this course to give dental students the basic of pharmacology

1. AUTONMOIC NEURVOUS
SYSTEM
DENTAL PHARMACOLOGY

6. ADRENERGIC AGONISTS
(SYMPATHOMIMETIC AGENTS)
• Adrenergic agonists mimic the
actions of sympathetic.
• Adrenergic neurons release
norepinephrine as the primary
neurotransmitter.
• NA from the synaptic cleft
diffuses into circulation and
gets inactivated by catechol-O-
methyltransferase (COMT) and
monoamine oxidase ( MAO)

8. Types, Distribution and Functions of
Adrenergic Receptors

10. 1. Direct-acting Sympathomimetics
Adrenergic Agonists Receptor Action Therapeutic Uses
1. Directly acting
Adrenaline a1-, a2-, B1-, B2- and Anaphylactic shock, Bronchial asthma
(acute), Cardiac arrest, to prolong the
Duration of local anaesthesia, to control
Epistaxis
(ABCDE)
• Noradrenaline a1-, a2- and B1-agonist Hypotensivestates
Isoprenaline B1- andB2-agonist Heart block, cardiac arrest
• Dobutamine Relatively selective Cardiogenic shock due to acute
B1-agonist myocardial infarction (MI), congestive
cardiac failure (CCF) or cardiac surgery
Salbutamol (Albuterol) SelectiveB2-agonists Bronchial asthma
Phenylephrine Selective a1-agonists Vasopressor agents, nasal decongestants,
as mydriatic (phenylephrine), allergic
rhinitis
• Naphazoline a1 + a2-agonists Nasal decongestants
(a1-stimulation),
• Clonidine, a-Methyldopa a2-agonists Hypertension

11. Adverse effects and contraindications
direct-acting
Adverse effects
– They are tachycardia, palpitation, headache,
restlessness, tremor and rise in BP.
– The serious side effects are cerebral haemorrhage
and cardiac arrhythmias.
contraindicated in most of the cardiovascular
diseases such as hypertension, angina, cardiac
arrhythmias, CCF, etc

12. 2. Indirect-acting Sympathomimetics
Adrenergic Agonists Receptor Action Therapeutic Uses
2. Indirectly acting
Amphetamine They act by releasing NA Narcolepsy, attention-deficit
hyperkinetic
Methamphetamine disorder (ADHD)
Methylphenidate
3. Mixed acting
Ephedrine a1, a2, B1 and B2 (direct
action)
Intravenous ephedrine is used
for the
+ releases NA (indirect
action)
treatment of hypotension due
to spinal
anaesthesia
Dopamine a1, a2, B1 and D1 +
releases NA
Cardiogenic shock, CCF with
oliguria

13. Adverse effects and contraindications
Indirect-acting
• The side effects are restlessness, insomnia,
confusion, fatigue, tremor, hallucinations and
suicidal tendencies.
• The cardiac side effects are tachycardia,
palpitation, hypertension, angina and cardiac
arrhythmias

14. ADRENERGIC RECEPTOR BLOCKERS
(SYMPATHOLYTIC AGENTS)
• Adrenergic-receptor antagonists block the
effects of sympathetic pathway.

15. ALPHA-ADRENERGIC BLOCKERS

16. Irreversible Nonselective a-Blocker
Phenoxybenzamine
• Peripheral vascular resistance is reduced due
to the blockade of vascular α1-receptors.
• Used in the treatment of pheochromocytoma.
• The side effects are hypotension, tachycardia,
palpitation, diarrhea, and impotence.

17. Reversible Nonselective a-Blocker
Phentolamine
• Has rapid onset but short duration of action. It
is used intra-operatively during surgery of
pheochromocytoma, in hypertensive
emergencies
• Adverse effects
– They include tachycardia, palpitation, arrhythmias;
angina and Myocardial Infraction may be
precipitated.

18. Selective α1-Blockers
Prazosin, Doxazosin, Tamsulosin, Terazosin
• Prazosin is a potent and selective a1-adrenergic
receptor blocker.
• Doxazosin is the longest-acting, selective a1-
blocker.
• Tamsulosin
– an uroselective a1-blocker (a1A). At low doses, it
reduces the resistance to flow of urine with little
effect on BP.
– It is the preferred a1-blocker for the treatment of
benign prostatic hyperplasia (BPH)

19. Selective α1-Blockers
• Therapeutic Uses
– Essential hypertension
– Benign prostatic hyperplasia
– Pheochromocytoma
• Adverse effects
– First-dose phenomenon: Within 30–90 min of oral
administration of prazosin, severe hypotension and
syncopal attacks may be seen with first dose.
• Therefore, the initial dose should be small . It is usually given
at bed time so that the patient remains in bed for several
hours and the risk of syncopal attack is reduced

20. BETA-ADRENERGIC BLOCKERS

21. BETA-ADRENERGIC BLOCKERS
Mechanism of action
– competitively block β-receptors.
Pharmacological actions
– Cardiovascular system:
• Decrease heart rate (negative chronotropic effect).
• Decrease the force of myocardial contractility (negative inotropic effect).
– Respiratory system:
• Blockade of B2-receptors in bronchial smooth muscle can produce severe
bronchospasm in patients with COPD and asthma.
• Selective B1-blockers such as atenolol, metoprolol, etc. are less likely to cause
bronchospasm.
– Skeletal muscle:
• On chronic use, B-blockers may cause skeletal muscle weakness and tiredness
due to blockade of B2-receptors of the skeletal muscle and blood vessels
supplying it. They also reduce stress-induced tremors.
– Metabolic effects:
• B-Blockers inhibit glycogenolysis and delay recovery from hypoglycaemia.
• They also mask the warning signs and symptoms of hypoglycaemia
– Eye: B-Blockers on topical administration decrease IOP

22. BETA-ADRENERGIC BLOCKERS
• Therapeutic uses
– Hypertension
– Angina pectoris and MI: B-Blockers reduce myocardial O2
demand
– Congestive cardiac failure , carvedilol, metoprolol and
bisoprolol
– Pheochromocytoma
– Glaucoma ,Timolol
– Prophylaxis of migraine: Propranolol, atenolol and
metoprolol
– Hyperthyroidism: The signs and symptoms of
hyperthyroidism such as tachycardia, palpitation, tremor,
anxiety, etc
– Acute anxiety states

23. BETA-ADRENERGIC BLOCKERS
• Adverse effects
– CNS: Sleep disturbances, fatigue and mental
depression.
– CVS: Bradycardia, heart block
– Muscular weakness and tiredness
– Withdrawal symptoms
– Mask the warning signs and symptoms of
hypoglycaemia

24. CHOLINERGIC AGENTS (CHOLINOMIMETICS,
PARASYMPATHOMIMETICS)
• Acetylcholine is rapidly
hydrolyzed by cholin-
esterases it has no
therapeutic application.
Cholinergic receptors
• Muscarinic: M1, M2, M3
Activated by muscarine, Ach.
• Nicotinic: NM (Skeletal muscle), NN
(neuronal ) Activated by nicotine,
Ach.

25. Muscarinic Receptor Stimulation
• Eye (M3) - miosis
• Heart (M2) - bradycardia and a decrease in
blood pressure
• Lungs (M3) – bronchospasm, increase
secretion
• Gastrointestinal - increase in motility (M3) , and
secretion (M1) .
• Glands (M3) - increase Secretion-sweat,
salivation, and lacrimation
• Blood vessels (M3) – vasodilatation

26. Cholinergic
agonists
Directly acting
(on the receptors)
Pilocarpine
Acetylcholine
Carbachol
Bethanechol
Indirectly acting
(anti-cholinesterase)
Reversible
Physostigmine
Edrophonium
Neostigmine
Irreversible
Organophosphorus
compounds
Parathion
Malathion
Sarin (nerve gases)

27. Clinical Uses
Directly acting
• Postoperative urinary retention, paralytic ileus
and dry mouth Bethanechol
• Glaucoma Carbachol, Pilocarpine
• Xerostomia Pilocarpine

28. Clinical Uses
Indirectly acting
Reversible Anticholinesterases
• Glaucoma Physostigmine
• Atropine poisoning Physostigmine
• Myasthenia gravis Neostigmine , Edrophonium
• Curare poisoning and reversal of non-depolarising
neuromuscular blockade Neostigmine
• Postoperative urinary retention and paralytic
ileus Neostigmine

29. Clinical Uses
Indirectly acting
• Irreversible Anti-cholinesterases
Organophosphorus compounds insecticides
Acute toxicity
• Excessive muscarinic and nicotinic stimulations
Muscarinic effects:
- Diarrhea
- Urination
- Miosis
- Bradycardia
- Bronchoconstriction
- Lacrimation
- Salivation
- Sweating
Nicotinic effects:
- Skeletal muscle excitation followed by
paralysis
- CNS stimulation :confusion, convulsions,
coma, and death occurs usually due to
respiratory failure.

30. Irreversible Anti-cholinesterases
Management of Organophosphorus compounds
toxicity :
• Muscarinic effects: atropine ( antimuscarinic)
• Regeneration of AChE: pralidoxime

31. ANTICHOLINERGIC AGENTS
(CHOLINERGIC RECEPTOR BLOCKERS)
SKELETAL MUSCLE RELAXENT

32. ANTIMUSCARINIC AGENTS
• These drugs block muscarinic-receptor-
mediated actions of acetylcholine on heart,
CNS, smooth muscles and exocrine glands.
• Leading to opposite action of
parasympathommetics.

33. Pharmacological Actions
• Central Nervous System
– Inhibit vomiting centre
– excitation , hallucinations, Sedation, coma (high dose)
• Exocrine Glands
– Decreased secretions (salivary, bronchiolar, sweat)
• Smooth Muscle
– Relax smooth muscles in gastrointestinal tracts and Delay gastric
emptying constipation
– Relax smooth muscles in the respiratory Bronchial dilation.
– Urinary retention
• Eye
– Mydriasis , decrease Lacrimation
• Cardiovascular
– Tachycardia

34. Clinical Uses
• Preoperative Medication : (Atropine )
– They inhibit salivary and bronchial secretions.
– To prevent bradycardia during anaesthesia.
• Sialorrhoea (hypersalivation):(glycopyrrolate,
propantheline)
– Used to decrease salivary secretion, e.g. during dental
procedures.
• COPD and bronchial asthma: (Ipratropium
,Tiotropium)
– They produce bronchodilatation

35. Clinical Uses
• Antispasmodics in intestinal, renal colic and
dysmenorrhoea. (hyoscine N- butyl bromide)
• Ophthalmologic Examinations (Tropicamide)
• Parkinsonism —Benzhexol
• Motion Sickness —Scopolamine (hyoscine).

36. ANTIMUSCARINIC
Adverse Effects
• Decreased secretions (salivary, bronchiolar,
sweat) ……. Dryness of the mouth
• Mydriasis
• Hyperthermia
• Tachycardia
• Sedation
• Urinary retention and constipation
• Behavioral: excitation and hallucinations

37. GANGLIONIC BLOCKERS
• Blockade of sympathetic
ganglia results in marked
hypotension.
• Blockade of parasympathetic
ganglia results in ‘atropine-like’
actions.
• Nicotine is obtained from
tobacco leaves. It has a
prolonged blocking effect on
the autonomic ganglia.

38. THE END