Module 1 Flashcards

Question

What is Therapeutic Classification | -Examples

Answer 1

Therapeutic Classification – organizing drugs according to their therapeutic usefulness in treating a particular disease Examples: anti-inflammatories – reduce inflammation anti-convulsants – reduce seizures immunosuppressants – suppresses immune system

Answer 2

Pharmacological Classification – organizing drugs according to the way a drug works at a molecular level, tissue and body system level Example: calcium channel blocker – blocks calcium channels α-agonist – stimulates α-receptors proton pump inhibitor – blocks proton pumps Addresses a drug’s mechanism of action

Answer 3

= HOW a drug produces its effect on the body Does it block a receptor (like a β-blockers)? Does it inhibit something (like an ACE-inhibitors)? Does it stimulate a receptor (like an α-agonist)? What action does it create (like a vasodilator)?

Answer 4

Chemical name: a direct description of the chemical structure - Gives information about it’s chemical makeup - Use is limited – sodium chloride (NaCl), calcium carbonate (CaCO3) - 2-[4-(2-methylpropyl)phenyl]propanoic acid Generic name: the unique name given to a chemical structure that somewhat describes it’s structure - Remains the same across languages (few exceptions) - Ibuprofen Brand/Trade name: the marketed name given to a drug, usually short and easy to remember [HAVE THE R] -Sometimes can sound-alike; differences between countries -Champix® vs. Chantix®; Losec® vs. Lasix® -Advil® Motrin®

Answer 5

Generic - reduces errors - efficient communication between disciplines and across borders

Answer 6

-When patents expire, any company can then manufacture that drug and charge less money for it (we call these generic companies) A generic company must prove bioequivalence before their product can be sold - A generic company cannot change the active ingredient - It can change non-medicinal ingredients such as fillers and excipients (lactose, colours)

Answer 7

Controlled substance = any drug in whose manufacture, possession, or use is regulated by the government -Well regulated

Answer 8

Food and Drug Act and Regulations – any drug requiring a prescription Controlled Drugs and Substances Act Narcotic Control Regulations - Control the import, production, export, distribution, and possession of narcotics and controlled substances - Govern manufacturers, pharmacies, hospitals and healthcare professionals – require proper security, detailed inventory records - Individual provinces cannot change the scheduling of any drug identified as a narcotic or controlled substance

Answer 9

Each province and territory decides where to schedule each individual drug (except controlled substances and narcotics – always Schedule I) Schedule 1 = prescription Schedule 2 = without prescription, must be behind counter (ensure pharmacist interaction) Schedule 3 = No prescription, sold in pharmacy (guarantee access to pharmacist) Unscheduled = Anywhere

Answer 10

The study of how a drug moves in the body Absorption Distribution Metabolism Excretion

Answer 11

care that a nurse provides directly affects the pharmacokinetics of a medicine -Covering a patient in a warm blanket reduces stress hormone levels and increases blood flow  directly influencing a drug’s movement within the body It is also important to know what to expect from a drug response in order to recognize problems We use this information to our benefit when trying to solve problems

Answer 12

In order to move within the body, drugs must pass through plasma membranes; they do this either by: Passive diffusion – moving from an area of high concentration to an area of lower concentration; does not require energy -Small, non-ionized, lipid soluble drugs can pass through a membrane using passive diffusion Active transport – moving against the concentration gradient; requires energy (ATP – adenosine triphosphate) -Large, ionized, non-lipid soluble molecules use carrier proteins or send a messenger within a cell via a receptor

Answer 13

1. Size of drug molecule 2. Ionization of a drug molecule 3. Lipid solubility of a drug molecule Small, non-ionized, lipid-soluble drugs can pass through a membrane using passive diffusion

Answer 14

Absorption is the process of moving a drug from the site of administration to the bloodstream -Oral, injection, topical, sublingual, buccal, inhalation A large factor in determining a drug’s onset of action (the time it takes for a drug to become effective) - Fast absorption = Fast onset (IV) - Slow absorption = Slow onset (IM)

Answer 15

``` Route of administration Drug formulation Drug dosage Gastrointestinal (GI) tract environment Blood flow to absorption site Drug ionization Drug interactions Surface area ```

Answer 16

Enteral, topical, parenteral

Answer 17

Enteral Route - Delivered to GI tract - Includes oral (PO), buccal, sublingual (SL), nasogastric (NG) tubes (and sometimes rectal) - Oral and NG – susceptible to gastric acid, enzymes, first pass effect, ability to swallow - Buccal (cheek), sublingual (under tongue) – absorbed through mucosa of oral cavity – avoids acid, enzymes and first pass effect First pass effect is drug enters the liver and undergoes extensive biotransformation and thus decreasing the concentration rapidly before it reaches its target.

Answer 18

Topical Route – delivered to skin or mucous membranes - Includes skin, eyes, ears, inhalation, vagina, (and sometimes rectum) - Usually used for direct application (antibiotic for skin infection, inhalation for asthma) - Generally slower absorption, less presence of drug in blood - We use these characteristics to our advantage, to prolong duration of action (nitroglycerin patches) or to minimize side effects (inhaled corticosteroid) - IF the area is compromised (abrasion, open sore - we see higher absorption  toxicity)

Answer 19

Parenteral Route – anything other than enteral or topical -Includes intravenous (IV), intramuscular (IM), subcutaneous (SC), intradermal, intraperitoneal (IP), intra-arterial, intra-osseous (bone), intrathecal (spinal canal), intraocular -Avoids gastric enzymes, acidity, and first pass effect SC, intradermal – limited by small volume -IM – larger volumes, faster absorption but often use depot injections -IV – fastest onset and most dangerous (adverse effects, cannot reverse)

Answer 20

Is the drug a tablet, capsule, liquid, aerosol, disintegrating tablet? - Liquid formulations dissolve faster and absorb faster than solid formulations (liquid > solid) - Tablets or capsules can be enteric-coated – coated to withstand acid of stomach, and not dissolve until in small intestine - Extended Release – designed to dissolve slowly, to lengthen duration of action (XR, SR, XL, CR) - Oral disintegrating tablets (ODT) or films are formulated to dissolve in mouth with no water - IM depot injections are formulated in an oily, viscous base to promote slow and continuous absorption from muscle

Answer 21

Higher doses or concentrations absorb faster and provide a faster response than lower doses or concentrations

Answer 22

- Most absorption occurs in small intestine – depends on gastric motility, pH level - Slower motility may leave drug more susceptible to enzymes in stomach - Faster motility may reduce absorption by speeding drug along before absorption occurs - Fatty foods usually slow drug absorption Acidic drugs need acidic environment to absorb.. Basic drugs need basic environment to absorb…

Answer 23

Drugs are absorbed faster from areas of the body where blood flow is high Muscles, buccal cavity, vagina, rectum Ice packs = vasoconstriction = slower absorption Heat = vasodilation = faster absorption

Answer 24

Ionized = a positive or negative charge Non-ionized = no charge Depends on pH of environment Acidic drugs need an acidic environment because they are non-ionized Basic drugs need a basic environment because they are non-ionized Small amounts of an antacid like calcium carbonate or aluminum hydroxide are added to the product to help treat or prevent heartburn or upset stomach - Antacid would increase/decrease ph surrounding environment - therefore increasing/dereasing absorption of ASA

Answer 25

Drug-drug interaction = tetracycline capsule + calcium carbonate (CaCO3) = delays absorption (bind to make a molecule too large to pass through plasma membrane) -Not all drug interactions occur at the receptor level Drug-food interaction = high fat meal + carbamazepine = higher rate of absorption

Answer 26

Larger surface area = faster absorption Examples: skin, villi and microvilli of small intestine, lung

Answer 27

Bioavailability is the fraction of an administered dose of an unchanged drug that reaches the site of action Expressed as “F” For IV drugs, F = 100% (no absorption!) All absorption variables effect the drug

Answer 28

Distribution describes how drugs are transported throughout the body Drugs interact with blood components and move throughout the entire body after they are absorbed May be chemically and physically changed before they reach the target tissue/area

Answer 29

``` Blood flow to tissues Drug solubility Tissue storage Drug-protein binding Barriers ```

Answer 30

Highly perfused tissues and organs receive the highest exposure to absorbed drugs -Heart, liver, kidneys = highest blood flow Example: treating a fungal infection of toenail with an oral antifungal takes a long time because of poor perfusion Drug is not distributed to the site of action

Answer 31

Lipid-soluble drugs cross plasma membranes easier and are therefore distributed more broadly throughout the body Water-soluble drugs have more barriers – more difficult to cross plasma membranes

Answer 32

Some tissues can accumulate and store drugs Depends on a drug’s affinity (the force by which atoms are held together - strength of attraction ) Example: lipid (fat)-soluble vitamins (A, D, E, K) can accumulate in adipose (fat) tissue and cause toxicity

Answer 33

-Protein such as albumin circulate in our blood -Drugs can bind to proteins, creating a complex -Complexes are often too large to then cross a plasma membrane and remain ‘trapped’ in the blood stream -Complexes can also prevent binding to a receptor (doesn’t fit anymore) -Only free or un-bound drug can act at (or get to) their target site -Expressed as a % Example: warfarin is 99% plasma-protein-bound

Answer 34

Blood-brain barrier (BBB) = to protect the brain from toxic substances or pathogens - Some drugs cross it, others can’t - Example: dopamine and levodopa Fetal-placental barrier = protects baby from harmful substances or pathogens -Not as efficient as BBB – most drugs cross it, even by a small fraction (alcohol, caffeine)

Answer 35

-Metabolism is a process that changes the activity of a drug and makes it more likely to be excreted -Hundreds of different pathways -In general, it is a chemical reaction that makes a molecule more water-soluble, so that it can be excreted in the urine -Usually, a metabolite (product of metabolism) is less active than the original molecule -A prodrug is a metabolite that is more active than the original molecule Example: codeine is given PO =morphine (exerts analgesic effect)

Answer 36

Hepatic enzymes | Patient variation

Answer 37

- Cytochrome P450 System (CYP450) is responsible for most metabolism of drugs, nutrients, and endogenous substances - Liver is main site, but does occur elsewhere -CYP450 is a family of enzymes, each assigned a name CYP1A2, CYP3A4, CYP2C19, etc. -Changes in enzyme activity alter drug action The result of the change depends on whether the drug is a substrate, an inducer, or an inhibitor of the CYP450 system

Answer 38

- Substrate = the substance on which an enzyme acts; when a drug is metabolized by a CYP450 enzyme - Naproxen is a substrate for 2C9 (naproxen = 2C9 =inactive metabolite) -Enzyme Inducer = when a drug has the ability to increase (speed up) metabolic activity in the liver Phenobarbital induces 2C9, therefore changing the metabolism of naproxen (decreased naproxen activity) -Enzyme Inhibitor = when a drug has the ability to decrease (slow down) metabolic activity in the liver Fluconazole inhibits 2C9, therefore changing the metabolism of naproxen (increased naproxen activity)

Answer 39

Drug - metabolized by enzymes - inactive metabolite Prodrug - metabolized by enzymes - active metabolite Inducers speed up metabolism Inhibitors slow down metabolism

Answer 40

When a drug is absorbed from the stomach or small intestine, it enters the portal vein and travels to the liver before it enters circulation and is distributed to other body tissues Some drugs can be completely converted to an inactive form before it even reaches the general circulation – this drug would have a high first-pass effect Buccal avoids first pass effect

Answer 41

Infants and patients with liver disease have lower hepatic enzyme activity = require lower doses Smoking and chronic alcohol consumption tends to induce hepatic enzyme = may require higher doses Genetic variations cause “slow metabolizers” and “fast metabolizers” Pharmacogenomics is a fast-developing area of research – customize therapy according to DNA

Answer 42

Excretion processes remove drugs from the body The rate at which a drug is excreted determines its concentration in the blood and ultimately, its duration of action (the length of time a drug is effective) Anything that affects the organ responsible for a particular drug’s elimination, will affect that drug’s rate of elimination

Answer 43

Renal Excretion Pulmonary Excretion Glandular Secretion Fecal and Biliary Excretion Often a combination

Answer 44

Kidneys filter 180L blood every day Filtrate = urine Eliminates drugs through: - Filtration – drugs move blood = filtrate in the glomerulus - (Reabsorption) – drugs move back from filtrate = blood - Secretion – drugs that were not filtered move blood = filtrate Impairment of kidney function dramatically changes the pharmacokinetics of a drug = usually results in a diminished ability to excrete medications, prolonging duration of action, causing accumulation and toxicity Also effected by pH (acid-base balance) and electrolyte and fluid balance of patient Pharmacists measure kidney function using serum creatinine (SCr), which we use to calculate Creatinine Clearance (CrCl) (an estimate for kidney function)

Answer 45

Primarily route of excretion for anesthetics More rapid breathing leads to faster excretion rates Alcohol is also partially excreted from the lungs (breathalyzer tests)

Answer 46

Saliva, sweat, or breast milk Explains “bad taste” or garlic breath Some drugs can colour sweat (rifampin colours all secretions a reddish-orange) Usually a minimal amount of elimination Breast milk secretion is significant when advising breast-feeding mothers

Answer 47

-Some drugs are not absorbed at all and are excreted in feces (Mebendazole for intestinal worms) Enterohepatic Recirculation occurs when a drug is excreted in the bile to duodenum and then reabsorbed and circulated back to liver (multiple times) (Explains longer duration of action than what we would expect (in calculations))

Answer 48

The therapeutic response of most drugs depends on their concentration in the plasma It’s impossible to measure the amount of drug that is present at the target tissue, so instead we take a serum lab test We don’t need lab tests for every drug – only those with a narrow therapeutic index (a very small window between effective and toxic dose) require Therapeutic Drug Monitoring

Answer 49

The length of time required for a drug’s concentration to decrease by ½ (1-2 minutes or months) Drugs with short t½ are good for short/minor conditions or procedures -Anesthetic for dental procedure Drugs with long t½ are good for chronic conditions -Felodipine for heart failure can be given once daily

Answer 50

Most conditions require repeated dosing in order to keep drug plasma concentrations within the therapeutic range Another dose should be given before the minimum effective concentration is reached = our goal is a plateau drug plasma level We reach plateau in approximately 4 t½ of the drug if we give equal doses

Answer 51

Loading dose = allows us to reach plateau levels faster by giving a larger dose Maintenance dose = the dose required to maintain drug in therapeutic range, given repeatedly

Answer 52

Therapeutic Drug Monitoring may include an attempt to see peaks and troughs of drug concentration – very particular about timing from time of administration To make sure peaks are below toxic levels, and troughs are above minimal effective levels (within the therapeutic window)

Answer 53

Refers to how a drug changes the body More concerned with mechanisms of action and relationship between drug concentrations and responses in the body Important in providing safe and effective treatment to patient

Answer 54

Pharmacokinetics = what the body does to the drug Pharmacodynamics = what the drug does to the body

Answer 55

- A graphical representation of the number of patients responding to drugs at different doses - Shows whether a measurable response occurred - Does not describe the magnitude of the response

Answer 56

The dose required to produce a specific therapeutic response in 50% of a group of clients Often referred to as standard or average dose We need to remember that this average dose only applies to half the population -Average doses do not apply to everyone 25% responded at a lower dose, 25% responded at a higher dose

Answer 57

The dose of a drug that would be lethal in 50% of a group of animals (determined in pre-clinical studies) The larger the difference between the ED50 and the LD50, the greater the therapeutic index (safety margin) Drugs with a narrow therapeutic index often require therapeutic drug monitoring

Answer 58

We don’t test the lethal dose in humans (not ethical) Instead, we either extrapolate data from animal trials or determine toxicity from adverse effects reported in clinical human trials The dose required to produce a given toxicity in 50% of a group of patients

Answer 59

Looks at an individual’s response to a drug Phase 1 – very few target cells have been affected by the drug Phase 2 – shows the linear relationship between amount of drug administered and degree of response obtained Phase 3 – plateau, where no further response occurs with a higher dose - How? Theories: all receptors are occupied, already obtained 100% relief - Even though no further response occurs, we will see adverse effects and signs of toxicity

Answer 60

Potency = a measure of drug activity or “power” A drug that is more potent will produce an identical therapeutic effect at a lower dose compared to another drug in the same class

Answer 61

Efficacy = the ability to produce the desired result; the magnitude of maximal response that can be produced from a drug A drug has more efficacy if it produces a higher maximal response than another drug

Answer 62

We usually value drugs with more efficacy -A patient would choose a drug that is more effective at killing cancer cells than one that is more potent Drugs with higher potency allow us to be more efficient with prescribing -We can switch opioids to a more potent drug when we have seen toxicity of a lower potency drug

Answer 63

What a drug does once it gets to the target site Cells receive information from their environment through receptors Ligand = a molecule that binds to a receptor Endogenous ligands: hormones, neurotransmitters Activation of a receptor causes some sort of cell response, which changes an existing physiological and biochemical process A drug binds to a receptor to cause a change in body chemistry or physiology Receptors often have sub-types (α,β), which allow drugs to be more specific for a desired activity (α2-blockers) - Receptors may be on a plasma membrane of a cell, allowing entry of chemical into a cell (Na+, K+, ATP pump), or activate a second messenger within a cell - Receptors may also be intracellular, affecting protein synthesis or DNA replication of a cell (some antibiotics)

Answer 64

Affinity = the force by which atoms are held together - the strength of attraction between a receptor and a ligand (like a magnet) Some drugs have a higher affinity for a receptor than an endogenous substance= can displace (some estrogens) Some drugs compete with each other for a receptor (a common drug interaction) Agonist = a drug that produces the same type of response as an endogenous substance (> or = response) Partial Agonist = a drug that produces a weaker response (but still a response) than an endogenous substance (lower efficacy than agonist) Antagonist = a drug that binds to a receptor and does not induce a cell response (BLOCKER)

Answer 65

A drug interaction occurs when a substance increases or decreases a drug’s actions Can be: Pharmacokinetic: affects absorption, distribution, metabolism or elimination Pharmacodynamic: affects the action at the receptor

Answer 66

Potential drug Effect ``` A: Lower Variable Lower Variable Variable ``` D: Increased M: Decreased increased E: Decreased Increased

Answer 67

Additive effect: two drugs that provide the same therapeutic action are combined (two antihypertensives) Synergistic effect: the effect of two drugs combined is greater than would be expected than just adding the two individual drug’s actions together (Bactrim® - sulfamethoxazole & trimethoprim) Antagonistic effect: two drugs that have opposite effects (epinephrine + β-blocker; immuno-suppressant + immuno-stimulant) -Can reduce adverse effects or work as an ‘antidote’

Answer 68

Grapefruit Juice – inhibits CYP3A4 Tyramine – an amino acid; normally metabolized by MAO (monoamine oxidase); when MAO is inhibited, tyramine crosses into circulation = hypertensive crisis4 Vitamin K – in green, leafy vegetables; a known clotting factor; directly opposes anticoagulant effect of warfarin

Answer 69

The continuous or repeated exposure to agonists can reduce the number of receptors present = down-regulation -Often the mechanism responsible for drug tolerance Tolerance = increasing doses of a drug are required to produce the same magnitude of effect Opioids – often need a higher dose to provide equivalent analgesia

Answer 70

Physical dependence on a drug occurs when the body adapts to repeated use of the substance and view the medication-altered environment as normal -Can also have psychological dependence When someone dependent on a drug stops taking it, they experience withdrawal Symptoms of withdrawal are generally the opposite of the drug’s intended effect (benzodiazepine withdrawal causes anxiety)

Answer 71

“Addiction” is used in a very vague way One way to define addiction is the presence of 4 C’s: - Craving - Loss of control of amount or frequency of use - Compulsion to use - Use despite consequences Dependence on a drug is a physiological matter – and addiction may occur, in part, due to dependence on a drug and the fact that withdrawal may occur upon discontinuation -Addiction is more psychological A person can be dependent, but not addicted to a drug