Pharmacology Notes Week 1 - 3.doc

Drug

any chemicals that can affect living processes.

Pharmacology

study of drugs and their interactions with living systems.

Clinical pharmacology

study of drugs in humans, includes study of drugs in patient as well as in volunteers.

Pharma-therapeutics

the use of drugs to diagnose, prevent, or treat disease or prevent pregnancy.

Effectiveness

elicits the response for which it is given / most important property.

Safety

no harm (no such things as safety drug).

Selectivity

elicits ONLY the response for which it is given / no such thing.

Reversible action

ex. anesthetics drugs- should wake up eventually.

Predictability

know drug effect in advance.

Ease of administration.

administered easily

administered easily

Freedom from drug interactions

if few meds at the same time- it can be side effect.

Low cost.

not expensive to buy

Chemical stability

expire day, chemical stability of drugs.

Possession of simple generic name

drugs have trade name thats easy to remember.

factors influencing intensity of drug response

1. Administration- dosage size, route, timing

2.  4 major pharmacokinetic processes

3. Pharmacodynamics process determine the nature and intensity of the response on drug

4. Pharmacokinetic process - how much of an administrated dose gets to its site of action.

Federal Pure Food & Drug Act (1906).

Protect from adulterated or mislabeled drugs

The Food, Drug, & Cosmetic act (1938).

Check for toxicity

Harries-Kefauver Amendments (1962).

Check for safety & efficacy.

Controlled Substances Act (1970).

Control drugs of potential abuse. RCMP is responsible for enforcement of the CDSA

Food and Drug Administration Modernization Act (1997).

Safety of foods, drugs, medical devices, cosmetics, and other products

Marihuana for Medical Purposes Regulations (2014).

Health Canada regulates the producers of marihuana for this purpose but is not involved in the decision-making process.

Consumed in resins, oils, extractions, and edible forms, as well as in dried form for smoking.

Preclinical testing

perform in animals before testing in humans. Required before a new drug may be tested in humans.

• Drug evaluated for

  • Toxicities

  • Pharmacokinetic properties

  • Potentially useful biologic effect

  •     May take 1 to 5 years

    • May be tested on humans after sufficient preclinical data are collected.

Clinical testing

done in humans in 4 phases.

Phase 1

Evaluation of drug metabolism and effects on humans in normal healthy volunteers (few people)

Phase 2 and 3

Tested in patients to determine therapeutic effects, dosage ranges, and patient safety.

• Patients with the disease being studied for drug

Phase 4 (Post marketing Surveillance)

Usage is for the general population, post marketing studies voluntarily conducted by companies to help discover new side effects.

Special Access Programs (Experimental drugs)

Allows health care providers compassionate access to drugs unavailable for sale in Canada, limited to those with serious or life-threatening conditions.

Women

BEFORE childbearing age women were not allowed to participate in phase 1 and 2 (exception if women have life-threatening illness that may response to the drug)

NOW, women can participate in drug testing.

Children

drugs now tested on children to determine dosage and therapeutic response.

Failure to detect all adverse effect

Due to: Small # of patients were tested during clinical.  Patients were carefully selected. Patients take drug for relatively short period time.

Chemical name

chemical description of the drug.

Generic name (nonproprietary name)

each drug has only one generic name.

Trade name (proprietary or brand name)

the name under which a drug is marketed.

Clinician and pharmacists.

5. Identify appropriate resources for pharmacology information and related patient care

Poison control centers.

Pharmaceutical sales representatives.

Text-like books newsletters reference books.

Internet.

Pre-administration assessment.

• Collecting baseline data

• Identifying high risk patients

• Assessing patient assessing patient’s capacity for self-care

Dosage and Administration.

• Indication for drug and modification of dose

• Route selection and dose

• IV route & extravasation

Evaluating & Promoting Therapeutic Effects.

• Evaluating response

• Promoting compliance

• Implementing non-drug measures

Minimizing Adverse Effects.

Knowing major side effects

2. Time when they might occur

3. Early signs / interventions to minimize

Minimizing Adverse Interactions.

  Thorough drug history including OTC’s

ii)  Monitoring for know interactions

iii) Being alert for unknown interactions

PRN Decisions.

indications and patient needs

Managing Toxicity.

early signs and treatment

Health Promotion and Teaching.

Pharmacokinetics

the study of the drug movement throughout the body. ADME

Absorption

the rate at which a drug leaves its site of administration and the extent to which it occurs.

Distribution

transport of a drug in the body by the blood to its site of action.

factors affecting distribution

-Blood flow to tissue

– Exiting the vascular system

– The blood-brain barrier

– Placental drug transfer

Metabolism (biotransformation)

• Biotransformation

• Enzymatic alteration of drug structure

• Liver—primary site of drug metabolism

• P450 system (cytochrome P450)

Therapeutic consequences are:

• Accelerated drug excretion.

• Drug inactivation

• Increased therapeutic action.

• Activation of prodrugs

• Toxicity variations Special considerations

• Age

• Induction of drug-metabolizing enzymes

• First-pass effect

• Nutritional status

• Competition between drugs

Excretion

removal of drug from the body, primarily occurs via the kidneys.

via three processes – Glomerular filtration – Passive tubular reabsorption – Active tubular secretion

Factors affecting drug absorption

rate of dissolution, surface area, blood flow, lipid solubility, pH partitioning.

More = better, More = better, More = better, Highly-lipid = faster absorption

if there is difference between plasma pH and the pH at the site of administration absorption is better

Enteral

Drug administration via the gastrointestinal tract. po, pr, buccal, subling

Parenteral

Drug administration outside of the gastrointestinal tract. IV, SVC, IM, topical, transdermal, inhalation

p.o

Oral or enteral route of drug administration.

p.r

Rectal route of drug administration.

Buccal

Drug administration between the lip and the teeth.

Sublingual

Drug administration under the tongue.

Intravenous (IV)

Drug administration directly into the vein.

Subcutaneous (SC)

Drug administration into the subcutaneous tissue.

Intramuscular (IM)

Drug administration into the muscle.

Topical

Drug administration applied to the skin or mucous membranes. no first pass effect, effects slow, onset slow

Transdermal

Drug administration via patches applied to the skin. no first pass effect

Inhalation

Drug administration through inhalation. easily absorbed thru alveoli

Oral Barrier

Layer of epithelial cells in the gastrointestinal tract that can affect drug absorption.

Advantages of oral

-easy, convenient, inexpensive

-safer than injection

-reversible (If wrong dosage, drug administrated)

disadvantages of oral

-Variability (absorption is variable from patient to patient)

-inactivation- some drugs are destroyed in the body by enzymes

-Patient requirements- problem if clients is comatose -Local irritation -some drugs can cause irritation of GI tract

IV barrier

no significant barriers

Advantages of IV

Rapid onset of drug action -Control the exact amount -Use of large fluid volumes - just IV -use of irritant drugs (some drugs can be administrated via IV due to strong chemical that may damage tissue).

Disadvantages of IV

-High cost, difficulty, inconvenience -Irreversibility- danger for over dosage therefore you need to inject slowly -fluid overload- a lot of IV -infection- from injection -Embolism -importance read label (route)

Capillary wall

Barrier that drugs must cross to enter the bloodstream in intramuscular

advantage of intramuscular

-Administration of poorly soluble drugs -depot preparation (preparations from which the drug is absorbed slowly over extended time)

Disadvantage of intramuscular

-discomfort- pain, (cause tissue or nerve damage if administrate impropriate) -less convenient than oral admin.

Chemical equivalence (packages of oral administration)

- drugs contain the same amount of identical chemical compound.

Equal bioavailability

- they contain is absorbed at the same rate and to the same extent.

Minimum effective concentration (MEC)

The plasma drug level at which therapeutic effects begin. if plasma drug level is low, effects wont occur, concen must be >MEC

Toxic concentration

The plasma drug level at which toxic effects begin.

Therapeutic range

The range of plasma drug levels between the minimum effective concentration and the toxic concentration. Narrow therapeutic range(index) – high toxicity

Half-life

the time needed for drug in the body to decrease by 50% doesn’t depend on how much drug is present. The half-life of a drugs determines the dosing interval.

Plateau

administering repeated doses causes that drug built up in the body until plateau. - When the amount of a drug eliminated between doses EQUALS the dose administered, average drug level will remain constant, and plateau will have been reached - As long as dosage remains constant, the time required to reach plateau is independent of dosage size

Onset

The time it takes for a drug to elicit a therapeutic response.

Peak

The time it takes for a drug to reach its maximum therapeutic response in the body.

Loading dose

A large initial dose administered to achieve a plateau level quicker.

Maintenance dose

A smaller dose given after achieving a high drug level to maintain stability.

Pharmacodynamics

is defined as the study of what drugs do to the body and how they do it (as the study of the biological and physiologic effects of the drugs and the molecular mechanisms by which those effects produce)

Maximal efficacy

The largest effect that a drug can produce.

Relative potency

The amount of drug needed to elicit an effect.

It is important to note that the potency of a drug implies nothing about its maximal efficacy. Potency and efficacy are completely independent qualities.

Therapeutic index

A measure of a drug's safety.

large index- safe

small- unsafe, easier for mistakes

Dose-response relationship

The relationship between the size of a dose and the intensity of response produced.

Dose response relationship determine:

a) minimum amount of drug we can use.

b) maximum response that drug can elicit.

c) how much we need to increase to produce the desired increase in response.

Dose response curve:

reveals 2 characteristics: maximal efficacy and relative potency (see previous page).

Receptor

molecular structure within cell

receptor families: cell-memb embedded enzymes, ligand-gated ion channels, g protein-coupled receptor system, transcription factors

Cell membrane-embedde d enzymes

Insulin

Ligand-Gated Ion channels

GABA

G protein-coupled receptor system

NE, histamine, serotonin

Transcription factors

thyroid and steroid hormone

Agonists

Molecules that bind to and activate receptors.

Agonist has:

affinity- allows the agonist bind to receptor.

intrinsic activity –allows the bond agonist to “activate” receptor function.

Antagonists

Molecules that bind to and inhibit receptors.