Pharmacology

The study of drugs and their effect on living tissue.

Pharmacologic Effects

The changes within a body caused by a drug.

Drug

A chemical substance used in Dx, Tx or prevention of Dz.

Generic Name

"Official" name of drug

Patent lasts 17 years

Lowercase

Proprietary Name

Brand Name

Capitalized

Drug Sources

Plants, Animals, Minerals, Synthetic and Active constituents of plants

Legend Drug

Secured only by prescription

Over-the-counter (OTC)

Formerly sold by prescription

Lower doses than prescription

Chemical Equivalency

Two formulations of a drug meet same chemical and physical standards required by FDA.

Biologically Equivalent

Ability of generic drug to reach blood levels equivalent to those reached by a brand-name drug.

Drug Classifications

Indication

Effect

Chemical categories

Food and Drug Administration (FDA)

Approves safe, effective drugs/removes

Sets standard for drug purity and strength

Adverse reaction reporting program

Federal Trade Commission (FTC)

Enforces federal consumer protection laws

Regulates marketing practices & advertising on food, OTC drugs, and dietary supplements.

Drug Enforcement Administration (DEA)

Identifies drugs capable of addiction

Sets requirements for prescribing abuse drugs (narcotics, barbituates, benzodiazepines)

FDA Approval Process

Preclinical Trials

Phase 1

Phase 2

Phase 3

Postmarketing Surveillance

Preclinical Trials

Tested on animals

3.5 years

Phase 1 of clinical trials

20-80 volunteers

1 year

Dosage Range and Safety Profile

Phase 2 of clinical trials

100-300 volunteers

2 years

Short-term drugs effectiveness

Adverse Drug Effects

Phase 3 of clinical trials

1000-3000 volunteers

3 years

Long-term effectiveness

Adverse drug effects

Postmarketing Surveillance

Determines true drug/risk benefit of new drug

Drug Information Sources

Detailed and complete drug infomation publications

Internet sources

Dental Drug References

Drug Interaction Publications

Dental Hygienist Role

Drug entered into tx record (Name, dosage, route administered)

Any drugs recommended or sample given written into record.  Instructions must be given and recorded.

Potential drug effects & modifications to tx plan assessed after drug or supplement history review

Drug Card Preparation

Investigate drugs reported on health history

Information

   Drug name (generic & brand)

   Indication

   Side effects relevant to hygiene care

   Clnical implications for each drug effect

   Oral health info topics related to drug effects, drug warning

Affinity

Force of attraction of a molecule to a receptor site

Agonist

Drug that has a direct stimulatory effect on a receptor

Antagonist

Drug that interferes with the action of an agonist

Ceiling Dose

Dose above which no further beneficial drug effect will occur

Enteral

Administration of a drug through the gastrointestinal tract (GI), by mouth

Efficacy

Magnitude of response obtained from optimal receptor site occupancy by a drug

Half-life

The time it takes for half the drug to be removed from the body

Intrinsic activity

The ability to cause an effect or action

Parenteral

Administration of a drug bypassing the GI tract, usually through injection into the body in various ways but also including inhalation and topical administration.

Partial Agonist

Drug with affinity for the receptor site, but unable to produce a strong effect or action

Pharmacodynamics

Mechanisms of drug action involving biochemical and physiologic effects of drugs

Science of molecular interactions between drugs and body consituents

Pharmacokinetics

The absorption, distribution, metabolism, and excretion of a drug

Pharmacotherapeutics

The use of pharmacologic agents to diagnose, treat, or prevent disease

Potency

Concentration at which the drug elicits 50% of its maximal response, related to the drug's affinity for the receptor

Receptor Site

Specialized area on a cell or within a cell where a drug acts to initiate a series of biochemical and physiological effects.

Strong Agonist

Drug that produces a significant physiologic response when only a relatively small number of receptors are occupied.

Toxicity

Overdose, undesirable effects, or poisoning

ROA

Route of administration

Basic Pharmacology Principles

Mechanism of action: how a drug works

Adverse Side Effects (ADE's)

Oral health education information (related to drug effects)

Risks of taking a drug

Drug delivery steps

- Delivery of molecule to tissue cell

- "Complex" formation with receptor (site of action)

- Molecular event causing an effect

- Mechanism of action (how it works)

Characteristics of Drug Receptors

- Cellular macromolecules

- Location on cell surface or within a cell

- Hundreds of different receptors on a single cell

- Complimentary fit between drug and receptor

- Electrochemical charge (+, -, ionized, polarized)

- Hydrophilic or hydrophobic

- Only one drug molecule can occupy a receptor at one time

Drug molecules move in:

- constant random motion

- binding then releasing the bond

- then binding again according to the:

      - affinity of the molecule and

      - competition from other drug molecules

Ionic bond

Weak and easily reversed

Hydrogen bond

Weaker than ionic

Covalent Bond

Bond often irreversible (strongest)

Dental ex: tetracycline & dentin

van der Waals Forces

Contribute to mutual attraction between molecules

The most common bonds between drugs and receptors

Ionic and Hydrogen

When a drug molecule moves so close to its receptor that the attractive force between them becomes great enough to overcome the random motion of the drug molecule, the drug binds to the receptor.  This is called?

Affinity

Good affinity is directly related to greater ___?

potency

Weak agonists must bind to _____ to produce the same effect as a strong agonist.

many more receptors

Threshold Dose

The lowest dose of a drug that will produce a measurable response.

Potency is related to the ____ of a drug to its _____.

affinity, receptor

Interfere with the action of agonists, but have no effect in absence of agonists.

Antagonist

Antagonists can be classified as:

Receptor antagonists that prevent binding of agonist by binding at the active site

Nonreceptor antagonists

Receptor antagonist

Competitive antagonists - affinity but no intrinisic activity.  Reduces potency of agonist

Noncompetitive antagonists - prevent receptor activation

Nonreceptor antagonist

Chemical antagonists (local anesthetics)

Physiological antagonists (vasoconstriction by epi vs. vasodilation)

Mixed agonist-antagonist

Have both agonistic and antagonistic properties

When used alone they act as agonists

When another drug competes, it antagonizes

Receptors are classified according to:

Type of drug they interact with

The specific physiologic response produced by the drug-receptor complex

Receptors are subclassified by

The effects of agonist in presence of antagonist

Adverse effects of toxicity

- Exaggeration of direct effects at higher dosages

- Multiple concurrent adverse effects at therapeutic dosage level

Median Effective Dose

Dose required to produce desired response in 50% of individuals

(ED50)

Median Lethal Dose

Dose that produces death in 50% of individuals

(LD50)

Median Toxic Dose

Dose that produces a specific toxic response in 50% of individuals

(TD50)

A steep dose-response curve indicates ?

A narrow dose range

A margin of safety of a drug is expressed by

The Therapeutic Index (TI)

Therapeutic Index is determined by ?

Ratio of LD50 and ED50 (LD50/ED50)

The higher the numeric value, the safer the drug.

Pharmacokinetics relates to:

- Drug absorption

- Distribution in the body

- Distribution to the site of action

- Metabolism of drug

- Excretion of drug

Properties that influence the movement of drug molecules across biologic membranes

- Molecular size

- Lipid solubility (nonionized able to pass easily)

- Degree of ionization (depends on pH at site)

     - Ionized must pass through via pores

Filtration

Small, water-soluble substance may pass through aqueous channels or water pores in cell membranes.

Passive Diffusion

Lipid-soluble, non-ionized cross membranes along a concentration gradient (from high to low concentration) until equilibrium is reached.

Can easily pass through.

Faclitiated Diffusion

Foms a complex with a component of the cell membrane on one side.  Then carried through the membrane and released.

Large, water-soluble drug molecules.

Active Transport

Movement against both a concentration and an electrochemical gradient.

Requires energy.

Factors influencing the rate of absorption

- Degree of ionization and pH of tissues

- Formulation of the drug (liquid or solid form)

- Drug concentration

- Degree of blood circulation to the area

- Area of absorptive surface

- Route of drug administration (enteral or parenteral)

Ionized forms of drugs are more _____ soluble.

Water

Non-ionized drugs are more _____ soluble.

Lipid

Biologic membranes are composed of:

- Layers of lipid material and proteins = allow passage of lipid-soluble molecules

- Small openings or water pores = allow passage of water-soluble molecules

Nonpolar, non-ionized drugs will pass across the membranes ______.

Easier (more readily)

Meals ______ the rate of absorption.

slow down

Liquids absorb at a ______ rate than solids.

faster

Enteric Coating

- Delay dissolution of drug

- Dissolves in upper intestine

- Reduces adverse gastric side effects

Greater concentration of drug absorbs _____ than lower.

faster

The greater the blood flow to tissue, the _____ the rate of aborption.

faster

Organs with significant blood flow include the:

Heart, GI tract and liver

What is the site of absorption for most oral drugs?

Upper small intestine

What type of drug administration is the safest yet most unpredictable?

Oral

First-pass effect

May reduce the concentration of drug molecules because the molecules attach to plasma proteins (albumin). Albumin carries the molecule in circulation to be distributed to site of action.  It is protected from metabolism as it moves the the liver.  Has a lower bioavailability.

What route of administration is the most predictible, causes an immediate effect, used in emergencies and less safe than oral?

Intravenous (IV)

Topical routes include:

- sublingual

- transdermal patches

- drops in eyes or ears

- placed in gingival sulcus

Distribution of drugs is achieved primarily through the _______ system.

circulatory

Redistribution may affect ?

The duration of the drug effect

Plasma protein binding tends to reduce the availability of drugs for diffusion into target organs because

only the free or unbound drug is capable of crossing biologic membranes.

Distribution of drugs to the CNS and cerebrospinal fluid is restricted due to the

Blood Brain Barrier

Placental Barrier

Drugs pass across the placenta by simple diffusion.  This is the reason for restriction of drugs, except prenatals, during pregnancy.

The majority of metabolism occurs in the ?

liver

Biotransformation

Phase I

Phase II

Can alter drugs in 4 ways

4 ways drugs are altered in biotransformation

- Convert active drug into inactive drug

- Convert active drug to an active drug or toxic metabolite

- Convert inactive drug into an active drug

- Convert an unexcretable (more lipophilic) drug into an excretable (more hydrophilic) metabolite

Phase I reactions

Chemical structure is modified through oxidation, reduction or hydrolysis.

Require very little energy.

Phase II reactions

Chemical structure modified by conjugation to large polar endogenous molecule.

Makes a pharmacologically inactive drug.

Cytochrome P450

Induced to increase metabolism

Inhibited to reduce rate of metabolism

Responsible for many adverse drug reactions

The most common and important mechanism of drug elimination from the body

Renal excretion

Enterohepatic recirculation

Metabolites that are hydrolized and reabsorbed from the gut, the drug action can be re-established.  This can delay the elimination of drugs from the body.

Other forms of excretion

Exhalation, perspiration and lactation

Glomerular filtration

The glomerulus is the primary location for drug elimination to occur.

Active tubular secretion

Passive tubular reabsorption

First order kinetics

(Half-life of drug)

Implies that a constant fraction (%) of the drug is eliminated per unit of time.

There are approximately how many half-lives to elminate drugs?

4

Steady-state concentration

Rate drug administered = Rate drug elimination

Zero-order kinetics

Constant amount of the drug is eliminated per unit time.

Most Drugs Are:

- Entered orally

- Absorbed in upper intestine

- Circulated in blood system

- Metabolized in liver

- Excreted through kidney glomerulus

Prescription

A legal document for which the prescriber and pharmacist are both responsible.

Prescriptions are regulated by ?

State and federal laws

Errors in prescribing can occur from a varaiety of reasons such as:

- Wrong dosage

- Medical condition contraidcation

- Poor handwriting

- Incorrect drug information

- Look-alike drug names

Rules for Prescription Writing

- Legible, accurate, complete info and in ink

- Schedule II must be in ink, indelible pencil or typewritten

- Avoid product endorsement

- Keep pads in secure location

- Place duplicate or record of Rx in patients record

- Use English instructions

Prescriber - Patient Relationship

- Patient record is established

- Dx is established: Medical history, exam, radiographs, tests

- Tx plan is prepared and need for medications determined

- Tx plan is presented and patient is counseled

- Follow-up care is provided as needed

Parts of the Prescription

Heading: Dr. name, address, phone number

              Patient information

Body: Drug, dose and amt. to be dispensed

         Directions for patient

Closing: Signature, DEA #, generic ok, refills

Prescription Labeling Regulations

- Name of drug

- Number of doseforms dispensed

- Strength of doseforms

- Pharmacy name, address, phone #, date filled

- Instructions on refills

- Refill prescription

Compliant patient

One who follows the therapeutic regimen recommended by the clinician.

Determinants of Compliance

- Patient trust in clinician and treatment

- Good communication

- Positive office visit and attitude

- Individualization of regimens

- Good follow-up

- Other: child?

Major factor influencing compliance

The patient's perception of the severity of the illness.

How to counsel the patient on a prescription

- Reason for the drug

- Problems if drug is not taken

- Clear instructions

- Possible side effects

- When to notify the dentist

a

before

a

before meals

disp

dispense

no

number

cap

capsule

tab

tablet

sig

label

po

by mouth

pc

after meals

stat

at once

hs

at bedtime

prn

as needed

qh

every hour

qd

every day

bid

twice a day

tid

3 times a day

qid

4 times a day

d/c

discontinue

Young's Rule

                                          child's age (in y) x adult dose

Child's dose (1-12 yrs) =  ---------------------------------------

                                      child's age (in y) + 12

Clark's Rule

                             weight of child (in lb) x adult dose

Child's Dose =  ----------------------------------------

                                                  150 lb

Body Surface Area Rule

                  surface area of child (in sq. meters) x adult dose

Child's dose = ----------------------------------------------------

                                                1.73

Most accurate rule for child dosage

Body surface area

Controlled Substances Act of 1970

Collects and conforms most of the diverse laws into one piece of legislation.

Designed to improve administration and regulation of manufacturing, distributing and dispensing of controlled drugs, and provide a "closed" system for the legitimate handlers of controlled substances.

Every practitioner who administers, prescribes or dispenses controlled substances must be registered with the ______.

DEA's Registration Unit

If a clinician has more than one office from which he/she prescribes drugs they need to be registered for each location.

T/F

True

Examples of Schedule I drugs

- Hallucinogens

- Marijuana

- Selected opiates (heroin, opion derivatives)

Examples of Schedule II Drugs

- Amphetamines

- Selected opiates (morphine, codeine congeners,

                             methadone)

- Some barbiturates (secobarbital)

- Oxycodone

Examples of Schedule III Drugs

- Anabolic steroids

- Selected opiate combinations (acetaminophen w/ codeine, hydrocodone mixtures [vicodin])

Examples of Schedule IV Drugs

- Benzodiazepines

- Selected opiates (propoxyphene [Darvon])

- Some barbiturates (phenobarbital)

Examples of Schedule V Drugs

- Selected opiates (cough & diarrhea preparation)