Pharmacology - Chapters 1-3

Chemically equivalent

When two formulations of a drug meet the chemical and physical standards established by the regulatory agencies, they are termed chemically equivalent

Biologically equivalent

If two formulations of a drug produce similar concentrations in the blood and tissues, they are termed biologically equivalent

Therapeutically equivalent

If two formulations of a drug have an equal therapeutic effect in a clinical trial, they are termed therapeutically equivalent

Federal regulations and regulatory agencies

Agencies that are involved in regulating the production, marketing, advertising, labeling and prescribing of drugs

Harrison Narcotic Act of 1914

Established regulations for opium, opiates and cocaine (marijuana added in 1937)

Controlled substances act of 1970

Regulates manufacture and distribution of any substance with potential for abuse (DEA)

Omnibus budget reconciliation Act 1990

Pharmacists must provide patient counseling and drug utilization review on all medicaid patients (all patients)

Food, Drug and cosmetic Act of 1938

Prohibits interstate commerce of drugs that have not been shown to be safe and effective

Durham Humphrey law of 1952

Requires that certain types of drugs be sold by "prescription only

Controlled substance act of 1970

Sets current requirements for writing prescriptions for drugs prescribed in the dental office (DEA)

Who can write prescriptions?

Physicians - Humans
Veterinarians - Animals
Dentists - Dental Problems
Optometrists - Eye problems
And under certain guidelines in certain states so can Physician's assistants, Nurse Practitioners and Pharmacists

Chemical Name

A drugs chemical name is determined by its chemical structure...sometimes a code name is assigned to the drug and is often used in place of the chemical name because it is easier to write and speak the code name rather than the chemical structure

Generic Name

The "official" name given to a drug before marketing. (NOT CAPITALIZED). Each drug has one generic name.
ie- acetylsalicyclic acid, acetaminophen

Trade Name

AKA: Proprietary Name. If a drug is found to be useful, it is marketed and the company that discovered the drug gives it a trade name. ie - Coke. The trade name IS CAPITALIZED.
Trade names are good for 17 years under the Federal Trademark Law.

Pharmacology

The science of drugs and their properties

Pharmacokinetic

The movement of a drug within the body

Human clinical testing (4 phases)

Phase I - Healthy human volunteers, determine biologic effects, metabolism, safe dose range and toxic effects
Phase II - Larger human groups, ADR's reported, effectiveness is tested
Phase III - Drug is given to patients that the drug is indicated for, Saf

Schedule I

Highest abuse potential. No excepted medical use. Examples are Heroin, LSD, marijuana

Schedule II

High abuse potential. Needs a written prescription with the providers signature - cannot be called into the pharmacy. NO REFILLS. Examples are oxycodone, morphine, amphetamine, secobarbital

Schedule III

Moderate abuse potential. Prescriptions may be telephoned in, no more than 5 prescriptions in 6 months. Examples are Codeine mixtures (Tylenol #3), hydrocodone mixtures (Vicodin)

Schedule IV

Less abuse potential. Prescriptions may be telephoned. No more than 5 prescriptions in 6 months. Examples are Diazepam (Valium), dextropropoxyphene forms (Davron)

Schedule V

Least abuse potential. Can be bought OTC in some states. An example is some codeine containing cough syrups.

1 teaspoon equivalent

1 tsp = 5 ml

1 tablespoon equivalent

1 Tbs = 15 ml

a or a with a line over it

before

ac

before meals

bid

twice a day

c with a line over it

with

cap

capsule

d

day

disp

dispense

gm

gram

gr

grain

gtt

drop

h

hour

hs

at bedtime

p with a line over it

after

pc

after meals

PO

by mouth

prn

as required, if needed

q

every

qid

4 times a day

s with a line over it

without

sig

write (label)

ss with a line over it

one-half

stat

immediately (now)

tab

tablet

tid

three times a day

ud

as directed

Heading

Name, address and phone #of prescriber
Name, address, age and phone # of patient
Date of prescription

Body

Rx
Name and dose size
Amount to be dispensed
Directions to the patient

Closing

Prescriber's signature
DEA #
Refill instructions

Drugs

chemical substances used for the diagnosis, prevention or treatment of disease or for the prevention of pregnancy

Potency

The potency of a drug is a function of the amount of drug required to produce an effect

Efficacy

Efficacy is the maximum intensity of effect or response that can be produced by a drug. Related to the maximal effect of a drug, regardless of dose. The efficacy and potency of a drug are unrelated

Median lethal-dose (LD50)

Median lethal-dose (LD50) is the dose when 1/2 of the subjects die. LD50 is only determined on animals

Neurotransmitters (chemical signaling)

transmit messages . There are at least 50 different neurotransmitters.
ie- acetylcholine, norepinephrine, epinephrine, dopamine, serotonin

Local (chemical signaling)

Some organs secrete chemicals near them (not into the circulation).
ie- prostaglandins, histamines

Hormones (chemical signaling)

Hormones are secreted to produce effects throughout the body. Hormones are usually slower than neurotransmitters.
ie - insulin, thyroid hormone, adrenocorticosteroids,

Endogenous

Originating or produced within an organism, tissue or cell

Agonists

An agonist is a drug that has an affinity for a receptor, combines with a receptor and produces an effect. Naturally occurring neurotransmitters are agonists.

Antagonist

An antagonist counteracts the actions of an agonist. There are 3 types of antagonists: 1) Competitive antagonist 2) noncompetitive antagonist 3) physiologic antagonist

Competitive antagonist

a drug that produces NO EFFECT

Noncompetitive antagonist

a drug that binds to a receptor site that is different from the agonist. REDUCES THE RESPONSE OF THE AGONIST

Physiologic antagonist

different receptor site than the agonist. produces an opposite effect via different receptors. PRODUCES OPPOSITE EFFECT OF THE AGONIST

Pharmacokinetics

The study of how a drug enters the body, circulates within the body, is changed by the body and leaves the body. The factors that influence the movement of a drug are divided into 4 steps: Absorption, Distribution, Metabolism, and Excretion

Passive Transfer

Lipid-soluble substances moves across the lipoprotein membrane by a passive transfer process called simple diffusion. It is proportional to the concentration gradient (difference) of the drug across the membrane and the degree of lipid solubility

Active Transport

A process where a substance is transported against a concentration gradient. Transport "carriers" give energy for the transportation of the drug.

Facilitated Diffusion

Does NOT move against a concentration gradient. Pinocytosis (pinching off little caves) may be the process by which substances pass into the cells.

Absorption

The process where drug molecules are transferred from the site of administration to the circulating blood

Weak acids

DO NOT easily penetrate tissues

Weak bases

DO penetrate tissues more easily

Oral absorption of tablet/capsule

goes through 4 stages
1) Disruption
2) Disintegration
3) Dispersion
4)Dissolution

Oral absorption of drug in solution

Drug in solution skips the steps of the absorption of tablet/capsule. Therefore, the ONSET OF ACTION IS QUICKER

Absorption from injection site

Depends on solubility of the drug and the blood flow at the site. Affected by dose form...drugs in suspension are absorbed slower than drugs in solution. The least soluble drugs have a LONGER DURATION OF ACTION

Distribution

Drugs occur in 2 forms in the blood: BOUND TO PLASMA PROTEINS (reservoir for the drug) and FREE DRUG (exerts pharmacological effect). All drugs enter the body and are split between bound and free drugs.

Distribution by Plasma

A drug is absorbed from its site of administration , is distributed to its site of action via blood plasma. The biologic activity of the drug is related to the concentration of free drug. Drugs bind to proteins & act as storage sites.

Half-Life

The amount of time (t1/2) for the concentration of a drug to fall to 1/2 of its blood level.
shorter 1/2 life = leaves body more readily = shorter duration of action
longer 1/2 life = slowly removed = longer duration of action

Blood-brain barrier

For drugs to penetrate the CNS, they need to cross the BBB, therefore they must be highly lipid soluble.
most drugs pass the placenta easily

Enterohepatic Circulation

Drugs are absorbed via intestines, distributed through the blood, metabolized in the liver and excreted via the kidneys.Once drug is metabolized, the metabolite is secreted via bile into the intestine, broken down by enzymes & released into the body. THE

Redistribution

Movement of a drug from the site of action to nonspecific sites of action. Drugs duration of action is affected by redistribution of the drug from one organ to another

Drugs can be metabolized 3 different ways, what are they?

1) Active to Inactive
2) Inactive to Active
3) Active to Active

Active to Inactive

Active parent compound forms an inactive metabolite

Inactive to Active

Inactive parent drug is transformed into an active compound (called a prodrug)

Active to Active

Active parent compound converted to a 2nd active compound then is converted into an inactive product. The action of the drug is PROLONGED

Metabolism

Body changes drug to metabolites so it can be excreted by the kidneys. The metabolite is more polar & less lipid soluble than the parent compound. Metabolites are less likely to be bound to plasma and less likely to be stored in fat tissue.
Metabolism of

Phase I

Occurs in the liver. Lipid molecules are metabolized 3 ways: Oxidation, Reduction & Hydrolysis

Phase II

Enzymes in liver break down drug through conjugation reactions. Most common conjugation occurs with glucuronic acid (glucuronidation). Basically, drugs bind to compounds already present in the body.

Oxidation

An enzyme system that breaks down (oxidative metabolism) drugs located in the liver. Enzymes are located in the Endoplasmic Reticulum and are called MICROSOMAL ENZYMES

Hydrolysis

Hydrolytic enzymes break up esters & add water. Ester local anesthetics are inactivated by plasma cholinesterases.

Reduction

Reduction reactions are mediated by the enzymes found in the hepatic microsomes.

Enzyme INDUCTION (stimulation)

Microsomal enzymes can be induced (stimulated) by some drugs or by smoking tobacco. Increase in enzyme action causes the drug to be metabolized faster and decreases the blood level of the drug which REDUCES the drugs effect.

Enzyme INHIBITION (slow-down)

With inhibition, the enzymes action is decreased therefore blood levels of the drugs and the effect of the drug will be INCREASED.

When a drug alters the liver microsomal enzymes, what effect can this have on metabolism?

It can either speed up (induction) or slow down (inhibition) metabolism which can either cause a decrease in the drugs effect or toxicity of the drug.

Excretion of drugs

Kidneys (most important route) - URINE, includes glomerular filtration, active tubular secretion & passive tubular secretion.
Drugs are also excreted through the lungs, biliary, milk, sweat, saliva (aspirin, phenytoin, ampicillin, diazepam, pen vk, phenob

Enteral Route

Placed directly into the GI tract by ORAL or rectal route.

Parenteral Route

Bypasses the GI tract via INJECTION, inhalation & topical

Oral Route (enteral)

Safest, least expensive & convenient route. May cause nausea & vomiting

Injection (parenteral route)

fast absorption, rapid onset, more predictable response. Also the most dangerous & expensive

Parenteral Routes include:

Intravenous, Intramuscular, Intradermal, Intrathecal, Intraperitoneal, Inhalation (nitrous) & topical (benzocaine)

Factors that alter drug effects

Patient compliance
Psychological factors
Tolerance - Tachyphylaxis
Pathologic state
Time of administration
Route of administration
Sex
Genetic variations
drug interactions
Age
weight
environment

Child dose calculations

2.2 lbs = 1 kg
convert lbs to kg by divide the weight in kg by 2
ie- 40kg divided by 2 = 20
then multiply that by the # of mg in the drug (5 mg)
ie- 20 times 5 = 100 mg