PHARMACOLOGY 1

Local Anesthetics
Pharmacology is one of the most tested topics on the INBDE and so a strong foundation is highly
recommended. In this set of notes, we will review all the pharmacology concepts tested on the INBDE,
including amides and esters, pharmacodynamics/pharmacokinetics, calculating local anesthetics,
vasoconstriction toxicity, needles and injection techniques, types of antibiotics, types of analgesics,
cardiovascular pharmacology, and ANS and CNS Pharmacology.

Local anesthetics can be categorized into two ‣ Bupivacaine (Marcaine)

main groups: amides and esters. Below, we - Longest duration of all local anesthetics
will discuss all the relevant information about - Not safe for use in children due to
these local anesthetics that you will need to prolonged soft tissue anesthesia
know for the INBDE: - 0.5% in solution

Esters
1 Types of Local Anesthetics
• Esters are metabolized in plasma by
pseudocholinesterase enzymes. Like
Amides amides, the names also end in the “-caine”
• Amides are metabolized by the liver and suf x.
the names commonly end with the suf x • Esters are usually more toxic and cause
“-caine”. Some important amide local more allergic reactions than amides due to
anesthetics are listed below: methylparabens.
• The following are some important esters to
‣ Lidocaine (Xylocaine) know for the INBDE:
- Safest for use in children ‣ Benzocaine
- 2% in solution - Commonly used as a topical anesthetic
‣ Mepivacaine (Carbocaine, Polocaine) prior to injection
- Causes the least amount of vasodilation - Risk of methemoglobinemia
- 2-3% in solution ‣ Cocaine
‣ Articaine (Septocaine) - Potentiates vasoconstriction
- Shortest duration of all the local ‣ Procaine
anesthetics
- Has an ester chain attached and so it is
metabolized by BOTH liver and plasma INBDE Pro Tip:
- 4% in solution Know the unique points associated with
‣ Prilocaine (Citanest) each local anesthetic. This is a topic heavily
- Risk of methemoglobinemia (Blood tested on the INBDE.
disorder where abnormal amount of
hemoglobin production) → can lead to
insuf cient O2 delivery to cells

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 PHARMACOLOGY 2

2 Pharmacodynamics/Pharmacokinetics ‣ ↓ pKa = faster onset of action

- Why? ↓ pKa ! drug gives up proton
Pharmacodynamics easily ! drug becomes non-ionized !
• Pharmacodynamics refers to the effect a drug crosses membrane
drug has on the body. Generally, local
anesthetics have the following
Drug pKa
pharmacodynamic characteristics:
‣ Sodium channel blockers Mepivicaine 7.6
- Sodium channels in neurons allow the
Articaine 7.8
in ux of sodium ions for depolarization
to signal pain Lidocaine 7.9
‣ Non-ionized (free base) forms can only
Prilocaine 7.9
cross the hydrophobic neuron membrane
- Blocking the channel can only be done Bupivacaine 8.1
from inside the cell
‣ Local anesthetics are much less effective
in in amed tissue 3 Calculating Local Anesthetics
- In amed tissue has a lower pH
- Excess H+ ions favor an equilibrium
where the drug is in an ionized form = A carpule/cartridge of local anesthetic has
cannot cross the membrane 1.8mL. A local anesthetic at a concentration of
‣ Critical length 1% local anesthetic has 18mg of local
- Complete anesthesia – when 3 anesthetic. For 100% solution, there is 1.8g or
consecutive nodes of ranvier are 1800mg of the drug. It’s important to know
blocked these numbers for the INBDE.
- There is a better chance of anesthesia,
when there is a longer length of nerve
Example 1.31
bathed in anesthetic
Question: The most common local
Pharmacokinetics
anesthetic used in dentistry is 2% Lidocaine
(1:100000 epinephrine). How many mg of
• Pharmacokinetics refers to how an lidocaine are present in a carpule (1.8mL)
individual’s body affects a drug. Below are
of this iteration?
some examples of how the body impacted
by local anesthetics. It is important to know
Solution:
these concepts for the INBDE.
The calculation is simple for Lidocaine: 1%
‣ ↑ protein binding leads to ↑ duration of contains 18mg of lidocaine; hence 18mg/
action
1% x 2% = 36 mg of lidocaine.
‣ ↑ lipid solubility/hydrophobicity leads to
↑ potency + duration of action
Therefore, there are 36mg of lidocaine.
‣ ↑ blood ow leads to ↓ duration of action

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 PHARMACOLOGY 3

4 4 Vasoconstriction & Toxicity

Example 1.41

Vasoconstriction
Question: The most common local
• As previously mentioned, epinephrine and anesthetic used in dentistry is 2%
other kinds of vasoconstrictors are often
Lidocaine (1:100000 epinephrine). How
packaged in a solution with local
many mg of epinephrine are present in a
anesthetic.
carpule of this iteration?
• There are 3 main purposes for this:
1. Hemostasis Solution:
‣ Counteracts vessel dilation of local With epinephrine, the amount is given
anesthetic
as a ratio, which should rst be
2. Longer anesthesia converted into a percentage: 1/100 000
‣ Decreased blood ow decreases the x 100% = 0.001%; hence 0.001% x
amount of anesthetic carried away from
18mg/1% = 0.018mg of epinephrine.
nerves
3. Reduced toxicity Therefore, there are 0.018mg of
- Increased blood vessel constriction epinephrine.
decreases the systemic impact of the
drug

Maximum Epinephrine Dosages

• The following are important numbers to
remember for maximum dosage limits in
healthy as well as cardiac patients:

Drug Max dose

Healthy Patient 0.2 mg

Cardiac Patient 0.04 mg

Maximum Local Anesthesia Dosages

• The maximum dosage of Lidocaine with and
without epinephrine is 4.4mg/kg and 7mg/kg
respectively.
• The maximum dosage of Articaine with
epinephrine is 7mg/kg

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 PHARMACOLOGY 4

Needles & Injections

1 Measurements • Numbs lips and gingiva of all teeth in
quadrant, except gingiva of molar region
Length • Tongue numbed in the quadrant if the
• Two options lingual nerve is blocked as well
‣ Long needle = 32mm • Vazirani-Akinosi = closed mouth technique
‣ Short needle = 20mm which can be useful in cases of truisms
• Gow-Gates = open mouth method which
Diameter blocks the anesthetizes virtually the
• Three options entirety of V3
‣ 30-guage = 0.3mm
‣ 27-guage = 0.4mm Injection Steps
‣ 25-guage = 0.5mm 1. Approach from the opposite side of the
mouth towards the molars/premolars
• Larger gauge/diameter needles are often • Aim 10-15mm above the mandibular
advantageous for the following reasons: occlusal plane and parallel to that plane
‣ They don’t bend as much 2. Advance the needle slowly until bone is
‣ They don’t break as often felt
‣ Better aspiration 3. Slowly withdraw the needle ~1mm and
- Aspiration – slightly drawing nger aspirate
back on the syringe to detect the 4. If no blood is detected, inject at 1 carpule/
presence of blood min

Buccal Nerve Block

2 Injection technique
• Anesthetizes soft tissue buccal to molars
(the tissue the IAN block does not target)
There are several different techniques for local
anesthetic injection. Aiming to deliver the
Injection Steps
anesthetic slowly over the course of 60
1. Inject from the buccal to the distal most
seconds will decrease the discomfort for the
molar, approximately parallel to the
patient.
occlusal plane

Inferior Alveolar Nerve Block (IAN Block)

Mental Nerve Block
• Injection in the center of the area bordered • Anesthetizes soft tissue facial to anterior
by
teeth
‣ Coronoid notch • Does not numb the teeth itself
‣ Pterygomandibular raphe
‣ Upper maxillary molars Injection Steps
• High failure rate due to dif culty of 1. Locate the rubbery neurovascular bundle
injection
with a nger
• Numbs all the mandibular teeth of the 2. Insert needle anterior to mental foramen
quadrant
by apices of premolars
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 PHARMACOLOGY 5

2. Insert needle anterior to mental foramen Injection Steps

by apices of premolars 1. Inject at muccobuccal fold directly over the
3. Aspirate and slowly inject 1st premolar into the infraorbital foramen

Incisive Nerve Block Greater Palatine Nerve Block

• Anesthetizes the anterior teeth and • Anesthetizes posterior hard palate and
premolars of the quadrant overlying tissue from 3rd molar to 1st
premolar up to the midline
Injection steps • Targets needle into the greater palatine
1. Follow the same steps as the mental nerve foramen
block, inject over 20 seconds • Often painful
2. Hold pressure on injection site for 2
minutes in order to increase the volume of Injection Steps
anesthetic into the mental foramen 1.Use a cotton tip to push gently along the
area where the alveolar ridge meets the
Posterior Superior Alveolar Block hard palate. The site where the cotton tip
• Anesthetizes maxillary molars and buccal dips down is your injection site
tissue
• Does not numb the mesio-buccal root of Nasopalatine Block
the 1st molar in 28% of patients • Most painful injection
‣ Supplied by middle superior alveolar • Anesthetizes the hard palate from canine to
nerve block canine on the maxilla
• High risk of hematoma due to injection • Most painful injection
being close to group of blood vessels
Injection Steps
Injection Steps 1. Inject palatal mucosa lateral to the incisive
1. Palpate for zygomatic process and aim papilla
needle posterior to that
2. Retract cheek; and inject needle into Local In ltration
mucosa above 2nd maxillary molar at a 45- • Local anesthetic diffuses through bone to
degree angle to occlusal and vertical plane numb the terminal branching nerves
3. Inject until the needle is 16mm in depth entering the pulp of the tooth
(half the length of a long needle) • Septocaine or Articaine are often used
4. Swing the needle so it is 45 degrees to the ‣ Best for bone penetration
back of the maxillary tuberosity • Works well in anterior teeth
‣ Facial cortical plate is thin = better
Infraorbital Block diffusion of anesthetic
• Also known as true anterior superior
alveolar block Injection Steps
‣ Targets anterior superior and middle 1. Inject the needle into the vestibule above
superior alveolar nerve the tooth of interest and aim for the root
• Anesthetizes maxillary anteriors and apex
premolars

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Summary

Figure 2.21 Injection sites

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 PHARMACOLOGY 7

Antibiotics
1 Requirement of Antibiotic Prophylaxis Carbapenems
• “-nem” suf x
‣ Meropenem
The use of antibiotic prophylaxis in dental • β-lactam – inhibit cell wall synthesis
practice is not common. However, there are • Bactericidal
certain instances where their use is required in
invasive treatments involving manipulation of
Penicillins
gingival tissue, or the periodical region of a • Majority have “-cillin” suf x
tooth. • β-lactam – inhibit cell wall synthesis
• Cross-allergenic with cephalosporins
Appropriate use of antibiotic prophylaxis
‣ penicillin is chemically related, so the
• Patients with cardiac conditions:
immune system might see them both as
‣ Prosthetic cardiac valve the same if the patient is allergic to either
‣ Previous or recurrent infective one
endocarditis
• Bactericidal
‣ Congenital heart disease
‣ Cardiac transplant patients with The following are speci c types of penicillin
valvulopathy
and their associated characteristics:
• Consider a consultation with the primary
physician for:
1. Penicillin V – oral administration
‣ Immunosuppresion secondary to 2. Penicillin G – IV administration
neutropenia, cancer chemotherapy or
3. Amoxicillin – broad spectrum
solid organ transplant
4. Augmentin – includes amoxicillin and
‣ Sickle cell anemia clavulanic acid (works against β-lactamase
‣ High dose corticosteroid use
resistant bacteria)
‣ Poorly controlled diabetes
5. Carbenicillin – for use against
‣ Diseases of autoimmunity
pseudomonas

Monobactams
• “-am” suf x
2 Types of Antibiotics
‣ Aztreonam
• β-lactam – inhibit cell wall synthesis
Tetracyclines • Bactericidal
• “-cycline” suf x
‣ doxycycline, tetracycline
• Protein synthesis inhibitor – binds to 30S
ribosomal subunit
• *Broadest antimicrobial spectrum
• Bacteriostatic

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 PHARMACOLOGY 8

Cephalosporins Lincosamides
• “Ceph-“ pre x • “-mycin” suf x
• β-lactam – inhibit cell wall synthesis ‣ Clindamycin, Lincomycin
• grouped into generations based on their • Protein synthesis inhibitor - binds to 50S
spectrum against speci c bacteria ribosomal subunit
‣ 1st Gen = Cephalexin (Ke ex) • Bacteriostatic
‣ 2nd Gen = Cefonicid
‣ 3rd Gen = Ceftriaxone 3 Medical Prescriptions (Rx)
‣ 4th Gen = Cefepime
• Bactericidal
Prescription of antibiotics will vary with each
Fluoroquinolones patient based on their age, medical history,
• “- oxacin” suf x is common current medications and other factors.
‣ Cirpo oxacin
• DNA synthesis inhibitor Rx for Infective Endocarditis Prophylaxis
• Bactericidal
Patient Time of
Rx
Sulfonamides /Case Admin
• “Sulfa-“ pre x
First choice Amoxicillin 2g 60 mins
‣ Sul soxazole prior to tx
• Folate synthesis inhibition
‣ Results in folate de ciency that impacts Children Amoxicillin 60 mins
DNA synthesis 50mg/kg prior to tx
• Bacteriostatic Penicillin Azithromycin 60 mins
allergy 500mg prior to tx
Macrolides
• “-thromycin” suf x Children and Azithromycin 60 mins
Penicillin 15mg/kg prior to tx
‣ Azithromycin
• Protein synthesis inhibitor - binds to 50S allergy

ribosomal subunit IV Ampicillin 2g 30 min

• Bacteriostatic before tx

Children, IV Ampicillin 50mg/ 30 min

kg before tx

Rx for Prosthetic Joint Prophylaxis

Antibiotic prophylaxis before dental treatment is no
longer recommended for prevention of prosthetic
joint infections according to the ADA.

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 PHARMACOLOGY 9

Side Effects Drug Concentration

Knowing the side effects of antibiotics is not • Tetracycline concentrates well in gingival
only important for general knowledge, but is crevicular uid
also important when it comes to prescriptions. • Clindamycin concentrates well in bone
• For example, it is best not to prescribe
tetracycline to a patient with liver issues. Antivirals & Antifungals
The following are common antivirals and
Associated antifungals prescribed in dental practice:
Side Effect • Acyclovir, Valcyclovir
Antibiotic
‣ “-vir” = antiviral
Pseudomonas colitis Clindamycin ‣ Used for herpes
Very Broad
• Fluconazole
Superinfection spectrum ‣ “-azole” = antifungal
antibiotics ‣ Used for candidiasis

Aplastic anemia Chloramphenicol

Liver damage Tetracycline

Drug Interactions
The following drug combinations are not
recommended and should not be prescribed:
1. Bactericidal and bacteriostatic drugs
‣ Bactericidal kills bacteria when they are
rapidly growing; bacteriostatic drugs
inhibit this rapid growth = drugs cancel
each other out
2. Antibiotics and oral contraceptives
‣ Antibiotics suppress normal
gastrointestinal ora involved in recycling
of active steroids in the contraceptive
3. Penicillin and probenecid
‣ Probenecid alters renal clearance of
penicillin
4. Tetracycline + antacids/dairy
‣ Antacids & dairy reduce absorption of
tetracycline via calcium/ion binding
5. Broad spectrum antibiotics and
anticoagulants
‣ Anticoagulants actions are enhanced

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 PHARMACOLOGY 10

Analgesics
1 Acetaminophen
Celecoxib COX 2
(Celebrex)
Acetaminophen is commercially known as
Tylenol; and there are several key points to Meloxicam COX 2 Treatment of
know about this drug. (Mobic) arthritis
• Maximum daily dose - 4000 mg
• Inhibits pain in the central nervous system
Therapeutic Effects of Aspirin
• Drug of choice for a feverish child
• Anti-in ammatory and Analgesic
‣ Aspirin is known to cause Reye’s
‣ Inhibits COX 1 & 2 (PG synthesis)
Syndrome
• Antipyretic
• Negatively impacts the liver
‣ Inhibits PG synthesis in the hypothalamus
‣ Toxic at higher doses
(temperature regulation center)
‣ Greater damage when combined with
• Inhibits clotting
alcohol
‣ Inhibits TXA2 synthesis = inhibits platelet
aggregation
2 NSAIDS
The mechanism of action for aspirin is very
Types of NSAIDS important to know and highly testable on the
NSAIDS work by inhibiting COX 1 and/or COX INBDE.
2. Normally, COX1 and COX2 promote
in ammation by generating prostaglandins Toxic Effects of Aspirin
(PG). By blocking COX1 & 2, there is a • G.I bleeding
corresponding reduction in the effects of PGs. • Metabolic acidosis
Below is a table summarizing important • Salicylism
NSAIDS to study for the INBDE. • Tinnitus
• Nausea & vomiting
• Delirium
Name Blocking Association • Hyperventilation
Aspirin (ASA) COX 1 & 2 Impacts GI
(irreversible)
INBDE Pro Tip:
Ibuprofen COX 1 & 2 Impacts
The maximum daily dose of ibuprofen is
(Motrin, Advil) (reversible) kidney
3200mg.
Naproxen (Aleve) COX 1 & 2
(reversible)

Ketorolac (Acular) COX 1 & 2 IV, IM, or oral

(reversible) route

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3 Steroids • Tramadol
• Fentanyl
Corticosteroids • Sufentanil
Corticosteroids are man made steroids which • Heroin
mimic the action of cortisol, which is produced
in the adrenal cortex of the adrenal gland. The Combination Narcotics
common suf x they share is “-one”. Therapeutic Effects & Side Effects of
• Prednisone Morphine
• Dexamethasone The effects of morphine can easily be
• Hydrocortisone memorized using the following acronym:

Therapeutic Effects Miosis (pupil constriction)

• Analgesic & Anti-in ammatory Out of it (sedation)
‣ Inhibit phospholipase A2 = inhibit Respiratory depression
arachidonic acid synthesis Pneumonia (aspiration pneumonia)
Hypotension
Side Effects of Steroids Infrequency of urination & constipation
• Immunosuppression if used chronically Nausea & vomiting
• Gastric ulcers Euphoria & dysphoria
• Osteoporosis
• Fat redistribution Overdose & Addiction
• Hyperglycemia The following drugs can be used when an
• Acute adrenal insuf ciency overdose or addiction of morphine occurs:
‣ Follows the Rule of Twos • Naloxone
- Adrenal suppression can occur if a ‣ Inverse agonist, for emergencies
patient is taking 20mg of cortisone (or • Naltrexone
its equivalent) for 2 weeks within 2 ‣ Antagonist, treats addiction
years of dental treatment In emergencies, half life of naloxone can be
- Patient may need supplemental doses shorter than the half life of the opioid,
of steroids prior to therapy therefore, multiple doses of naloxone may be
required.

4 Narcotics/Opioids
INBDE Pro Tip:
Methadone is a synthetic opioid agonist that
Types of Narcotics
• Codeine can be used not only for relief of pain, but
for opioid addiction
• Hydrocodone
• Oxycodone
• Oxycontin
• Meperidine
• Morphine

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Drug Schedule

Drugs and substances are classi ed into ve

schedules or categories which are based on
their potential to be abused. Substances in the
Schedule I category have the highest abuse
potential. These schedules are not exclusive to
opioids. Examples of opioids and various
categories are included in the table below.

Name Opioid

Schedule I Heroin

Schedule II Oxycodone, fentanyl, meperidine

Schedule III Acetaminophen + codeine

Schedule IV Tramadol

Schedule V Cough medicines with codeine

5 Nitrous Oxide

Nitrous oxide is commonly known as laughing

gas; and is often in a blue colored tank in
dental of ces. The following are a few
characteristics of nitrous oxide:
• Tingling sensation before onset
• A ow rate of 5-6L is generally acceptable
• Patient must breathe through their nose
• Nausea (side effect)
• Peripheral neuropathy from long term
exposure
• Minimum alveolar concentration (MAC) =
105%
‣ MAC – concentration in alveola required
for 50% of patients to be immobile
‣ Impossible to go over 100%, so 105%
implies N2O has very low potency
• Diffusion hypoxia
‣ N2O can get trapped in lungs
‣ Always give patient 100% O2 for 5
minutes to eliminate N2O from the body
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Pharmacokinetics
1 Steps of Pharmacokinetics • Systemic drugs need to enter the
bloodstream to reach the rest of the body
Pharmacokinetics in simple words, is the study ‣ Cross cell lumen ! apical membrane !
of what the body does to a drug. It does not basolateral membrane ! interstitium !
study what the drug binds to, its therapeutic or endothelial lining ! reaches blood
its toxic effects. After the administration, the • 100% bioavailability can only occur if drug
following are the steps is administered through IV
The following are the sequential steps of a
drug’s path through the body: The effect of pH is also important to consider.
1. Absorption The way an acidic or basic drug interacts with
2. Distribution its environmental pH can alter the charge of
3. Metabolism the drug and subsequently its absorption.
4. Elimination Generally, drugs should be of neutral charge
for absorption to take place.
Routes of Administration
• Enteral - oral, sublingual, and rectal Acidic Drug Basic Drug
• Parenteral - intravenous, intramuscular, and
subcutaneous Acidic Non-ionized Ionized
• Other routes - intranasal, inhalation, topical Environment
and vaginal Basic Ionized Non-ionized
Environment
Absorption
Generally, drugs must cross several epithelial
• Weak acids – pH < pKa for absorption
or endothelial cell layers (barriers) to enter the
• Weak bases – pH > pKa for absorption
body, in order for absorption to take place.
• We want the drug to be non-ionized for it
Different methods of administration have
to be absorbed at the appropriate location
different barriers to cross. Here are a few facts
to know: Distribution
• Epithelial cell layers need to be crossed • For adequate systemic distribution, a drug
when administering drugs that absorb must rst reach the blood stream.
through the skin, intestines, respiratory ‣ Topical drugs are an exception
system and genitourinary tract • Once the drug arrives at the target tissue,
• Endothelial cells need to be crossed to
it passes through endothelial cells, cellular
reach blood vessels interstitium and nally the basolateral
• Local drugs are active at the site of
membrane of the tissue cell type
administration/absorption • Systemic drugs normally reach vessel rich
organs quickly
‣ Heart, liver, lungs

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 PHARMACOLOGY
First Pass Effect
• Drugs absorb through the GI system and
are sent from the hepatic portal system to
the liver
• The liver metabolizes the drug, leaving a
smaller fraction of the drug to travel
through the circulatory system
• Oral drugs undergo the above noted
process, which is known as the First Pass
Effect
Volume of Distribution (Vd)
• Volume (L) of total body water in which a
drug will partition
• Describes distribution of a drug across
three body water compartments
‣ Plasma (4%)
‣ Interstitial (16%)
‣ Intracellular (40%)
• People who have less body water than the
average male adult should be given a lower
drug dose to properly aid distribution
‣ Women
‣ Obese
‣ Elderly
• Brain and muscle have the highest water
content, while adipose tissue has the
lowest water content
Metabolism
Metabolism refers to the way a drug is
chemically altered and inactivated in the body.
There are two main phases of drug metabolism
reactions:
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Phase I
• Functionalization (oxidation, reduction,
hydrolysis)
‣ oxidation is the most common
• Achieved through Cytochrome P450
enzymes
Phase II
• Conjugation (glucouronide, glutathione,
glycine
‣ Covalently add polar side chains to the
drug
‣ Glucuronide is the most common side
chain added via UDP-
glucuronosyltransferase
Both phase I and II reactions share the
following common characteristics:
• Drugs sometimes go through both phases
or just one phase
• Both phases decrease the ef cacy of the
drug/inactivate the drug
• Both phases increase drug polarity, which
prevents passive diffusion and facilitates
renal and GI clearance of the drug
Figure 5.11 Drug metabolism
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 PHARMACOLOGY 15

Elimination Examples of Dental Drug-Drug Interactions

Elimination refers to how a drug is removed Factors In uencing Drug Effectiveness
from the body The effect of the same drug can vary amongst
• Elimination occurs mostly in the kidneys different people due to several factors:
• Phase I creates polar molecules, which 1. Prescribed dose
goes to the kidneys for urinary clearance ‣ Medical errors
• Phase II creates polar and larger molecules, ‣ Patient compliance
2. Administered dose (affected by
which tend to clear in the GI tract as feces
pharmacokinetics)
‣ Absorption
‣ Distribution
2 Drug-Drug Interactions
‣ Metabolism
‣ Elimination
When drugs interact, one drug can affect the 3. Active dose (affected by pharmacodynamics)
pharmacokinetics of the other drug. These ‣ Drug-receptor interaction
interactions normally occur in the metabolism 4. Intensity of effect
phase. There are commonly two kinds of
effects from drug interactions:

• Induction – drug A induces liver

cytochrome enzymes = ↑ metabolism = ↓
effect of drug B
• Inhibition – drug A competes for
metabolism or inhibits liver cytochrome
enzymes = ↓ metabolism of drug B = ↑
toxicity of drug B

Dental Interacting Interaction risk

Drug Drug

NSAIDS Lithium ↑ lithium toxicity

NSAIDS Hypotensives ↓ effect of

hypotensive

NSAIDS Anticoagulants ↑ risk of bleeding

Penicillins Oral ↓ oral contraceptive

contraceptives effect

NSAIDS Methotrexate ↑ methotrexate

toxicity

Metronidaz Warfarin ↑ risk of bleeding

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 PHARMACOLOGY 16

Pharmacodynamics
Pharmacodynamics in simple words, is the
study of the effects drugs have on the body.
These can be viewed from two different
perspectives:
1. Drug targets - these are often protein
carriers, channels, enzymes, or receptors.
2. Drug interactions - these often involve
agonists, inverse agonists, and
antagonists. Figure 6.11 Response Curve

2 Dose Response Curves

1 Interactions
Type I Dose Response Curve
Agonists
A type I dose-response curve is used to
Agonists mimic the effects and cause the same
correspond the response/ef cacy of a drug (Y-
action as an endogenous agonist molecule.
axis) to the drug dose (x-axis). Its shape can
Agonists can produce a full 100% of its
either be log form, or hyperbolic.
intended effect (full agonist) or less than 100%
(partial agonist.)
A dose response curve can be used to describe
the characteristics of a drug
Antagonist
• Intrinsic activity (Emax) - maximal effect of a
Antagonists work opposite to agonists in that
drug
these will inhibit the action of the endogenous
‣ Full agonist Emax = 1
agonist. The mechanism in which this inhibition
‣ Partial agonist Emax = 0-1
occurs is through 2 main ways:
‣ Antagonist Emax = 0
1. Competitive antagonist – competing
• Ef cacy – effect of a drug when it binds to
directly with an agonist for the same
the target
binding site located on the receptor. This
• Af nity – level of attraction of a drug to its
site is called an active site.
receptor
2. Non-competitive antagonist – binds to a
‣ Dissociation constant (Kd) –
position other than the active site, but
concentration of drug needed to occupy
manages to prevent the binding of the
50% of receptors
agonist. Oftentimes, non-competitive
‣ Lower Kd represents a higher or greater
antagonism will chance the shape or
af nity
conformation of the receptor at the active
• Potency – strength of a drug at a certain
concentration
Inverse Agonist
‣ Effective concentration (EC50) describes
Inverse Agonists not bind at the same active
the concentration at which half the
side as an agonist (preventing their
maximal effect is achieved
interactions) but will produce an effect that is
‣ the more potent the drug, the lower the
opposite that of the agonist
EC50

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 PHARMACOLOGY
The presence of antagonists may change the
shape of the Type I dose Response Curve
• Competitive antagonists will shift the curve
to the RIGHT
• Non-competitive antagonists will shift the
curve DOWN
Figure 6.21 Type 1 Response
Type II Dose Response Curve
In a type II dose-response curve, the x-axis
measures the drug dose; and the y-axis
measures the quantity of subjects responding
to a drug.
Type II dose-response curves can show 3
different curves representing the following
scenarios:
• Therapeutic effect curve
‣ ED50 – dose at which the desired effect
effect is produced in 50% of the
population
• Toxic effect curve
‣ TD50 – dose at which a toxic effect is
produced in 50% of the population
• Lethal effect curve
‣ LD50 – dose at which a lethal effect is
produced in 50% of the population
17
Figure 6.22 Type 2 Response
Therapeutic Index (TI) is an indicator of drug
safety. A larger index indicates a safer drug, as
it implies a larger difference in dose between
the therapeutic dose and the toxic dose.
• In animal studies…. TI = LD50/ED50
• In human studies…. TI = TD50/ED50
3 Effects of Drug Interaction
Additive
• Drugs interact to combine their individual
degrees of effect
• Effects are combined
Antagonist
• Drugs interact to lessen the effect than if
one drug were to be used alone
• Chemical antagonism – a drug binds to
another drug to prevent the other’s
function
• Receptor antagonism – competition
between two drugs for the same receptor
• Pharmacokinetic antagonism – one drug
affects the pharmacokinetics of another
drug
• Physiologic antagonism – two drugs with
opposing effects on the same tissue on
distinct receptors
Synergist
• Combining drugs leads to a greater effect
than the sum of their independent effects
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Autonomic Nervous System

The following are examples of the opposing

1 ANS Physiology
effects of the SNS and PNS:

The sympathetic nervous system (SNS) and

Fight or Flight (SNS) Rest & Digest (PNS)
parasympathetic nervous system (PNS) are
branches of the ANS. In many systems, they Slows digestion Increases digestion
have opposing effects.
↑ Heart rate ↓ Heart rate
• SNS effects promote “ ght or ight”
• PNS effects promote “rest and digest”; ↓ Saliva production ↑ Saliva production
• Some important exceptions to this rule are
Pupillary dilation Pupillary constriction
‣ The vasculature to skeletal muscles are
controlled by the SNS Bladder relaxation, Bladder constriction,
‣ The sweat glands are controlled by the increase urination decrease urination
SNS
Bronchi dilation Bronchi constriction

All nerve pathways originate from the CNS

(brain & spinal cord) 2 Receptors in the ANS
• 12 cranial - PNS
• 0 cervical – autonomic nerves do not
Receptors in the ANS can be described in
originate here
different ways.
• 12 thoracic - SNS
Ionotropic – ion channel
• 5 lumbar - SNS
Metabotropic – G-protein coupled receptor
• 5 sacral – PNS
• 7-transmembrane domain
• Activates a secondary messenger system
• All receptors in target organs of the
autonomic nervous system are
metabotropic

Receptors in the ANS are most often referred

to as cholinergic and adrenergic.
• Cholinergic - respond to acetylcholine
(Ach) and are found in the PNS and SNS
‣ Nicotinic (nAchR)
- Also binds nicotine, Ionotropic
- All receptors in the medulla and
ganglion
‣ Muscarinic (mAChR)
- Also binds muscarine, GPCR
• Adrenergic = binds Epinephrine and
Norepinephrine; GPCR
Figure 7.11 Autonomic Nervous o Receptors in the SNS

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 PHARMACOLOGY 19

SNS vs PNS Muscarinic Receptors

Differences between the SNS and the PNS can There are different types or isoforms of
be distinguished by the following methods: muscarinic post-ganglionic receptors,
• Effect on organs differentiated by their target organ.
‣ SNS – ght or ight 1. M1 = CNS - autonomic ganglia
‣ PNS – rest and digest 2. M2 = Heart
• The spinal cord region they originate in ‣ Bradycardia = ↓ heart rate + electrical
‣ SNS - thoracolumbar conduction
‣ PNS - craniosacral 3. M3 = Smooth muscle & Exocrine glands
• Neurotransmitters used ‣ Salivation, urination, defecation, sweating
‣ SNS – Ach to ganglion, NE from nerves ‣ Smooth muscle contraction
and Epi/NE from adrenal gland ‣ Vascular endothelium vasodilation
‣ PNS – Ach throughout 4. M4 = CNS
• Neurotransmitter receptors used 5. M5 = CNS
‣ SNS – adrenergic metabotropic receptors
at target organs
‣ PNS – muscarine metabotropic receptors 3 M Agonist Drugs
at target organ
• Length of pre & postganglionic neurons
M agonists activate muscarinic receptors in the
‣ SNS – short preganglionic to sympathetic PNS. Some are non-selective to target all M
trunk, long post-ganglionic receptors, while others are selective to certain
‣ PNS – long preganglionic, short M receptor types.
postganglionic • Non-selective M agonists will affect M1-5
receptors if systemic in its distribution and
Synthesis of Neurotransmitters should not be used systemically in patients
• Acetyl CoA + choline = acetylcholine
with these following conditions
‣ The enzymes involved in the creation and ‣ Asthma/COPD - these conditions result
breakdown of acetylcholine are in air ow obstruction to the lungs.
acetyltransferase and Muscarinic agonists can
acetylcholinesterase respectively bronchoconstriction, thereby
exacerbating the disease
• Tyrosine ! L-DOPA ! dopamine ! NE !
‣ Peptic ulcers - muscarinic agonists can
Epi cause an increase in the secretion of
‣ Catecholamines = dopamine, NE, Epi gastric acid, worsening peptic ulcers
‣ Monoamines = dopamine, NE, Epi, ‣ Coronary Heart Disease - the cardiac
serotonin (5-HT), histamine inhibition observed with muscarinic
agonists can worsen cases of coronary
heart disease
‣ Hyperthyroidism - muscarinic agonists
can cause a depression of the cardiac
system, causing the body to compensate
and release epinephrine. Epinephrine in
patients with hyperthyroidism can cause
arrhythmias.
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 PHARMACOLOGY 20

M-Agonists List N-Antagonists/Neuromuscular Blockers

Neuromuscular blockers block nicotinic
Direct acting Activates M-receptor receptors of the somatic nervous system.

Pilocarpine Used to stimulate saliva or eye

drops to constrict pupils and Depolarizing Irreversible N-antagonist
reduce pressure
Succinylcholine Relieve laryngospasm & helps
to facilitate tracheal intubation
during surgery
Indirect acting Non-competitively
inhibits
acetylcholinesterase

Physostigmine & Reversible inhibit 5 Sympathetic Nervous System

Neostigmine cholinesterase

Insecticides and Irreversibly inhibits In the sympathetic nervous system,

Nerve gases cholinesterase. High
poison potential!
Treatment with Pralidoxime
M-Antagonists/Ganglionic Blockers
epinephrine (Epi) and norepinephrine (NE) act
on the effector organs to elicit the ght or
ight autonomic response. These
neurotransmitters are synthesized through the
following process:

Tyrosine ! L-DOPA ! dopamine ! NE ! Epi

Competitive Block Muscarinic receptor,

Inhibitors compete with acetylcholine
Scopolamine Helpful in the reduction of
saliva
Atropine Helpful in the reduction of
saliva, as well as the treatment
of acute bradycardia.
4 Nicotinic Antagonist Drugs
Non-depolarizing Allosteric inhibitor
Mecamylamine & Previously used as an
Hexamethonium antihypertensive
• Dopamine, Epinephrine, Norepinephrine
= catecholamines
• Dopamine, Epinephrine, Norepinephrine,
serotonin (5-HT), histamine =
monoamines
Adrenergic Receptors
There are different types of adrenergic post-
ganglionic receptors based on the organ they
affect.
1. ⍺1 – smooth muscle in blood vessels
‣ vasoconstriction, urinary retention, pupil
dilation (mydriasis)
2. ⍺2 – smooth muscle in blood vessels
i. vasoconstriction

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 PHARMACOLOGY 21

3. β1- heart Sympathomimetics

‣ ↑ cardiac output, heart rate, electrical
conduction, and strength of contraction
‣ Renin release from kidneys, leading to
vasoconstriction
4. β2- smooth muscle
‣ bronchodilation, vasodilation, thickened
salivary secretions
Sympathomimetics are agents that are used in
order to increase the effects of endogenous
catecholamines. They can be direct (act at an
adrenergic receptor) or indirect (by other
means.)
Name Effect

Adrenergic Agonist Amphetamine & Stimulates release of stored

Ephedrine norepinephrine

Name Receptor Activated Tricyclic Inhibits reuptake of

antidepressants serotonin & norepinephrine
Phenylephrine ⍺1, reduces swelling through
(Sudafed) peripheral vasoconstriction Monoamine Prevents the breakdown of
oxidase inhibitors monoamines
Norepinephrine ⍺ & β1 receptors
Methylphenidate Psychostimulant for AHD,
Epinephrine ⍺ & β receptors prevents the reuptake of
Albuterol β1 receptor, bronchodilator monoamines
used as an emergency inhaler Cocaine Prevents the reuptake of
for asthma monoamines

Adrenergic Antagonist Sympatholytics

Sympatholytics oppose the effects of neuron
Name Receptor Blocked ring at effector organs by the sympathetic
nervous system. This can be done by any
Phentolamine Blocks all ⍺ receptors,
mechanism. With this de nition, one could
used in the reversal of
argue that adrenergic antagonists are also
soft tissue anesthesia
considered sympatholytics.
Chlorpromazine ⍺1 receptor
(CPZ)
Name Effect
Metoprolol & β1 receptor
Guanethidine Inhibits release of
Atenolol (cardioselective)
catecholamines
Propranolol β receptors, prolongs
Reserpine Depletes the stored not
lidocaine duration
epinephrine

Clonidine & ⍺2 agonist (CNS) which blocks

Metyldopa SNS signal. It is NOT
potentiating the SNS signal

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 PHARMACOLOGY 22

Epinephrine Reversal
• Epinephrine has a vasoconstriction effect
• In the presence of an alpha blocker, such as
phentolamine, β2 vasodilatory effect
dominates and becomes the major vascular
response

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 PHARMACOLOGY 23

Cardiovascular Pharmacology
1 The Circulatory System 2. Hydralazine causes vasodilation by
opening K+ channels in cells and allowing
The human circulatory system is a system which easier ow of blood
consists of a heart (the pump) pumping blood 3. Calcium channel blockers block in ux of
(the uid) through vessels (the tubing) to their calcium in cells to cause vasodilation
target organs. ‣ Verapamil
Another way to describe the circulatory system ‣ Amlodipine
is as follows ‣ Nifedipine
• Heart = cardiac output (CO) 4. ACE inhibitors inhibits the conversion of
• Vessels = peripheral resistance (PR) angiotensin I ! angiotensin II (potent
• Blood = blood volume (SV) vasoconstrictor)
‣ “-prils” (suf x)
Blood pressure (BP) and cardiac output (CO) 5. Angiotensin receptors blockers (ARBs)
can be calculated using the following formulas: competitive antagonist at angiotensin II
BP = CO X PR receptor
CO = SV X HR ‣ “-sartans” (suf x)
Additional terms include:
• Preload – the amount of lling pressure of
the heart at the end of diastole Antihypertensive Side Effects
• Afterload – the pressure the heart gives to drugs
eject the blood during systole Diuretics Xerostomia, nauseas
• Systole – period of heart contraction and
ejection Adrenergic Blocking Xerostomia, depression,
• Diastole – period of heart relaxation and Agents sedation, sialadeuosis

lling Lichenoid reaction

Angiotensin- Lichenoid reaction,

2 Cardiovascular Drugs Converting Enzyme burning mouth, loss of
Inhibitors. (ACEIs) taste
Antihypertensives
Caldium Antagonists Gingival hyperplasia,
Antihypertensives are used in treatment of
xerostomia
high blood pressure and have several different
mechanisms of action. Other Vasoldilators Cephalgia, nauseas
1. Diuretics block renal absorption of sodium
increases urination and uid loss = ↓ BP
‣ Furosemide – acts on the ascending limb
of the loop of Henle
‣ Hydrochlorothiazide (HCTZ) – thiazide
(hypokalemia), acts in distal tubule
‣ Spironolactone – K+ sparing
(hyperkalemia), acts in collecting duct

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 PHARMACOLOGY 24

Antiarrhythmic
INBDE Pro Tip: An arrhythmia is simple an irregular heart beat.
It’s easier to understand the mechanism of With this being said, antiarrhythmic drugs work
action of ARBs and ACE inhibitors by learning to suppress and treat the irregular or abnormal
the process of angiotensin II synthesis. rhythms of the heat
There are 4 classes of antiarrhythmic drugs
• Class I - Na+ channel blockers for cardiac
Angina Management muscle only
Anti-angina medication help to treat • Class II – Beta-blockers
individuals who have insuf cient oxygen to • Class III – Potassium-channel blockers
supply the heart. • Class IV – Calcium channel blockers (CCBs)
1. Propranolol – reduces oxygen demand by
reducing heart stimulation, resulting in
reduced heart rate
2. Nitroglycerin – vasodilation of the
coronary arteries to aid in increasing
oxygen supply. The use of
phosphodiesterase-5 (PDE5) inhibitors (ex.
Sildena l (Viagra®)) is contraindicated in
patients
3. Calcium Channel Blockers – reduces
oxygen demand by reducing peripheral
resistance via vasodilation and decreasing
the contraction force of the heart

Anti-Cardiac Heart Failure Drugs

Anti-cardiac heart failure drugs are used to
help pump blood through the heart during
heart failure.

1.Cardiac glycosides work by blocking Na+/

K+ ATPase to increase calcium in ux and
promote positive force in cardiac muscle
cells. An example of a cardiac glycoside is:
‣ Digoxin

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 PHARMACOLOGY 25

Central Nervous System

1 Central Nervous System Antidepressants
Antidepressants are used to increase
stimulation, an opposite of antipsychotics
CNS drugs target receptors in the brain and • This is achieved through increasing the
spinal cord. In the CNS, there is a continuum of
number of monoamines (dopamine,
excitability, from too little stimulation to
epinephrine, norepinephrine, serotonin,
excessive stimulation.
histamine) in the brain
Generally, from low to high excitability, the • Generally, all antidepressants have
continuum is:
anticholinergic side effects, because an
excess can activate adrenergic receptors in
Anesthesia ! sedation ! homeostasis !
the ANS
activation ! excitation ! seizure

Some examples of classes of antidepressants

2 CNS Drugs
and medications that fall into them include:
• SSRI – selective serotonin reuptake
Antipsychotics inhibitor
Antipsychotics, known as neuroleptics in some ‣ Fluoxetine
circles, are used when the brain is too active. • SNRI – serotonin and NE reuptake inhibitor
This can include conditions such was ‣ Duloxetine
schizophrenia, and psychosis. They work • TCA - tricyclic antidepressants
through two main mechanisms of action: ‣ Amitriptyline
• MAOI – monoamine oxidase inhibitors
1. Dopamine D2 receptor blockers – ‣ Phenelzine
blocking the dopamine receptors of the • NDRI – norepinephrine-dopamine reuptake
brain to decrease the effect of dopamine. inhibitor
Haloperidol and chlorpromazine are two ‣ Bupropion
examples in this category, with a main side
effect being tar dive dyskinesia. General Anesthetics
2. Serotonin 5-HT receptor blockers - General anesthetics induce a coma in patients
inhibition of serotonin receptors all along during surgery. The onset of anesthesia is
the central nervous system. These tend to inversely proportional to the solubility of the
bind long enough to produce their anti- analgesic in blood. There are 4 stages of
psychotic effects, but not too long so that general anesthesia:
their side effects are kept low 1. Stage I – analgesia/feeling better
2. Stage II - delirium
3. Stage III – surgical anesthesia
INBDE Pro Tip: 4. Stage IV – medullary paralysis
Xerostomia is the most likely oral side
effect of antipsychotic medications GA example: Halothane – can be toxic to the
liver

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 PHARMACOLOGY 26

Anxiolytics/ Sedatives
1. Benzodiazepines
‣ ↑ GABA binding and Cl- in ux = slow
down CNS
‣ Ideal oral sedative for dentistry
‣ Wider therapeutic index, less addiction
potential and less respiratory depression
compared to other counterparts
‣ Diazepam, Triazolam, Midazolam

INBDE Pro Tip:

Benzodiazepines can be used for
dental oral sedation, as well as for the
treatment of seizures.

2. Barbiturates
‣ GABA receptor agonists
‣ Contraindicated in those with
intermittent porphyria and severe asthma
‣ Like most sedatives, overdoses can cause
respiratory depression
‣ Methohexital – rapid onset, short
duration of action, predictability

Pathophysiology
• Caused by a dopamine de ciency in brain

3 Parkinson’s Disease

• Dopamine in made in the brain from L-

DOPA. L-DOPA has the ability to cross the
blood brain barrier (BBB) while Dopamine
does not.
• DOPA decarboxylase is an enzyme that
normally breaks down L-DOPA
• Carbidopa – blocks DOPA decarboxylase
o This allows L-DOPA to cross the BBB, so
that it can be converted to dopamine
once in the brain

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