Unit 1 Flashcards
PHARMACODYNAMICS
What the drug does to the body/How it changes the body
PHARMACOKINETICS
What the body does to the drug
Movement of the drug through the body after Absorption, Distribution, Metabolism and Excretion
10 RIGHTS OF DRUG ADMINISTRATION
Drug
Informed consent (right to refuse)
Dose
Time (delivery & Frequency)
History & Assessment
Education & Info
Documentation
Route
Interactions Evaluations
Patient
3 CHECKS
When gathering medication
During Med Prep
Right before administering
PHARMACOTHERAPEUTICS
Administration of drugs for the purpose of disease prevention or treatment and relief of suffering
NATURAL HEALTH PRODUCTS
Naturally occurring health substances used to maintain or restore health
Eg) herbs, vitamins, minerals etc
BIOLOGICS
Agents naturally produced in animal cells that are used to treat and prevent various illnesses Eg) vaccines, hormones
Canadian Drug Regulation
The company must prove that the drug is both safe AND effective for a specified purpose
Steps for Marketed Drug Approval
1) Initial drug research is conducted
2) Preclinical studies in cultured cells, living tissue and species of animals are performed
3) Has 3 phases
4) Pharma company completes a New Drug Submission to Health Canada (includes safety and efficacy info like testing data, how it’ll be produced and packaged, expected therapeutic and adverse reactions)
5) A committee of drug experts reviews the NDS to identify potential risk and benefits
6) Health Canada reviews information
about the drug product and passes
on important details to healthcare
provider and consumers
7) Health Canada issues a Notice of Compliance (NOC) and DIN (both are required for manufacturing)
8) Health Canada monitors the drug for an concerns after it’s marketed
3 Phases of Step 3
Phase 1 - “Safety Phase”, small group of healthy humans
Phase 2 - “Effectiveness Phase”, Small group of humans WITH target disorder
Phase 3 - “Confirmation Phase”, LARGE group of humans with disorder
Therapeutic Classification
Organizes drugs based on their therapeutic usefulness in treating disease
Eg) Anticoagulant, Antihypertensive
Pharmacological Classification
Describes how the drug works at the molecular, tissue and body system level
Eg) Vasodilator, Calcium channel blocker
3 Drug Names
Chemical - Drugs named after chemical composition
Generic - assigned international non-proprietary name (ONE name per drug)
Eg) Ibuprofen
Brand/Trade - Name selected by company
Eg) Tylenol, Advil
Bioavailability
amount of drug that is absorbed into the systemic circulation and is physiologically available to reach the target cells and produce a reaction
Controlled Substances
Drugs whose use is restricted by the Controlled Drugs and Substances Act (CDSA) and the Narcotic Control Regulations, because of the potential for ABUSE
Adverse Vs Side Effect
Adverse = Negative effect
Side Effect = Associated effect that isn’t necessarily bad (Eg Viagra originally for heart but had other good effects too)
Nursing Process with Pharmacotherapeutics
A-D-P-I-E
Assessment
Diagnosis
Plan (whatcha gonna do)
Intervention
Evaluation (How did it work)
Responsibilities to ensure effective pharmacotherapy
- Ensuring all drugs and treatment options have been considered before beginning pharmacotherapy
- Determining the ideal drug to be prescribed to the client to treat the current condition
Factors Affecting Medication Administration Routes
Drug to target tissues
Clinical setting
Medical situation
Drug Dynamics
Medication Administration Routes
ORAL (PO) - Systemic, Enteral, passes through lower GI tract By mouth or by tube Eg) Peg tube
SUBLINGUAL (SL) - Under the tongue, capillary absorption into bloodstream Faster than PO because no GI Tract
INTRANASAL - Absorbed through caps, can have systemic, localized or CNS depending on preperation
INHALATION (INH) - breathed into lungs, rapid effects into lung capillary
ENDOTRACHEAL
TOPICAL (TOP)
IV - Best bet to get close to 100% viability and have exact amount of medication systemic effect
INTRAMUSCULAR - 90 degrees insertion
SUBCUTANEOUS - 45 degrees insertion, injected into adipose tissue of the hypodermis
TRANSDERMAL - slow and steady medication release Eg) nicotine patch
RECTAL - lower GI/rectum insertion
Lipid Bilayer/Plasma Membrane
Lipophilic (attracted to lipids) and semi-permeable
Small, non-ionized & lipid-soluble molecules can pass through via diffusion (O2 & CO2)
Small, water-soluble molecules enter through pores of the membrane
Large, Ionized and Water-soluble molecules need active transport or a carrier protein
Passive Diffusion
Movement from higher concentration to lower concentration WITHOUT ENERGY
Molecules have to be small and lipophilic with no electric charge!
Facilitated Diffusion
Movement into a cell along its concentration gradient WITH THE HELP OF A CARRIER PROTEIN*
NO ENERGY
Selective proteins
Active Transport
Movement of molecules across the cell membrane AGAINST the concentration gradient (low to high)
ATP IS REQUIRED
Carrier proteins are called ‘pumps’
ADME General Rule
Lipophilic, non-ionized, small = easy Absorption & Distribution
Hydrophilic, ionized = east excretion
Absorption
Movement of substance from its site of administration to the bloodstream
**Primary pharmacokinetic factor in determining medication’s onset of action (SMALL INTESTINE is the primary pace for medication absorption)
Effects on Absorption
-Route of Administration
-Molecular Characteristics (size, lipid solubility, ionization)
-Physical Form (tablet vs coated vs syrup)
-Blood Flow (to site of administration)
-Digestive Motility (and interaction with food or other medications)
First-Pass Effect
Drugs absorbed from the stomach and small intestine first travel to the liver before they reach target organs
Degree of Ionization
Acids in acids (because they are nonionized) and bases in bases
Stomach is acidic and Small intestine is basic.
Absorption of Drug Forms
REGULAR - (uncoated) acidic products dissolve and absorb in the stomach
COATED - Enteric-coated products are intended to be absorbed in the small intestine (alkaline). Coating protects it from the acidic stomach (if crushed or opened, can react and upset stomach producing nausea/vomiting
BUFFERED - Contain ions that decrease gastric acidity and slow the absorption of acid drugs
Food Interaction
-Acidic drug absorption can be quickened by ingesting citric juices which increase gastric acidity
-Alkaline bevies (milk) can break down the enteric-coated coating before reaching small intestine
-High fat meals can slow stomach motility and delay stomach absorption
-Grapefruit juice inhibits activity of an enzyme which affects the absorption of some drugs
-Dairy products can bind some antibiotics and make them ineffective
Peristalsis
Wavelike muscular contraction of GI Tract that propels stomach and intestinal content through GI system
Drugs exerting Laxative Effect
decrease time spent in GI system and decrease absorption (herbal weight loss products, dietary supplements)
MAOIs
Block monoamine oxidase (enzyme that breaks down excess tyramine in body) which can help relieve depression
DISTRIBUTION
Describes how pharmacological agents are transported throughout the body after they are absorbed or injected
Explains transportation of drug from systemic circulation to target tissue
5 Factors Affecting Distribution
1) Blood Flow to Tissues
2) Molecular Characteristics
3) Tissue Storage - some tissues can store drugs after absorption Eg) bone marrow, teeth, eyes, adipose tissue
4) Special Barriers - Eg) Blood Brain Barrier
5) Plasma-Protein Binding** MAIN FACTOR
Blood Brain Barrier
-Highly selective
-Caps in CNS are lined with endothelial cells that are sealed by tight junctions and a thick basement membrane
-Protects the brain from pathogens and toxic substances
-NOT in the hypothalamus
-Becomes MORE permeable when it is inflamed from infections
-Not developed in neonates so drugs flow through very easily
Fetal-placenta barrier
Serves an important protective function by preventing potentially harmful substances from passing from the mother’s bloodstream to the fetus.
Alcohol, cocaine, coffee and meds can EASILY cross this barrier
Plasma-Protein Binding**
- MAIN FACTOR
-Drugs have a different affinity to plasma proteins and bind reversibly to form drug-protein complexes (Eg. Basic = albumin, acidic = Alpha-1-acid glycoprotein)
-DECREASES DISTRIBUTION - Unbound drugs = Higher distribution
-Competitive, reversible and saturable
Volume of Distribution (Vd)
Estimates a drug’s tendency to either remain in the plasma or redistribute to other tissue compartments
HIGH Vd = Propensity to LEAVE plasma = MORE distribution (need more of a drug Eg) morphine))
LOW Vd = Propensity to REMAIN in plasma = LESS distribution (need less of a drug Eg. furosemide
Metabolism Definition
-AKA Biotransformation
-Process of chemically changing a drug to something that is more easily removed from the body
-Detox
-LIVER is PRIMARY site for this (Kidneys, lungs and cells also help)
Biotransformation
Active drug -> inactive metabolite
Active drug -> active metabolite
Inactive drug -> active drug
Prodrug
Medications that require metabolism to produce their therapeutic actions Eg) Codeine (Codeine + CYP 2D6 = Morphine (Inactive to active)
CYP 2D6
Enzyme that is lipophobic and hydrophilic
Enzymes do what…?
Inactivate drugs and accelerate their excretion by changing them from Lipid-soluble to water-soluble (Polar/ionized)
“Active drug to Active Metabolite”
2 Phases of Metabolism
Phase 1:Involves hydrolysis, oxidation and reduction to remove hydrogen ion and add oxygen. Removes electrons so that is becomes charged and water-soluble. Catalyzed by CYP enzyme (3A4 & 2D6)
Phase 2: Involves “conjugation” (increases water solubility by adding a group)
CYP Inducers and Inhibitors
INDUCER: Increased production = increased metabolism Eg. Tobacco, rifampin
INHIBITOR: Decrease production of CYP = Decreased metabolism Eg. Grapefruit juice, some other antibiotics
Hepatic Enzyme Activity in older Adults
= Reduced Metabolism, lower doses needed
Excretion Definition
Elimination of drugs from the body by the kidneys
Renal Excretion
-Free drugs, inactive metabolites, water-soluble agents,
electrolytes, and small molecules are easily filtered by the glomerulus.
- Protein, blood cells, conjugates, and drug-protein complexes are NOT filtered because they’re too big (they need to be actively transported to the distal tuble via Tubular Secretion)
Reabsorption***
Following filtration, small non-ionized and lipid-soluble (hydrophobic) drugs cross renal tubular membranes easily and return to the circulation.
-Ionized and water-soluble drugs remain in filtrate for excretion
Kidney Function Indicators
Creatinine and estimated Glomerular Filtration Rate (eGFR)
are important indicators of kidney function.
Clearance
-Rate of elimination of a drug in an hour
-In 1st Order Elimination K, Elimination is proportionate to drug serum
-In Zero Order Elimination Kinetics clearance is CONSTANT
4 Factors AffectingRenal Excretion
1) Molecular Characteristics - Plasma Protein binding, Urinary pH, Lipid soluble, metabolic activity
2) Cardiac Output - Renal blood flow
3) Renal History - 1%/yr decline in elderly, young infants/neonates have low function, renal disease
4) Urinary Output - pH changes can cause quick excretion (weak acids excreted faster when filtrate is slightly alkaline)
Non-Renal Excretion
1) Pulmonary Excretion
2) Glandular Excretion
3) Fecal Excretion
4) Biliary Excretion
Pulmonary Excretion
Drug diffuses from the plasma into the
alveolar space and is excreted during
expiration.
Gaseous lipophilic substances.
E.g. inh anesthetics, nebulized medication.
-Depends on pulmonary blood flow, gas solubility and diffusion
Glandular Excretion
-Some water-soluble drugs may be secreted into the saliva, sweat, or mammary glands.
-Eg. Sweat
Breast milk excretion is important because drugs can affect nursing baby
Fecal Excretion
Certain oral drugs travel through the GI tract without being absorbed and are excreted in the feces.
Biliary Excretion
Secreted into bile in the liver
-Will enter the duodenum and eventually leave via feces
However, most bile is circulated back to the liver via “Enertohepatic Recirculation” (Then ultimately metabolized by liver and excreted by kidneys)
Minimum Effective Concentration
Amount of drug required to produce a therapeutic response
Total Concentration
Level of drug that will result in serious adverse effects
Therapeutic Drug Range
Plasma drug concentration between the minimum effective concentration and the toxic (Total) concentration.
Range where the medication works but it’s not toxic
Ideally a Wide/large range
Therapeutic Drug Monitoring
Helps keep drug dose in therapeutic range
Onset of Action
Amount of time it takes for drug to kick in and produce therapeutic reaction
Dependent on A-D-M-E
Duration of Action aka Half-life
Time required for a medication
to decrease concentration in the plasma by one-half after administration.
-How long the medication works
Loading Doses
-Higher amount of a drug, given once
or twice, to “prime” the bloodstream to quickly induce a therapeutic response.
-Therapeutic level is reached faster* and then intermittent maintenance doses are given to keep it in range
-Drug Plasma levels fluctuate
-Important for drugs with pro-longed half-life and critical situations
Continuous Infusion
Quicker plateau level with little
or no fluctuation in drug plasma levels.
Repeated Dosing
Allows a plateau drug plasma level to be reached
Therapeutic Index
expressed mathematically as (lethal Dose) LD50÷ (effective dose) ED50, is a value representing the margin of safety of a drug. The higher the therapeutic index, the safer the drug.
What phase may toxicity occur in?
Phase 3
Dose-Response Curve
Describes how the therapeutic response to a medication increases as the dose increases.
Potency
-The dose of medication required to produce a particular response
-It is a reflection of a drug’s ability to bind to a receptor.
Potent Drug = Lower dose needed
Efficacy
Magnitude of maximum response to drug
Difference in how effective it is
Drug Receptor Binding
Drug-Receptor interactions may produce a response that mimics the effect of the endogenous regulatory molecule
Receptor are saturable
Intrinsic activity
Intrinsic Activity vs Receptor Affinity
INTRINSIC - The extent to which a
drug activates or stimulates a receptor once bound.
RECEPTOR - “Strength” of drug binding to receptor
High Affinity = High Receptor = Strong Action
Tolerance vs Resistance
Tolerance: Cellular response diminishes with repeated use
Resistance: Doesn’t work at all and never did
3 Types of Agonists
Agonist: Drug mimics endogenous substance, readily binds to receptor
Inverse Agonist: Induces opposite effect as regular agonist
Partial Agonist: Maximum response is smaller even if receptors are all occupied
Functional Antagonist
inhibit the effects of an
agonist by changing pharmacokinetic factors.
Overdose Treatment
Adsorption (substance binds to drug to decrease absorption Eg Activated charcoal)
Induce Metabolism
Increase Elimination
Pediatric Pharmacotherapy
-Calculated by body mass
