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Actions, Effects and
Administration of Drugs
Pharmacology
Human Biology II
ADOH
Dr. Troy Longbottom
Pharmacology
Pharmacology is the science of drugs
A drug is any chemical substance (except food) which is
used as an aid in diagnosis, treatment or prevention of
disease, or to control or improve any physiological or
pathological condition
Why is Pharmacology important to the Dental Hygienist
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Hygienists frequently utilise non-prescription drugs/chemotherapeutic agents
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Legal definition of drug vs scientific definition
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Hygienists should apply principles of drug therapy to all chemotherapeutic regimes
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Drugs impact on the risk factors for oral disease and patient response to hygiene treatment
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Drugs impact on the safety of hygiene treatment – subgingival debridement is invasive
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Drugs, existing or administered at appointment, can result in adverse reactions & emergencies
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There is a medico-legal requirement to record all details
Pharmacology and the Role of the Dental Hygienist
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Investigate and record patient medical and drug histories
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Design non-prescription drug therapies (chemotherapeutic agents)
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Assess the effectiveness of non-prescription drug therapies
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Recognise and manage the adverse systemic and oral effects of specific drugs
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Adjust treatment planning and general patient management in response to medications
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be prepared for potential emergencies from adverse drug reactions including the
prevention and management of these emergencies
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Record administered and recommended drugs/chemotherapeutic agents including
instructions given
Drug Forms (Presentation)
Solids - tablets, powders, capsules, lozenges
Liquids - injectable, drops, suspensions, sprays
Gasses - nitrous oxide
Chemical Structure
• Usually organic (have carbon structure).
• Some found in nature (natural & semi-synthetic)
• May be synthesized in a laboratory (synthetic)
Sources of Drugs
Micro-organisms - fungi, bacteria and yeasts.
Plants
Humans and animals
Minerals
Laboratory - synthetic and semi-synthetic drugs
Naturally occurring substances are not safer than those synthesized in laboratories
Drug Action
• Drugs have individual chemical structures
• Drugs exert their effects by chemically interacting with
biological tissue
• Drug molecules bind to certain receptor sites on the cell
membrane
• When a drug molecule approaches close enough to the
receptor, the attractive forces between them cause them
to bind
Bonding
• Most drug receptor interactions are weak chemical
bonds and so are easily broken
• Almost as soon as a drug binds to a receptor it
disengages and may be replaced by another drug
molecule
Question:
Why is it essential that this bonding reaction is temporary?
Affinity
The tendency for actual coupling of a
drug to a receptor is called affinity
High affinity vs. low affinity
Specificity
• Each drugs reacts with specific drug receptors
• The interaction depends on the chemical structure of the
drug and the receptor
• More than one type of drug may interact with the same
receptor (at different times)
• One drug may be able to bind with more than one type of
receptor
Dose Response Curves
Amount administered vs. effect produced
Lowest dose at which a drug will produce a measurable response is called the
Threshold Dose
As the amount of drug is increased, response increases, until a maximum effect is reached
Efficacy
The slope of the curve represents the rate of change or the response, relative to
the dose
Minimal Effective Dose
• A measure of the minimal effective dose
needed to produce a certain effect in a
given group of people
• Not the same as the Threshold Dose
Variability in Response
Most people tend to fall within a common range but some are different from the majority
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Some need smaller doses and some need higher doses to achieve the same response
Number of subjects responding
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Hyperreactive
Hyporeactive
Mean
Minimal Effective Dose
Pathway of Drugs within the Body
• Absorption
• Distribution
• Metabolism
• Excretion
Routes of Administration
Parenteral - absorption of drug which bypasses the GI system
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Topical (skin or mucous membrane)
Inhalation
Injection (IV, IM, Subcutaneous)
Enteral - drug delivered directly into the GI tract for absorption
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Oral Administration
Suppositories
Drug Absorption
• After oral administration of a drug, there is a period of
time before any perceptible effect of the drug is observed
• The effect then increases in time to a maximum effect (or
peak effect) and then the effect falls away
• IV administration results in reduced lag time at the
beginning
IV Administration Concentration & Effect over Time
Oral Administration – effect over time
Drug Half-Life
• Time taken for plasma concentration to fall 50%
• Important for establishing a steady-state concentration
• The time of onset is mainly determined by the
rate and degree of drug absorption
• The duration of action is primarily effected by the
rate of inactivation and excretion of the drug
• Absorption and inactivation (metabolism) &
excretion occur at the simultaneously but with a
shifting balance between one and the other
• As a drug is absorbed it enters the systemic
blood circulation
• In the blood, the drug molecules exist either in a
free form or bound to plasma protein
• These two forms are in equilibrium, but only the
free form of the drug can diffuse out of the blood
for distribution to the tissues of the body
Absorption
Absorption involves passage of the drug molecules
through cell membranes
Filtration
Passive diffusion
Carrier Facilitated Diffusion
Active Transport
Factors affecting absorption
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Form of drug
Chemical nature of drug eg. pH
Drug concentration at site
Blood circulation at site
The area of absorptive surface
Route of administration
Exercise
List the advantages and disadvantages of…
a. The oral administration of drugs
b. The IV administration of drugs
Distribution
When the drug is in contact with the greatest number of
reactive cells, the peak/maximum effect is reached.
The time at which this maximum effect is reached will be
effected by both the rate of absorption and the rate of
distribution of the drug
Factors affecting distribution
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The relative rate of blood flow to various tissues
Ability of a drug to penetrate certain tissues
The availability of binding sites
The concentration gradient within a given tissue
Lipid solubility
Binding to receptors in storage tissues
Acidity (pH)
Competition for receptor sites
Competition for Receptor Sites
• 2 drugs with a similar structure may compete for the
same binding sites on the plasma protein in the blood
• If Drug A has a greater binding affinity then it will
displace Drug B and result in more free-form (unbound)
Drug B in the blood stream
• Only free-form drug molecules are free to leave the
blood stream and effect the tissues
Exercise
• Chlorpropamide is a drug used to treat Diabetes. It stimulates insulin
secretion which reduces blood glucose preventing hyperglycaemia
• Aspirin competes with Chlorpropamide for binding sites on plasma
proteins
• Aspirin has a greater affinity for binding than Chlorpropamide
What will happen to a diabetic patient on Chlorpropamide if they
take Aspirin?
Metabolism (Biotransformation)
• Ends drug activity
• Metabolites are usually less pharmacologically active
than the drug (except for pro-drugs)
• Metabolites are more soluble
• Main site is the Liver but rarely also blood stream, lung,
intestine & kidneys
Factors affecting Metabolism
• Lipid solubility of drug
• Function of enzyme system (CYP450)
• Liver function and age
• Alcohol use
• Combinations of drugs
Excretion
• Mainly through the kidneys
(small amounts by sweat, saliva, lactation, bile & exhalation)
• Metabolism & Excretion ability are important in
determining dose for individual patients
Factors effecting dose
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Weight
Age
Gender
Disease
Psychological factors
Genetics
Presence of other drugs
Drug Nomenclature
• The Chemical Name
• The Generic Name
• The Proprietary (Brand) Names
For Example:
• Chemical Name: D(-)-α-amino-p-hydroxybenzylpenicillin
• Generic Name: Amoxycillin
• Propriety Names: Alphamox, Amohexal, Amoxil, Cilamox, Moxacin
Drug Classification
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Source
Chemical Formula
Pharmokinetic Parameters
Activity
Mechanism of action
Clinical Use
Body System
Drug Schedule
Pregnancy: tga.gov.au Prescribing medicines in pregnancy database
Legality in Sport
Drug and Poisons Schedule
Schedule
Description
Unscheduled
May be sold in supermarket
Schedule 1
No longer used
Schedule 2
Pharmacy Only Medicine - may be advertised
Schedule 3
Pharmacist Only Medicine - no advertising permitted
Schedule 4
Prescription Only Medicine
Schedule 5
Caution - low poison danger
Schedule 6
Poison - medium poison danger
Schedule 7
Dangerous Poison
Schedule 8
Controlled Drug
Schedule 9
Prohibited Substance
Local Anaesthetics
Anaesthesia vs. Analgesia
Topical Anaesthetics
Injectable Anaesthetics
Non-injectable Anaesthetics
Ideal Properties of Local Anaesthetic Agents
• Non-irritating to tissues
• Fully reversible action on nerves without nerve damage
• Low toxicity
• Effective for topical and injected applications
• Rapid onset of anaesthesia
• Suitable duration of action
• High safety margin and therapeutic ratio
• Can be combined with a vasoconstrictor
Components of Local Anaesthetic Solutions
• Anaesthetic agent
• Sodium Chloride
• Distilled water
• pH adjusting agent
• Vasoconstrictor + antioxidant
Commonly Used Anaesthetics
SEPTODONT (carpules are latex free)
Lignospan Special – Lignocaine 2%+ Adrenaline (1:80,000)
Scandonest 2% Special – Mepivacaine + Adrenaline (1:100,000)
Scandonest 3% Plain – Mepivacaine without vasoconstrictor
Septanest 1:100,000 – Articaine 4% + Adrenaline (1:100,000)
Septanest 1:200,000 – Articaine 4% + Adrenaline (1:200,000)
DENTSPLY
Xylocaine 2% - Lignocaine + Adrenaline (1:80,000)
Citanest 3% with Octapressin (1.8 mL) – Prilocaine + Felypressin
Oraqix Periodontal Gel - lignocaine 25 mg/g, Prilocaine 25 mg/g
3M ESPE
Ubistesin (1.8 mL) – Articaine 4% + Adrenaline (1:200,000)
Ubistesin Forte (1.8 mL) – Articaine 4% + Adrenaline (1:100,000)
LABORATOIRE ZIZINE
Lidocaine 2% - Lignocaine + Adrenaline (1:80,000)
Mepivacaine 3% – Mepivacaine without vasoconstrictor
Image: novocol.com
Structure of Local Anaesthetic Agents
Top Image: Brown: Atlas of Regional Anesthesia, 3 rd ed, 2006 Saunders
Bottom Image : faculty.weber.edu
Nerve Conduction
Resting potential
Depolarisation
Threshold Potential
Repolarisation
Impulse Propogation
Effects of Local Anaesthetic Agents
Displaces Ca2+ from Na+ channel receptor sites (competitive antagonism)
Reduces permeability of Na+ channels
Depressed rate of depolarisation
No threshold potential achieved
No action potential generated or propagated
Conduction blockade / Membrane Stabilisation
Factors Effecting Onset & Duration
• Myelination and nodes
• pH affects diffusion
• Diameter of nerve fibre
• Distance deposited from nerve
• Density and thickness of bone (infiltration only)
• Vascularity of tissues
• Use of vasoconstrictor
• Infiltration vs. Block
• Inflammation
• Individual response (hypo / hyper)
Pharmacokinetics
route of Administration
vascularity
drug vasoactivity
vasoconstrictors
toxicity risk
level of perfusion in tissues
elimination half-life
renal impairment
toxicity risk
esters vs. amides
prilocaine vs. other amides
liver function
toxicity risk
Lignocaine 2% with Adrenaline
• Plain Lignocaine - a vasodilator with 5 to 10 mins pulpal action (infiltration)
• Lignocaine with Ad 1:100,000 – 1 hour pulpal and 3 to 5 hours soft tissue action
• Distribution – throughout all body tissues
• Half-life is 1.6 hours
• Metabolism is almost entirely in liver – potentially sedative metabolites produced
• Low hepatic blood flow (hypotension, congestive heart failure)
• Poor liver function (cirrhosis)
Toxicity
• Up to 3% of dose excreted unchanged.
• Poor kidney function
Toxicity
Toxicity
Prilocaine 3% with Felypressin
• Plain Prilocaine - a vasodilator with 10 to 15 mins pulpal action (infiltration)
• Prilocaine with Felypression – Shorter action than Lignocaine + Adrenaline
• Distribution – throughout all body tissues
• Half-life is 1.6 hours. Toxicity is lower than Lignocaine & Mepivacaine
• Primary metabolism is in liver with some in lungs and kidneys
• Renal clearance is faster than other amides but still be wary of toxicity
• Prilocaine
Biotransformation
Orthotoluidine
Methaemoglobinaemia
Mepivacaine 3% (plain)
• Very mild vasodilator = longer action without vasoconstrictor
• 20 mins pulpal action for infiltration and 40 mins for block
• 2 to 3 hours soft tissue anaesthesia
• Distribution – throughout all body tissues
• Half-life is 1.9 hours (slightly longer than Lignocaine and Prilocaine)
• Primary metabolism is in liver, similar to Lignocaine
• Low hepatic blood flow, poor liver or kidney function
Toxicity
Articaine 4% with Adrenaline
• Contains both an Amide and an Ester group
• Vasodilating action is similar to Lignocaine
• Available in Adrenaline 1:100,000 and 1:200,000
• Potency is higher than Lignocaine and toxicity similar to Lignocaine
• Short half-life of 30 mins
• Metabolism in blood (plasma esterase) and liver enzymes
• Primary metabolite (articainic acid) is inactive. 5-10% excreted unchanged
• Reports of Paraesthesia, especially with IAN block