WS0201:Biomedical Pharmacology

UNIT 1- The Basics

Pharmacognosy

Sources of Drugs

§ Animals

§ Plant

§ Minerals

§ Synthetics

§ Biologicals- recombinant DNA (rDNA)

§ Herbs,

§ Animals,

§ Plants, and

§ Minerals

§ Herb examples:

☆ Aspidium, (tapeworm)

☆ Cinnamon, (antioxidant)

☆ Ergot, (migraine)

☆ Hyoscyamus, henbane (sedative)

☆ Foxglove, (Digitalis)

☆ Belladonna (atropine)

☆ Opium (morphine)

☆ Rauwolfia Serpentina (reserpine)

shégēn mù (蛇根木) or

yìndù shémù (印度蛇木).

Sources of Drugs

§ Plant Sources-

Seeds, Roots, Leaves, Resins

§ Animal Sources- Glandualr products-

insulin, thyroid; Microbes

§ Mineral Sources-

Potassium, Calcium, Lithium

§ Synthetic-

Barbiturates, Sulfonamides, Aspirin

FACT:

§ Over 20 new drugs launched between 2000-2005 originated from:

plants/ animals/ microorganisms/ marine species/

§ Anticancer drugs- campothecin, paclitaxel, epipodophyllotoxin, vinblastine

? DRUGS

§ Drugs are chemicals used to diagnose, treat and prevent disease.

? Pharmacology

§ The study of drugs and their actions on the body.

Medication Names

§ Chemical Name:

§ Ethyl-1-methyl-4-phenylisonipecotate hydrochloride

§ Generic Name:

§ Meperidine hydrochloride

§ Trade Name:

§ Demerol

Drug References

§ Physician’s Desk Reference

§ Drug Inserts

§ Pharmacy

§ Physician

§ Internet

§ USP- the only legally recognized source

Drug Forms

§ Solution = Dissolved in water

§ Suspension = mixed in water shake before use

§ Elixir = mixed in alcohol

§ Syrup = mixed in sugar water

§ Tablet = firmly compressed pieces

§ Capsule = encased in gelatin shell

§ Suppository = solidified in glycerin or wax, to melt at body temperature

Terminology of Pharmacology

§ Indication

§ Contraindication

§ Agonism

§ Antagonism

§ Additive effect

§ Synergistic effect

§ Tolerance

§ Habituation

§ Hypersensitivity

§ Refractory

Terminology of Pharmacology

§ Side Effects

§ Therapeutic Action

§ Untoward Effect (Adverse Effects)

§ Anaphylaxis

Medication History

§ Clue to medical conditions

§ Safeguard against interactions

§ Safeguard against allergic reactions

Special Considerations

§ Age

§ Allergies

Implanted Port

Peripherally Inserted Central Catheter (PICC)

FDA LAWS

The first drug law of the land

§ 1906

§ The original Food and Drugs Act is passed by Congress on June 30 and signed by President Theodore Roosevelt.

§ It prohibits interstate commerce in misbranded and adulterated foods, drinks and drugs.

§ cure-all claims for worthless and dangerous patent medicines were the major problems leading to the enactment of these laws.

1914

§ The Harrison Narcotic Act requires prescriptions for products exceeding the allowable limit of narcotics and mandates increased record-keeping for physicians and pharmacists who dispense narcotics.

§ First time the word narcotic introduced into the vocabulary

§ Narcos (Greek)= sleep

1938

§ The Federal Food, Drug, and Cosmetic (FDC) Act of 1938 provisions:

§ Extending control to cosmetics and therapeutic devices.

§ Requiring new drugs to be shown safe before marketing-starting a new system of drug regulation.

§ Providing that safe tolerances be set for unavoidable poisonous substances.

§ Authorizing standards of identity, quality, and fill of-container for foods.

§ Authorizing factory inspections.

§ Adding the remedy of court injunctions to the previous penalties of seizures and prosecutions.

1951

§ Durham-Humphrey Amendment defines the kinds of drugs that cannot be safely used without medical supervision and restricts their sale to prescription by a licensed practitioner.

§ Birth of the legend:

§ ‘Not to be sold without a prescription’

§ Defined the new category of OTC drugs

1962

§ Thalidomide, a new sleeping pill, is found to have caused birth defects in thousands of babies born in western Europe.

§ Kefauver-Harris Drug Amendments passed to ensure drug efficacy and greater drug safety. For the first time, drug manufacturers are required to prove to FDA the effectiveness of their products before marketing them.

§ Consumer Bill of Rights is proclaimed by President John F. Kennedy in a message to Congress. Included are the right to safety, the right to be informed, the right to choose, and the right to be heard.

1970

§ The Comprehensive Drug Abuse Prevention and Control Act replaces previous laws and categorizes drugs based on abuse and addiction potential compared to their therapeutic value.

§ DEA and DOJ responsible of administering the act

CSA Schedules

§ Schedule I-LSD; Cannabis; Heroin, MDMA= methylene-dioxy-meth-amphetamine (Ecstasy)

§ Schedule II- Cocaine; Morphine; Methylphenidate (Ritalin); Oxycontin, Vicodin;

§ Schedule III -Opioid derivatives, Anabolic steroids, Hydrocodone

§ Schedule IV-Sedatives/ Tranquilizers- Barbiturates, Benzo- Valium (Diazepam), Xanax (Alprazolam); Ambien (Zolpidem); Phenobarb

§ Schedule V-Found in OTC drugs – loperamide, robatussin AC

1983

§ Orphan Drug Act passed, enabling FDA to promote research and marketing of drugs needed for treating rare diseases.

1994: DSHEA

§ Dietary Supplement Health and Education Act establishes specific labeling requirements, provides a regulatory framework, and authorizes FDA to promulgate good manufacturing practice regulations for dietary supplements.

§ This act defines "dietary supplements" and "dietary ingredients" and classifies them as food. The act also establishes a commission to recommend how to regulate claims.

§ Important for TCM herbalists

Public Health Security and Bioterrorism Preparedness and Response Act of 2002

§ designed to improve the country's ability -

§ to prevent and respond to public health emergencies, and

§ provisions include a requirement that FDA issue regulations to enhance controls over imported and domestically produced commodities it regulates.

2004 Project BioShield Act

Authorizes FDA to expedite its review procedures to enable rapid distribution of treatments as countermeasures to chemical, biological, and nuclear agents that may be used in a terrorist attack against the U. S., among other provisions.

FDA Pregnancy Categories

Approval

§ Research pharmaceutical companies invested $12.6 billion in R&D in 2001

§ Average cost per successful drug is between $100-$300 million

§ 1 chance in 5000 from bench top

§ 1 chance in five through clinical trials

Approval

§ Rituximab – an anti-cancer antibody against non-Hodgkin’s lymphoma grossed $1.3 billion in the first 18 months

Drug Receptors

Binding

Signal Transduction

Receptor?

Major Classes of Receptors

§ Ligand-Gated Ion Channels

§ Tyrosine Kinase-Linked Receptors

§ G-Protein Coupled Receptors

§ Ligand-Activated Transcription Factors

Absorption Distribution Metabolism Excretion

Some Definitions!

§ Pharmacodynamics: is the study of what a drug does to the body, whereas

§ Pharmacokinetics: is the study of what the body does to a drug.

Pharmacokinetics

§ study of the chemical alterations a drug may undergo in the body, ("biotransformation"), and study of the means by which drugs are stored in the body and eliminated from it.

Bioavailability:

§ The percent of dose entering the systemic circulation after administration of a given dosage form.

First Pass Effect:

§ The biotransformation and/or excretion of a drug by intestinal and hepatic, including biliary, mechanisms following absorption of the drug from the gastrointestinal tract, before drug gains access to the systemic circulation.

Potency:

§ An expression of the activity of a drug, in terms of the concentration or amount needed to produce a defined effect; an imprecise term that should always be further defined

(Refer Data on Page 21) Drug Half-Life t½:

§ The "half-life" of a drug; the amount of time required for the concentration of a drug in, e.g., a body fluid such as plasma, serum, or blood, to be halved.

WHY DRUGS?

§ Ultimate goal of pharmacologic therapeutics:

§ “to achieve a desired beneficial effect with minimal adverse effects”

Routes of Administration

Routes of Drug Delivery

Bioavailability- amount of drug available in the blood stream

Body fluid compartments

Drug Absorption

§ Process by which a drug moves from site of administration to blood or site of action

§ Requires passage across biological membranes

§ Mostly by passive diffusion

§ Sometimes by active transportation

Physiological Factors Affecting Oral Drug Absorption

§ GI Motility-

1.if decreased delays drug absorption

2.can be decreased by drugs/ food/ disease

§ GI Blood flow

§ Surface Area Small Intestine surgery

§ Metabolism and efflux- small intestinal lymphatics

§ Changes in pH affects polarity of drug

pH can be altered by food/ disease/ other drugs

Drug Absorption : Summary

§ Most drugs absorbed by passive diffusion

§ Lipid soluble drugs are more readily absorbed than non lipid soluble drugs

§ Non-ionized drugs are more readily absorbed than ionized ones

§ Weak acids /Weak bases are more readily absorbed than strong acids/bases

§ Most drugs are absorbed in the

small intestine

?BIOAVAILABILITY

§ The amount of administered drug that reaches the systemic circulation following administration by any route:

IV = 100%

Oral = Less than 100%

Other routes = ~ 100%

Drug Distribution: Issues

§ Drug Affinity-

Bones/ Teeth-

Tetracycline has high affinity for calcium

Thyroid- Iodine containing drugs

Adipose tissue-

Can accumulate lipid soluble drugs

§ Blood brain barrier; placental barrier inhibits certain drugs from reaching the brain/ fetus

Distribution- Plasma Protein Binding

§ Many drugs bind reversibly with proteins in blood and tissues

§ Binding to serum albumin is the common method: Albumin bound drugs are not ‘available’

Albumin bound drugs can act as a reservoir

§ Amount of ‘free’ drug can be increased by

Displacement by another drug

Decreased albumin levels due to disease

Very important for drugs which are highly protein binding- like Coumadin (Warfarin)

§ Also forms the basis of some of the herb/drug interactions

Elimination of Drugs

§ Drugs work only for a finite length of time

§ The duration of the drug action is determined by biotransformation and excretion

(elimination process)

Cytochrome P450: CYP450

§ Metabolize 50-70% of drugs

§ Inhibitors- Antifungals; Antibiotics;

Diet (grapefruit juice)

§ Inducers- Anticonvulsants/ Steroids/ HIV drugs/ Antibiotics

Ethnic variation!

§ The rate of metabolism can vary up to 50 fold within the population

Sites of Drug Excretion

§ Kidney

§ Liver

§ Other – Sweat/ Tears/ Milk/ Lung

LD 50 & ED 50

§ LD 50- Lethal Dose of a drug required to kill at least 50% of the animals tested

§ ED 50- Effective Dose of a drug required to achieve therapeutic levels in at least 50% of animals tested

§ Toxic Dose

Therapeutic Index: TI

§ A number ratio , LD50/ED50, which is a measure of the approximate "safety factor" for a drug; a drug with a high index can presumably be administered with greater safety than one with a low index (ratio 1~ or less than 1).

§ In case of humans it is Toxic dose divided by (therapeutic) effective dose (TD50/ED50)

BIOMEDICAL PHARMACOLOGY:WS0201

ABSORPTION : Q&A