Autonomic nervous system dental

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Pharmacology of Drugs Affecting
Autonomic Nervous System

Basic Functions of the
Nervous System
 Recognizing changes in
 Internal environment
 External environment
 Processing and integrating environmental
changes
 Reacting to environmental changes by
producing an action or response

Two Major Divisions of the
Nervous System
 Central Nervous System (CNS)
 Brain and spinal cord
 Peripheral Nervous System
 all nervous tissues outside the CNS, including
sensory and motor neurons

Divisions of human nervous
system
Human
Nervous
system
Central
Nervous
System
Peripheral
Nervous
System

Brain
&
Spinal Cord
Nerves
enter or leave
CNS
Carry massage
from CNS to
peripheral tissues
Carry massage
from
peripheral tissues
to CNS

Divisions of the Peripheral
Nervous System
 Somatic nervous system
 Voluntary control over skeletal muscles
 Autonomic nervous system
 Involuntary control over smooth and cardiac
muscle and glands

Basic anatomy of ANS
Sympathetic NS Parasympathetic NS Enteric NS
Two main differences
-Origin
-Function
-Collection of nerve fibers that
innervate GIT, pancrease & gall
bladder
-Called “brain of gut”
-They control motility, exocrine
& endocrine secretion, as well as
microcirculation of gut
-Modulated by sympathatic &
Parasympathatic systems

Autonomic Pharmacology
 Autonomic Nervous System
 This system is divided into two separate systems.
 These systems are called the parasympathetic
nervous system and the sympathetic nervous
system.
 These systems often produce opposite effects,
but branches do not always produce opposite effects.
 Homeostasis – proper balance of the two
branches achieved by changing one or both
branches
2

Autonomic Nervous System: Sympathetic and
Parasympathetic Divisions
 Drugs in this group are designed to either enhance or
mimic the autonomic nervous system or to block the
effects of the neurotransmitters at their receptor sites.

Steps of Neurotransmission
 Propagation of the nerve impulse in
the preganglionic nerve fiber
+ + + + + + + + + + +
- - - - - - - - - - - - - - -
-- - - - - - - - - - - - - -
+ + + + + + + + + +
Polarized
Resting Membrane Potential
+ + + + - - - - + + +
- - - - - + + + + - - - -
- - - - - + + + + - - - -
+ + + - - - - + +
Depolarized
Nerve Action Potential

Synaptic Transmission
 Synapse – junction of neurons
 Connection of two neurons outside CNS –
ganglionic synapse.

Efferent neurons
 Preganglionic neurons:
Cell body within CNS
 Ganglia: aggregation of nerve cell bodies
located in the peripheral nervous system.
 Postganglionic neurons: cell body originate in
the ganglia, terminates on effector organ.
 Divided into sympathatic and
parasympathatic

Origin
Symp. NS
Thoracolumbar
outflow
Parasymp. NS
Function
Craniosacral
outflow
Short pre-ganglionic nerve
Long post-ganglionic nerve
Long pre-ganglionic nerve
Short post-ganglionic nerve

Figure 13.4 Receptors in the autonomic nervous system: (a) sympathetic division; (b) parasympathetic division

Role of CNS in autonomic control
functions
 CNS centers in hypothalamus,
medulla oblongata & spinal
cord
 Reflex arc
 Emotions

Organs Supplied by ANS
 Heart
 Smooth Muscles
- Eye -Bronchi
- GIT - Urinary Bladder
- Blood Vessels
 Glands
- Exocrine Glands: Lacrymal, Salivary, Sweat
- Endocrine Glands: Adrenal Medulla
 Metabolism
 Liver
 Adipose Tissue
 Kidney

Sympathetic Nervous System
 Sympathetic Nervous System
 This nervous system is designed to
cope with emergency situations.
 This is commonly known as the “fright or
flight” response.
 Its neurotransmitters are epinephrine
and norepinephrine.
 Its receptors are the α and β receptors.
4

Sympathetic nervous system
Fight or flight response results in:
1. Increased BP
2. Increased blood flow to brain, heart and
skeletal muscles
3. Increased muscle glycogen breakdown for
energy
4. Increased rate of coagulation
5. Pupil dilation

parasympathatic Nervous
System
 Parasympathetic Nervous System
 This system is concerned with the
conservation of the body processes.
 Activated under non stressful conditions
 Rest-and-digest response
 Digestive processes promoted, heart rate
and blood pressure decline
 Its main neurotransmitter is
acetylcholine.
 Its receptors are muscarinic, nicotinic.
3

Figure 13.2 Effects of the sympathetic and parasympathetic nervous systems. Source: Biology Guide to the Natural
World, 2nd ed (p. 558) by David Krogh, 2002 Upper Saddle River, NJ, Prentice Hall. Reprinted by permission.

Symp. NS
Parasymp. NS
Single
Innervations
Dilator pupilae muscle
Adrenal Medulla
Ventricles
BV
Sweat Gland
Kidney
Constrictor pupillae
muscle

Figure 13.1 Functional divisions of the peripheral nervous system.

Primary Neurotransmitters of
 Norepinephrine (NE)…………..adrenergic
neurotransmission
 Acetylcholine (Ach)…………….cholinergic
neurotransmission

Acetylcholine
 Released by
1. All preganglionic nerve fibers
2. Preganglionic sympathatic nerves to adrenal
medulla
3. All postganglionic parasympathatic nerves
4. Postganglionic sympathatic nerve to sweat
glands
5. All somatic nerves.
6. CNS

Cholinergic Transmission (Cont.)

Rate limiting
step
ATP &
proteoglycan

Cholinergic Receptors
Muscarinic Receptors
(Peripheral Cholinergic )
Nicotinic Receptors
(Central Cholinergic) R.)
Strong affinity to muscarine
Weak affinity to nicotine
Weak affinity to muscarine
Strong affinity to nicotine
-Parasympathetic supplying
effector organs
-Sweat gland
- CNS
-Autonomic ganglia (Nn)
- Adrenal Medulla (Nn)
- Neuromuscular junction (Nm)
-CNS (Nn)

Nicotinic receptors
 Composed of 5-subunits and functions as ligand-gated channel
 Binding of two Ach molecules elicits a conformational change that
allows the entry of sodium ions, resulting in depolarization of the
effector cell
 Nm (blocked by tubocurarine) differs from Nn (blocked by
hexomethonium)

Muscarinic Receptors
M1 (Neural) M2 (Cardiac) M3 (Glandular)
- CNS
- Gastric parietal cells
-CNS Presynaptically
- Atria and conducting
tissue
-Exocrine gland
-Smooth muscles
-Vascular endothelium
↑ Phospholipase C
Atropine & Pirenzepine
↓ Adenylate cyclase
Atropine & Gallamine
↑ Phospholipase C
Atropine

Sympathatic neurotransmission
 Norepinephrine is released by most
postganglionic sympathatic nerves
 Dopamine is released by postganglionic
nerves stimulating the kidney.
 ACH is released by Postganglionic
sympathatic nerve to sweat glands
 Adrenal medulla acts as ganglia releasing
epinephrine and NE.

Adrenergic Transmission
 Neurotransmitter: Two catecholamines NA
& Ad
 Sites of Release:
- Post ganglionic sympathetic nerve ending (80% NA &
20% Ad)
- Adrenal Medulla (80% Ad & 20% NA)
- CNS

Adrenergic receptors
 α—α1 and α2
 β—β1, β2, β3
 Dopamine—subsets D1-5

Adrenergic Receptors
α Subtype β Subtype
↑ Phospholipase C ↓ Adenylate cyclase
α1 α2 β1, β2 & β3
↑ Adenylate cyclase
smooth muscles
- Presynaptic adrenergic
nerve terminal
-CNS
-β cells of pancreas
β1 (heart)
β2 (smooth muscles)
β3 (lipocytes)
β Subtype
α Subtype

α1-adrenergic Receptors
 In all sympathetic target organs except heart
 Response
 Constriction of blood vessels
 Dilation of pupils
 Constriction of sphincters

α2-adrenergic Receptors
 At presynaptic adrenergic neuron terminals
 Activation inhibits release of norepinephrine
 Inhibits release of insulin

β1-adrenergic Receptors
 In heart and kidneys
 Response
 Activation increases heart rate and force of
contraction of heart.
 Increases release of renin

β2-adrenergic Receptors
 In all sympathetic target organs except the
heart
 Inhibit smooth muscle (relaxes)
 Stimulates glycogenolysis and
gluconeogenesis

Organ Sympathetic R Parasympathetic R
Heart Stimulant β1 Depressant of atria M2
Smooth Muscles
a- BV Constriction
Dilation
(BV Sk. M.)
Kidney Vasculature
α
β2
D
No innervation
(dilation by EDRF)
M3
b- Bronchi No innervation β2 Constriction
↑ Secretion
M3
M3
c- GIT
Smooth muscle
Sphincter
Glands
↓ motility
Constriction
-----
β2
α1
↑ motility
Dilation
↑ Secretion
↑Gastric acid
Enteric system
M3
M3
M3
M1
M1
d- Urinary Bladder
Smooth muscle
Sphincter
Relaxation
Constriction
β2
α1
Contraction
Dilation
M3
M3

Organ Sympathetic R Parasympathetic R
e- Eye:
* Iris
-Radial muscle
-Circular muscle
*Ciliary Muscle
Contraction
Relaxation
(slight)
α1
β2
Constriction
Contraction
M3
M3
Glands:
Salivary Glands
Lacrimal Glands
Sweat Glands:
Thermoregulatory
Apocrine (stress)
↑ Secretion
No effect
↑ Secretion
↑ Secretion
α1, β2
--------
M3
α1
↑ Secretion
↑ Secretion
M3
M3
Metabolic Functions:
Liver
Adipose tissue
Kidney
Gluconeogenesis
Glycogenolysis
Lipolysis
Renin release
β2
β2
β3
β1

Five Mechanisms by Which
Drugs Can Affect Synaptic
Transmission
1. Affect the synthesis of the neurotransmitter
in the presynaptic nerve.
2. Prevent storage of the neurotransmitter in
vesicles within the presynaptic nerve.
3. Influence release of the neurotransmitter
from the presynaptic nerve.

Five Mechanisms by Which Drugs Can
Affect Synaptic Transmission (cont'd)
4. Prevent the normal destruction or reuptake
of the neurotransmitter.
5. Bind to the receptor site on the postsynaptic
target tissue

Drugs Not Given to Correct
 System is relatively free of disease
 Drugs used to stimulate or inhibit target
organs of the autonomic nervous system

Classification and Naming of
Autonomic Drugs
 Based on four possible actions of sympathetic
and parasympathetic nervous systems
1. Stimulate sympathetic nervous system
 Adrenergic agents or sympathomimetics
2. Inhibit sympathetic nervous system
 Adrenergic-blocking agents, adrenergic
antagonists, or sympatholytics

Classification and Naming of
Autonomic Drugs (cont'd)
3. Stimulate parasympathetic nervous system
 Cholinergic agents or parasympathomimetics
4. Inhibit parasympathetic nervous system
 Cholinergic-blocking agents, anticholinergics,
parasympatholytics, or muscarinic blockers

Cholinergic Agonists
 They act:
 Directly → Receptor (choline receptors)
 Indirectly → Drugs that inhibit destruction of ACh

Direct-Acting Cholinergic Agonist

 These agents are:
 Synthetic ester of choline e.g. carbachol & bethanichol
 Naturally occurring alkaloids e.g. pilocarpine
 They are called “Muscarinic Agonists”
 ACh has NO therapeutic value
 The key features of Ach molecule:
 The quaternary ammonium group
 The ester group

Muscarinic Agonists
 Substitution of acetyl
gp by carbamyl gp →
Carbachol
 Addition of methyl gp
on β carbon →
Methacholine
 Combining these two
modification →
Bethanichol
 Pilocarpine: Tertiary
amine

Effects of Muscarinic Agonists
 Cardiovascular effect:
 Heart: Slowing the heart
 BV: Dilation
 BP: ↓
 Exocrine Glands:
 Sweating
 Lacrymation
 Salivation

Effects of Muscarinic Agonists
Smooth Muscles:
 Bronchi: Bronchoconstriction & ↑ secretion
 GIT: ↑ motility, sphincter dilation, ↑ gastric secretion
 Urinary Bladder: ↑ motility of detrusor urinae muscle,
sphincter dilation (bladder emptying)
 Eye: - Contraction of pupillae sphincter muscles → miosis and
widening of filtration angel
- Contraction of ciliary muscles → accommodation to near
vision and opening of canal of schlemm

Clinical Uses of Muscarinic Agonists
 Glaucoma: Pilocarpine (action lasts for 1 day), the most
effective as being a tertiary amine, it can cross the conjunctival
membrane.
 Bladder emptying in case of neurological disease or
surgery: Carbachol & Bethanichol
 Hair preparation: Pilocarpine, it promotes hair growth by
dilation of scalp blood vessels.
 Atropine Poisoning: Pilocarpine

Adverse Effects of Muscarinic Agonists
 Hypotension
 Sweating & Salivation
 Bronchospasm
 Nausea, abdominal pain & diarrhea
 Urinary urgency
 Miosis

Indirect-acting
cholinergic agonist
 Inhibition of ChE is
either reversibly or
irreversibly
 Accumulation of Ach
in the synaptic
spaces which can
stimulate:
 Both M & N of ANS
 Nm
 In brain

Reversible Anticholinesterase
 Quaternary amines:
 Neostigmine
 Pyridostigmine
 Edrophonium
 Tertiary amines:
 Physostigmine (eserine)

Effects of Reversible antiChE
 An enhancement of cholinergic transmission at
cholinergic autonomic synapses & the
neuromuscular junction
 Physostigmine → Eye, GIT, Urinary bladder & CNS
 Neostigmine → GIT, Urinary bladder & Sk. M.
 Pyridostigmine & Edrophonium → Sk. M.

Clinical Uses of Reversible antiChE
 In glaucoma: Physostigmine (eye drops)
 In intestinal & bladder atony: Physostigmine & Neostigmine
 In anesthesia: Neostigmine (IV), it reverses the action of non-
depolarizing neuromuscular blocking drugs.
 In overdose of drugs with anticholinergic actions such as
atropine, phenothiazines & TCA
 In treatment of Myasthenia gravis

Dental choliergic
 1- encourage patients to use good oral
hygiene.
 2- Raise the patient from the dental chair
slowly to avoid hypotension

Cholinergic Antagonists
 They include 3 classes:
1. Muscarinic Antagonist
2. Ganglion Blockers (Nn)
3. Neuromuscular Blockers (Nm)

1. Muscarinic Antagonists
 They block muscarinic receptors competitively,
causing inhibition of all muscarinic functions
 They are effective in several clinical situations
unlike cholinergic agonists

Muscarinic Antagonists (cont.)
 Drugs belong to this group
a- Atropine & Hyoscine (scopolamine) (natural
alkaloids)
b- Homatropine (synthetic comp.)
c- Atropine methonitrate (quaternary comp.)
d- Ipratropium (quaternary comp.)
e- Pirenzepine (selective M1 antagonist)
f- Cyclopentolate and tropicamide (tertiary amines
developed for ophthalmic use)

Effects of Muscarinic Antagonists
 Cardiovascular effect:
• Heart: (block M2 at SA node, tachycardia 80- 90 beat/min)
• BV: No effect
• BP: No effect
 Exocrine glands:
• At low dose, it inhibits salivary, lachrymal, bronchial & sweat
glands
• Inhibition of secretions by sweat glands can cause elevated
body temp
• It produces uncomfortable dry mouth & skin
• Gastric secretion is only slightly reduced

Effects of Muscarinic Antagonists (cont.)
 Smooth Muscles:
• Eye:
- Iris: Passive mydriasis & becomes unresponsive to light
- Ciliary Muscle: Paralysis of accommodation (cycloplegia)
- In patient with narrow angel glaucoma, IOP may rise dangerously, so
short acting antimuscarinic tropicamide or α agonist phenylephrine are
more preferred in ophthalmic examination
 CNS:
• Excitatory, at low dose (restlessness) & at high dose (agitation &
disorientation)
• In poisoning, rise in body temp. & hypereactivity

Clinical Uses of Muscarinic Antagonists
 Cardiovascular:
• Treatment of heart block (atropine)
 Ophthalmic:
• Mydriatic
 Neurological:
• Prevention of motion sickness (scopolamine)
• Reduce involuntary movement & rigidity in case of
Parkinsonism (benztropine)
• Nocturnal enuresis

Clinical Uses of Muscarinic Antagonists (cont.)
 Respiratory:
• Treatment of asthma & COPD (ipratropium)
• To dry secretions & prevent reflex bronchconstriction during
anesthesia (atropine or hyoscine)
 GIT:
• Antispasmodic action & suppress gastric acid secretion
• Hyoscine is used in case of endoscopy & pirenzepine in case of
peptic ulcer (H2 antagonists are more preferred)

Clinical Uses of Muscarinic Antagonists (cont.)
 Antidote for cholinergic agonists:
• Atropine is used for the treatment of overdoses of
cholinesterase inhibitors such as:
• physostigmine & organophosphate insecticides
• Mushrooms (muscarine)
• The ability of atropine to enter CNS is of particularly
importance

Adverse Effects of Muscarinic Antagonists
 Dry mouth & blurred vision
 Tachycardia
 Restlessness, confusion, hallucination & delirium
 Flushing & fever
In elderly:
 Glaucoma
 Prostatic enlargement

2. Ganglion Blockers (Nn)
 They block nicotinic receptors of autonomic
ganglia, therefore they are rarely used
therapeutically (experimental tools in
pharmacology)

3. Neuromuscular Blockers
 Drugs can block neuromuscular transmission in three
main ways:
1. By inhibiting Ach synthesis
e.g. hemicholinum & triethylcholine
2. By inhibiting Ach release
e.g. botulinum toxins, excess Mg, aminoglycosides
antibiotics

3. By interfering with the
postsynaptic action of Ach:
a- Depolarizing Blocking Agents (DNMB)
• Produce initial stimulation followed by failure of transmission
• e.g. succinylcholine & decamethonium
b- Competitive Blocking Agents (CNMB)
• They are pure antagonists
• e.g. curare & gallamine

Dental antichloinergic
These drugs are used to create a dry, oral
field.
SIDE EFFECT.
xerostomia:
 1-you have to direct the patient for meticulous
oral hygine including floss and brushing
 2- plenty of water
 3- instruct the patient to avoid alcohol
containing preparations, as well as
caffeinated beverages as they increase
xerostomia

 4- instruct the patient not to use fruit juice and
soda as they contain sugar and increase risk
of caries
 5- recommend to chew sugarless candy to
minimize dry mouth.

Adrenergic Drugs
 These drugs stimulate α and β receptors
throughout the body.
 Adrenergic drugs can be classified as having
direct action, indirect action, or mixed action.
1. Drugs with direct action (epinephrine,
norepinephrine, isoproterenol) produce their
effect by directly stimulating the receptor site.
2. Drugs with indirect action:
a- Stimulate release of endogenous
norepinephrine which then stimulates the
receptor; amphetamine. 20

b- Inhibition of the membrane reuptake of
catecholamines by drugs such as cocaine
and tricyclic antidepressants.
c. Inhibition of monoamine oxidase by drugs
such as Tranylcypromine.
3. Drugs with mixed action (ephedrine) either
directly stimulate the receptor or release
endogenous norepinephrine.

Adrenergic Drugs
 Pharmacology
 Central Nervous System (CNS)
• These drugs produce CNS excitation or
alertness.
• Higher doses produce anxiety, apprehension,
restlessness, and tremors.
 Eye
• These drugs can cause mydriasis.
 Respiratory System
• These drugs cause a relaxation of bronchiole
smooth muscles.
21

Effects of Adrenergic Agonists
 Cardiovascular:
 Heart: ↑HR, contractility » ↑CO + O2
consumption
↑Conductivity (atria, AV node & ventricles)
↑Excitability » arrhythmia
 BV: VD or VC depending on the selective activity
of drug and the anatomic site of vessels
e.g. Skin, Splanchnic, Sk.M., renal BV
 BP: Depends on effect on heart, PR & venous
return
The effect of α-agonist is different from β-agonist

Adrenergic Drugs
 Metabolic Effects
1. Hyperglycemia:
 Increase liver glycogenolysis (β2)
 Increase glucagon release (β2)
 Decrease insulin release (α2)
2. Lipolysis:
 Increase hydrolysis of TG into free fatty acids &
glycerol (β3)
 Salivary Glands
• These drugs produce vasoconstriction of the
salivary glands which leads to decreased salivary
flow which results in xerostomia.
22

Adrenergic Agents (Sympathomimetics)
 Primary use: depends on receptors activated
 Alpha1-receptors: phenylephrine. nasal
congestion, hypotension, dilation of pupils for
eye examination
 Alpha2-receptors: clonidine. Hypertension ?
 Beta1-receptors: dobutamine and isoprenaline.
cardiac arrest, heart failure, shock
 Beta2-receptors: sulbutamol and terbutaline.
asthma and premature-labor contractions as
they relax uterine smooth muscle (tocolytics)
 Dopaminergic receptors : dopamine. shock

 Anaphylactic reactions:
Adrenaline is the first line of treatment for
bronchoconstriction & CV collapse
Haemostatic: adrenaline and ephedrine
Mydriatic: Ephedrine
Glaucoma: Adrenaline decrease IOP in
open angel glaucoma & decrease aqueous
humor production by VC of ciliary body BV
With local anesthetics: Ad & NA
Depression: Amphetamine

Dopamine
 Immediate precursor of NE
 Occurs in
 CNS (act as neurotransmitter)
 Adrenergic nerve ending
 Adrenal medulla
 Activates:
 α1(at high doses)
 β1 (at small doses)
 D1(occurs in renal vascular bed)
 D2 (occurs in presynaptic adrenergic neurons)

Pharmacological Effects of
Dopamine
 CVS:
 +ve chronotropic & inotropic effects
 At high doses: VC of BV
 Renal & visceral:
 VD of renal and splanchnic arterioles
 Effective in treatment of shock (the drug of choice
taken by continuous infusion)

Dental Use
 Vasoconstriction
• These drugs are used in dentistry because of their
vasoconstrictive actions on blood vessels. They
are added to local anesthetics because they
prolong the action of the local anesthetic, reduce
the risk for systemic toxicity, and help to create a
dry field.
• Act as homeostatic agent aids in control
bleeding
• Cocaine has limited use as a local anesthesic
and vasoconstrictor in surgical procedures
involving oral, laryngeal or nasal cavities.
• But close monitoring regard to cardiac effects
• These drugs raise blood pressure .
24

Cautions Relevant to Dentistry
1) Cocaine and amphetamine-like agents (tricyclic
antidepressants as well) could potentiate the
effects of direct acting agonists such as
epinephrine.
2) epinephrine can be absorbed systemically after
intraoral administration. This epinephrine can
be taken up by nerve terminals and this uptake
contributes to the termination of the actions of
epinephrine. Thus, the risk of hypertension and
other problems associated with systemic
absorption of epinephrine will be greater in
patients taking cocaine or amphetamine-like
drugs.

Adrenergic Drugs
 Adverse Reactions
 The adverse reactions associated with
these drugs are an extension of the drugs’
pharmacologic effects.
 They include:
• Anxiety
• Tremors
• Tachycardia
• Increased blood pressure
• Arrhythmias
23

Contraindications to use of
adrenergics
 Cardiac dysrhythmias, angina pectoris
 Hypertension
 Hyperthyroidism
 Cerebrovascular disease
 Distal areas with a single blood supply such
as fingers, toes, nose and ears
 Renal impairment use caution

epinephrine
 Affects both alpha and beta receptors
 Usual doses, beta adenergic effects on heart
and vascular smooth muscle will
predominate, high doses, alpha adrenergic
effects will predominate
 Drug of choice for bronchospasm and
laryngeal edema of anaphylaxis

epinephrine
 Excellent for cardiac stimulant and
vasoconstrictive effects in cardiac arrest
 Added to local anesthetic
 May be given IV, inhalation, topically
 Not PO

Clonidine
 ALPHA2 AGONISTS
 Actions and Therapeutic Uses
1. This drug stimulates alpha2 receptors in the
nucleus tractus solitarius (NTS) to decrease
sympathetic outflow to the heart and blood
vessels.
2. The decrease in sympathetic tone results in a
decrease in blood pressure.
3. Clonidine is used in dental practice in the
management of chronic pain. It can be given
orally or in patch form.

Inhibits NE
release

 Clonidine is a second-line antihypertensive
that has many other uses including opiate
withdrawal, nicotine withdrawal, vascular
headaches, diabetic diarrhea, glaucoma,
ulcerative colitis.
 Side Effects
The use of clonidine may result in clinical
symptoms related to dry mouth, such as
difficulty in swallowing and speech. Chronic
use of xerostomia-producing drugs is
associated with a higher incidence of oral
candidiasis and dental caries.

Monoamine Oxidase Inhibitors
 These drugs inhibit monoamine oxidase and
are used as antidepressants in psychiatric
practice.
 Can precipitate a hypertensive crisis. Patients
taking MAO inhibitors must not be given
drugs that have indirect sympathomimetic
activity or are inactivated by MAO.

 Occasionally, the dentist may find reason to
use the vasoconstrictor phenylephrine.
Because it causes even
a minor release of norepinephrine from
adrenergic nerves and is subject to
metabolism by MAO.
 phenylephrine must be avoided in patients
taking MAO inhibitors.
 Epinephrine and levonordefrin, which are
most commonly found in local anesthetic
solutions, are not contraindicated, since they
are direct agonists and are largely inactivated
by catechol-O-methyltransferase.

 Nonetheless, the avoidance of hemostatic
preparations containing high concentrations
of epinephrine is
recommended.
 Opioids and other CNS depressants should
be used cautiously and usually at lower
doses in
patients who are taking MAO inhibitors.
Meperidine is absolutely contraindicated.

Adrenergic Receptor Antagonist
 α-Blockers:
- Non selective: Phenoxybenzamine & Phentolamine
- α1-Blocker: Prazosin, Terazosin, Doxazosin &
Tamsulosin
- α2-Blocker: Yohimbine (Sympatholytic ?)
 β-Blockers:
- Non selective: Propranolol, Timolol & Nadolol
- β1-Blocker: Atenolol, Metoprolol & Esmolol
 α & β Blocker: Labetalol & carvedilol

Effects of α-adrenoceptor
Antagonists
 The most important effect is CVS effect
 They block α1 receptors causing decrease in
peripheral resistance and consequently BP
 The resultant hypotension provokes reflex
tachycardia
 pupillary constriction
 increased motility of GI tract


Alpha 1 antagonists
 Used in Benign Prostatic Hyperplasia.
Produces smooth muscle relaxation of
prostate gland and bladder neck.
 Pulmonary hypertension in newborns. Can be
given SC , IM or IV.
 May be useful in treating pheochromocytoma
 May be used in Raynaud’s disease.
 Side Effect : orthostatic hypotension

Orthostatic hypotension in
dentistry
 Orthostatic hypotension is a problem with prazosin
analogs and to a lesser extent tamsulosin.
Significantly, orthostatsis is a problem that can be
seen with any vasodilator that affects the tone on
venous smooth muscle.
 This would include, organic nitrates, hydralazine,
clonidine, minixodil and the many drugs.
 Orthostatic hypotension or postural hypotension
occurs when systemic arterial blood pressure falls by
more than 20 mmHg upon standing.

 In this situation, cerebral perfusion falls and
an individual may become light headed, dizzy
or fatality may occur.
 In changing from the supine to the standing
position, gravity tends to cause blood to pool
in the lower extremities. However, several
reflexes, including sympathetically mediated
venoconstriction minimize this pooling and
maintain cerebral perfusion. If these reflex
actions do not occur, then orthostatic
hypotension could result.

 By blocking the alpha1-receptors associated
with venous smooth muscle, prazosin-like
drugs, inhibit the sympathetically mediated
vasoconstriction associated with postural
changes. Hence, orthostatic hypotension can
occur.
 Drugs like clonidine cause orthostasis due to
its CNS actions that block the sympathetic
reflexes.
 Vasodilators such as nitrates, minoxidil,
hydralazine or impotence medications cause
orthostasis because of their actions directly
on the vasculature.

 A consideration for patients being treated with
some sympatholytics is the patient's position
during and after dental procedures.
Suddenly standing upright after being in a
supine position in the dental chair is very
probable to cause syncope.

beta blocking drugs
 Decreased heart rate
 Decreased force of contraction
 Decreased Cardiac Output
 Slow cardiac conduction
 Decreased automaticity of ectopic pacemakers
 Decreased renin secretion from kidneys
 Decreased BP
 Bronchoconstriction
 Less effective metabolism of glucose. May result
in more pronounced hypoglycemia and early s/s of
hypoglycemia may be blocked (tachycardia).

Uses of Beta blocking
medications
 Inderal (propranolol) is prototype
 Mainly for cardiovascular disorders (angina,
dysrhythmias, hypertension, Myocardial
Infarction and glaucoma.
 In angina, beta blockers decrease myocardial
oxygen consumption by decreasing rate, BP and
contractility. Slow conduction both in SA node
and AV node.
 Useful in pheochromocytoma in conjunction with
alpha blockers (counter catecholamine release)
 migraines

Combination selectivity
 Labetalol and carvedilol (Coreg) block alpha
1 receptors to cause vasodilation and beta 1
and beta 2 receptors which affect heart and
lungs
 Both alpha and beta properties contribute to
antihypertensive effects
 May cause less bradycardia but more
postural hypotension
 Less reflex tachycardia

Application to dentistry
 Because nonselective β-blockers block β2-
receptor mediated vasodilation, there is a
risk of a hypertensive episode following
administration of local anesthetic agents that
contain epinephrine.
 In this situation, the vasoconstrictor actions of
epinephrine at α1 -receptors are not opposed
by the vasodilatory actions of β2-receptors
resulting in an exaggerated blood pressure
response that could be deleterious in patients
with hypertension or ischemic heart disease.

2. What is implied by «active transport»?
a) Transport of drugs through a membrane by
means of diffusion
b) Transport without energy consumption
c) Engulf of drug by a cell membrane with a
new vesicle formation
d) Transport against concentration gradient

3-Parenteral administration:
a) Cannot be used with unconsciousness patients
b) Generally results in a less accurate dosage than
oral administration
c) Suitable for drugs not absorbed from the gut
4. Pharmacodynamics involves the study of
following?
a) Mechanisms of drug action
b) Biotransformation of drugs in the organism
c) Distribution of drugs in the organism
d) Excretion of drug from the organism

5- Target proteins which a drug molecule binds are:
a) Only receptors b) Only ion channels
c) Only transporters d) All of the above
6-An agonist is a substance that:
a) Interacts with the receptor without producing any
effect
b) Interacts with the receptor and initiates changes in
cell function, producing various effects
c) Interacts with plasma proteins and doesn’t produce
any effect

Autonomic nervous system dental

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