Pharmacology Principles 1 Flashcards
1
Q
Drug Origin
A
-Any chemical can be considered a drug
-Drugs come from plants, animals, minerals, and most commonly synthetic sources
-Natural health products and over the counter drugs are not always safer (safety is not related to origin)
2
Q
Natural/Biologic vs Synthetic Drugs
A
-Natural = plants, animals, minerals
-Synthetic = chemically developed
-Both = for the most part are made in laboratories
-Although most drugs in use today are synthetic drugs, over 50% of those had their beginnings as natural products
3
Q
Safety, Efficacy, Effectiveness, and Side effects
A
-are functions of the chemical structure of the molecule, not it’s origin
-whether the drug is natural or synthetic origin is irrelevant
4
Q
Many of the most toxic chemicals known are…
A
Natural products
-some of the safest most effective and widely used drugs are of synthetic origin
5
Q
Synthetic drugs are less likely to cause …
A
-allergic reactions
6
Q
Important to ask ..
A
-About what medications the patient takes, remind them to also include herbs, vitamins, and any other natural health products
7
Q
Health Canada
A
Approves medications
-specifically a branch of health Canada called health products and food branch
8
Q
Food and Drug Regulations
A
Over the counter (OTC) drugs are regulated by the food and drug regulations
9
Q
National Association Scheduling Advisory Committee of the National Association of Pharmacy Regulating Authorities (NAPRA)
A
Sets out the level of professional intervention that is required for each type of medications
- all provinces except Quebec use this national drug schedule to ensure consistency across the country
10
Q
Level of professional intervention required: Schedule 1
A
Prescription only
11
Q
Level of professional intervention required: Schedule 2
A
Available only through a pharmacist and kept behind the counter
12
Q
Level of professional intervention required: Schedule 3
A
Available only within a pharmacy but accessible to anyone
13
Q
Level of professional intervention required: Unscheduled
A
Nonprescription drugs available over the counter at any store
14
Q
Controlled drugs and substances act
A
-Canada’s federal drug control stature
-Controls drugs like narcotics and marijuana
-These drugs can be prescribed by healthcare providers in certain situations
-Schedules are different than this
-These drugs are labelled with a C (controlled) or N (narcotic)
15
Q
OTC Labelling Include
A
- Indications for use
- Safety
- Practicality
16
Q
Criteria for OTC Status: Indication for Use
A
-The consumer must be able to easily:
- Diagnose condition
- Monitor effectiveness
- Benefits of usage must outweigh the risk
17
Q
Criteria for OTC status: Safety
A
-Drugs must have:
-Favourable adverse profile
-Limited interactions with other drugs
-Low potential for misuse
-Wide (high) therapeutic index
18
Q
Criteria for OTC Status: Practicality
A
Drugs must be
-Easy to use and easy to monitor
19
Q
Therapeutic Index
A
-Drugs with a high (wide) therapeutic index tend to be safer
-Drugs with a narrow therapeutic index are more dangerous (means they only have therapeutic benefits within a very small dosing range)
-a drug with a high/wide therapeutic index is less likely to be toxic in high doses
20
Q
Chemical Name
A
-Describes the chemical makeup and molecular structure of the drug
-The chemical name is not used in practice, unless the drugs generic name is the same as the chemical name
-Eg. Calcium gluconate
-A drug only has 1 chemical name
21
Q
Generic Name
A
-Official name of the drug (non-proprietary name)
-In most cases, this is the drugs universal name, regardless of country
-Few exceptions to this rule = acetaminophen, in other parts of the world called for paracetamol
-In Canada the original company that researched and created the medication gives it a generic name and it is approved by health Canada
-Can sell without competition for 20 years under a patent, then other companies can start producing the drug under different trade names = generic version = cheaper
22
Q
Trade/Brand Name
A
-Sometimes called commercial name
-Given by the manufacturer
-Often catchy = marketable
-Name often gives you an idea of what the drug does
-Often similar, making it easier to mix them up (increases risk of med error)
23
Q
Classification
A
-Once a drug has been named it is then places in a “class” or category
-Drugs can be organized by their therapeutic classification or pharmacological classification
24
Q
Therapeutic Usefulness Examples
A
-Inhibiting blood clotting
-Lowering cholesterol
-Lowering blood pressure
25
Therapeutic Class Examples
-Anticoagulant
-Antihypertensives
-Antihyperlipidemics
26
Mechanism of Action Examples
-Lowering plasma volume
-Blocking beta receptors
-Dilating blood vessels
27
Pharmacological class examples
-Diuretic
-Beta blocker
-Vasodilator
28
Pharmacokinetics
-Refers to what the body does to the drug (what happens to the drug as it moves through the body)
-Study of drug absorption, distribution, metabolism, and excretion
-Onset of action, peak effect, duration of action
29
Onset of Action
-The time it takes for the drug to elicit a therapeutic response (or a therapeutic effect)
-How long it takes for the drug to reach minimal effective control concentration
30
Peak effect
-The time it takes for the drug to reach maximal therapeutic response
-This point corresponds to increasing drug concentrations at the site of action
31
Duration of action
-The total length of time that the drug will elicit a therapeutic response
32
Therapeutic Range
-Range of drug dosage which can treat disease effectively without having toxic effects or no effects
-meds with a narrow range must be administered with care and control, frequently measuring blood concentrations of the drug/ effects to avoid harm
33
Supraatherapeutic Effect
-Too high a dose
34
Subtherapeutic effect
-too low a dose
35
Bolus (rapid acting) Name, Onset, Peak, Duration
-N: Insulin aspart
-O: 10-15 minutes
-P: 1-1.5 hours
-D: 3-5 hours
36
Bolus (short acting) Name, Onset, speak, Duration
N: Humulin R
O: 30 mins
P:2-3 hours
D: 6.5 hours
37
Basal (Intermediate) Name, onset, peak, duration
N: novolin
O: 1-3 hours
P: 5-8 hours
D: up to 18 hours
38
Basal (long acting) Name, onset, peak, duration
Name: insulin glargine
O: 90 mins
P: no peak
D: up to 24 hours
39
Why is knowing onset, peak, and duration important?
-Which drug will work fastest?
-When will you reassess the patient to determine if the drug is working?
-Which drug will last the longest?
-When will it be safe to repeat the dose?
40
What factors impact a drugs onset, peak and duration?
-how it’s absorbed, distributed, metabolized, and excreted (ADME) aka pharmacokinetics
41
Absorption
-Describes how the drug gets into the bloodstream
-Most important factor affecting absorption is the route
-Within a route other things can affect absorption
42
Absorption and IV meds vs PO meds
-IV meds are injected directly into the blood stream so they do not need to be absorbed
-For other routes, factors can affect absorption
-Eg. Taking a PO med with food or liquid can alter the rate or degree of absorption
43
Distribution
-Once the drug is absorbed into the bloodstream there are several factors that can affect the movement and distribution of a drug to the tissues where it will have its action
44
Most common route for absorption.
Enteral or oral
45
Bioavailability
-% of drug that makes it into the blood stream
-Administering a drug by IV = 100% bioavailability
-PO drugs will always result in a bioavailability less than 100% since it is not injected into the blood
46
Bioavailability and PO drugs
-Usually a PO drug is swallowed and absorbed from the small intestine into the portal vein which travels to the liver
-At the liver some or sometimes all of it is metabolized
-This usually means the drug is changed into an inactive or less active form long before it ever makes its way through the systemic circulation and into tissues
47
First Pass Effect
-The initial metabolism of a PO drug that occurs BEFORE it reaches systemic circulation
-Drugs that have a 100% first pass effect will have 0% bioavailability and therefore will have no effect on the body Eg insulin/nitroglycerin
48
First pass effect is the reason why…
-ALL PO medications will have less than a 100% bioavailability
-primary reason why most drug doses need to be significantly decreased when switching from PO to IV
-also reason why a drugs dose usually needs to be increased when switching from IV to PO
49
How to avoid first pass effect
-Different routes have been invented = transdermal, inhaled, sublingual/buccal
50
Why not use IV meds all the time ?
-Expensive (cost of drug, IV catheter, pumps, poles, nurses, hospitalization)
-Invasive (does place patient at risk of infections, uncomfortable)
-Increases risk of adverse effects because the drug cannot be removed one it’s in and works FAST
51
Which route is always preferred ?
PO
52
What 2 things can alter PO absorption
1. PH balance
2. Food
53
PO drugs and pH
-the acidity and alkalinity of the GI tract can affect absorption
-most drugs require an acidic environment in the stomach and small intestine to be broken down and absorbed
-taking medication along with acid controlling drugs (within 1-2 hours) can increase the pH of the GI tract and greatly impair absorption
54
Common acid controlling drugs
-Ranitidine (Zantac)
-Omeprazole (Losec)
-Calcium Carbonate (Tums)
55
PO meds and Food
-Many drugs should be taken on an empty stomach (1-2 hours before eating or 2 hours after)
-Food can delay stomach emptying and since most drugs are absorbed in the small intestine = delay
-Sometimes it is recommended that a drug be taken with food to decrease occurrence of unpleasant side effects like nausea
56
Examples of drugs to be taken with food
-Levothyroxine = hormone replacement for individuals with hypothyroidism
-At best absorption in the GI tract is incomplete and variable when taken with food or following a meal
-Very little gets absorbed which means the patient does not get the hormone they need
57
Examples of Drugs that need to be taken with Food
Prednisone
58
PO drug manipulation (2)
1. Enteric coating
2. Modified release
59
Enteric Coating
-This is a barrier added to the outside layer of a PO med that prevents it from dissolving in an acidic environment (like the stomach)
60
Why is an Enteric Coating Used
-To protect the drug from an acidic environment like the stomach
-To protect the stomach lining from the drugs
-Prevent the drug from dissolving/getting absorbed too early (for drugs that need to be absorbed into the small intestine or large intestine)
61
Example of Enteric Coating Med
-Acetylsalicylic acid (ECASA)
-Done to protect the stomach lining from the drug (to reduce the incidence of gastric ulcers for long term use of the drug)
62
Modified release
-Drugs can also be formulated so meds are released (dissolved) at a predetermined rate
-Allow there to be a more constant level of drug in the blood stream
63
Abbreviations associated with modified release medications
CD, CR, LA, SR, TR, XL, XR
64
CD meds
-Controlled delivery
65
CR meds
Controlled release meds
66
LA meds
Long acting meds
67
Sr Meds
Sustained release meds
68
TR meds
Timed release meds
69
XL meds
Extended release meds
70
XR meds
Extended release meds
71
Safety alert for Modified Release Meds
-Modified release drugs cannot be altered
-They should not be crushed/split unless clearly indicated in the package or stated by the pharmacy
72
How a drug is distributed through the body depends on
1. Blood flow
2. Drug solubility
3. Protein binding
73
Distribution and Blood Flow
-Parts if the body that are highly perfused are distributed first (heart, liver, kidney, brain)
-Patients with an increased metabolic rate (Eg. Due to fever or SNS response) may have their medication distributed more quickly because of increased CO
74
Distribution and Drug Solubility
-How well the drug dissolved and can reach the tissues
75
Drug Distribution and Protein Binding
-How it will be “stored” and carried around in the bloodstream
-Most abundant plasma protein is albumin
76
Solubility
-How a drug “dissolved” into surrounding tissues
-Eg, lipid soluble/water soluble
77
Lipid Soluble Drugs
-Are lipophilic
-Means they easily dissolve into tissues because cell membranes have a lipid bilateral (less in bloodstream)
-Since majority of the cell membranes of our tissues have a lot of lipids, drugs that are highly lipid soluble enter into cells quickly while water soluble drugs much slower
-Can cause CNS effects
78
Water Soluble Drugs
-Hydrophilic
-Means they less easily move into tissues and more of the drug stays in the bloodstream
-Pass much slower into cells
-Easily excreted by kidneys
79
BBB (Blood Brain Barrier)
-Network of capillaries that protect the brain from chemicals in the blood stream
-Unlike other capillaries these are almost leak proof with no pores
-Prevents drugs that are water soluble from entering at all
-Only fat soluble drugs can enter
- = all psychoactive drugs pass BBB but penicillin does not
80
Distribution and protein binding process
-When drugs are absorbed into the blood stream, they are either attached to plasma proteins (bound) or not attached (free)
-Drugs have different affinities for protein (some have a high affinity =bind easily)
81
Most Common Protein for Drugs to bind to
-Albumin (a protein synthesized in the liver)
82
Protein binding: If a drug is free/unbound
-It is therapeutically active
-it will have a therapeutic effect on the body because it can move out of the bloodstream and attach to tissue receptors
83
Protein binding: If a drug is “bound”
-It will not have a therapeutic or toxic effects because they are bound to protein and remain in the blood stream
-Once free, the drugs are distributed to tissues then can be metabolized and excreted
-Bound drugs are like reservoirs in that as more drug that is free is metabolized and excreted, more of the protein bound drug will be released so it can now have an effect
84
Drugs that are highly protein bound often require ..
-The patients albumin level to be tested
-Especially true if the drug has a narrow therapeutic index and highly protein bound
-Eg warfarin = an anticoagulant and phenytoin = an anticonvulsant
85
What if you give a med with a high affinity for protein followed by another one?
-Some drugs are bullied
-SULFA DRUGS (class of antibiotics) can actually knock warfarin off protein in order to attach itself to the protein making warfarin “free” and therapeutically active
-Physician may need to alter the dose of drug based the patients albumin level and whether or not they are on other drugs which are highly protein bound
86
Another Term for Metabolism
Biotransformation
87
During Metabolism the Following usually happens to a drug
-The drug becomes a less active metabolite
-The drug becomes hydrophilic (water soluble) so it can be easily excreted
-Sometimes drug becomes a more potent metabolite = active and continues to have an affect
88
Metabolism of most drugs is done by…
-Hepatocytes in the liver
89
Prodrugs
-Drugs that have no effect on the body UNTIL they are metabolized into active metabolites
-Once metabolized into an active form, they are then distributed through the systemic circulation and can reach the tissues
90
Only about _ % of all drugs are considered prodrugs
5
91
Why were prodrugs invented?
-ultimately to improve bioavailability
92
Examples of Prodrugs
-Simvastatin = gets metabolized into its active form simvastatin acid
-Prednisone = has no effect on the body until it is metabolized and turns into prednisolone
-Heroin if taken orally undergoes extensive first pass and once metabolized it becomes morphine (heroin is simply morphine with an extra acetyl molecule attached which allows it to passs through the BBB more easily)
93
Liver Functions
-Metabolizes drugs
-Metabolizes and stores CHO
-Synthesizes proteins
-Conjugation of bilirubin
-Converts ammonia into urea
-Bile production and excretion
94
Liver (Metabolizing drugs)
-The liver breaks down drugs, but it can also break down various hormones like aldosterone, lipids, carbohydrates
95
Liver (Synthesizes Proteins)
-Like albumin and clotting factors
96
Liver (Conjugation of Bilirubin)
-By product of destroyed RBC’s
-Once bilirubin is conjugated it can be excreted
97
Liver (Converts ammonia into urea)
-Ammonia (by product of protein catabolism in the gut) is harmful to the body so it is converted to urea so it can be excreted
98
Liver (Bile production and excretion)
-Bile salts are excreted into the gut and help break down fatty vitamins like vitamin K so it can be used in the body
99
How can we tell if the liver is functioning?
Liver function tests (determine function)
-Albumin
-INR
-Bilirubin
Liver Enzyme Tests (Identify injury or inflammation
100
Liver Functioning Test: Albumin
-Which is produced (synthesized) by the liver
101
Liver Function Test: INR
(International normalized ration)
-Calculation (ratio) that represents prothrombin time (clotting time)
-The higher the number the longer it takes for the patients blood to clot
-Because the liver synthesized the clotting factors measured by the INR, this test can tell us if the liver is performing this function well or not
102
Liver Function Test: Bilirubin
-A by-product of normal RBC catabolism
-It should be conjugated by the liver (made water soluble) so it can be excreted In bile
-When someone has HIGH indirect bilirubin, this means they have elevated unconjugated bilirubin which suggests liver is not working
103
Liver enzymes
-Are proteins which determine inflammation/injury
-Excess enzymes are released when tissues are injured or inflamed
-Alanine transaminase (ALT)
-Aspartate transaminase (AST)
-Alkaline phosphate (ALP)
-Gamma-glutamyl transferase (GGT)
104
ALT and AST
Leak out of liver cells and into the blood when liver cells are damaged
105
ALT is…
-More accurate indicator of liver injury as AST is also found in other organs like the heart and other muscles
106
ALP
-Found on the edges of cells that join to form bile ducts and can be elevated if bile ducts become blocked (secondary to inflammation of the gallbladder or gallstones)
-Smaller increases of blood ALP are seen in liver cancer, cirrhosis, and hepatitis
107
A patient can have elevated liver enzymes and still…
Have a normally functioning liver
108
A functioning ___ is integral to effectively metabolizing drugs
Liver
109
Cytochrome P450s
-Most drugs that move through the small intestine and liver are metabolized by these specific group of enzymes
-The # of P450 enzymes vary from person to person
-Deficiencies are believed to be genetic = metabolism of drugs vary from person to person
-There are tests that can measure the amount and effectiveness of these enzymes (genotyping) but not routinely done
110
What do Cytochrome P450 Enzymes do
-Transform drugs into hydrophilic substances and (most often) less active metabolites
-These enzymes can vary in number and effectiveness depending on the person
-Genotyping can identify variations in these enzymes (not commonly done)
111
Which Cytochrome P450 Enzyme is most researched
CYPP3A4
112
Isozyme P3A4
-Belongs to P450 family
-Has the most drug/food integrations meaning certain drugs or foods a patient consumes can change the way this enzyme metabolized drugs
-Many of these interactions take place in the small intestine (metabolism happens here too)
113
Enzyme Inhibition
-Means that something is preventing the cytochrome P450 enzyme from metabolizing the drug
-In most cases prevents the enzyme form turning the drug off
-May occur with the concurrent administration of 2 or more drugs that compete for the same enzyme
-Increased risk for drug accumulation if dose is not decreased = risk of toxicity = supratherapeutic levels
114
Enzyme Inhibition Things that Block/Delay Metabolism
-Cimetidine
-Erythromycin
-Ketoconazole
-Grapefruit juice
-Diltiazem
-Verapamil
-Clopidogrel
=Supratherapeutic = increase bioavailability
115
Enzyme Induction
-Something causing liver cells to produce more enzymes or these enzymes work more efficiently to turn off (metabolize) the drug
-With chronic drug administration, some drugs stimulate liver cells to produce more enzymes
-Accelerates drug metabolism which means sub therapeutic drug levels will result requiring larger doses to be given
116
Enzyme Induction Examples
-Accelerates metabolism
-Alcohol
-Cigarettes
-Phenytoin
-Phenobarbital
-St johns wart
-Subtherapeutic = decreased bioavailability
117
Excretion
-Most drugs are excreted in the urine
-Water soluble drugs are excreted through glomerular filtration
118
most drugs excreted by
Kidneys
-also responsible for eliminating other wastes (urea, uric acid), maintaining fluid and electrolyte imbalance, pH, and endocrine synthesis
119
Drugs and Glomerular Filtration
-Drugs are selectively filtered in the glomerulus and reabsorbed into the blood stream or secreted into the tubular fluid
-Not all drugs can be excreted, only those that are not bound to proteins (free)
-Water soluble drugs are easily excreted through glomerular filtration
120
Drug and Tubular secretion
-To a lesser extent drug metabolites can also be excreted via tubular secretion
-This would be r/t drugs that do not get filtered out in the glomerulus
121
What is a pt has a low GFR
-Less of the drug is likely to be excreted and if the drug has active metabolites this could be harmful
-These drugs often require a reduced “renal dose” in someone with decreased GFR
122
Kidney Function
-Can also be assessed
-Monitoring urine output not best way to determine
-Pt can be voiding adequate amounts but that doesn’t mean the kidneys are doing their jobs well (actually getting rid of waste and balancing pH)
123
Ways to Measure Kidney Function
-Glomerular filtration rate (eGFR) = calculation of Cr, age, and gender
-Serum/plasma creatinine (CR)
-Serum/plasma urea (Ur)
124
The Most Accurate way to Assess Kidney Function
Glomerular Filtration Rate
125
Glomerular Filtration Rate
-Measures how well your blood is being filtered by your kidneys
-An estimated glomerular filtration rate is calculated from plasma creatinine levels
126
Creatinine
-By product of muscle breakdown
-Fully excreted by the kidneys at a predictable rate making it a reliable measure of kidney function
-Lower glomerular filtration rates correlate with higher plasma creatinine levels
127
Urea
-By product of protein breakdown and is also secreted by the kidneys
-Liver created urea from products of protein breakdown
128
Excretion Half Life
-Need to know in order to figure out how much and how often we need to give a drug
-Time it takes to eliminate half of the drug out of the body (closely associated with duration)
-Drug does not stop working once it reaches its half life
129
Half Life Calculation
-If you completely filled the bucket with water (1000ml) and after 2 hours there was only half left (500ml) then the half life would be 2 hours
130
Short half life
-Drugs with short half life are sometimes important to use for short procedures
131
Long half life
-Drugs with a long half life are better suited for treating chronic illness (when drugs need to always be present in the blood)
132
Excretion Steady State
-Occurs when the amount of drug removed by excretion is equal to the amount of drug being absorbed with each dose = concentration stays in therapeutic range
-Although not all medications need to reach a steady state in the body, many drugs used to treat chronic conditions need to be at a steady state in order to have a therapeutic effect meet all the time (antihypertensives/anticonvulsant)
133
Most Drugs Will Reach Steady State After..
5x’s their half life
134
Steady State Calculation
-Need to consider how fast water leaks out (drugs half life)
135
Loading Dose
-is an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose
-Done when the drug has a very long half life and/or when it is important that a steady state is reached quickly
136
Drugs with a long half life
-Warfarin (60 hrs)
-Digoxin (3 days)
-Amiodarone (50 days)
137
The longer a drugs half life…
The longer it will take to research steady state
138
Drugs that are not absorbed, distributed or metabolized
-Timolol ophthalmic drops (anti glaucoma med)= minimal systemic absorption so the drug never metabolize/excreted
-Lactulose (laxative)= syrup taken PO with minimal systemic absorption, takes action in the large bowel metabolized there by bacteria and excreted in feces
-Metformin (anti diabetic drug)= Taken PO this drug is absorbed systemically but is never metabolized, it is excreted unchanged (it is water soluble)
