2535- Pathophysiology & Pharm Integration I York University

What is a drug?

Any chemical that affects the physiological processes of a living organism

Pharmacology

The broadest term for the study or science of drugs.

What 3 names can a drug have?

1.Chemical name

2.Generic name (nonproprietary, official name)

3.Trade name (proprietary name)

Chemical name

•Describes the drug's chemical composition and molecular structure

•Generic name (nonproprietary, official name)

•Name given to a drug approved by Health Canada

•Trade name (proprietary name)

•The drug has a registered trademark; use of the name is restricted by the drug's patent owner (usually the manufacturer).

what 2 methods are drugs classified by?

structure and therapeutic use

what are the 3 basic phases of pharmacology

pharmaceutics

pharmacokinetics and

pharmacodynamics

what is pharmaceutics?

The study of how various drug forms influence the way in which the drug affects the body

What is dissolving

Ødissolving of solid dosage forms and their absorption

What is pharmacokinetics

The study of what the body does to the drug

From the time drug is put into the body until the parent drug and metabolites have left the body

what are the 4 phases of pharmacokinetics

ØAbsorption

ØDistribution

ØMetabolism

ØExcretion

what factors does are included within absoprtion

Bioavalibility and first-past effect

What routes are in the body

•Enteral route

•Sublingual and buccal routes

•Topical route

•Transdermal route

•Inhalation route

what parenteral routes are there

Intradermally

subcutaneously

Intravenously

Intramuscularly

Intrathecally

intra-articularly

intra-arterially

What is the first pass effect?

After oral administration, many drugs are absorbed intact from the small intestine and transported first via the portal system to the liver, where they undergo extensive metabolism, therefore usually decreasing the bioavailability of certain oral medications.

what is the entreal route?

The drug is absorbed into the systemic circulation through the mucosa of the stomach, small intestine, or large intestine

ØOral

ØSublingual

ØBuccal

ØRectal (can also be topical)

what are topical routes?

Skin (including transdermal patches)

Eyes

Ears

Nose

Lungs (inhalation)

Rectum

Vagina

What is a Peak Level

highest blood level of a drug

What is a trough level

lowest blood level of a drug

What is toxicity

occurs if the peak blood level of the drug is too high, which is why we use therapeutic drug monitoring

what is a loading dose

Øa higher amount of the drug is given, often only once or twice to increase the drug level in the bloodstream with a level sufficient to induce a therapeutic response

What is a maintenance dose

Øintermittent doses of the drug are given to maintain a therapeutic level of the drug in the bloodstream

what mechanims of actions do drugs go through

ØReceptor interactions

ØEnzyme interactions

What is Pharmacotherapeutics

The clinical use of drugs to prevent and treat diseases

Desired therapeutic outcomes is patient-specific, established in collaboration with the patient.

Outcome goals need to be realistic.

what types of therapy are there

ØAcute

ØMaintenance

ØSupplemental (or replacement)

ØPalliative

ØSupportive

ØProphylactic

ØEmpirical

What is tolerance

decreasing response to repeated drug doses

What is Dependence

physiological or psychological need for a drug

What is physical dependence

Øphysiological need for a drug to avoid physical withdrawal symptoms

what is psychological dependence

Øobsessive desire for a drug

What is the Nursing process

•A research-based organizational framework for professional nursing practice

What is the assesment step within Drug health

•Data collection, review, and analysis

•Medication profile

•Any and all drug use

•Home or folk remedies; natural heath products or homeopathic treatments

•Alcohol, tobacco, caffeine intake

•Current or past illicit drug use

•Prescriptions and over-the-counter medications

•Past or present health history and associated drug regimen

Family history; growth and developmental stage

What is planning step within Drug health

•Identification of goals and outcome criteria

•Goals

•Objective, measurable, and realistic, with an established time period for achievement of the outcomes that are specifically stated in the outcome criteria

•Outcome criteria

What is the analysis step within Drug health

•Identifies actual and potential client problem(s) based on review and interpretation of client data.

•Analyze Cues: The nurse reviews the relevant client data and determines what they mean.

What is the Implementation step within Drug health

•Implementation is guided by the preceding phases of the nursing process.

•Initiation and completion of specific nursing actions as defined by nursing diagnoses, goals, and outcome criteria

•Independent, collaborative, dependent

•Statements of interventions include frequency, specific instructions, and any other pertinent information.

What is the evalution step within Drug health

•Systematic, ongoing, and dynamic part of the nursing process

•Determining the status of the goals and outcomes of care

•Monitoring the patient's response to drug therapy

What are the 10 Rights of Medication Administration

•Right drug (or Right Medication)

•Right dose

•Right time

•Right route

•Right patient

•Right reason

•Right documentation

•Right evaluation (or right assessment)

•Right patient education

•Right to refuse

what is Disease

•Structural or functional change in the body that is harmful to the organism

•Cellular environment changes to degree that tissues cannot perform functions optimally

•Definition and treatment varies by culture

What is pathology?

•Study of basic structural and functional changes associated with disease

•Sequence of events leading from abnormalities to clinical manifestations (pathogenesis)

what are 2 manesfestations of disease

Diagnoses and Syndrome

What is Diagnosis

•Process of assimilating information from history, physical examinations, and laboratory findings to identify condition causing disease

•Also refers to name given to that disease

•Sometimes cannot immediately be made

what is syndrome

•Cluster of findings commonly encountered with more than one disease

•Description of constellation of symptoms, signs, and/or laboratory tests

what are structural diseases

•Organic diseases characterized by structural changes (lesions) within body

•Major categories:

•Genetic and developmental diseases

•Degenerative and inflammatory diseases and trauma

•Hyperplasias and neoplasms

What are functional Diseases

•Diseases without visible lesions at onset

•Physiologic or functional change

•Common functional disorders:

•Tension headache

•Irritable bowel syndrome

•Diabetes

•Hypertension

What are 2 causes of disease

•Exogenous causes of disease:

•Physical

•Chemical

•Microbiologic

•Endogenous causes of disease:

•Vascular

•Immunologic

•Metabolic

What is an idiopathic disease

cause is unknown

what is a latrogenic disease

adverse reaction to treatment

what is a nosocomial disease

acquired from hospital envirment

What is absorption

movement of a drug from its site of administration into the bloodstream for distribution to the tissues

What are entreal routes

The drug is absorbed into the systemic circulation through the mucosa of the stomach, small intestine, or large intestine • Oral • Sublingual • Buccal • Rectal (can also be topical)

Parental Route

• Intravenous (fastest delivery into the blood circulation) • Intramuscular • Subcutaneous • Intradermal • Intra-arterial • Intrathecal • Intra-articular

Topical route

Skin (including transdermal patches) • Eyes • Ears • Nose • Lungs (inhalation) • Rectum • Vagina

types of enteral routes

p.o. (per os ): oral or enteral route p.r. (per rectal): rectal route Buccal: between the lip and the teeth Sublingual: under the tongue

types of Parenteral routes (via injection):

ID (Intradermal injection): in the dermis layer SC or SubQ (Subcutaneous injection): into the subcutaneous tissue IM (Intramuscular injection): into the muscle IV (Intravenous injection): into a vein Inhalation agent: into the lungs

Passive diffusion

high to low concentration

Facilitated difusion

hgih to low needs protein carrier

active transport

low to high and needs ATP

endocytosis

needs receptor mediated endocytosis, then exocytosis to the vasculature

Factors affecting absortption(pH)

Absorption low- weak acid drugs in alkaline environments or weak base drugs in acidic environement

absorption high- weak acid drugs in acidic enviornment , or weak base drugs in basic envionrment

Factors affecting absortption(blood flow)

Absorption low- low perfusion to organs that absor drugs this can occur in shock states

absortption high- high perfusion to organs that absorb drugs

Factors affecting absortption(contact time)

low contact time(ex. diarrhea) for low absorption

high contact in terms of constipation for high absoprtion

Factors affecting absortption(P-glycoprotein)

low absorption are found in apical surface of GIT cells

No P-glycoproteins are associated with high absorption

Factors affecting absortption(total surface area)

lower surface area, this occurs in diseases that destory the brush border of the GIT cells(Lower absorption)

more absoprtion is associated with total surface area

Factors affecting bioavavilibility

Factors affecting bioavailability: solubility of drug hydrophobic vs hydrophilic instability of environment stomach & intestine enzymes first pass effect oral admin→portal circulation→liver→drug metabolized→approx. 30% passes to bloodstream for distribution

What is distribution affect by

a) blood flow b) capillary permeability c) protein binding d) solubility e) volume of distribution

Blood flow

(1) Organs with an increase blood flow Theoretically more distribution of drugs to these organs

(2) Organs with a decrease blood flow Theoretically less distribution of drugs to Distribution

Capiliary permaiability

related to tissue type

Protein binding

Albumin is the most common blood protein and carries the majourity of protein-bound drug molecules. produced by liver If a given drug binds to albumin, only a limited amount of the drug is not bound. This unbound portion is active and is considered "free" drug. high protein bound drugs→ decreased distribution low protein bound drugs→ increased distribution

Solubility

The ability of the drug to move easily from the blood stream across the interstitial fluid and into the tissues al Blood fo

(1) Small nonpolar hydrophobic drugs --High solubility and high distribution ↑DISTRIBUTION SMALL NONPOLAR HYDROPHOBIC LARGE POLAR HYDROPHILIC

(ii) Large polar hydrophilic drug →Poor solubility and increased distribution (iii) Drugs bound to albumin →Poor solubility due to its charge and large size. →Very little distribution

volume of distriution

low→less penetration into tissue high→easily penetrates into tissue

Metabolism

Also referred to as biotransformation

Phase 1 & Phase 2

Most drugs go through phase I then phase II Some go through only phase I Some go through only phase II Some go through phase II then phase I

Biochemical alteration of a drug into an inactive metabolite

a more soluble compound

a more potent metabolite (as in the conversion of an inactive prodrug to its active form)

or a less active metabolite • usually occurs in the liver • makes excretion easier

Phase 1 biotransformation

Drug which is nonpolar and lipid soluble goes through the CYP450 system which makes the drug go through oxidation, reduction, and hydrolysis which makes the drug polar and water soluable

Phase 2 biotransformation

not related to the CYP450 system An already polar drug, by phase II biotransformation, becomes even more polar The drug may be a result of phase I biotransformation but not necessarily

Excretion

Elimination of drugs from the body • Primary organ responsible is kidney • Liver and bowel also play a role • Renal excretion • Biliary excretion

What is a half-life?

the time required for the amount of drug in the body to decrease by 50% and be removed from the body

Steady state

• occurs when the amount of a drug being absorbed is the same amount that's being cleared from the body when the drug is given continuously or repeatedly. • consistent concentration of drug

• takes 4 - 5 half lives

What is pharmacodynamics?

The study of what the drug does to the body The mechanism of drug actions in living tissues 1) Drug receptor interactions

2) Dose-response relationship

3) Potency & Efficacy

4) Drug Activity Profile

5) Classes of Medications

Drug-Receptor Interactions

extracellular receptors: hydrophilic, large, polar charged drugs

1. ligand gated ion channels drug binds to receptor→ opens or closed channels→ ions flow in, or out→ associated response

2. g-protein coupled receptors drug binds to protein→ changes shape of protein→ second messenger system is activated→ cellular response

3. tyrosine kinase receptors drugs target and bind with particular kinases to target desired response examples of kinases: growth factors, cytokines, hormones

intracellular receptors: hydrophobic, small, non-polar, uncharged drugs • passes through cell membrane & binds to an intracellular receptor • slower→ takes time

Dose-reponse relationship

dose response curves - data re the ability of a drug to produce a given physiological effect

• answers the question: how much drug is needed to produce a therapeutic response?

Potency vs Efficacy

Efficacy • maximal therapeutic response that a drug is able to produce • related to # of drug-receptor complexes formed

Potency • how much drug is required to produce a therapeutic response • the lower the amount of drug needed the greater the potency

Drug activity profile

Duration of action

• the length of time a drug exhibits a therapeutic effect

Onset of action • time it takes for drug to meet the minimum effective concentration

Therapeutic index • the ratio of the minimum concentration of drug that produces toxic effects & the minimum concentration that produces the desired effect→Therapeutic index • narrow TI: high incidence of side effects eg, digoxin, lithium, warfarin • large TI: safer, less chance of toxicity eg naloxone

Classes of Medications

• Agonist drugs • Mimic ligand-receptor activation responses→ same effect as endogenous ligand itself • full or partial

• Antagonist drugs • Block the receptor's activation response • Include different types • competitive: blocks the ligand site preventing the normal ligand from interacting with the receptor site • non-competitive: binds to a site different from the endogenous site but still able to block the receptors 'normal' physiological response

• Irreversible receptor anagonists • covalent bonds→ cannot dissociate from the receptor • can't be undone

Symptomatic Disease

Most diagnoses can be made from:

➢ Detailed history

➢ Physical examination

History includes: ➢ Circumstances of emergence of problem

➢ Description of severity, quality, and timing of symptoms

what does a physical examination include?

➢ Visual inspection

➢ Inspection with specialized instruments

➢ Auscultation ➢ Percussion

➢ Palpation

History and physical examination are supplemented by:

➢ Special procedures

➢ Radiologic tests ➢ Laboratory tests

Asymptomatic Disease

Diagnosing disease early requires regular: ➢ Dental appointments

➢ Well-baby examinations

➢ Physical examinations

Screening

➢ Attempting to discover disease before it manifests

➢ Goal is to cure or delay progression of disease

Screening techniques

➢ Patient history ➢ Physical examination

➢ Targeted laboratory and radiologic tests

eg. fecal occult blood test, mammography

When and who to screen depends on:

➢ Likelihood of patient developing disease

➢ Availability of treatment

➢ Cost of screening test Screening procedures are reactive, not proactive

Potential Disease

Preventive medicine

➢ Deals with prevention of disease

Examples of preventable diseases:

➢ Smallpox

➢ Measles

➢ Whooping cough

➢ Periodontal disease

Methods of disease prevention:

➢ Lifestyle and behavior changes ➢ Vaccination

➢ Public health improvements

Diagnostic Tests and Procedures

Test ➢ Analysis performed on specimen removed from patient

Procedure ➢ Involves some manipulation of patient beyond that usually done during physical examination

Clinical Procedures

Primary healthcare practitioners may: ➢ Perform common tests such as urinalysis, vaginal smears, and throat cultures ➢ Procure samples sent to laboratory for analysis

Specialists perform: ➢ Manipulative procedures ➢ Procedures requiring specialized equipment

Radiologic Procedures

Radiology diagnoses disease using techniques such as:

➢ X-rays

➢ Computed tomography (CT) scans

➢ Ultrasound

➢ Nuclear medicine

➢ Echocardiogram ➢ Magnetic reasonsance imaging(MRI)

X-ray procedures

➢ Depend on differing absorption properties of tissues as x-rays pass through them • Radiodense material leaves white shadow • Air-filled cavities appear dark

Fluoroscope

➢ Produces a dynamic x-ray image

Computed tomography (CT)

➢ X-ray technique in which a computer records and analyzes x-ray absorption patterns through planes of tissue

➢ Creates cross-sectional images of body

➢ Preferred diagnostic modality for detecting acute processes and delineating deep-seated lesions

Magnetic resonance imaging (MRI)

➢ Records tissue characteristics in tissue planes ➢ Image produced by displacing protons in atomic nuclei with radio-frequency signals while the body is surrounded by a strong magnet ➢ T1 images give a strong signal for lipids ➢ T2 images give a strong signal for water

Ultrasound

➢ Measures reflection of high-frequency sound waves as they pass through body tissues ➢ Greatest contrast provided by interfaces between soft tissues and liquids ➢ Commonly used during pregnancy and to detect gallstones

Nuclear medicine

➢ Involves injecting radioactive materials into bloodstream and determining their degree of localization within tissue ➢ Can evaluate functional activity of an organ ➢ Expensive and exposes patient to radiation

Surgical pathology

➢ Involves diagnosis of lesions in pieces of tissue removed from patient

➢ Diagnosis based on gross and microscopic examination by pathologist