PKPD 1&2

• Pharmacotherapeutics lectures cover the study of medicines.
• Readings can be found in the Course Outline on eclass.
• PowerPoint presentations serve only as guidelines.
• It is important to add/write custom notes during the lecture, and to understand the lecture material presented.

Pharmacology: The Study of Medicines

• Pharmacon means medicine or drug.
• Logos means to study.
• The purpose of pharmacology is to:
• Cure diseases
• Relieve symptoms
• Improve quality of life.
• Prior to the 20th century, remedies were sourced from nature.
• Therapeutic effects were due to an active ingredient.
• The 20th century brought synthetic manufacturing of active ingredients.
• Examples include aspirin from willow bark, penicillin from molds, digoxin from digitalis, Taxol from Pacific Yew and morphine from poppy milk

Pharmacotherapeutics

• It is the utilization of medicines or drugs to heal or manage patient care.
• Practical application involves administration and knowledge of drug movement through the body.
• Monitoring the body’s responses to the drug is part of the nursing process, as well as identifying the medications interactions.
• There are approximately 500,000 prescription drugs used per year, which equals about 10 per person demonstrating the widespread medication use.
• 18% of healthcare budgets are spent on drugs.

Drug/Medication Categories

• Medication is a chemical agent.
• Biologics are naturally produced in animal cells (e.g., antibodies, blood products, hormones).
• Natural health products are naturally occurring and used as adjunct treatments, such as vitamins and minerals.

Drug Approval Process

• Health Canada evaluates/monitors the safety, efficacy, quality & advertising of medications.
• The Canadian Pharmaceutical Association collaborates with Health Canada and publishes the CPS.
• CPS (first edition in 1960) is a compilation of drug information and adverse effects.
• Drug approval process involves stages of:
• Research
• Preclinical trials on non-humans (3-5 years).
• A CTA (clinical trials application to Health Canada) comprised of 3 phases.
• Phase I - small group (up to 100 healthy volunteers).
• Phase II - up to 300 volunteers with the disease.
• Phase III - up to 3,000 participants.
• Only 10% of drugs make it to phase III.
• New Drug Submission (NDS) to Health Canada with about 80 submissions per year with only 10% approved.
• If approved, a NOC (notice of compliance) & DIN (drug ID) is assigned.
• Post approval, the drug is monitored via MHDP (marketed health product directorate) for adverse effects (there are 2 databases used for this).
• Each province decides whether to add the new drug to their formulary and how the drug cost will be covered.
• The Special Access Program (SAP) via Health Canada allows for not yet approved drugs to be used in special circumstances.
• Natural Product Health approval is not as stringent, does not fall under the above process
• Each province has its own healthcare system so drugs may be available in one place but not another.

Placebo In Clinical Trials

• A Placebo is a substance 'said' to have an effect, which may lead to an actual effect: the 'Placebo effect'.
• Declaration of Helsinki (2000) states anti-placebo should be used as a comparative substance, unless no better clinical trial can be used, then only it the comparative substance shall be the one primarily used at this time.

Types of Drug Names

• A drug has 3 types of names.
• Generic:
• It describes the drug without a proprietary affiliation
• It is the assigned (international non-proprietary name).
• It's the same throughout the world.
• There is 1 generic name per drug.
• It is found on NCLEX exams.
• Brand/trade:
• It's named by the manufacturing company.
• There can be many trade names per one generic drug.
• Often protected for 20 years before other manufactures are allowed to manufacture the drug themselves.
• Chemical:
• It is the chemical composition of the drug.
• It’s assigned by IUPAC (international union of pure and applied chemistry).

Brand vs. Generic

• Generics are cheaper and often covered by insurance companies.
• Brand names are more expensive and sometimes not covered by insurance.
• Generic name may be substituted if the trade name is not available and visa versa
• Bioequivalence is the amount of drug in circulation
• Sometimes debates over non-active ingredients. If the non-active ingredients not exactly the same, is the drug effectiveness affected?

Prototype Drug

• It’s the selection of a single drug from a drug class to serve as a reference drug within that particular class.
• Prototype drugs serve as role models to predict actions and adverse effects of other drugs within the same class.
• Often the original and most prevalent drug from that class.

Drug Classes

• Drugs are organized into drug classes.
• There are 2 types of naming drug classes:
• Therapeutic drug class nomenclature: it specifies a treatment/therapy of for particular disease.
• The name describes the molecular/receptor activity, and explains how it works.

Drug Schedules for Dispensing

• In hospital settings, all drugs are prescribed.
• Schedule I drugs are available only by prescription and dispensed by a pharmacist.
• It is only dispensed by prescription to specific health care professionals.
• Schedule II drugs are exclusively available from a pharmacist and must stay where there's no public access.
• Schedule III drugs are available via open access in a pharmacy.
• Unscheduled drugs can be sold in any store without supervision.

Right of Medication Administration

• Assessment of alterations to physiology should be performed
• Implementation should include patient education.
• Evaluation includes assessment of drug action and side effects.

Pharmcotherapy in Patient Assessment

• Subjective data of the health history should be taken including:
• Any medications?
• Supplements?
• Vitamins?
• Chief (presenting) concern
• Any medications tried for this concern.
• Personal and Social History: Recreational drug use?

Drug Administration Rights

• The nurse should confirm that the drug 'makes sense' for the patient.
• It's important is to understand the therapeutic goal.
• The nurse can know the drug is actioning by monitoring for respiratory effect, LOC, and BP.
• Patient teaching includes explaining the drug treatment and all possible side effects.

Drug Administration

• It is part of implementation’ in the Nursing Process.
• The 6 rights are critical during drug administration.
• Right patient
• Right drug
• Right dosage
• Have I confirmed the correct dosage and measured it accurately
• Right route. Am I administering the medication by the correct route.
• Right time; Are you giving at the correct time described.
• Right documentation; Have you documented the amount accurately in the patient reports.

Drug Formulations and Routes of Administration

• Drug formulation is how the drug ingredients are prepared to be administered in a specific form.
• Drug route of administration tells how the drug is taken into the body and specifies by which drug formulation.
• The route of administration depends on these factors:
• The medical situation
• How the drug moves throughout the body.
• Formulation availability
• Clinical setting.
• Administration by the GI tract is considered Enteral

Routes of Administration

Oral route:

• Given by mouth (PO).
• Can be liquid, tablets/pills, or powder
• Absorption is affected by acidic environment and peristalsis dependent.
• It enters portal circulation (liver) before systemic circulation.
• It leads to a systemic effect. Sublingual (SL) route:
• Held under the tongue
• Capillary absorption moves into blood stream
• It bypasses GI system and first pass metabolism.
• Faster acting than PO.
• It has a systemic effect. Intranasal
• Into the nasal cavity
• Often in the form of Can be a spray
• It's transported along cranial nerve network.
• Does not cross the BBB
• Effect is drug dependent
• Can produce local effects that are systemic Inhalation route:
• Inhaled into the lungs.
• Pulmonary capillary network enables rapid effects.
• Can be localized or systemic effect. Endotracheal route
• It goes directly to the lungs
• Often utilizes ER/ICU situations
• Only certain drugs Topical route:
• Applied directly to a surface (e.g., skin/eye creams).
• It produces a local effect.
• There's minimal systemic presence. Topical route of administration may be contraindicated due to caution. Transdermal route:
• It utilizes a 'patch' format.
• It uses dermal capillary absorption.
• The molecules must be small enough to penetrate the skin layers for systemic effect. Rectal route:
• It is inserted into the rectum.
• Both local and Systemic effect.
• 50-75% bypasses 1st pass metabolism.
• The systemic effect is unreliable with many affecting it. 'parenteral' administration:
• All require an injection.
• Intravenous (IV): a needle enters directly in a vien to cause systemic effect for immediate absorption.
• Intramuscular (IM): uses an injection that goes into the muscle.
• Subcutaneous (SC): uses an injection into the adipose tissue.
• Implanted ports: what is used for cancer pts.

Terms and Abbreviations

• q = every
• qh = every hour
• qd = every day
• qod = every other day
• qhs = every night
• q2h = every 2 hours
• q4h = every 4 hours
• q6h = every 6 hours
• q8h = every 8 hours
• q12h = every 12 hours
• /d = per day
• bid = 2 times a day
• tid = 3 times a day
• qid = 4 times a day
• h = hour
• hr = hour
• hs = hours of sleep
• tab = tablet
• cap = capsule
• gtt = drop

Pharmacokinetics and Pharmacodynamics

• Pharmacokinetics: pharma (medicines), kinetics (motion)
• Movement across cell membranes via lipid bilayer.
• 4 phases of ADME: Absorption, Distribution, Metabolism, Excretion
• Pharmacodynamics.

Molecular Kinetics

• Can be affected by:
• Molecular characteristics.
• Charge.
• Lipophillicity vs hydrophilicity. (An acidic drug stays acidic).
• Size, smaller is better.
• Membrane transport.
• Molecules need to be small/non-ionized/lipophilic for easy absorption and distribution.
• Hydrophilic and ionized molecules have easy excretion.

Absorption

• Time for drug to reach systemic circulation
• Factors effecting it:
• Medications administration route (Example IV vs PO)
• Molecular characteristics (See general rule)
• Bioavailability.
• Drugs undergo first pass metabolism through the liver.

Therapeutic Range

• Occurs when you have enough drug to reach a target effect.
• Cmax is the max concentration of a drug at peak performance.
• Cmax will decrease as it is metabolized.
• It's essential to have dosing in therapeutic range. ED50 is medician therapeutic dose that elicits " recommended therapeutic response".

Therapeutic Index

• How safe a drug is. ED 50 dose required to produce a therapeutic effect in 50% of the population

• TD 50 median toxic dose TD is "Median toxic dose" 50 Drugs TD 50 : median toxicity dose

• Low TI' = drug more likely to result in overdose

• High TI = drug less likely to land in overdose

Mnemonics Digoxin, Warfarin, Tacrolimus - Dogs walk to Paris