Pharmacology

Local Anesthetics
 Local Anesthetics
• Amides vs. Esters
• Pharmacodynamics and Pharmacokinetics
• Calculating LAs
• Injections
 Amides Esters
• Metabolized in the • Metabolized by
liver pseudocholinesterase
in plasma
 Amides Esters
• Lidocaine • Procaine
• Bupivicaine • Cocaine
• Mepivicaine • Tetracaine
• Articaine • Benzocaine
• Prilocaine • More toxic, more
allergic
(methylparaben)
 Amides
• Lidocaine (Xylocaine) safest in children
• Bupivicaine (Marcaine) not safe in children
• Mepivicaine (Carbocaine, Polocaine) causes least vasodilation
• Articaine (Septocaine) has one ester chain
• Prilocaine (Citanest) methemglobinemia
 Esters
• Procaine
• Cocaine vasoconstrictor
• Tetracaine
• Benzocaine
 Pharmacodynamics
• Sodium channel blocker
• Only non-ionized (free base) form can
penetrate neuron membrane
• Critical length
 Pharmacokinetics
• ↑ blood flow shorter duration of action
• ↑ lipid solubility/hydrophobicity more potent
longer duration of action
• ↑ protein binding longer duration of action
• ↓ pKa faster onset of action
– Mepivicaine: 7.6
– Lidocaine, prilocaine, articaine: 7.8
– Bupivicaine: 8.1
 Calculating Local Anesthetic
• 1mL of liquid at sea level weighs 1g
• Carpule/cartridge of anesthetic contains
1.8mL
• So entirety of liquid in carpule weighs how
much?
• 1.8g or 1800mg
• But this isn’t very relevant clinically…
 Calculating Local Anesthetic
• For 100% solution, 1.8g or 1800mg
• For 1% LA, 18mg

• For 2% lidocaine, 36mg per carpule

• For 4% articaine, 72mg per carpule
 Practice Question
• A carpule of 2% lidocaine solution with
1:100,000 epinephrine would contain how
much epinephrine in mg?

• For .001% epinephrine, 0.018mg

 Vasoconstrictor
1. Prolong numbness
2. Reduce toxicity
3. Promote hemostasis
 Toxicity
• Max epinephrine for ASA I patient= 0.2mg
• Max epinephrine for cardiac patient= 0.04mg
• Max lidocaine without vasoconstrictor= 4.4mg/kg
• Max lidocaine with vasoconstrictor= 7mg/kg
Local Anesthetics
 Delivering Local Anesthetic
• “Slow” injection is 1 carpule per minute
 Needle Dimensions
• Length
– Short= 20mm
– Long= 32mm
• Diameter
– 30-gauge= 0.3mm
– 27-gauge= 0.4mm
– 25-gauge= 0.5mm
 3/4 carpule

Inferior Alveolar Nerve Block

• Highest failure rate
• Halstead= classic
• Gow-Gates= open mouth
• Akinosi= closed mouth
 1/4 carpule

Buccal Nerve Block

• Done in tandem with IAN
block
 1/3 carpule

Mental Nerve Block

• Locate rubbery bundle
with finger
• Mental foramen by apices
of premolars
 1/3 carpule

Incisive Nerve Block

• Same as mental nerve block except hold
pressure for 2 minutes after injection to force
anesthetic into mental foramen
 1/2 carpule

Posterior Superior Alveolar Block

• Maxillary molars
• 16mm depth (half the
length of long needle)
• High hematoma risk
 1/2 carpule

Infraorbital Block
• Maxillary anteriors +
premolars
• Also called true ASA block
• Infraorbital foramen
 1/4 carpule

Greater Palatine Nerve Block

• Posterior hard palate
• Greater palatine foramen
 1/4 carpule

Nasopalatine Block
• Hard palate from canine to
canine
• Most painful
 1/2 carpule

Local Infiltration
• Enter in vestibule
• Aim for root apex
• Works well in anterior
because facial cortical
plate is thin
Antibiotics
 Sulfonamides
• Bacteriostatic
• Folate synthesis inhibitor (competes with
PABA)
• Sulfadiazine, Sulfamethoxazole
 Fluoroquinolones
• Bactericidal
• DNA synthesis inhibitor
• Ciprofloxacin, Levofloxacin
 Penicillins
• Bactericidal
• Cell wall synthesis inhibitor, β-lactam
• Cross-allergenic with cephalosporins because they are chemically related

• Penicillin G IV, more sensitive to acid degradation

• Penicillin V oral
• Amoxicillin broad spectrum
• Augmentin amoxicillin + clavulanic acid (β-lactamase-resistant)
• Methicillin β-lactamase-resistant
• Dicloxacillin “
• Ampicillin best/broadest gram-negative spectrum
• Carbenicillin used specifically against pseudomonas
 Cephalosporins
• Bactericidal
• Cell wall synthesis inhibitor, β-lactam
• 1st Gen= Cephalexin (Keflex)
• 2nd Gen= Cefuroxime
• 3rd Gen= Ceftriaxone
• 4th Gen= Cefepime
• 5th Gen= Ceftaroline
 Monobactams
• Bactericidal
• Cell wall synthesis inhibitor, β-lactam
• Aztreonam
 Carbapenems
• Bactericidal
• Cell wall synthesis inhibitor, β-lactam
• Imipenem
 Tetracyclines
• Bacteriostatic
• Protein synthesis inhibitor (30S ribosomal
subunit)
• Tetracycline, Doxycycline, Minocycline
• Broadest antimicrobial spectrum
 Macrolides
• Bacteriostatic
• Protein synthesis inhibitor (50S ribosomal
subunit)
• Erythromycin, Clarithromycin, Azithromycin

Mac likes to throw mice

 Lincosamides
• Bacteriostatic
• Protein synthesis inhibitor (50S ribosomal
subunit)
• Clindamycin, Lincomycin

Link also hides mice

 When is Antibiotic Prophylaxis
Required?
• Cardiovascular conditions
– Prosthetic heart valve
– History of endocarditis
– Heart transplant with valvulopathy/valve dysfunction
– Congenital heart problems
• Compromised immunity
– Organ transplant
– Neutropenia
– Cancer therapy
 Rx for Infective Endocarditis
Prophylaxis
• First choice Amoxicillin 2g 1 hr before tx
• Children, first choice Amoxicillin 50mg/kg 1 hr before tx
• PCN allergy Clindamycin 600mg 1 hr before tx
• Children, PCN allergy Clindamycin 20mg/kg 1 hr before tx
• Non-oral (IV or IM) Ampicillin 2g 30 min before tx
• Children, non-oral Ampicillin 50mg/kg 30 min before tx
 Rx for Prosthetic Joint Prophylaxis
• First choice Keflex 2g 1 hr before tx
 When is Antibiotic Prophylaxis NOT
Required?
• Cardiovascular conditions
– Cardiac pacemaker
– Rheumatic fever without valvular dysfunction
– Mitral valve prolapse without valvular
regurgitation
 Side Effects
• What causes GI upset and pseudomonas colitis? Clindamycin

• What is most likely to cause superinfection? Broad spectrum

antibiotics

• What is associated with aplastic anemia? Chloramphenicol

• What is associated with liver damage? Tetracycline

• What is associated with allergic cholestatic hepatitis?

Erythromycin estolate
 Drug Interactions
• Cidal and static drugs cancel each other out
• Penicillin & probenecid
• Tetracycline & antacids/dairy
• Broad spectrum antibiotics & anticoagulants
• Antibiotics & oral contraceptives
• Macrolides & seldane/digoxin
 Drug Concentration
• Clindamycin à bone
• Tetracycline à gingival crevicular fluid
 Antivirals & Antifungals
• Acyclovir, Valcyclovir à herpes
• Fluconazole, Ketoconazole à candidiasis
– Clotrimazole (Mycelex) is in troche form
Analgesics

• Aspirin (ASA)
• Ibuprofen (Motrin, Advil)
• Naproxen (Aleve)
• Ketorolac (Acular)
• Indomethacin
• Phenylbutazone (“Bute”)
• Diflunisal (Dolobid)
• Celecoxib (Celebrex)
• Meloxicam (Mobic)
NSAIDs
COX 1 and 2 blocker (irreversible) GI
COX 1 and 2 blocker (reversible) kidney
COX 1 and 2 blocker (reversible)
COX 1 and 2 blocker (reversible) IV, IM, or oral
COX 1 and 2 blocker (reversible) blood dyscrasias
COX 1 and 2 blocker (reversible) for animals
COX 1 and 2 blocker (reversible) longer half-life
COX 2 blocker
COX 2 blocker arthritis
 Acetaminophen
• Acetaminophen inhibits pain in CNS liver
• Drug of choice in feverish child, whereas aspirin can cause Reye’s Syndrome
 Maximum Dose
• Ibuprofen 3.2g/day
• Acetaminophen 4g/day
 Therapeutic Effects of Aspirin
• Analgesic à inhibit COX 1 and 2 (PG synthesis)
• Anti-inflammatory à same
• Antipyretic à inhibit PG synthesis in
temperature regulation center of
hypothalamus
• Bleeding time à inhibit TXA2 synthesis
thereby inhibiting platelet aggregation
 Toxic Effects of Aspirin
• Occult bleeding from GI tract
• Tinnitus
• Nausea and vomiting
• Metabolic acidosis
• Decreased tubular resorption of uric acid
• Salicylism
• Delirium
• Hyperventilation
 Corticosteroids
• Prednisone
• Hydrocortisone
• Triamcinolone
• Dexamethasone
 Therapeutic Effects of Steroids
• Analgesic à inhibit phospholipase A2 (AA
synthesis)
• Anti-inflammatory à same
 Side Effects of Steroids
• Gastric ulcers
• Immunosuppression
• Acute adrenal insufficiency
• Osteoporosis
• Hyperglycemia
• Redistribution of body fat
 Narcotics/Opioids
• mu-opioid receptor agonists (in CNS)
• Morphine
• Hydrocodone
• Oxycodone
• Oxycontin controlled release
• Codeine suppresses cough reflex, cough syrup
• Tramadol (Ultram) similar to codeine
• Heroin
• Fentanyl
• Sufentanil
• Carfentanil
• Meperidine (Demerol) lethal if combined with an MAOI
 Combination Narcotics
• Vicodin Hydrocodone + APAP
• Percocet Oxycodone + APAP
• Tylenol 1 300mg APAP + 8mg Codeine
• Tylenol 2 300mg APAP + 15mg Codeine
• Tylenol 3 300mg APAP + 30mg Codeine
• Tylenol 4 300mg APAP + 60mg Codeine
 Therapeutic & Side Effects of
Morphine
• Miosis
• Out of it
• Respiratory depression
• Pneumonia
• Hypotension
• Infrequency
• Nausea and vomiting
• Euphoria and dysphoria
 Overdose and Addiction
• Naloxone inverse agonist, emergency
• Naltrexone antagonist, treat addiction
• Methadone treat addiction
• Pentazocine mixed agonist-antagonist
• Nalbuphine mixed agonist-antagonist
• Buprenorphine mixed agonist-antagonist
 Nitrous Oxide
• Horace Wells was first to use for own
extraction by his assistant
• Sensation before onset à tingling
• Side effect à nausea
• Long term exposure à peripheral neuropathy
• MAC 105%
• Diffusion hypoxia
 General Principles
• Pharmacokinetics
– pH
– First Pass Effect
– Volume of Distribution
– Phase I vs. Phase II Metabolism
– First-order vs. Zero-order Kinetics
– Drug-drug interactions
• Pharmacodynamics
– Type I vs. Type II Dose Response Curves
 Pharmacokinetics
What the body does to the drug

0. Administration
1. Absorption
2. Distribution
3. Metabolism
4. Clearance/Elimination
 (0) Administration
How is a drug delivered?

• Oral= ingestion through mouth

• Sublingual= dissolved under the tongue
• Subcutaneous= injected under the skin
• IM= intramuscular, injected into muscle
• IV= intravenous, injected into vein
• Inhalation= breathed in
• Topical= applied to skin or mucous membrane
 (1) Absorption
How does a drug get into the body?

• Drugs must cross epithelial and/or endothelial

cell layers to enter the body

Local drugs Passive diffusion

Facilitated diffusion
Active transport

Systemic drugs Bioavailability

 pH Considerations
• Acid/base properties of drug and pH of the
environment can affect the charge state of a
drug and hence alter its absorption
– For weak acids, we want pH < pKa
– For weak bases, we want pH > pKa
Acid Drug Base Drug
Acidic Non-ionized Ionized
Environment
Basic Ionized Non-ionized
Environment
 (2) Distribution
How does a drug get to the target site?

• Most drugs must reach the blood in order to

be distributed effectively
 First Pass Effect
• Oral drugs undergo the first pass effect

Hepatic portal system

 Volume of Distribution (Vd)
• Describes distribution of drug across the three
body water compartments
– Plasma (4%)
– Interstitial (16%)
– Intracellular (40%)
• Women, obese, and older people generally have
less body water than the “average man”
– Adipose has lowest water content
– Brain and muscle have highest water content
• Binding to serum proteins lowers Vd and “traps”
drugs in the blood as hydrophilic molecules
75 kg
 (3) Metabolism
How is a drug molecule chemically altered by the body?

Drug Phase I Metabolite Phase II Inactive

(possibly inactive)

• Phase I
– Functionalization (oxidation, reduction, hydrolysis)
– Cytochrome P450
• Phase II
– Conjugation (glucouronide, glutathione, glycine)
– UDP-glucouronosyltransferase
 Acetaminophen

Phase I Phase II
Reduction Glutathionation
(4) Clearance/Elimination
How is a drug molecule eliminated from the body?

Drug

Phase I Phase II

Urine
Feces
 Elimination Kinetics
• First-order kinetics
– Constant fraction of drug is eliminated per unit
time (%/hour)
– More common
• Zero-order kinetics
– Constant amount of drug is eliminated per unit
time (mg/hour)
– Less common
– Higher risk of drug accumulation
 Drug-Drug Interactions
• One drug affects the pharmacokinetics of
another drug, most commonly metabolism
– Induction à drug #1 induces liver cytochrome
enzymes resulting in increased metabolism and
reduced effect of drug #2
– Inhibition à drug #1 competes for metabolism or
directly inhibits liver cytochrome enzymes
resulting in decreased metabolism and increased
toxicity of drug #2
 Drug-Drug Interactions
Dental Drug Interacting Drug Effect
Diazepam Clarithromycin Increased sedation because of reduced
metabolism of benzodiazepine
Tetracyclines Oral antacids Reduced absorption of tetracyclines
(TUMS)
Aspirin Anticoagulants Increased bleeding tendency
Aspirin Probenecid Decreased effect of probenecid
Aspirin Methotrexate Increased methotrexate toxicity
Acetaminophen Alcohol Increased risk of liver toxicity in chronic
alcoholics
Local anesthetics Acetylcholinester Reduced effectiveness of acetylcholinesterase
ase inhibitors inhibitor
 Prescribed
Dose
Medical errors
Patient compliance
Administered
Dose
Absorption
Distribution
Pharmacokinetics
Metabolism
Clearance
Active Dose

Drug-receptor
interaction Pharmacodynamics
Intensity
of effect
 General Principles
• Pharmacokinetics
– pH
– First Pass Effect
– Volume of Distribution
– Phase I vs. Phase II Metabolism
– First-order vs. Zero-order Kinetics
– Drug-drug interactions
• Pharmacodynamics
– Type I vs. Type II Dose Response Curves
 Pharmacodynamics
What the drug does to the body

• Almost all drug targets are proteins

– Receptors
– Ion channels
– Enzymes
– Carriers
• How a drug interacts with its target to produce
therapeutic (and toxic) effects
– Agonist
– Antagonist
– Inverse agonist
 Agonist
• Mimics the effects of an endogenous agonist
molecule
– Full agonist= can produce 100% of its desired effect
– Partial agonist= cannot produce 100% of its desired
effect
 Antagonist
• Inhibits normal function of endogenous agonist
– Competitive antagonist= competes with agonist for the
same binding site on the receptor
– Non-competitive antagonist= binds to a different non-
overlapping binding site, but still prevents the binding of
agonist
 Inverse Agonist
• Inhibits the basal activity of a receptor in the
absence of the normal agonist
• Binds to a special kind of receptor that is
active at rest in order to inhibit its basal
activity
 Type I Dose Response Curve
• X-axis indicates dose of drug
• Y-axis indicates response/efficacy of drug
• Can be either hyperbolic or sigmoid/log form
 Type I Dose Response Curve
• Intrinsic activity=
maximal effect (Emax) of
a drug
– Full agonist has intrinsic
activity of 1
– Partial agonist is between
0 and 1
– Antagonist has intrinsic
activity of 0
 Type I Dose Response Curve
• Efficacy= effect of a drug as a function of binding
• Affinity= attractiveness of a drug to its receptor
– The lower the dissociation constant (Kd) the higher
the affinity
• Potency= power of a drug at a specific
concentration
– Usually measured by the effective concentration of
drug (EC50) leading to half its maximal effect (50%
response)
 Type I Dose Response Curve
• Competitive antagonist shifts agonist curve RIGHT
• Noncompetitive antagonist shifts agonist curve DOWN
 Type II Dose Response Curve
• X-axis still indicates dose of drug
• Y-axis indicates number of subjects responding to
a drug, rather than the efficacy of a drug
 Type II Dose Response Curve
• ED50= effective dose where 50% of population responded effectively
(treated)
• TD50= toxic dose where 50% of population experienced toxic side effects
• LD50= lethal dose where 50% of population responded lethally (died)

TI= LD50/ED50
In animal studies

TI= TD50/ED50
In human studies

Therapeutic window
 Dose Response Curves
• Type I: dose vs. efficacy of drug
• Type II: dose vs. response of patient
 Additive
• Combining drugs combines their individual
degrees of effect
 Antagonistic
• Combining drugs causes a lesser effect than either one alone
– Chemical antagonism= drug binds directly to another drug to put it out of
commission
– Receptor antagonism= competition between two drugs for a single receptor
– Pharmacokinetic antagonism= one drug affects the PK of another via pH, etc.
– Physiologic antagonism= two drugs producing opposing effects on the same
tissue via distinct receptors
 Synergistic
• Combining drugs leads to more than the sum
of the two independently
 ANS Pharmacology
• Autonomic Nervous System
– Sympathetic Nervous System
– Parasympathetic Nervous System
• Receptors in the ANS
• Cholinergic Drugs (PSNS)
• Adrenergic Drugs (SNS)
 ANS Physiology
PSNS SNS
• In general, PSNS and SNS
nerves control the same
organs, but have opposing
effects on them!
– SNS is fight or flight
– PSNS is rest and digest, feed
and breed
• All nerve pathways originate
from the CNS (brain + spinal
cord)
– 12 cranial
– 0 cervical
– 12 thoracic
– 5 lumbar
– 5 sacral
 Rest and Digest,
Feed and Breed Fight or Flight
• Pupil constriction • Pupil dilation

• Stimulated salivation • Dry mouth

• Decreased heart rate • Increased heart rate

• Airway constriction • Airway relaxation

• Stimulated digestion • Slowed digestion

• Bladder constriction • Bladder relaxation

 Receptors in the ANS
• Ionotropic= ion channel
• Metabotropic= G-protein coupled receptor
 Receptors in the ANS
• Cholinergic= binds acetylcholine
– Nicotinic (nAChR)= also binds nicotine; ionotropic
– Muscarinic (mAChR)= also binds muscarine; metabotropic
• Adrenergic= binds Epi/NE; metabotropic

SNS

PSNS
 Receptors in the ANS
• Cholinergic= binds acetylcholine
– Nicotinic (nAChR)= also binds nicotine; ionotropic
– Muscarinic (mAChR)= also binds muscarine; metabotropic
• Adrenergic= binds Epi/NE; metabotropic

N A
SNS
N A

N M
PSNS
 SNS vs. PSNS
• By the distinct effects they have on the same organs
– PSNS à promote “rest and digest” and “feed and breed”
– SNS à promote “fight or flight”
• By the region of the spinal cord from which they arise
– PSNS à craniosacral
– SNS à thoracolumbar
• By the lengths of their pre- and postganglionic neurons
– PSNS à long pre-ganglionic, short post-ganglionic near target organ
– SNS à short pre-ganglionic to sympathetic trunk, long post-ganglionic
• By the neurotransmitters they use
– PSNS à ACh everywhere
– SNS à ACh to the ganglion, NE from nerves and Epi/NE from adrenal gland
• By the neurotransmitter receptors that they use
– PSNS à muscarinic metabotropic receptors on target organs
– SNS à adrenergic metabotropic receptors on target organs
 Synthesis of Acetylcholine
• Acetyl CoA + choline = acetylcholine
– Catalyzed by choline acetyltransferase
– Reversed by acetylcholinesterase

N
ACh M
 Muscarinic Receptors

M1 M2 M3 M4 M5

CNS Heart Smooth CNS CNS

muscle
 Muscarinic Receptors
• Bradycardia= ↓ heart rate
M2
(chronotropy) and ↓ electrical
conduction (dromotropy)

• SLUDS= salivation, lachrymation,

urination, defecation, sweating M3
• BAM= bronchoconstriction,
abdominal cramps, miosis
 M
M Agonists
• Non-selective for muscarinic receptors so will
affect all of them (M1-5) if systemic
• Therefore should not be used systemically
with:
– Peptic ulcers—gastric acid
– Asthma/COPD—bronchoconstriction
– CHF—decreased cardiac output
 M
M Agonists
Direct-acting activates M receptor, congener (mimic) of ACh
Pilocarpine stimulates saliva or eye drops to constrict pupils
Methacholine methacholine acetylcholine

Indirect-acting non-competitively inhibits acetylcholinesterase

(anticholinesterase)
Neostigmine reversibly inhibits cholinesterase, but can also directly affect
NMJ
Physostigmine “
Edrophonium “
Organophosphate irreversibly inhibits cholinesterase, poisoning can be treated
insecticides with Pralidoxime
Nerve gases “
 M
M Antagonists/Antimuscarinics
Competitive inhibitors block M receptor, compete with ACh
Atropine reduces saliva or emergency drug to treat bradycardia (can
also cause tachycardia)
Scopolamine “
Propantheline “
 N
N Antagonists/Ganglionic Blockers
Non-depolarizing blocks N receptor at allosteric site
Mecamylamine used to be used as an antihypertensive
Hexamethonium “

Depolarizing binds to N receptor but cannot be removed

Nicotine addictive substance found in tobacco products
 N
N Antagonists/Neuromuscular Blockers
Non-depolarizing blocks N receptor at active site
Tubocurarine arrow poison

Depolarizing binds to N receptor but cannot be removed

Succinylcholine prevent laryngospasm and as a skeletal muscle relaxant
during surgery

N
 Synthesis of Epinephrine and
Norepinephrine
• Tyrosine à L-DOPA à dopamine à NE à Epi
– Catecholamines= dopamine, NE, Epi
– Monoamines= dopamine, NE, Epi, serotonin (5-
HT), histamine

NE
Epi
A
 Adrenergic Receptors

α1 α2 β1 β2

Smooth Smooth Heart Smooth

muscle muscle muscle
 α-receptors
• Vasoconstriction, urinary retention,
pupil dilation (mydriasis) α1

• Vasoconstriction*
α2
 β-receptors
• Tachycardia= ↑ heart rate and ↑
electrical conduction and ↑ β1
strength of contraction (inotropy)
• Renin release from kidneys

• Bronchodilation, vasodilation*,
stop peristalsis β2
 A
Adrenergic Agonists
Isoproterenol activates all β receptors
Norepinephrine activates all α receptors and β1
Epinephrine activates all α and β receptors
Phenylphrine (Sudafed) activates α1 receptor, reduce swelling via
peripheral vasoconstriction
Oxymetazoline (Afrin nasal spray) “
Dobutamine activates β1 receptor, kickstarts the heart
Albuterol activates β2 receptor, bronchodilator used as an
emergency inhaler
 A
Adrenergic Antagonists
Competitive antagonists block adrenergic receptors, compete with NE
Prazosin blocks α1 receptor
Chlorpromazine (CPZ) blocks α1 receptor and D2 receptor
Metoprolol blocks β1 receptor (cardioselective)
Atenolol “
Propranolol blocks all β receptors, prolongs lidocaine
duration
Carvedilol blocks all β receptors and α1
Phentolamine blocks all α receptors
Phenoxybenzamine “
 Sympathomimetics
Amphetamine stimulates release of stored NE
Tyramine (wine, cheese, chocolate) “
Ephedrine “
Cocaine inhibits reuptake of NE and dopamine
Methylphenidate “ psychostimulant for ADHD
Tricyclic antidepressants inhibits reuptake of serotonin and NE
Monoamine oxidase inhibitors blocks enzymatic degradation of monoamines

NE A
 Sympatholytics
Guanethidine inhibits release of NE
Reserpine depletes NE stores thus inhibiting release
Clonidine α2 agonist (CNS) which actually blocks SNS
signal
Methyldopa α2 agonist (CNS) which actually blocks SNS
signal

NE A
 Epinephrine Reversal
• Vasoconstrictor effect of epinephrine is
converted into a vasodilator effect in the
presence of an α-blocker whereby the β2
vasodilator effect becomes the major vascular
response
• Basically α-blocker cancels out epinephrine’s α
activation effects and it only activates β
receptors
 Vasovagal Reflex
• NE can activate baroreceptors
which stimulate vagal reflex to
reduce heart rate, leading to an
opposite response to what NE
usually does
• Atropine blocks this reflex
 Circulatory System
• Human circulatory system is
a closed system
• Pump= cardiac output (CO)
• Tubing= peripheral
resistance (PR)
• Fluid= blood volume (SV)
 Circulatory System
• BP= CO x PR
BP= SV x HR x PR
• CO= SV x HR
• Systole= pressure in arteries
when heart contracts 120/80
• Diastole= pressure in arteries
when heart relaxes
• Preload= pressure in
ventricles before heart
contracts
• Afterload= pressure in
arteries against which the
ventricles must pump
 Antihypertensives
For high blood pressure

Diuretics decrease renal reabsorption of sodium thus resulting

in net fluid loss and reduction in blood pressure
Furosemide Loop or high-ceiling
Hydrochlorothiazide (HCTZ) Thiazide (hypokalemia)
Spironolactone K+ sparing (hyperkalemia)
 Antihypertensives
For high blood pressure

Vasodilators open K+ channels to cause vasodilation

Hydralazine

CCBs block calcium influx in order to cause vasodilation

Verapamil may induce gingival hyperplasia
Diltiazem “
Amlodipine “
Nifedipine “
 Antihypertensives
For high blood pressure
ACE Inhibitors blocks the enzyme that converts angiotensin I into angiotensin
II the latter of which is a potent vasoconstrictor
-prils

ARBs competitive antagonist at angiotensin II receptor again

blocking a potent vasoconstrictor
-sartans

Renin

ACE
 Antianginals
For insufficient oxygen to cardiac muscle
Antianginals
Nitroglycerin vasodilation of smooth muscle in coronary arteries to ↑ O2
supply
Propranolol reduces oxygen demand by relaxing the heart
CCBs reduces oxygen demand by reducing peripheral resistance via
vasodilation
 Anti-CHF Drugs
For failure of heart to pump enough blood
Cardiac Glycosides block Na/K ATPase to increase calcium influx and promote
positive inotropy in cardiac muscle cells only
Digoxin
Digitalis

ACE Inhibitors blocks the enzyme that converts angiotensin I into angiotensin
II the latter of which is a potent vasoconstrictor
-prils
 Anti-Arrhythmics
For an irregular heartbeat

• Type 1 drugs= Na+ channel blockers for

cardiac muscle only
– 1A= lengthens refractory period to slow heartbeat
– 1B= shortens refractory period to hasten
heartbeat
• Type 2 drugs= beta blockers
• Type 3 drugs= K+ channel blockers
• Type 4 drugs= Ca2+ channel blockers (CCBs)
 Anti-Arrhythmics
For an irregular heartbeat
Drug Name Type Arrhythmia
Quinidine Type 1A a-fib, supraventricular tachyarrhythmia
Procainamide “ “
Lidocaine Type 1B ventricular arrhythmia
Propranolol Type 2 paroxysmal tachycardia
Verapamil Type 4 a-fib, paroxysmal tachycardia, supraventricular
tachyarrhythmia
Digitalis Cardiac a-fib, paroxysmal tachycardia; digitalis-induced
glycoside arrhythmia can be reversed with Phenytoin
Continuum of CNS Excitability

N M A

D S GABA
 D
Antipsychotics
For schizophrenia S
1st Generation D2 blocker
Haloperidol tardive dyskinesia
Phenothiazines tardive dyskinesia; specific examples are Chlorpromazine,
Thioridazine, and Fluphenazine

2nd Generation D and 5HT blocker

Clozapine not as many side effects
 Antidepressants
For depression

SSRI selective serotonin reuptake inhibitor

Fluoxetine anticholinergic side effects
Citalopram “
Trazodone “

SNRI/TCA serotonin and NE reuptake inhibitor, tricyclic antidepressants

Amitriptyline “
Imipramine “

MAOI monoamine oxidase inhibitors

Phenelzine “
Tranylcypromine “

Lithium is drug of choice for manic depression (bipolar disorder).

 Anxiolytics/Sedatives
For anxiety or sedation

• Benzodiazepines
• Barbiturates
 Benzodiazepines GABA

• Increase GABA binding and chloride

ion influx to slow down the CNS
• Ideal drug for oral sedation in the
dental setting
• Propylene glycol can induce
thrombophlebitis in large veins

Benzodiazepine (BZD)
Diazepam 2-10mg Valium 1 hour before dental appointment
Triazolam Halcion
Chlordiazepoxide
 Barbiturates GABA

• Same mechanism as BZD

• Barbs are contraindicated in patients with
intermittent porphyria because they will
aggravate the disease
• Barb overdose causes respiratory depression

Barbiturate
Thiopental quick onset, short duration of action
 General Anesthetics
• The more soluble the agent in blood, the more
you need to reach critical tension in the brain
• Stage I: analgesia/feeling better
• Stage II: delirium
• Stage III: surgical anesthesia
• Stage IV: medullary paralysis
General Anesthetic
Halothane hepatotoxicity
 Parkinson’s Disease
• Substantia nigra to striatum is main pathway
• Due to dopamine deficiency in brain
• Dopamine cannot cross the BBB, but its precursor
levodopa (L-DOPA) can
• Carbidopa blocks DOPA decarboxylase, allowing
L-DOPA to cross the BBB where it can be
converted to dopamine once in the brain