PHARMACOLOGY LECTURE 1

Pharmacotherapeutics- refers to the use of specific drugs to prevent, treat, or diagnose a disease.

 

Pharmacokinetics is the study of how the body deals with the drug –its absorption, distribution, and elimination.

 

 

Pharmacology is the study of drugs.

Pharmacodynamics is the analysis of what the drug does to the body, and how the drug exerts its effect.

 

Pharmacy deals with the preparation and dispensing of medications.

 

Toxicology is the study of the harmful effects of chemicals (drugs).  

Trade name (also known as the brand name) is assigned to the compound by the pharmaceutical company

Generic name -(also known as the “official” or “nonproprietary” name) shorter and often derived from the chemical name; the easiest and most effective way to refer to a drug,

When are two drugs said to be “bioequivalent”?

 

DRUG DEVELOPMENT

Animal (preclinical) studies come first before human (clinical) testing.

 

Human (clinical) testing:

 

Phase I• Determine effects, safe dosage,

pharmacokinetics• Small number (_ 100) of healthy

volunteers• < 1 year

 Phase II• Assess drug’s effectiveness in

treating a specific disease/disorder

• Limited number (200–300) patients with target disorder

• 2 years

Phase III• Assess safety and effectiveness

in a larger patient population• Large number (1000–3000)

patients targeted• 3 yrs

 

Phase IV (postmarketing surveillance)

• Monitor any problems that occur after NDA approval General patient population

• Indefinite

nonprescription, or over-the counter (OTC); can be purchased

prescription medications may be ordered or dispensed only by an authorized practitioner (i.e., physician, dentist, or other appropriate health care provider).

What can PTs do?

PTs can provide information about the proper use and potential benefits of these medications.

 

Schedule I.

with the highest potential for abuse

not typically used as an acceptable medical treatment restricted to approved research studies or therapeutic use in a very limited number of patients

Examples heroin, lysergic acid diethylamide (LSD), psilocybin, mescaline, peyote, marijuana, tetrahydrocannabinols, and several other hallucinogens.

 

Schedule II.

approved for specific therapeutic purposes but still have a high potential for abuse and possible addiction.

Examples include opioids such as morphine and fentanyl, and drugs containing methamphetamine.

 

Schedule III.

have a lower abuse potential than those in schedules I and II, but with the possibility of developing mild to moderate physical dependence, strong psychologic dependence, or both.

certain opioids (e.g., codeine) that are combined in a limited dosage with other nonopioid drugs.

Other drugs in this category are anabolic steroids, certain barbiturates, and amphetamines that are not included in schedule II.

 

Schedule IV.

have a lower potential for abuse than schedule III drugs, with only a limited possibility of physical dependence, psychologic dependence, or both.

Examples: certain antianxiety drugs (meprobamate), certain barbiturates (barbital, phenobarbital), and a variety of other depressants and stimulants.

 

Schedule V.

have the lowest relative abuse potential.

Examples: low doses of opioids that are used in cough medications and antidiarrheal preparations.

 

threshold dose, the dose where the response begins to occur and continues to increase in magnitude

before reaching a plateau. The plateau indicates that there will be no further increment in the response even if the dosage continues to be increased---ceiling effect, or maximal efficacy of the drug.

 

Dose-response curves

provide information about the dosage range over which the drug is effective, as well as the peak response that can be expected from the drug.

median effective dose (ED50) dose at which 50 percent of the population respond to the beneficial effects of the drug.

median toxic dose (TD50) dose at which 50 percent of the group exhibits the adverse effect

median lethal dose (LD50) .dose that causes death in 50 percent of the animals studied.

The median effective and toxic doses are used to determine the therapeutic index (TI).

calculated as the ratio of the TD50 to the ED50:

 TI = TD50

ED50

 The greater the value of the TI, the safer the drug is considered to be.

Potency is related to the dose that produces a given response in a specific amplitude.

 

The less amount needed to produce the response, the more potent is the drug.

All methods of drug administration that do not use the gastrointestinal tract are termed parenteral.

allows the drug to be delivered to the target site more directly

Drugs will diffuse more readily through the lipid layer if they are in their neutral, nonionized form.

Active or carrier-mediated transport involves using membrane proteins to transport substances across the cell membrane

• Carrier specificity. • Expenditure of energy • Ability to transport substances

against a concentration gradient

Facilitated Diffusion

Has features of both active transport and passive diffusion.

protein carrier is needed

But no energy is expended

inability to transport substances uphill against a concentration gradient.

Entry of glucose into skeletal muscle cells via facilitated diffusion is an example

The extent to which a drug is uniformly distributed depends on

• Tissue permeability. • Blood flow. • Binding to plasma proteins. • Binding to subcellular

components.

storage sites of drugs:• Adipose  • Bone• Muscle• Organs

Very high doses of acetaminophen can react with hepatic proteins and cause severe liver damage.

Controlled-release preparations,

designed to permit a slower and more prolonged absorption of the drug from the gastrointestinal tract and other routes of administration.

Advantage: decrease the number of doses needed each day

Drugs are eliminated by chemically altering the original compound while still in the body so that it is no longer active (biotransformation), by excreting the active form of the drug from the body (excretion),

Biotransformation usually results in an altered version of the original compound known as a metabolite, usually inactive or with reduced level of pharmacologic activity

Cellular Mechanisms of Drug Biotransformation

• Oxidation• Reduction• Hydrolysis• Conjugation of the original

compound.

Enzyme Induction

Prolonged use of certain drugs “induces” the body to be able to enzymatically destroy the drug more rapidly

drugs are metabolized more rapidly decreasing their therapeutic effect.

May explain why there is tolerance to some drugs (occurs when drug is used for extended periods)

Tolerance refers to the need for increased drug dosages to produce the same effect.

Long-term ingestion or inhalation of other exogenous compounds such as

alcohol, cigarette smoke, or environmental toxins may cause enzyme induction

Clearance of a drug refers to the ability to eliminate the drug.

Bioavailability, which is a parameter expressed as the percentage of the drug administered that reaches the bloodstream.

 

Drug metabolism, or biotransformation, refers to chemical changes that take place in the drug following administration.

 The kidneys are the primary sites for drug excretion.

 

Half-life is defined as the amount of time required for 50 percent of the drug remaining in the body to be eliminated.

Factors responsible for variations in the response to drugs:

• Genetic factors.  • Disease. • Drug interactions.  • Age.  • Diet. • Sex

Affinity -attraction between a drug and a receptor

A drug with a high affinity binds readily to receptors, even in low concentrations. Drugs with

moderate or low affinity require a higher concentration in the body before the receptors become occupied.

 

A drug that can bind to a receptor and initiate a change in the function of the cell is referred to as an agonist.

An agonist is identified as having affinity and efficacy.

Efficacy indicates that the drug will lead to a change in the function of the cell.

Whereas an agonist has both affinity and efficacy, an antagonist has only affinity.

the drug will bind to the receptor but it will not cause any direct change in the function of the receptor or cell.

Antagonists are significant because, by occupying the receptor, they prevent the agonistic compound from having any effect on the cell.

Antagonists are often referred to as blockers because of their ability to block the effect of another chemical.

decrease in responsiveness - desensitization due to addition of phosphate residues (phosphorylation) or some other chemical modification to the receptor protein.

Receptor desensitization and down-regulation appear to be examples of a negative feedback system used by the cell to prevent overstimulation by an agonist.

Receptor down-regulation describes a slower, more prolonged process in which the actual number of available receptors is diminished

A prolonged decrease in the stimulation of the postsynaptic receptors can result in a functional increase in receptor sensitivity-

denervation supersensitivity

seen when a peripheral nerve is severed

the lack of presynaptic neurotransmitter release results in a compensatory increase in postsynaptic receptor numbers on the muscle cell

Drug tolerance is the need to take more of a drug to exert the same effect.

Dependence is described as the onset of withdrawal symptoms if drug intake is stopped.

therapeutic index -used as a measure of the relative safety of the drug

adverse drug event vs.adverse drug reaction

adverse drug event -“an injury resulting from the use of a drug. Under this definition, the term ADE includes harm caused by the drug (adverse drug reactions and overdoses)

adverse drug reaction -harm directly caused by the drug at normal doses, during normal use.

PRESCRIPTIONan order by a physician, for the

preparation and administration of a medicine, therapeutic regimen, assistive or corrective device, or other treatment.

Essential Parts of a Drug Prescription/Order:

1. Superscription consists of the heading where the symbol Rx (an abbreviation for recipe, the Latin for "take thou") is found. The RX comes before the inscription.

2. Inscription- called the body of the prescription, and provides the names and quantities of the chief ingredients of the prescription. The dose and the form--tablet, suspension, capsule, syrup, etc.

3. Subscription- specific directions for the pharmacist on how to compound the medication. In the old days, the pharmacist prepares the medications so directions can be "mix and place 10 capsules," "dispense 10 tablets,". Today, doctors just name the pill.

4. Signatura Sig or transcription- gives instructions to the patient on how, how much, when and how long the drug is to be taken.

5. Below the signatura line is room for special instructions, such as the number of times the prescription may be refilled, warnings.

THE END