatropine is used because it has shorter duration of action
- Abdominal pain or spasm
Hyoscine (scopolamine is better)
- Bradycardia; atropine I.V

32. Cont. atropine clinical uses…
- Bronchial asthma
Ipratropium bromide…atropine-like drug given by inhalation to patients with bronchial asthma
- Parkinson’s disease
Benzhexol…atropine-like drug reduces over activity of Ach in patients with Parkinsonism

33. Cont. atropine clinical uses…
- Peptic ulcer disease
Atropine ↓ acid secretion, but replaced recently by newer drugs due to it’s side effects
- Congenital pyloric stenosis
Atropine methonitrate is used. It relaxes the pylorus and given orally ½ hr before feeds
- Poisoning with anticholinesterases

34. Atropine side effects (anticholinergic effects):
- Dry mouth
- Blurred vision
- Constipation
- Difficulty in micturition
- Loss of accommodation to near vision
- Hallucination
- Delirium

35. Hyoscine (scopolamine)
- Atropine-like drug
- Synthetic
- Has more CNS effects e.g. drowsiness and sedation
- Used as an antiemetic and antispasmodic
- Given orally, parenterally and rectally