Drugs roll in prostho/endodontic courses

DRUG’S ROLE INDRUG’S ROLE IN
PROSTHETICPROSTHETIC
CONSIDERATIONCONSIDERATION
INDIAN DENTAL ACADEMY
Leader in continuing Dental Education
www.indiandentalacademy.com

CONTENTSCONTENTS
Introduction
Definition
Classification
1. Drugs used directly for therapeutic purpose.
a. Drugs causing localized effect in the oral cavity.
- Local Anaesthetics
- Agents for Gingival Retraction & astringents
- Hemostatic agents
- Sialogogues
- Antisialogogues
- Mouth rinses containing local anti-infective agents
- Topical fluorides
b. Drugs used for systemic pharmacological effects
-Analgesics
- Steroids
- Antibiotics
- Antianxiety drugs

- Centrally acting muscle relaxants
- Vitamins and minerals
2. Drugs which influence the success of prosthodontic treatment
- Drugs causing Xerostomia(Dry mouth)
- Drugs which cause changes in oral flora
- Drugs affecting gingiva & oral mucosa
- Drugs causing sialorrhoea
- Drugs affecting bones or residual ridge
- Drugs causing dysphagia
- Drugs causing orthostatic hypotension
- Drugs causing bronchospasm, bradycardia & dyspnea
- Drugs causing hypoglycemic shock
- Drug induction of parkinson- like syndrome & other
Bizzare Muscle Movement, including Facial Muscles
Drugs used in emergency
Conclusion
Reference

INTRODUCTIONINTRODUCTION

DEFINITIONSDEFINITIONS
PHARMACOLOGYPHARMACOLOGY
Greek: Pharmacon - Drug
Logos - Discourse in
Pharmacology is the science of drugs.
In broad sense, it deals with
interaction of exogenously
administered chemical molecules
(drugs ) with living systems.www.indiandentalacademy.com

DRUGDRUG
French: Drogue - A dry herb
Drug is any substance or product
that is used or is intented to be
used to modify or explore
physiological systems or
pathological states for the benifit
of the recipient.

Drugs causing localized effect in the
oral cavity:-
1. Local anaesthetics
2. Agents for Gingival Retraction & astringents
3. Hemostatic agents
4. Sialogogues
5. Antisialogogues
6. Mouth rinses containing local anti-infective
agents
7. Topical fluorides
CLASSIFICATIONCLASSIFICATION

1. LOCAL ANAESTHETICS1. LOCAL ANAESTHETICS
They are drugs that will temporarily interrupt
conduction when absorbed into the nerve.
They are most widely used drugs in dentistry.
CLASSIFICATIONCLASSIFICATION:-
Injectable:-Injectable:-
1.Lower potency,short duration
PROCAINE
CHLOROPROCAINE
2.Intermediate potency and duration
LIDOCAINE(Lignocaine)www.indiandentalacademy.com

3.High potency, long duration
TETRACAINE
BUPIVACAINE
RUPIVACAINE
DIBUCAINE
Surface Anaesthetics:Surface Anaesthetics:-
1.Soluble 2.Insoluble
COCAINE BENZOCAINE
LIDOCAINE BUTYLAMINOBENZOATE
TETRACAINE OXETHAZAINEwww.indiandentalacademy.com

Depending upon their composition:-
Esters:-Esters:-
COCAINE
PROCAINE
CHLOROPROCAINE
Amides:-Amides:-
LIDOCAINE
BUPIVACAINE
DIBUCAINE

PROPERTIES OF AN IDEAL ANAESTHETIC:-PROPERTIES OF AN IDEAL ANAESTHETIC:-
1.Action must be reversible.
2.Nonirritating to tissues & produce no
secondary local reaction.
3.Should have low degree of systemic toxicity.
4.Should have rapid onset& be of sufficient
duration to be advantageous.
5.Potency sufficient to give complete anaesthesia
without the use of harmfulconcentrated
solutions.
6.Should have sufficient penetrating properties to
be effective as a topical anaesthetic.www.indiandentalacademy.com

7.Relatively free from producing allergic
reaction.
8.Should be stable in solution and
undergo biotransformation readily
within the body.
9. Should be either sterile or capable of
being sterilized by heat without
deterioration.

MECHANISM OF ACTION:-MECHANISM OF ACTION:-
LA blocks nerve conduction by decreasing
the entry of Na+
ions during upstroke of
action potential.
As the concentration of LA is increased the
rate of rise of AP and maximum
depolarization decreases  causing slowing
of conduction.
Finally local depolarization fails to reach the
threshold potential & ensures conduction
block.
The LA interact with a receptor situated
within the voltage sensitive Na+
channel &
raise threshold of channel opening: Na+
permeability fails to increase in response to
the impulse or stimulus.

At physiological pH the LA molecule is partly
ionized.
The equilibrium between the unionized base
form (B) and ionized cationic form (BH+
)
depends on the PKa of the LA.
The predominant active species (Cationic form
of LA) is able to approach its receptor only
when the channel is open at the inner face and
it binds more avidly to the inactive state.
Thus a resting nerve is rather resistant to
blockade.
Degree of blockade is frequency dependent,
greater blockade at higher frequency of
stimulation. www.indiandentalacademy.com

LOCAL ACTIONS:LOCAL ACTIONS:-
LA’s have no or minimal local irritant action
and block sensory nerve endings, nerve trunks,
neuromuscular junctions, ganglionic synapse &
receptors i.e. structures which function through
increased Na permeability.
Reduce release of Ach from motor nerve
endings.
Sensory & motor fibers are inherently equally
sensitive.
Sensitivity is determined by diameter of fibers
as well as by fibre type.

Smaller fibers are more sensitive than larger
fibers.
Non myelinated fibers are blocked more easily
than myelinated fibers.
BIO TRANSFORMATION:-BIO TRANSFORMATION:-
ESTER GROUP:- are inactivated by
hydrolysis.i.e. water molecule is added at the
ester linkage, thus splitting the molecule into 2
entities. The bulk of hydrolysis reaction occurs
in plasma & is catalyzed by the enzyme plasma
cholinesterase. Some hydrolysis occurs in liver.
AMIDE TYPE:- undergoes biotransformation
primarily in the liver by microsomal enzyme.

PRECAUTIONS:-PRECAUTIONS:-
Care should be taken with the use of
amides in patients with Hepatic Disorders.
Care should be taken with use of ester
group in any suspected genetic based
plasma pseudocholinesterase deficiencies.
Allergy to methyl paraben, which is used
as a preservative should be kept in mind.
Least possible volume should be used.
Solution should be deposited slowly.
Aspiration must be done before injection.www.indiandentalacademy.com

COMPLICATIONS:-COMPLICATIONS:-
Resulting from absorption of anaesthetic
solution:-
1. Toxicity
2. Idiosyncracy
3. Allergy
4. Anaphylactic Reaction
5. Infections caused by contaminated
solutions
6. Local irritation or tissue reaction.www.indiandentalacademy.com

Resulting from insertion of the needle:-
1. Syncope
2. Muscle Trismus
3. Pain or hyperalgesia
4. Edema
5. Infection
6. Broken needle
7. Prolonged anaesthesia
8. Hematoma
9. Sloughing
10. Bizzare neurological symptoms.www.indiandentalacademy.com

VASOCONSTRICTING AGENTS:-VASOCONSTRICTING AGENTS:-
They are an integral and necessary part of most
local anaesthetics.
Can be grouped into 3 categories:-
1. Pyrocatechin derivatives- Epinephrine
Nor epinephrine
2. Benzol derivatives- Levonordefrin
3. Phenol derivatives- Phenyl ephrine

MECHANISM OFMECHANISM OF ACTION:-ACTION:-
With the exception of cocaine & ropivacaine all
LA’s cause same degree of vasodilation.
Act by:-
1. Attaching to & directly stimulating adrenergic
receptor’s(alpha 1 receptors) in peripheral
arterioles, resulting in local vasoconstriction.
2. Acting indirectly by provoking the release of
endogenous catecholamines from their
intraneuronal storage sites.
3. A combination of direct & indirect actions.

DRUG INTERACTIONS:-DRUG INTERACTIONS:-
Potentially dangerous drug interactions can
occur between vasoconstrictor agents & any
drug that disturbs adrenergic transmission.
1.Tricyclic antidepressants increase synaptic
levels of adrenergic transmitters & may
aggravate the unwanted cardiovascular
complications of LAs that contain
vasoconstrictor.
2. Monoamine oxidase inhibitors also increase
biogenic amine neurotransmitter levels.
3. Antihypertensives like guanidine & reserpine,
deplete adrenergic neurons at

4. Beta blockers like propranalol augument
adrenergic effects.
5. Rauwolfia compounds also compliment the
adrenergic effects.
CONTRAINDICATIONS:-CONTRAINDICATIONS:-
1. Pheochromocytoma
2. Uncontrolled or unstable angina
3. Cardiac arrythmias
4. Congestive heart failure
5. Hyperthyroidism
6. Diabetes
7. Stroke/ MI within past 6 months

Use:-
Vasoconstrictor is added
e.g. Adrenaline( 1:50,000 to 1:200,000) or
Phenylephrine( 1:2,000)
1. Prolongs duration of action of LAs by
decreasing their rate of removal from the local
site into the circulation
2. Reduces systemic toxicity of LAs : rate of
absorption is reduced & metabolism keeps the
plasma concentration lower.

Vasoconstrictors as accepted by the Council on Dental
Therapeutics, American Dental Association
Drug
Concentr-
ation
mg/ml
Milligrams
in 1.8ml
cartridge
Maximum
recommen
ded dose
(mg)
Epinephrine
Lovonorde-
frin
Nor-
epinephrine
1:200,000
1:100,000
1:50;000
1:20,000
1:30,000
0.005
0.01
0.02
0.05
0.033
0.009
0.018
0.036
0.09
0.059
0.2
0.2
0.2
1.0
0.34

AGENTS FOR GINGIVALAGENTS FOR GINGIVAL
RETRACTION & ASTRINGENTRETRACTION & ASTRINGENT
By combining chemical action with pressure
packing, enlargement of the gingival sulcus as
well as control of fluids seeping from the walls
of the gingival sulcus can be accomplished.
Cotton cords impregnated with recemic
epinephrine or aqueous solutions of metal salts
have been used for gingival retraction.

The criteria for selection of gingival retraction
materials are:-
1. Effectiveness in gingival displacement &
hemostasis.
2. Absence of irreversible damage to the
gingiva.
3. Paucity of untoward systemic effects.
Racemic epinephrine is approximately half as
potent as L- epinephrine, the form that
accounts for most of the pharmacologic activity
of drugs.
All the precautions for epinephrine as used in
LAs apply to its use in retraction cords because
systemic absorption is nearly as rapid aswww.indiandentalacademy.com

I.M. injection in areas of gingival abradement,
and cords contained large amount of
epinephrine contraindications can also exhibit
“Epinephrine Syndrome”(tachycardia, rapid
respiration, elevated BP,anxiety&postoperative
depression)
The vasoconstrictor properties of epinephrine
that contribute to its therapeutic usefulness in
LA preparations are also used for gingival
retraction.
Shrinkage of gingival tissue presumably is a
result of local epinephrine absorption, alpha
adrenergic receptor activation, vasoconstriction
& the resultant decrease in volume of this
highly perfused tissue.www.indiandentalacademy.com

ASTRINGENTS:-ASTRINGENTS:-
They are metal salts that cause gingival
retraction by precipitating protein or in some
cases by a dessicant effect.
Precipitated protein- physically obstructs
hemorrhaging, thus making astringents used as
hemostatics.
Denatured proteins can also delay healing.
Administration -
1. By retraction cords already impregnated
with the agent.
2. Applying them to cotton pellets.www.indiandentalacademy.com

Aluminium chloride- is the most widely used
agent - it is irritating & may cause local tissue
damage in conc. <1%.
Zinc chloride- causes tissue damage at higher
conc. (20%)
Ferrous sulfate- is the only astringent accepted
by Council on Dental Therapeutics but it is
irritating & causes staining.

Agents for gingival retraction and astringents
Drug
Official or
trade name
Manufacturer
Conce-
ntration
Preparation
form
Aluminium
acetate
Aluminium
chloride
Aluminium
sulfate
Epinephrine
Ferrous
sulfate
Zinc
chloride
Burrow’s
solution
Hemodent*
Pascord
Gingibraid
Gingi-Pak
Astringedent
*
-
-
Premier Dental
Products
Pascal
Van R Dental
Products
Surgident
Ultradent
Products
-
5%
0.9-1.8mg/"
0.48-1.45mg/"
1.0mg/"
0.5mg/"
15.5%
8-20%
Solution
Retraction cord
Retraction cord
Retraction cord
Retraction cord
Solution
Retraction cord

HEMOSTATIC AGENTSHEMOSTATIC AGENTS
They are agents that reduce or control blood
flow.
Epinephrine may be applied topically as a local
hemostatic agent.
It is most effective in the control of superficial
capillary bleeding but will not control bleeding
from larger vessels.
Absorption is rapid from sites of trauma & the
usual precautions must be observed in patients.

Thrombin:-Thrombin:-
Is a blood clotting foctor that maybe applied
as a powder or a liquid on sites that are free of
clotted blood.
Thrombin must not be injected because of
extensive intravascular clotting that may result
in death.
Absorbable gelatin sponge is available as a
powder or porous sheet.
The hemostatic properties of absorbable gelatin
sponge are improved by soaking it in a
thrombin solution before application.

Oxidised cellulose is surgical gauze that is
treated with nitrogen dioxide.
It is absorbed slowly, particularly if it contains
a great deal of blood & may retard wound
healing.
Astringents produce hemostasis by causing
tissue contraction followed by coagulation of
blood in the local area. e.g. styptics.
Ferric subsulfate solution(Monsel’s solution) is
a hemostatic agent but causes a black stain on
teeth.

Hemostatic Agents
Drug/Product Trade name Manufacturer Concentration
Absorbable
gelatin sponge
Aluminium
chloride
Epinephrine
Ferric
subsulfate
Oxidized
Cellulose
Thrombin
Gelfoam*
Hemodent
Adrenalin
Monsel’s
solution
Surgicel*
Oxycel
Thrombostat
Upjohn
Medical Products
Parke-Davis
-
Johnson & Johnson
Becton-Dickinson
Parke-Davis
-
5%-10%
1:100,000
20%
-
-
-www.indiandentalacademy.com

SIALOGOGUESSIALOGOGUES
Xerostomia may result from disease states like
Sjogrens syndrome, rheumatoid arthritis,
diabetes insipidus, pernicious anaemia, from
radiation, as a side effect of a wide variety of
drugs, or from natural aging.
It may lead to complications that reduce
denture wearing time & cause difficulty in
swallowing, loss of taste, difficulty in speaking,
stomatitis, burning tongue, rampant caries &
periodontal disease.

Edentulous patients - problem with dentures &
an increased incidence of intraoral infection
with candida albicans.
The treatment rationale for xerostomia is- to
activate muscarinic cholinergic receptors of the
parasympathetic nervous system to increase
salivary flow.
Most cholinergic agonists cause the side effects
of activation of the entire parasympathetic NS
resulting in gastrointestinal cramping, nausea
& diarrhoea.
Pilocarpine, a naturally occuring cholinergic
agonist, produce a short duration increase inwww.indiandentalacademy.com

salivary flow without any side effects,
suggesting that it may possess some degree of
selectivity as salivary gland cholinergic
receptors.
Use of pilocarpine limited to- Sjogren’s
syndrome & radiation.
Not used in patients with drug induced
xerostomia & patients with uncontrolled
asthma.
It causes mild to moderate sweating .
Treatment of chronic xerostomia limited to oral
rinses & saliva substitutes.

SALIVA SUBSTITUTESSALIVA SUBSTITUTES
Most saliva substitutes contain either
carboxymethyl cellulose or hydroxyethyl
cellulose as lubricant & a variety of artificial
sweetners, preservatives & chloride or fluoride
salts.
Mucin containing preparations have better
wetting & lubricating properties than the other
two cellulose preparations , have a limited
duration of action, making frequent
applications necessary.

Over the counter saliva substitutes:
Trade name Manufacturer Dose form Lubricating ingredient
Entertainer’s secret
Glandosane
Moi-Stir*
Orext
Saliva substitute*
Salivart*
Xero-Lube*
Salix
Optimoist
MouthKote II
Saliva Orthana
KLI Corp.
Kenwood
Kingswood Lab
Young Dental
Roxane
Gebauer
Scherer
Scandinavian
Pharmaceuticals
Colagte-Palmolive
Parnell
Orthana, Kimisk,
Fabrik Kastrup,
Denmark
Solution, pump spray
Pump spray, swabsticks
Solution
Spray
Lozenges
Solution
Spray,lozenges,gum
Carboxymethylcellulose
hydroxypropylmethyl
cellulose
Hydroxyethylcellulose
Mucopolysaccharide
Mucin

3. MOUTH RINSES CONTAINING FLUORIDE:-MOUTH RINSES CONTAINING FLUORIDE:-
Useful in- controlling plaque formation &
reducing caries formation, especially in patients
with xerostomia, part of the anticaries activity
of fluoride is from an antibacterial effect.
Mechanism of antibacterial effect is complex
but is, in part, caused by the suppression of
enzymatic pathways involved with bacterial
glycolysis.
Flourides become more effective in acid
medium, as occurs in vicinity of cariogenic
plaque.

Mouth rinses containing fluoride
Trade name Manufacturer OTC Ethanol
(%)
Fluorid
e (%)
ACT*
Fluorigard*
Oral-B Fluorinse*
MouthKote F/RT+
Oral-B Anticavity
Rinse*
Point-Two
Prevident*
Reach*
Johnson & Johnson
Colgate-Palmolive
Oral-B lab
Parnell
Orachem Pharmaceuticals
Oral-B lab
Colgate Oral Pharm
Colgate Oral Pharm
Johnson & Johnson
Yes
Yes
No
Yes
No
Yes
No
No
Yes
7
6
0
0
0
0
6
6
7
0.02
0.02
0.2
0.04
0.05,0.2
0.05
0.09
0.2
0.02

ANTISIALOGOGUESANTISIALOGOGUES
Agents used to decrease salivary secretion .
They are cholinergic antagonists & thus block
the same receptors that are activated by the
sialogogues or cholinergic agonists.
For reduction in salivary flow, oral
administration of Atropine, Scopolamine, or
Methantheline & Propantheline should precede
the clinical procedure by 1 to 2 hours, one-half
to 1 hour, or one- half hour respectively.
Atropine - is prototype anticholinergic drug.
A reduction in salivary flow for 4-6 hours after
oral administration.

Atropine differs from scopolamine in that, at
high doses it causes CNS stimulation, whereas
scopolamine causes sedation.
The sedative and slight amnesic effect of
scopolamine is the basis for its clinical use; it
is usually combined with meperidine and
promethazine as a preanesthetic medication.
Methantheline and propantheline are
pharmacologically identical except
propatheline is approximately five times more
potent. Neither drug offers any particular
advantages over atropine.

SIDE EFFECTS OF ANTICHOLINERGIC DRUGS
Side effects of all the anticholinergic drugs are those
expected when the parasympathetic nervous system
is blocked.
Dose-dependent adverse effects include:-
- Flushing,
- Rapid pulse,
- Papillary dilation,
- Blurred vision,
- Hyperthermia,
- Dry skin,
- Urinary retention and
- Constipation.

CONTRAINDICATIONS:-
In patients with glaucoma
Prostatic hypertrophy
Severe gastrointestinal disorders like
ulcerative colitis
Obstructive diseases
Intestinal atony
Myasthemia gravis.

INTERACTIONS:-
Drugs such as tricyclic antidepressants and
antihistamines, which have anticholinergic
activity, can have an additive effect.
Centrally acting anticholinergic drugs, used to
treat parkinson’s disease, would interact with
antisialogogues.
Also anticholinergic blockade of the vagal
action on the heart could antagonize the
desired therapeutic effect of β-blockers such as
propranalol.

Antisialogogues
Drug
Trade
name
Manufacturer Dose (mg)
Duration
(hr)
Atropine sulfate*
Belladonna
tincuture*
Scopolamine
Methantheline
Propantheline
-
-
-
Banthine
Pro-Banthine
-
-
-
Schiapparelli Searle
Schipparelli Searle
0.2-0.4
See text
0.4-0.6
50-100
15-30
4-6
-
4-6
5-6
5-6

MOUTH RINSES CONTAININGMOUTH RINSES CONTAINING
LOCAL ANTI-INFECTIVE AGENTSLOCAL ANTI-INFECTIVE AGENTS
Mouth rinses that contain local antiinfective agents
also have a variety of other ingredients, including
flavouring agents, sweeteners, dyes, preservatives and
wetting agents.
Mouth rinses are acidic with a pH ranging from 4.2 to
8.2 and many contain ethanol which is a local
antiinfective agent.
Phenolic derivatives such as thymol have limited
usefulness and objectionable taste.
Hydrogen peroxide, has little or no antibacterial
activity but many loosen debris by physical action of
the nasant oxygen that is released by its
decomposition. www.indiandentalacademy.com

Cetylpyridinium, a surface-active agent, is
a quaternary ammonium derivative that
has slight bacteriostatic activity but has
bitter and unpleasant after taste.
Povidone-iodine, an iodophore, is a
halogen-releasing compound combined
with a surface active agent. It is probably
the most effective antibacterial agent.
The iodophores do not stain or sting as
iodine solutions do, but they have an
unpleasant taste.

2% to 4% chlorhexidine, a biguamide is most
effective against gram-positive organisms, less
effective against gram-negative organisms and
fungi, and ineffective against spores and viruses.
Chlorhexidine digluconate, at concentrations of
0.12%, is used for treating gingivitis and
suppression of the formation of plaque.
Chlorhexidine protein and is slowly released, a
desirable characteristic for plaque control.
Undesirable effects include a reversible, altered taste
perception, especially to salt; staining of teeth,
tongue, and margins of anterior restorations that
cannot be removed by burnishing with toothpaste;
and local irritation if applied to abraded tissue.
Chlorhexidine containing mouth rinses are useful
adjuncts that may facilitate healing after insertion of
dentures.

TOPICAL FLUORIDESTOPICAL FLUORIDES
MECHANISM OF ACTION

-Analgesics
- Steroids
- Antibiotics
- Antianxiety drugs
- Centrally acting muscle relaxants
- Vitamins and minerals
DRUGS USED FOR SYSTEMIC
PHARMACOLOGICAL EFFECTS

ANALGESICS
Algesia or pain is an ill defined, unpleasant sensation,
usually evoked by an external or internal noxious
stimulus.
Analgesic is a drug that selectively relieves pain by
acting on the CNS or on the peripheral pain
mechanisms, without significantly altering
consciousness.
Classification:-
1. Opioid/ Narcotic/ Morphine like analgesics.
2. Non opioid / Non-narcotic / Aspirin like / Non
steroidal anti-inflammatory analgesics.

OPIOID ANALGESICS
Classification:-
1.Natural opium alkaloids – e.g. Morphine
and cocaine.
2.Semisynthetic opiates – e.g.
Diacetylmorphine,
Ethyl morphine,
Pholcodeine.
3.Synthetic opioids – E.g. Pethidine
(Meperidine), Fentamyl,
Methadone.

Morphine - is the prototype or standard
opioid to which all other drugs are compared.
Morphine is rarely used in dentistry, because
it undergoes significant first-pass metabolism
and is therefore usually parenterally
administered.
Codeine - First-pass metabolism of codeine
results in formation of small amounts of
morphine. Codeine is frequently used in
dentistry as an analgesic, particularly in
combination with aspirin or acetaminophen.
Codeine is an excellent antitussive at doses
less than those used for analgesia.

Side effects of all opiate analgesics :
i) Respiratory depression
ii) CNS depression.
iii) Nausea and vomiting
iv) Release histamine which can cause
bronchospasm.
v) Cause spasm of gastrointestinal smooth
muscle.
vi) Spasm of biliary tract musculature
consisting of severe pain.
vii)Spasm of bladder sphincter causing
urinary retention.
viii) Induce hyperglycemia.www.indiandentalacademy.com

Contraindications:
i) In patients with any condition in which
respiration is compromised.
ii) In patients on CNS depressants.
iii) In epilepsy.
iv) In asthma.
v) In diabetics.
Individuals receiving opioids who are
not in severe pain frequently experience
dysphagia rather than euphoria.

NON STEROIDAL ANTI-
INFLAMMATORY ANALGESICS
Classification:
1. Analgesic and anti-inflammatory.
2. Analgesic but poor antiinflammatory.
1. Analgesic and antiinflammatory:
a. Salicylates- e.g. Aspirin, salicylamide.
b. Pyrazolone derivatives – e.g. Phenylbutazone,
oxyphenbutazone.
c. Indole derivatives – e.g. Etodolac, indomethacin.
d. Propionic acid derivatives – e.g. Ibuprofen, naproxen,
ketoprofen, fenoprofen.
e. Anthranitic acid derivatives – e.g. Mephenamic acid,
enfenamic acid.
f. Aryl-acetic acid derivatives – e.g. diclofenac.
g. Oxicam derivatives – e.g. piroxicam.www.indiandentalacademy.com

2. Analgesic but poor antiinflammatory:
a. Para aminophenol derivatives – e.g. Paracetamol
(Acetaminophen).
b. Pyrazolone derivatives – E.g. Metamizol,
Propiphenazone.
c. Benzoxazocine derivatives – E.g. Nefopam.
Mechanism of Action:
 NSAID’s are peripherally acting because their analgesic
and anti inflammatory effects are, to a large extent,
produced through a peripheral mechanism.
 They block the cyclooxygenase pathway by inhibiting
cycloxygenase, an enzyme involved in the biosynthesis of
arachidonic acid into prostaglandins, which are involved
in the pain mechanism.
 There are 2 isoforms of cyclooxygenase COX-1 and COX-
2 and although all NSAID’s inhibit both forms, the two
isoforms differ slightly in their sensitivity to NSAIDwww.indiandentalacademy.com

 This difference becomes therapeutically
important because COX-2 appears to be more
involved with synthesis of prostaglandins at
sites of inflammation, whereas COX-1 is more
involved at sites where adverse effects of
NSAID’s are expressed.
 Aspirin is the classic and prototypical drug and
along with NSAID’s is more effective for the
intermittent, sharp pain caused by inflammation
which is characteristic of dental pain.

SIDE EFFECTS:
i) They cause gastric irritation  if severe  gastric
ulceration  occult blood loss  iron deficiency
anemia.
ii) NSAID’s prolong bleeding time because of the
inhibition of cycloxygenase results in decrease
formation of thromboxane A2, a compound that
causes platelet aggregation.
Hypersensitivity to aspirin is common and manifests
as rhinitis, urticaria, bronchoconstriction, and
laryngeal edema.
Aspirin causes a dose dependant hepatotoxicity.
Salicylism is a toxic reaction to long-term use of high
doses of aspirin. This reaction might occur during the
treatment of arthritis or a result of drug overdose.www.indiandentalacademy.com

CONTRAINDICATIONS:
1. Peptic ulcers.
2. Bleeding tendencies or disorders.
3. Asthma (Arachidonic acid gets biosynthesized
by the lipoxygenase path way resulting in
leucotrines which are bronchoconstrictors).
4. Children with chickenpox or influenza.
5. Patients on phenytoin, penicillin,
anticoagulants, and oral hypoglycemics.
6. Diabetics.
7. Alcoholics.

Few NSAID’s deserve a special mention
because of their different characteristics:
a. Ibuprofen for example, appears to have a
higher “ceiling effect” than aspirin and causes
fewer gastric side effects.
b. NSAID’s like Naproxen have once or twice a
day dosing with longer duration of action.
c. NSAID’s like paracetamol or acetaminophen
have negligible antiinflammatory action but
have potent antipyretics and analgic effect. It
also has a higher ceiling effect than aspirin.

STEROIDS
The adrenal cortex secretes steroidal hormones like
glucocorticoids from the zona fasciculate,
mineralocorticoids from the zona glamerulosa and
androgens from the zona reticularis.
Glucocorticoids are:
a. Hydrocortisone
Short acting
b. Cortisone.
c. Prednisolane.
Intermediate acting
d. Methyl prednisolane
e. Triamcinolane.
f. Paramethasone.
g. Dexamethasone. Long acting
h. Betamethasone. www.indiandentalacademy.com

Mineralocorticoids are:
a. Desoxycorticosterase acetate.
b. Fludrocortisone.
c. Aldosterone.
Mechanism of Action:
 Corticosteroids inhibit phospholipase A2, an enzyme
involved in the formation of arachidanic acid.
 As a result the formation of both prostaglandins and
leukotriences is inhibited by corticosteroids, which
may account for their greater antiinflammatory effect
compared to the NSAID’s.
 Suppression of growth factors necessary for cell
growth and the suppression of the influx of cells of
inflammation into tissues offer additional
inflammatory effects:www.indiandentalacademy.com

USES:
1. Acute adrenal insufficiency.
2. Chronic adrenal insufficiency (Addisons disease).
3. Congenital adrenal hyperplasia (Adrenogenital syndrome).
4. Rheumatoid and osteoarthritis.
5. Rheumatic fever and gout.
6. Severe allergic reactions.
7. Bronchial asthama.
8. Lung, eye, skin, intestinal diseases.
9. Collagen autoimmune diseases.
10. Cerebral edema.
11. Malignancies.
12. Organ transplants.
13. Septic shock.
14. To test adrenal pituitary axis function.

ADVERSE EFFECTS:
1. Cushings habitus: characteristic appearance with rounded
face, narrow mouth, supraclavicular hump, obesity of
trunk with twin limbs.
2. Fragile skin with purple striae.
3. Hyperglycemia.
4. Muscular weakness.
5. Susceptibility to infections.
6. Delayed healing.
7. Peptic ulcers.
8. Osteoporosis.
9. Glaucoma.
10. Growth retardation.
11. Suppression of hypothallamo-pituatory-adrenal axis,
which occurs depending both on dose and duration of the
therapy.

CONTRAINDICATIONS:
1. Peptic ulcers.
2. Diabetes mellitus.
3. Hypertension.
4. Pregnancy.
5. Tuberculosis.
6. Osteoporosis.
7. Psychosis.
8. Epilepsy.
9. Renal failure.

Steroid Preparations:
Generic name Trade
name
Manufacturer Dose Route
Bethamethasone
Dexamethazone
Hydrocortizone*
Methylprednisolone
Prednisone
Prednisolane
Triamcinoiane
-
-
-
Medrol
Deltasone
Delta-Cortef
Kenalog
Schering
Merck
Colgate/Hoyt
Upjohn
Upjohn
Upjohn
Westwood
Squbb
0.6-7.2mg/day
0.5-9.0mg/day
2-3 times daily
4mg/day
5-60mg/day
5-60mg/day
2-3 times daily
Oral
Oral, topical
Topical
Oral
Oral
Oral
Topical

ANTIBIOTICS
CLASSIFICATION:
1. Bacteriostatic
2. Bactericidal
1. Bacteriostatic agents - interfere with the synthesis of
cellular components and inhibit bacterial growth.
Bactericidal agents inhibit synthesis of the cell wall or
membrane and kill the bacteria.
- Systemic antibiotics
- Topical antibiotics
And also as:
a. Antibacterial.
b. Antifungal.
c. Antiviral.
d. Antiprotozoal. www.indiandentalacademy.com

Adverse Effects:
1. Toxicity.
2. Hypersensitivity reactions.
3. Drug resistance.
4. Supra or superinfection.
5. Nutritional deficiencies.

Therapeutically, antibiotics are used in
dentistry either to treat oral infections,
most of which are caused by aerobic gram
positive cocci and anaerobic
microorganisms, or as a prophylaxis to
prevent bacterial endocarditis caused by
α-haemolytic streptococci or as a
prophylactic regimen for dental
procedures in patients who have
prosthetic heart valves and other high risk
patients.

Prophylactic regimen for dental procedures in
patients who are at risk*
Drug standard
regimen
Dosing regimen
Amoxicillin
Patients allergic to
amoxicillin/penicillin
Erythromycin
Clindamycin
3.0gm orally 1 hr before procedure; then
1.5gm 6hr after initial dose
Erythromycin ethylsuccinate 800mg or
erythromycin stearate 1.0gm orally 2hr
before procedure; then half the dose 6 hr
after initial dose
300mg orally 1hr before procedure and
150mg 6hr after initial dose

Alternate prophylactic regimens for dental
procedures in patients who are at risk
Drug During regimen
Patients unable to take
oral medications
Ampicillin
ampicillin/
amoxicillin/ penicillin
and unable to take oral
medications
Clindamycin
Intravenous or intramuscular administration
of ampicillin, 2.0gm, 30 min before
procedure; then intravenous or intramuscular
administration of ampicillin 1.0gm or oral
administration of amoxicillin 1.5gm 6 hr
after initial dose
Intravenous administration of 300mg 30 min
before procedure and an intravenous or oral
administration 150mg 6hr after initial dose

Patients considered
high risk and not
candidates for
standard regimen
Ampicillin,
gentamicin
ampicillin/amoxicilli
n/ penicillin and
considered high risk
Vancomycin
Intravenous or intramuscular administration
of amoxicillin and ampicillin 2.0gm plus
gentamicin 1.5mg/kg (not to exceed 80mg)
30 min before procedure, followed by
amoxicillin 1.5gm orally 6hr after initial
dose alternatively, the parenteral regimen
may be repeated 8 hr after initial dose
Intravenous administration of 1.0gm over a
1hr period, starting 1hr before procedure;
no repeated dose necessary

ANTIFUNGAL ANTIBIOTICS
Classification:-
a. Antibiotics
1. Polyenes
2. Heterocyclic benzofuran
a. Antimetabolite
b. Azoles
1. Imidazoles
2. Triazoles
d. Allylamine
e. Other topical agentswww.indiandentalacademy.com

Most common drugs used in dentistry to treat
fungal infections of the oral cavity are nystatin
(mycostatin) and amphotericin B.
They have a dose-dependent fungistatic or
fungicidal effect on several fungi, including
candida albicans. C.albicans causes oral
moniliasis (thrush) and can also infect prosthetic
devices.
Nystatin is not absorbed, tablets are usually
held in the mouth for several minutes until they
dissolve, colonized dentures can be treated by
soaking them in a solution of nystatin.
Nystatin tablet may be crushed and suspended
in glycerine for application in mouth.

Fluconazole - is rapidly absorbed into
body fluids, including saliva and
cerebrospinal fluid, after oral
administration.
Side Effects - nausea and vomiting.

ANTIANXIETY AGENTSANTIANXIETY AGENTS

These are an ill-defined group of mild CNS
depressants which are aimed to control the
symptoms of anxiety, produce a restful state of
mind without interfering with normal mental
or physical function
CLASSIFICATION:-
1. Benzodiazepines – E.g. Diazepam,
Alprozolam.
2. Others – E.g. Antihistamines like
promethazine and hydroxyzine,
β-blockers like propranalol.www.indiandentalacademy.com

Antianxiety agents are perhaps most
appropriately used in clinical dentistry for
those patients who become usually
apprehensive to the stress.
The safest and most popular drugs for such
clinical situations are the benzodiazepines.
Dentists require an anxiolytic effect that is
rapid in onset and short in duration, rapidity to
onset is less important than prolonged
duration to a physician.
Diazepam is one of the most popular of the
benzodiazepines for clinical dentistry and
serves as a prototype for the class.

MECHANISM OF ACTION:-
All benzodiazepines appear to act by
facilitating the binding of the major
inhibitory transmitter of the brain, α-
aminobutyric acid (GABA) to GABA
receptors in the midbrain ascending
reticular formation which maintains
weakfulness and on the limbic system
which is responsible for the thought
process and mental functions.

Adverse effect:-
In therapeutic doses, they have little effect on
cardiovascular function or respiration. Because they are CNS
depressants, they can cause drowsiness and impaired motor
function, and patients should be cautioned regarding operation
of motor vehicles. The safety of the benzodiazepines, when
used alone, is remarkable.
Interations:-
1. Benzodiazepines, in combination with some CNS depressant
drugs, can be lethal.
2. Alcohol causes potentiation of the CNS depressant effect of
benzodiazepines rather than an additive effect.
Flumazenil is a benzodiazepine antagonist available for the
treatment of benzodiazepine overdose and should be available
as an emergency drug if benzodiazepines are used clinically.www.indiandentalacademy.com

CENTRALLY ACTINGCENTRALLY ACTING
MUSCLE RELAXANTSMUSCLE RELAXANTS
CLASSAFICATION:-
1. Mephenesin group – E.g. Chlorzoxazone,
Methocarbamol, Mephenesin.
2. Benzodiazepines – E.g. Diazepam.
3. GABA derivative – E.g. Baclofen.
These are drugs which reduce skeletal muscle tone by
selective action in the CNS, without altering
consciousness.
They selectively depress spinal and supraspinal
polysynaptic reflex involved in the regulation of
muscle tone without significantly affecting
monosynaptically mediated stretch reflex.www.indiandentalacademy.com

All these drugs cause slight sedation that may
contribute to their muscle relaxant effect.
These drugs are sometimes used in treating
TMJ disorders, but their efficacy is not
consistent, predictable, or well established.
They are also used for acute muscle spasms,
releaving anxiety and tension, tetany etc.
Centrally acting muscle relaxants can be
abused, and dependence occurs, because of
which prolonged administration should be
avoided and doses should be tapered off to
avoid withdrawal symptoms in a patient who
is dependent.

VITAMINS & MINERALSVITAMINS & MINERALS
 Are important for body function
 2 types:
1. Fat soluble – Vitamin A, D, E & K.
2. Water soluble – B complex and C
 Vitamin A – Play an important role in maintenance of
normal mucosa, keratinization of mucosal tissue
including oral mucosa.
Dose 800 – 1000 (RE)
 Vitamin D – Classified as sterol
2 forms - D2 or Ergocalciferol
- D3 or Cholecalciferol
- Vitamin D increases absorption of calcium from the
intestinal tract and promotes the deposition of calcium
and phosphate by specifically acting on bone cells.

- Over doses results in bone resorption including
loss of alveolar bone
- Dose 0.1mg
 Vitamin B complex –
- Niacin causes pellegra characterized by stomatitis,
glossitis. Desquamative lesions reported in gingiva
including ulceration interdental papilla.
- Dose 6.6mg/kcal
 Vitamin B6 – deficiency causes cheilosis, glossitis,
stomatitis.
- Dose 2mg
 Vitamin B2 – deficiency causes cheilosis, angular
stomatitis, glossitis, sorethroat & anaemia.
- Dose 0.6mg/1000 kcal

 Vitamin B1 – deficiency causes pernicious
anaemia.
- Dose 0.003µg
 Vitamin C – deficiency causes scurvy.
- Dose 6mg/day
MINERALS
 Sodium and potassium help to maintain
water and electrolyte balance.
- Dose 5g & 1g respectively.
 Calcium and phosphorous.
- Dose 1.7 & 1.2 mg respectively.

Drugs which influence the success of
prosthodontic treatment:-
1. Drugs causing Xerostomia(Dry mouth)
2. Drugs which cause changes in oral flora
3. Drugs affecting gingiva & oral mucosa
4. Drugs causing sialorrhoea
5. Drugs affecting bones or residual ridge
6. Drugs causing dysphagia
7. Drugs causing orthostatic hypotension
8. Drugs causing bronchospasm, bradycardia &
dyspnea
9. Drugs causing hypoglycemic shock
10. Drug induction of parkinson- like syndrome & other
Bizzare Muscle Movement, including Facial Muscles

Drugs causing XEROSTOMIADrugs causing XEROSTOMIA
Xerostomia is a symptom . It is most frequently
associated with alterations of salivary functions, other
causes can be radiation therapy, systemic diseases &
medications.
Xerostomia causes oral mucous membrane to
beecome hot, dry & fragile. Materia alba accumulates
due to lack of self cleansing by saliva. It also changes
the tongue. Accumulation of epithelial debris on the
dorsum forms the coated tongue & causes loss of taste
due to degeneration of taste buds. Dentures cannot be
tolerated by dry & fragile mucosa & retention of
denture is difficult in dry mouth.

ANTIHISTAMINESANTIHISTAMINES
Drugs - Diphenhydramine(benedryl)
Promethazine(phenergan)
Pheniramine(avil)
Indications:-
1. Allergic disorders
2. Pruritides
3. Common cold
4. Motion sickness
5. Parkinsonism- Promethazine in early cases

Adverse affects:-
1. Sedation
2. Diminished alertness & concentration
3. Light headedness
4. Motor incoordination
5. Fatigue
6. Restlessness & nervousness
Oral side effects:-
Dryness of mouth
H1 blockers in addition antagonise muscarine
actions of acetylcholine

The anticholinergic action can be graded as :-
High:- Promethazine
Diphenhydramine
Dimenhydrinate
Low:- Chlorpheniramine
Antazoline
Hydroxyzine
Cyclizine
Minimal/ Absent:- Cetrizine
Loratidine

ANTIPARKINSONIAN AGENTS
Drugs:- Levodopa
Amantadine
Trihexphenidyl
Promethazine
Adverse effects:-
At initiation of therapy
- Nausea & vomiting
- Postural Hypotention
- Cardiac Arrythmias

After prolonged therapy:-
- Abnormal movements
- Behavioural effects
Oral side effects:-
Alteration in taste sensation
Reduction in salivary secretion
These are the drugs having a higher central and
peripheral anticholinergic action.
ANTIPSYCHOTIC DRUGS
TRICYCLIC ANTIDEPRESSANTS

Drugs - Quidine, procainamide, disopyramide
Adverse effects – Nausea, vomiting, diarrhoea, fever,
angioedema.
Oral side effects – Dry mouth.
ANTIHYPERTENSIVE DRUGS
Used to lower blood pressure in hypertension.
Drugs – ACE inhibitors – Enalapril
- Ca channel blockers – Verapamil
- α adrenergic blockers – Prazosin
- β adrenergic blockers – Propranolol
Adverse effects – Dry persistent cough (ACE
inhibitors)
Headache, drowsiness, blurred vision and dry mouth
(Prazosin).
ANTIARRHYTHMIC DRUGS

ANTIBIOTICS
Use of most antimicrobial agents causes some
alteration in normal microbial flora of the body.
Lack of competition may allow even a normally non
pathogenic component of flora, which is not inhibited
by the drug to predominate and invade.
Suprainfection is commonly associated with broad
/extended spectrum antibiotics such as tetracycline,
chloranphenicol, ampicillin and newer
cephalosporins.
Suprainfection are most common when the host
defense is compromised.
- Corticosteroid therapy, Leukemias, AIDS, Diabetes
Sites – Oropharynx, respiratory tract.
DRUGS CAUSING CHANGES IN ORAL FLORADRUGS CAUSING CHANGES IN ORAL FLORA

DRUGS AFFECTING GINGIVA &DRUGS AFFECTING GINGIVA &
ORAL MUCOSAORAL MUCOSA
GINGIVAL HYPERPLASIA – refers to an
increase in size of a tissue or an organ
produced by an increase in the number of its
component cells.
- Drugs - Phenytoin – Antiepileptic
- Nifedipine – Ca channel blockers
- Cyclosporine – immunosuppressive
agent

NSAID’s – chemical burns of the oral tissues are
common occurrences that may be accidental or from
misuse of products that are being used for self
medication. The ‘aspirin burn’ represents the typical
example. Aspirin is detrimental to dentures.
Agranulocytosis caused by its prolonged
consumption can account for low tissue tolerance
and subsequent ‘sore spots’ under dentures.
TRANQUILIZERS – leads to agranulocytosis.
Anaemia in any form leads to lowered tissue
tolerance.
LICHENOID DRUG ERUPTIONS – Lichen Planus
occurs on the oral mucosa.
Prosthodontists are likely to encounter patients with
this disorder, particularly if it causes any discomfort
or concern. www.indiandentalacademy.com

Drugs are - NSAID’s
- Antibiotics
- Antihypertensives
- Oral hypoglycemics
ORAL HYPOGLYCEMICS
- Drugs – Tolbutamide
- Chlorpropramide
- Phenformin
- Glipizide
- Giclazide
- Adverse effects – Hypoglycemia
- Nausea
- Vomitingwww.indiandentalacademy.com

ANTICANCER DRUGS
- Drugs - Alkylating agents – Mechlorethamine
- Dacarbazine
- Antimetabolites - Methotrexate
- Side effects – Loss of hair
- Xerostomia
- Brownish discoloration of teeth
& tongue
- Burning sensation of oral mucosa
- Erythematous areas
- Local ulcerations
- Increased tooth mobility

DRUGS CAUSING SIALORRHOEADRUGS CAUSING SIALORRHOEA
Excessive salivation causes difficulty in impression
making and can affect retention of dentures.
CHOLINERGIC DRUGS
Classified as
– Direct acting drugs - includes derivates of choline
and pilocarpine. They produce their effect by acting
like acetylcholine.
- Indirect acting drugs - Physostigmine
- Neostigmine
They produce their effect by inhibiting the enzyme
cholinesterase.
Adverse effects – Salivation, Lacrimation, Urination,
Confusion.

DRUGS AFFECTING BONEDRUGS AFFECTING BONE
CORTICOSTEROIDS
- Drugs - Hydrocortisone
- Cortisone
- Prednisolone
- Uses - Acute adrenal insufficiency
- Addison‘s disease
HEPARIN
- Used as an anticoagulant
- These drugs manifest osteoporosis but their role
in resorption of alveolar bone is not known.
VITAMIN D
- Influences the absorption of Ca from
gastrointestinal tract & its subsequent deposition in
bone. It leads to bone loss including alveolar
bone.

DRUGS CAUSING DYSPHAGIADRUGS CAUSING DYSPHAGIA
Difficulty in swallowing, gagging, could
cause difficulty during the making of an
impression.
a.Phenothiazine derivatives (Thorazine,
Sparine, Prolixin)
b. All agents that produce xerostomia
could lead to dysphagia.

DRUG CAUSING ORTHOSTATICDRUG CAUSING ORTHOSTATIC
HYPOTENSIONHYPOTENSION
Drugs - Phenothiazine derivatives
- Tricyclic anti depressants
- Antihypertensives
- Glyceryl trinitrite (Anti anginal)
GLYCERYL TRINITRITE (Anti anginal)
- Uses - Angina pectoris
- CHF & acute LVF
- MI
- Adverse effects - Fullness in head, throbbing
headache, flushing, dizziness and fainting.
Postural hypotension is a common side effect of these
drugs, raising the patient suddenly from the supine
position causes loss of consciousness. Therefore
abrupt movements of the patient should be avoided.

DRUGS CAUSINGDRUGS CAUSING
BRONCHOSPASM, BRADYBRONCHOSPASM, BRADY
CARDIA & DYSPNOEACARDIA & DYSPNOEA
Propranolol (Inderal) it is a β blocker.
Uses - Arrhythmias
- Angina
- Hypertension
- Migraine headache
Adverse effects - Depresses heart
- Produces broncho-
constriction
- Causes hypoglycemia
Bronchospasm or dyspnoea can cause difficulty inwww.indiandentalacademy.com

DRUGS CAUSINGDRUGS CAUSING
HYPOGLYCEMIC SHOCKHYPOGLYCEMIC SHOCK
Insulin – is used therapeutically to treat diabetes
mellitus.
In diabetics taking insulin, hypoglycemic reactions
may result from failure to eat, stress or inadvertant
administration of too large a dose of insulin.
The other symptoms include sweating, weakness,
hunger, tachycardia, mental confusion, headache.
Dental appointments for patients taking insulin
should not interfere with meals, stressful situations
should be minimized.

DRUG INTERACTION OF PARKINSON-DRUG INTERACTION OF PARKINSON-
LIKE SYNDROME & OTHER BIZARRE MUSCLELIKE SYNDROME & OTHER BIZARRE MUSCLE
MOVEMENTS INCLUDING FACIAL MUSCLESMOVEMENTS INCLUDING FACIAL MUSCLES
ANTIPSYCHOTIC DRUGS
Drugs - Chlorpromazine, Thiothixene,
Halopirdol
Uses - Psychoses, Anxiety, Antiemitic
Adverse effects – Drowsiness, lethargy, mental
confusion, postural hypotension (α adrenergic
blockade), dry mouth (anticholinergic).
Extra pyramidal disturbance (parkinsonism
like manifestation, acute muscular dystonias).

TRICYCLIC ANTIDEPRESSANTS
Drugs – Imipramine, desipramine, trazodone.
Adverse effect – Dry mouth (anticholinergic),
mental confusion, postural hypotension
(specially in older patients), fine tremors are
relatively common.
Uses – Endogenous depression, peptic ulcer,
migraine.
These movements can cause difficulty in
establishing & recording jaw relations.

CONCLUSIONCONCLUSION

REFERENCESREFERENCES
1. Ciancio G. Sebastian – Clinical pharmacology for dental
professionals 2nd
Edition – 1984.
2. Felpel P. Leslie – A review of pharmacotherapeutics for
prosthetic dentistry, Part I, JPD, 77(3); 1997.
3. Felpel P. Leslie - A review of pharmacotherapeutics for
prosthetic dentistry, Part II, JPD, 77(3); 1997.
4. Heartwell M. Charles, Rahn O. Arthur – Syllabus of
complete dentures, 4th
Edition – 1992.
5. Joglekar P. Anil – Biologic approach to complete dentures,
JPD, 30(4); 1973.
6. Jones M. Philip – Complete dentures and the associated soft
tissues, JPD, 36(2); 1976.
7. Moore A. Paul – The Dental Clinics of North America, 46(4);
2002.
8. Rutkauskas S. John – The Dental Clinics of North America,
41(4); 1997.
9. Tripathi D.K. – Essentials of medical pharmacology, 4th
Edition – 1999.

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