Download WS0201 - Cat`s TCM Notes

WS0201:
Biomedical Pharmacology
UNIT 1- The Basics
Pharmacognosy
Sources of Drugs
Sources of Drugs
Animals
Plant
Minerals
Synthetics
Biologicals- recombinant DNA (rDNA)
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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 SourcesSeeds, Roots, Leaves, Resins
Animal Sources- Glandualr productsinsulin, thyroid; Microbes
Mineral SourcesPotassium, Calcium, Lithium
SyntheticBarbiturates, Sulfonamides, Aspirin
FACT:
Over 20 new drugs launched between 2000-2005 originated from:
plants/ animals/ microorganisms/ marine species/
Anticancer drugs- campothecin, paclitaxel, epipodophyllotoxin,
? DRUGS
vinblastine
? Pharmacology
Drugs are chemicals used to diagnose, treat and prevent disease.
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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
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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
Extending control to cosmetics and therapeutic
Requiring new drugs to be shown safe before
of 1938 provisions:
devices.
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
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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
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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
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 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 Motility1.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
 Changes in pH affects polarity of drug
pH can be altered by food/ disease/ other drugs
lymphatics
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 AffinityBones/ TeethTetracycline has high affinity for calcium
Thyroid- Iodine containing drugs
Adipose tissueCan 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
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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/
Ethnic variation!
HIV drugs/ Antibiotics
The rate of metabolism can vary up to 50 fold within the population
Sites of Drug Excretion

Kidney

Liver
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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
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