Basic Pharmacology and Pharmokinetics

1
Basic Pharmacology and Pharmokinetics

• Unit 9

2
Objectives

• Discuss drug nomenclature and classifications.
• Describe the processes involved with
  pharmacokinetics and pharmacodynamics.
• Discuss potential drug interactions.

3
What are the goals of Pharmacology?

• To understand all aspects of drug action and
  efficacy-to develop drugs/treatment regimes that
  have selective (beneficial) actions without
  adverse effects. i.e. to help without making the
  situation worse.

4
What is a drug?

• Chemical substance that is usually used to treat
  a disease/condition
• When administered appropriately, it causes a
  range of physiological and biochemical changes in
  a complex biological system that relate to its
  composition, structure, and target

5
When is a drug not a drug?

• Drugs sold and marketed for the treatment of
  disease must have regulatory approval (FDA) and
  have gone through evaluation procedures
• Food supplements must not make claims about
  therapeutic properties-only drugs can be sold on
  that basis

6
Five medical uses for drugs

• Therapeutic use
• Diagnostic use
• Curative use
• Replacement use
• Preventive or Prophylactic use

7
Drug Nomenclature

• Drugs are identified by one of three names
• Chemical-long name, refers to the chemical
  structure of the drug
• Generic-shorter preferred name, derived from the
  chemical name
• Trade-brand name assigned by the manufacturer

8
Naming Complications

• Brand names can change over time as patents
  expire or companies merge
• Most drugs are marketed by numerous names in
  different countries
• Even generic names can differ in different
  countries

9
Drug Nomenclature

• Abbreviations for dosages
• Bid-twice a day
• Tid-three times a day
• Qid-four times a day

10
Where do drugs come from?

• Plants
• Human-derived proteins/steroids
• Fungi/Bacteria
• Synthetic chemicals
• Recombinant proteins

11
Drugs from the Natural World

• 121 prescription drugs in use today for cancer
  treatment-90 are derived from plant species.
• Recent example Taxol
• 1981-2002 48 of 65 approved cancer drugs were
  natural products, based on natural products, or
  mimicked them in some way

12
Drug Origination Sites

• Extracts from plants and herbs
• Opium poppy juice from seeds yields morphine
  powerful painkiller
• Foxglove leaves contain digoxin used to treat
  congestive heart failure (CHF)
• Can be fatal at high enough doses

13
Drug Origination Sites

• From the body itself
• Hormones
• Insulin-used for diabetes
• Thyroxine-hypothyroidism
• Growth hormone

14
Drug Origination Sites

• Micro-organisms (bacteria)
• Antibiotics
• Penicillin product of mold discovered by
  Alexander Fleming in 1928
• Interferes with bacterial cell wall synthesis

15
Drug Origination Sites

• Chemical modification of the bodys own
  hormones/regulators
• Hormonal drugs
• Estradiol form of estrogen
• Prednisolone synthetic steroid
• Anti-cancer drugs modified base components of
  DNA/RNA-interfere with RNA synthesis

16
Drug Classification

• Over-the-counter (OTC)
• Prescription (controlled substances)
• Schedule 1-highest abuse potential
• Schedule 2
• Schedule 3
• Schedule 4
• Schedule 5-lowest abuse potential

17
Drug Classification

• Most narcotic pain prescriptions are classified
  as Schedule 3
• Anabolic steroids are also classified as Schedule
  3

18
Drugs according to schedules

• Schedule 1 Heroin, LSD, Marajuana
• Schedule 2 Demerol, Morphine, Percocet, Ritalin
• Schedule 3 steroids, arbituates, Tylenol with
  codeine
• Scheule 4 Ativan, Valium, Xanax
• Schedule 5 Robitussin

19
Drug Legislation

• Controlled Substance Act of 1970
• Controls the manufacture, importation, selling,
  dealing in, and dispensing drugs that have the
  potential for addiction and abuse.

20
The Study of Drugs

• Pharmacology science of drugs
• Pharmacokinetics process related to how the body
  acts on the drug
• Pharmacodynamics process related to how a drug
  acts on the body

21
Pharmacokinetics

• How the body handles a drug
• Two primary routes of administration
• Enteral, Parenteral
• 4 Phases (ADME)
• Absorption
• Distribution
• Metabolism
• Excretion/Elimination

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Routes of Drug Administration

• Enteral enters the body by way of alimentary
  canal or digestive system
• Parenteral uses pathway other than above
• Usually allows drug to be delivered directly to
  the target tissue

23
Routes of Drug Administration

• Enteral
• -Oral
• -Sublingual
• -Rectal
• -Parenteral
• -Inhalation
• -Injection
• -Topical/transdermal application

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Routes of Drug Administration

• Systemic Effects
• -Oral
• -Injection
• -Intranasal
• -Oral inhalation
• -Sublingual
• -Buccal
• -Rectal

25
Routes of Drug Administration

• Local effects
• Ophthalmic (eye)
• Otic (ear)
• Topical (skin)

26
Routes of Drug Administration

• Most immediate effects produced by
• Intravenous
• Inhalation (oral or nasal)
• Sublingual absorption
• Drugs administered orally may require 30 minutes
  before relief is provided.
• Liquids or powders dissolved in water will act
  more rapidly than tablets or capsules.

27
Drug Concentrations

• A drugs most intense effects occur during the
  peak serum concentration. (when the highest level
  of the drug is circulating through the
  bloodstream.)

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ADME Process

• Absorption
• Distribution
• Metabolism
• Elimination/Excretion

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Absorption

• For a drug to produce a therapeutic effect, it
  must be absorbed into the bloodstream and
  distributed through the circulatory system.
• Requires the drug molecules to move across a
  membrane through either
• Simple diffusion
• Facilitated diffusion

30
Absorption

• Drugs taken by mouth pass to the stomach and then
  the intestines.
• They are absorbed from the GI tract into the
  circulatory system.
• Lipid-soluble drugs can easily pass through the
  BBB to affect the CNS.

31
Absorption

• Exercise decreases the absorption of drugs taken
  by mouth.
• Blood is diverted away from the GI tract to the
  skeletal muscles.
• When the body absorbs less of a drug, the
  therapeutic effectiveness is decreased.

32
Absorption

• Can be affected by the bioavailability amount of
  drug active in the tissues
• Ex. If the drugs bioavailability is 50, the
  body will only absorb 250 mg of a 500 mg dose.
• Naproxen Sodium bioavailability is 95

33
Distribution

• Once absorbed into the bloodstream, the drug is
  distributed to target sites throughout the body.
• Exercise increases the distribution of most drugs.

34
Distribution

• Affected by a drugs lipid solubility
• Drugs with a high lipid solubility can easily
  penetrate fat stores and cross membrane barriers
  giving a broader distribution
• Water soluble drugs can be easily eliminated from
  the body
• Fat soluble drugs can be stored in the body,
  providing longer lasting effects.

35
Metabolism

• Clearing process that breaks down substances into
  water soluble form for easy elimination
• Primary site-liver
• May also occur in the kidneys, GI tract, and
  lungs.

36
Metabolism

• Exercise can decrease the clearance of some drugs
  due to the blood being diverted away from the GI,
  kidneys, and liver to the working skeletal
  muscles.
• However, since the duration of the drugs effect
  is usually longer than an exercise session, the
  overall effect of exercise on drug metabolism is
  insignificant.

37
Elimination or Excretion

• Exercise can slow the rate of excretion since
  blood flow will be diverted away from the kidneys
  to the skeletal muscles.
• Excretion rate is also affected the drugs
  half-life

38
Elimination or Excretion

• Half-life time required for the body to
  eliminate one-half of a dosage of a drug by
  regular, physical processes.
• Ex. If a drug has a half-life of 8 hours, it will
  take 8 hours for the blood concentration of the
  drug to be decreased by 50.

39
Elimination or Excretion

• Naproxen has a half-life of 12-17 hours
• Water soluble drugs will have shorter half-life
  than lipid soluble drugs
• Lipid soluble drugs will remain in the system the
  longest

40
Pharmacodynamics

• For drugs to work, they must bind with a
  receptor.
• The receptor can be a molecule within a cell or
  on the cell membrane.
• Relationship between a drug and its receptor is
  much like a lock and key configuration

41
How do drugs work?

• Bind to a target to either activate or inactivate
  it.
• Most drug targets are proteins
• Common drug targets include
• Receptors
• Enzymes
• Ion channels
• Transporter molecules

42
Pharmacodynamics

• Drug dosing based on the drugs potency,
  patients age, patients condition
• Potency strength of the drug the greater the
  potency, the smaller the dose needed to produce
  therapeutic effects

43
Examples of Drug Dosing

• Aspirin
• Usually manufactured in 325 mg tablet
• Typical dose 2 tablets per 4 hours
• Ibuprofen
• Typical dose 400 mg

44
Drug Interactions

• Occur when one drug alters the effect of another
  drug
• May change how the body handles one or both of
  the drugs
• May change the way a drug acts on the body

45
Drug Interactions

• Can be additive or inhibitive
• Additive effects occur when someone takes two
  drugs of the same type at the same time. i.e. two
  stimulants or two depressants
• The effects of the drug add together

46
Drug Interactions

• Additive effects (agonistic)
• Diet pills (appetite suppressant) which is a
  stimulant combined with several cups of coffee,
  also a stimulant may cause heart palpitations,
  jitteriness, and insomnia.

47
Drug Interactions

• Can easily occur through innocent use of OTC
  medications.
• Medications for colds/allergies
• Inhibitory effects many occur with the
  combination of two unrelated drugs.

48
Drug Interactions

• Inhibitory effects (antagonistic)
• Some antibiotics may inhibit or reduce the
  effectiveness of oral contraceptives
• Aspirin may increase the effects of insulin
• Dairy products may reduce the effectiveness of
  tetracycline

49
Drug Interactions

• Inhibitory effects (antagonistic)
• Alcohol ingested with aspirin may cause GI
  bleeding
• Chronic alcohol consumption and acetaminophen can
  cause permanent liver damage

50
Adverse Drug Reactions

• Range from a side effect to hypersensitivity
• Examples of side effects drowsiness, loss of
  appetite
• Examples of hypersensitivity allergic reactions
  that range from simple rash to bronchial spasm or
  anaphylactic shock

51
Adverse Drug Reactions

• Can occur immediately or be delayed
• Most delayed effects occur with chronic use of a
  drug
• Ex. Chronic use of Tylenol has been linked to
  liver damage.

52
Drug References

• Pharmacopeia official list of standardized drugs
  published every 5 years
• PDR Physicians Desk Reference
• Nurses Drug Handbook