Intro to Pharmacology Flashcards
Drug
Any chemical compound that can influence living processes
*Includes those that have therapeutic application and those that do not
Compare and contrast generic drugs and brand drugs
Inactive ingredients are different
3.5% difference in absorption
Same active ingredients, strength, dosage form, and route of administration
Same bioequivalence
Pharmacology
Study of drugs and their interaction with living systems
Pharmacokinetics
The study of drug movement throughout the body: “what the body does to the drug” //how medications move around in the body
4 basic processes:
Absorption
Distribution
Metabolism
Excretion
Pharmacodynamics
Study of biochemical and physiolgical effects of drugs and the molecular mechanisms by which those effects are produced
“What drugs do to the body and how they do it”
Clinical Pharmacology
The study of drugs in human beings
Pharmacotherapy
The use of drugs to diagnose, cure, prevent, or treat a disease/condition
What is the difference between therapeutics and pharmacotherapy?
Therapeutics is a broader term that includes other modalities besides drugs
(example: behavioral therapy, physical therapy, speech therapy, etc)
What are some characteristics of an ideal drug?
Effective - useful in clinical practice
Safe - has no ability to cause injury
Selective - elicits only the anticipated response
Adverse Drug Reaction (ADE)
Any undesirable effect caused by the usage or misuse of a drug with a patient
May be preventable or non-preventable
Side effects, interactions, ADE
Medication Error
Can occur at any point along the medication management cycle, or drug-use process by the consumer
Preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in control of the healthcare professional, patient, or consumer
Where in the medication management cycle do medication errors occur the most?
During administration
What are the most common student errors?
Extra dose
Dose omission
Wrong time
Wrong dose/overdosage
Wrong patient
What is medication reconciliation?
Process of comparing the medications a patient is taking and should be taking with newly ordered medications to identify and resolve discrepancies.
Includes Rx, ITC, herbal/supplemental medications in med rec
What is patient adherence?
The extent to which a person’s behavior corresponds with agreed recommendations from a healthcare provider
What is an enteric-coated drug?
The coating is designed so that the drug dissolves in the small intestine, not the stomach
What are sustained-release or extended release drugs?
A drug that is designed so that it dissolves at variable times –> drug is released steadily throughout the day
Permits once-daily or twice-daily dosing
When a person is allergic to a medication, which part are they usually allergic to?
The active ingredient
What is an off-label indication?
Refers to when a drug is used for other reasons than its FDA-approved indication
What is an issue with generic vs. brand drug’s bioequivalence?
They are supposed to prove bioequivelance, but it is not always 100%
This means that a patient may not respond the same to a generic drug (not as effective, different ADEs, etc.)
What are the factors that determine individual responses to drugs?
Administration
Pharmacokinetics
Pharmacodynamics
Is medication use in humans risk-free?
NO - we must always do a risk-benefit calculation when it comes to prescribing medications.
Desired outcome: Benefit > Risk
How does a patient “owning their disease” relate to their adherence?
It helps them become motivated to take their medications or other forms of therapeutics to better themselves in relation to their disease.
This is done in addition to education
What drugs use units as a unit of measurement?
Insulin and heparin
What is the difference between a solution and a suspension?
A solution has everything mixed in even distribution
A suspension contains particles
What is the main ingredient in an emulsion?
Oil
Enteral - Route of Administration
Via the GI tract
Oral (PO), enteral feeding tube
Parenteral - Route of Administration
Outside the GI tract, often via injection
IV, SQ, IM, intra-dermal, intra-arterial, epidural,
Transdermal (some say this is its own category) ex: patch –> skin absorption
Topical - Route of Administration
Applied to the body surface, skin, or mucus membrane, local action
Skin, eye, ear, nose, lungs, vagina
Does NOT mean there is no systemic absorption!
Ex: inhalers has some systemic absorption
Sublingual or buccal - Route of Administration
SL = under tongue, buccal = between the cheeks
Largely bypasses the GI system and is rapidly absorbed into the bloodstream
What happens if you crush a sustained-release or extended-release medication and administer it via a feeding tube?
Will result in a large dose of the medication being rapidly absorbed, potentially harming the patient
What does ADME stand for?
Administration
Distribution
Metabolism
Excretion
ADME Summary/Steps Description
Drugs have to cross biological membranes to
- be ABSORBED from the site of administration into the blood
- DISTRIBUTE/move from the blood to the site of action
- be METABOLIZED
- leave the body by EXCRETION
How do drugs move through membranes?
Transcellular! Meaning they move through it rather than between
What are the 3 methods drugs use to pass through cell membranes?
- Through channels/pores
- Via transporter systems (mainly proteins)
- Direct penetration
Do most drugs move through channels and pores?
No bc the channels/pores are too tiny!
They are specific for particular molecules (ex. Na/K channels
What are transporters? (Pharmacokinetics - Administration)
Proteins that move molecules from one side of the cell membrane to the other
They transport specific biological molecules
Can be selective and will transport only certain drugs
Can also transport drugs to sites of action or sites of metabolism and excretion
What are P-glycoproteins?
Transporters that move drugs out cells
This is an ATP-dependent process
Describe how P-glycoproteins transport drugs out of the liver, kidney, placenta and the brain.
Liver: transport drugs into bile for elimination
Kidney: transport drugs into the urine
Placenta: transports drugs back to the maternal bloodstream, limiting fetal drug exposure
Brain: transports drugs into blood, limiting drug access to the brain
How can P-glycoproteins be a source of drug-drug interactions?
Related to how they transport drugs out of the intestine:
They transport drugs back into the intestinal lumen, out of circulation –> leading to decreased absorption / ready for excretion
Therefore, if P-glycoproteins are inhibited (by another drug), there will be an increase in absorption of a drug since it will not be transported out of the circulation.
What are the 3 requirements needed for a drug to cross membranes by direct penetration?
- Lipid solubility (lipophilicity/lipophilic)
- Non-polar molecule
- Small size
What characteristics result in no membrane penetration or poor membrane penetration?
Polar molecules
Ions (pos/neg electrical charge, weak acid/base ionized)
Absorption - Pharmacokinetics
The movement of a drug from the site of its administration into the bloodstream
Factors that affect absorption: Drug dissolution
Drug has to dissolve before it can be absorbed
Rate of dissolution helps determine the rate of absorption
Factors that affect absorption: absorptive surface area
microvilli of the small intestine provides greater surface area than the stomach
Factors that affect absorption: Blood flow at the absorptive site
higher absorption when blood flow is higher
Factors that affect absorption: Membrane penetration of the drug
lipophilic drugs are absorbed more quickly than polar drugs
What is enterohepatic cycling?
When a drug moves repeatedly from the liver to the duodenum and back to the liver again
What organ do all drugs absorbed from the GI tract have to pass?
The liver via the portal vein, on their way to the heart and then the general circulation
What is bioavailability?
The extent to which the administered drug becomes available in the general circulation
Barriers to absorption: Epithelial lining of the GI tract
Tight junctions make it difficult for dugs to be absorbed
Barriers to absorption: Capillary wall
Due to gaps between capillary endothelial cells, polar, ionized, and lipid-soluble drugs can all pass between these gaps, in and out of the bloodstream
BUT ONLY lipid-soluble drugs can also pass directly through the cells of the capillary wall.
Distribution - Pharmacokinetics
Movement of a drug, following absorption, from the bloodstream to other body tissues
“getting to where it needs to go”
What 3 main factors affect distribution? - Pharmacokinetics
Blood flow to tissues
The ability of a drug to exit the vasculature
The ability of a drug to enter cells (if the drug’s site of action is intracellular)
How does blood flow to tissues affect distribution?
-Tumors have their own blood flow
- Abscesses have a capsule around the infection which has low blood flow
- Certain tissues have low blood flow (external ear)
What factors affect a drug’s ability to exit the vasculature? - Distribution
- Lipophilicity (if lipophilic –> direct penetration)
- Plasma protein binding
- Tissue permeability: blood-brain-barrier, placenta
How does the ability of a drug to enter cells affect distribution?
- Lipophilicity
- Degree of ionization
- Transporter proteins
Explain how the blood-brain barrier affects the distribution of drugs.
Makes the delivery of drugs to the brain more challenging
BBB has P-glycoproteins
Tight junctions in brain capillaries prevent drugs from passing between cells to exit the vasculature meaning drugs must pass directly through cells of capillary walls. They must be:
- Lipophilic
- Be able to use an existing transport system present in the brain
Explain how the distribution of drugs in the placenta - exit from the vasculature
To enter the fetal circulation, drugs must cross both maternal & fetal vascular systems
Placenta has P-glycoproteins
Does NOT constitute an absolute barrier to the passage of drugs
- Lipophilic drugs easily pass through into fetal circulation (ex. EtOH/alcohol)
- Ion, polar molecules, and protein-bound drugs largely prevented from reaching the fetal circulation
Which drugs can leave the vasculature and exert a biochemical effect? - Distribution: plasma protein binding
Only FREE UN-bound drugs can leave the vasculature and exert a biochemical effect
Albumin is too large to leave, so bound drugs (to albumin) cannot leave, not exert a biochemical effect
What comorbidities can affect plasma-protein binding? How?
Kidney disease
- Release of proteins in urine results in loss of albumin
Liver disease
- Liver makes the albumin, but won’t make enough when diseased
Catabolic states/cachexia
- Muscle wasting wastes protein state
How do bound fractions affect the effect of a drug? - Distribution: plasma-protein binding
If a drug is 90% bound, only 10% exerts an effect
How is albumin binding a source of drug interactions?
Competition for albumin binding
If Drug A is 99% normally protein bound, what percentage of Drug A is able to exert a clinical effect?
1% effective dose
If Drug B competes with Drug A for albumin binding sites and reduces Drug A’s protein bound to 98%, what has happened to Drug A’s effective dose?
It has increased (doubled)
Increased risk of ADE
What is metabolism?
Transformation of a drug’s chemical structure by enzymatic reactions
Where does metabolism occur?
Most often in the liver
But also: small intestine, lungs, kidneys, skin, placenta, plasma
What is the major effect metabolism does to a drug?
It makes the drug become more polar/water-solube, which increases its excretion via the kidneys
Lipophilic –> Hydrophilic
What is a phase I reaction? - Metabolism
Makes the drug more polar by introducing or uncovering a functional group
ex. -OH, -NH2, -SH
What is a phase II reaction? - Metabolism
It comebines an endogenous substrate with the drug’s functional group to form a more polar conjugate/combination
What is a metabolite?
Chemical product of metabolism
Different from the parent drug
What is a prodrug?
A drug in which the parent is inactive and the metabolite is active
Activated after metabolism
What is the enzyme family involved in phase I reactions?
CYP enzyme family
Which enzyme family is involved in phase II reactions?
UGT enzyme family
What is the first-pass effect?
The removal of a substantial amount of an enterally administered drug dose prior to it reaching the systemic circulation
Affects bioavailability
How does age affect drug metabolism?
Both infants and older adults have decreased ability to metabolize drugs
How does a person’s nutritional status affect drug metabolism?
Hepatic metabolizing enzymes require certain cofactors to function. Malnutrition can cause these co-factors to be deficient
How do comorbidities affect drug metabolism?
Some drugs may require dose reduction in severe liver disease
What is excretion?
The removal of drugs and their metabolites from the body
What is the major organ involved in the excretion for most drugs?
The kidneys!
Through what ways do metabolized drugs exit the body?
Urine
Bile –> feces
Sweat
Saliva
Breast milk
Expired air
What factors modify renal drug excretion?
pH-dependent ionization
competition for active tubular transport
Age
How does pH-dependent ionization modify renal drug excretion?
Drugs that are ionized at urinary pH will stay in the urine (NOT be reabsorbed) and be eliminated more quickly
How does competition for active tubular transport modify renal drug excretion?
If two drugs use the same transporter to move from plasma to the renal tubules, less of them will be transported to the tubules at any given moment
Delays the excretion of both drugs
How does age modify renal drug excretion?
Infant kidneys do not reach full capacity until a few months after birth
Older adults may have decreased glomerular filtration rates, decreasing drug excretion
What 3 processes result in urinary excretion? - Renal Route
- Glomerular filtration
- drugs not bound to proteins move from blood –> urine - Passive Reabsorption
- lipid-soluble drugs move back into the blood.
- Polar and ionized drugs stay in the urine - Active Transport
- Requires ATP
- Drugs are pumped from blood to urine
- P-glycoproteins are also present in the tubules and may pump drugs into the urine
Describe the hepatic route of excretion
Metabolites may leave the liver via:
1. Blood, which will take them to the kidneys for elimination
- Bile, which will take them into the gut and out of the body via feces (hepato-biliary excretion)
What is hepato-biliary excretion?
When metabolites leave the liver via bile
The bile then takes them into the gut and out of the body via feces
What is the minimum effective concentration?
The plasma drug level BELOW which therapeutic effects will NOT occur
What is toxic concentration?
Plasma drug leves at or ABOVE which toxic effects WILL occur
What is therapeutic range?
The range of drug levels between the minimum effective concentration and the toxic concentration –> sufficient concentration to produce desired therapeutic effect
“safe range”
AKA therapeutic window
What is a drug’s half-life?
TIme required for the concentration of the drug in the body to decrease by 50%
Can be measured by hours, minutes, seconds, days, weeks
Why should we care about a drug’s half-life? What does it help us determine/calculate?
It helps figure out dosing schedule
All about the dosing interval
What might happen if we gave the usual dose of kanamycin on the usual dosing schedule to a patient with renal failure?
The half-life would increase
There would be more drug inthe system –> more toxicity
More ADE
Need to change the dosing schedule for a pt with renal failure
What is the onset of a drug?
Time after administration until the drug begins to have a clinical effect
What is the peak of a drug?
Time after administration at which the drug is having its maximal effect
Drug is at its highest concentration
What is the trough of a drug?
Time after administration at which the drug is having its minimal effect
Drug is at its lowest concentration
What is the “duration” of a drug?
The lenght of time the drug has a clinical effect
- important, along with half-life, for determining dosing interval
- Also important for tapering/withdrawal considerations
What is a steady-state? - Drug Levels
When the amoun of drug administered = the amount of drug eliminated in the same period
Reaching plateau
What is the average amount of half-lives needed for most drugs to reach their steady-state?
4 to 5 half lives
What is a loading dose?
A dose that is significantly higher than the maintenance dose given to pt taking a drug with a long half-life.
Done to “speed up” the time to steady state
Often done with Abx
If a drug mimics a bioloical process, it is a ____ drug
Agonist
If a drug blocks a biological process, it is a ___ drug
Antagonist
The size and intensity of an administered dose determines what 3 things?
The minimum amount of drug that can be used
The maximum response a drug can elicit
How much to increase the dosage to produce the desired increase in response
What are the 3 phases in the dose-response relationship? - Pharmacodynamics
Phase 1: Dose it too low to elicit a response
Phase 2: Increasing the dose increases the response
Phase 3: Increasing the dose further does not yield further increase in response (but can increase adverse drug effects) –> plateau in response but increase in ADE
What is maximal efficacy?
The largest effect/response that a drug can produce
“How effective is the drug?” ex. pain relief, diuresis
What is potency?
The amount of drug (dose) needed to have an effect
“how much drug needed to have an effect?”
Which axis do you look at to determine a drug’s maximal efficacy?
The y-axis // height of the curve
Highest curve has the greatest maximal efficacy and is themost efficacious
Which axis do you look at to determine a drug’s potency?
The x axis
Curve farthest to the left has greatest potency (requires the smallest dose) for that response
Why is greater efficacy not always desired?
We want to match the intensity of drug’s effect with its desired effect
Example: we give a lower effective dose of a diuretic to a person regulating their hypertension vs. higher effective dose to a person who needs to urgently drain excess fluid
Why is potency not always an important clinical characteristic of the drug?
It implies nothing about the maximal efficacy; refers to the dosage needed to produce effects
What are some instances in which the potency of a drug can matter?
If a lack of potency forces an inconvinient larger dose (which can result in increase in ADE, including the production of toxic metabolites)
Important to keep in mind when administering certain drugs (eg. morphine in mgs and fentanyl in micrograms)
What are adverse effects?
Unintended, undesireable effects of a medication
- side effects
- Adverse drug reactions
- interactions
Side effects are ____ predictable while adverse drug reactions are ____ predictable
Side effects are MORE predictable while adverse drug reactions are LESS predictable
What is biochemical effect?
The ability of the drug to affect chemical processes related to cells, tissues, or the entire organism
Broad term that encompasses all of a drug’s chemical effects on the body
What do pharmacokinectic drug-drug interactions alter in the body?
- Alter absorption
- Alter distribution
- Alter renal secretion
- Alter metabolism
What are some ways pharmacodynamic drug-drug interactions occur?
Interaction at the same receptor –> compete
At separate sites but affect same physiologic processes (additive or inhibitory)
Combined toxicity
What do drug-food interactions affect?
- Alter absorption
- Alter metabolism (grapefruit juice)
- Toxcity
- Action
What are the 4 primary receptor types?
- Cell membrane-embedded enzyme
- Ligand-gated ion channel
- G protein-coupled receptor system
- Transcription factor
What is the single occupancy theory? What is its limitation?
States that the intensity of response to a drug is proportional to the number of receptors occupied by that drug
Maximal response will then occur when all receptors are occupied
It DOES NOT account for all observed drug-receptor interactions/results (potency, efficacy)
What is the modified occupancy theory?
It takes into account affinity and intrinsic activity
Agonist have ___ affinity and ____ intrinsic activity
Agonist have GOOD affinity and HIGH intrinsic activity
Antagonist have ___ affinity and ____ intrinsic activity
Antagonist have GOOD affinity and NO intrinsic activity
What is the difference between a competitive and noncompetitive antagonist?
Competitive: binds reversibly to receptor, competes with agonists
Noncompetitive: binds irreversibly to receptor, its effects last until new receptors are synthesized; reduces maximal response that an agonist can elicit
What are partial agonists?
Mimic physiologic actions to a lesser degree
Good affinity, moderate intrinsic activity
Give no response when increase dose of partial agonists (plateau) –> may still increase ADE
Continued exposure to an agonist results in ____regulation. What does this mean?
Downregulation –> fewer receptors
The body becomes less responsive to the agonist –> desensitized or refractory
why? reduced # of receptors –> reduced response bc agonist have lesser rceptors to bind to
Continous exposure to an antagonist results in ____regulation. What does this mean?
Upregulation –> more receptors
Hypersensitivity occurs, resulting in more receptors
why? –> body does not sense the physiologic process occurring, so it makes more receptors (which continue to be taken up by antagonist) resulting in hypersensitivity to the antagonist drug
What factors increase a drug’s ability to be excreted in breast milk?
Whether the drug is:
- lipid-soluble
- small molecule
- has a long half-life
- not highly protein-bound
- easily crosses the BBB
How can genetic variations cause differing responses from one individual to another?
- Alter drug metabolism
- Alter drug transporters
- Alter drug targets
- Alter immune responses
- Genetic variations can be the cause of significant adverse effects
What is pharmacogenomics?
The study of how genomic variation influences drug response, looking at variation across the genome - COMPLEX interactions
Across the WHOLE genome
What is pharmacogenetics?
Study of genetic influence on drug respone, typically looking at a few genes (genetic variation)
Neonates and Infants - Absorption
Oral
- Prolonged and irregular gastric emptying time
- Gastric acidity does not reach adult values until 2 years of age
IM
- Slow, erratic
- low blood flow during the first few days of life
- during early infancy, rapid absorption of IM drugs
Transdermal
- more rapid and complete for infants
- stratum corneum of infant’s skin is very thin
- blood flow to skin greater in infants
Neonates and Infants - Distribution
Limited protein binding
- amount of serum albumin is low
- limited drug/protein binding –> increase free drug –> incr in ADE
- reduced dosage needed
- 10-12 months when reach adult protein binding capacity
Neonates and Infants - Blood Brain Barrier
- Not fully developed at birth
- Infants sensitive to CNS-active drugs
- reduce dosage for drugs with possible CNS toxicities even if used for actions outside the CNS
Neonates and Infants - Hepatic Metabolism
Have low drug-metabolizing capacity
Neonates sensitive to drugs metabolized by liver
complete liver maturation at 1 year of age
Neonates and Infants - Renal Excretion
- Low renal blood flow, glomerular filtration, and active tubular secretion from birth to 1 year
- Reduce dose and/or give longer dosing intervals
- Adult renal function achieved by 1 year
Older Adults - Absoprtion
- Slow with age
- Delayed gastric emptying and reduced GI tract blood flow
- Increased gastric pH (more alkaline, drugs may require acidity)
Older Adults - Distribution
- Increased percentage of body fat
- Decreased percentage of lean body mass
- Decreased total body water
- Reduced concentration of serum albumin, especially if malnourished
- Reduced cardiac output in patients with heart failure
Older Adults - Metabolism
- Reduced hepatic blood flow, reduced liver mass, decreased activity of some heaptic enzymes
- Longer half-lives, prolonged responses
- First-pass metabolism may be decreased –> risk of increased blood levels of certain drugs
- Changes in drug metabolism can vary greatly from individual to individual
Older Adults- Excretion
- Reduced in renal blood flow, GFR, active tubular secretion, and number of nephrons
- Averafe renal function of an 80 year old is around 50% of a 20 year old
Older Adults - Pharmacodynamic Changes
Alterations in receptor properties
- some drugs may have a more intense effect
- beta-blockers less effective, even in the same concentrations
