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Foundations of Medicine PA S1 > Introduction to Pharmacological Principles > Flashcards

Introduction to Pharmacological Principles Flashcards

1
Q

Functional Definition of a Drug

A

a chemical substance that produces a biological response
sources:
- small organic molecules
- proteins synthesized by bacteria, yeast, or mammalian cells

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2
Q

Legal Definition of a Drug

A

articles intended for use in the diagnosis, cure, mitigation, treatment or prevention of disease in man or other animals
- articles (other than food) intended to affect the structure or any function of the body of man or other animals

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3
Q

Pharmacology

A

study of drugs and their interactions w/living systems
- the info used in decision making for drug use for pts comes from this
- focuses on chemical properties of a drug and its effects
a. biochemical effects: at the cellular level
b. physiologic effects: effects on body
*looks at therapeutic effects and adverse effects on body

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4
Q

Pharmacotherapy

A

the use of drugs to diagnose, prevent and treat disease
- what happens in clinical practice
- includes looking at four main things w/drugs:
1. Indication
2. Effectiveness
3. Safety
4. Convenience

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5
Q

Pharmacotherapy Indication (I)

A

why was this drug prescribed?
is it actually needed?
- if drug isn’t necessary, then should not be prescribed. asking this is important to assess in pts, especially those taking many drugs

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6
Q

Pharmacotherapy Effectiveness (E)

A

is it working?
is there a better option?
- looking at all drug options for a condition is important especially if pt is experiencing side effects or wants to return to a certain level after illness

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7
Q

Pharmacotherapy Safety (S)

A

are there adverse effects?
drug interactions?
what’s the therapeutic index?
- if drug is being prescribed at unsafe levels, can it be brought down? what are other options? good to know so that other options can be explored if drug is not safe

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8
Q

Pharmacotherapy Convenience (C)

A

does it work with the pt’s lifestyle?
is the pt willing to take it?
can the pt afford it?
- if pt cannot afford the drug or it doesn’t work with their lifestyle, then other options need to be looked at to ensure pt comfortability

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9
Q

Drug Safety in law

A

In the United States, new drugs weren’t regulated to be safe until 1940!! Before then, new drugs did not have to be proven to be safe to be on the market

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10
Q

Drug Classifications

A
  1. Therapeutic Category (“class”)
  2. Chemical Structure
  3. SubClass
  4. Target
  5. Generation
  6. Legal Restriction
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11
Q

Therapeutic Category Classification

A

also known as the class of a drug, based on what it is treating
- ex: antimicrobials

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12
Q

Chemical Structure Classification

A

based on the structure-activity relationship of a drug
- ex: Beta-lactams

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13
Q

Subclass Classification

A

further refinement of a specific category of drugs
- ex: cephalosporins (have SO MANY categories)

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14
Q

Target Classification

A

looks at the molecular mechanism that the drug is targeting
- ex: direct serine protease inhibitor

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15
Q

Generation Classification

A

when the drug was developed
- ex: 1-5 cephalosporins

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16
Q

Legal Restriction Classification

A

drugs are classified legally in “schedules” as to how dangerous they are:
1. Schedule I
2. Schedule II
3. Schedule III
4. Schedule IV
5. Schedule V
6. Legend Drug
7. OTC Drugs

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17
Q

Schedule I Drugs

A

no accepted medical use with high potential for abuse

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18
Q

Schedule II Drugs

A

high potential for abuse and psychological or physical dependence

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19
Q

Schedule III Drugs

A

moderate-low potential for abuse/dependence

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20
Q

Schedule IV Drugs

A

low potential for abuse/dependence

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21
Q

Schedule V Drugs

A

lower potential for abuse/dependence than schedule IV
- may contain small amounts of narcotics

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22
Q

Legen Drugs

A

prescription drugs

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23
Q

OTC Drugs

A

prescription not required and accessible at drug stores

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24
Q

Generic vs Brand Name Drugs

A

Generic drugs provide an effect within 10% (+/-) of the branded product
- however, there are some instances where the consistency of the manufacturer matters, whether brand or generic

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25
Q

Biologic Drugs

A

include blood, blood components, somatic cells, gene therapy, tissues, recombinant proteins, and vaccines
- typically derived from microorganisms, plants, animal or human cells
- composed of sugars, proteins, nucleic acids, or combinations of these
- complex, unique large mixtures not readily identifiable or easily duplicated
- sensitive to heat and vulnerable to microbial adulteration
- requires aseptic techniques from the initial manufacturing stages

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26
Q

Pharmacognosy

A

the science of drugs prepared from natural-sources including preparations from plants, animals and other organisms as well as minerals and other substances include in material medical

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27
Q

Pharmacokinetic Processes

A
  1. Absorption: drug being absorbed into the body and circulated where it needs to go
  2. Distribution: circulating drug and distributing it to targeted organ or tissue
  3. Metabolism: metabolized for removal from body but in some cases also activated through metabolism
  4. Excretion: leftovers excreted through urine, sweat, or other such excretions (created through enzymes in liver or kidneys)
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28
Q

Drug Transport over Membranes

A

MOST drugs can be diffused over membranes either through passive or facilitated diffusion
- in some cases they may need to be bound to an anion or cation if they have a charge themselves to get through an active transport channel
to get out of the cell, drugs are usually ejected using the P-glycoprotein channel

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29
Q

Two Compartment Model of Pharmacokinetic Processes

A

A. Central Compartment
B. Peripheral Compartment

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30
Q

Central Compartment of Pharmacokinetic Processing

A

systemic circulation + organs important to drug distribution and metabolism of drug
- includes: blood, heart, liver, lungs, kidney

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31
Q

Peripheral Compartment of Pharmacokinetic Processing

A

where drugs tend to stop after circulation for distribution into proper tissue to have effect
- can stop at organs but tends to stop at: adipose tissue, muscles, cerebrospinal fluid

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32
Q

Bioavailability (F)

A

the fraction of a dose that reaches systemic circulation around body
- oral dosage forms encounter barriers that reduce bioavailability
- if drug is given IV, F=1

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33
Q

Factors Affecting Absorption & Distribution

A
  1. Size: smaller molecules will diffuse more easily than larger molecules
  2. Lipid solubility: Lipophilic molecules cross membranes more easily
  3. Ionization/pH: polar (ionized) molecules have difficulty crossing membranes and pH varies in different body tissues
  4. Protein Binding: can range for 0-9% depending on the drug and needs to dissociate from protein to be active drug
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34
Q

Drug pH

A

lots of drugs are weak basics or acids to get where they need to go and absorb there
- acidic drugs are better absorbed in acidic fluid (stomach)
- basic drugs are better in basic fluids (gut)

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35
Q

Physiological Factors Affecting Rate of Absorption

A
  • surface area
  • blood flow
  • gastric motility
  • transporters
  • pH
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36
Q

Drug Factors Affecting Rate of Absorption

A
  • route of administration
  • particle size
  • rate of dissolution
  • solubility
  • pKa
  • lipophilicity
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37
Q

Enteral Administration

A

site of absorption:
- GI mucosa
- oral mucosa
- small intestine
- rectum
example of dosage forms:
- tablets/capsules
- oral liquids
- SL tablets/films
- suppositories

38
Q

Parenteral Administration

A

site of absorption:
- direct injection into systemic circulation
- subcutaneous tissue
- muscle
- intraosseous
- intrathecal
- intravitreal
example of dosage forms:
- vials
- IV bags
- prefilled syringes
- pens
-autoinjectors

39
Q

Inhaled Administration

A

site of absorption:
- pulmonary epithelium
- mucous membranes of respiratory tract
Example of dosage forms:
- inhalers
- nebulizer solution

40
Q

Topical Administration

A

site of absorption:
- skin
-eyes
-ears
-nose
-vagina
-oral mucosa
example of dosage forms:
-creams/ointments
-transdermal patches
-nasal spray
-opththalmic/otic drops

41
Q

Oral (PO) Administration

A

absorption pattern:
- slow and variable
advantages:
- easy/convenient
- inexpensive
- ideal for self-administration
- potentially reversible (vomiting)
disadvantages:
- variability
- inactivation by GI on occasion
- N/V from local irritation
- pt must be conscious

42
Q

Intravenous (IV) Administration

A

absorption pattern:
- instantaneous
advantages:
- rapid onset
- precise control
- permits use of large fluid volumes, irritants drugs
- increased bioavailability
disadvantages:
- irreversible
- expensive
- inconvenient
- risk of fluid overload
- drug must be water soluble

43
Q

Intramuscular/Subcutaneous (IM/SQ) Administration

A

absorption pattern:
- rapid: water soluble drugs
- slow: poorly soluble drugs
advantages:
- permits use of poorly soluble drugs, depot injections
disadvantages:
- possible discomfort
- inconvenient

44
Q

Dosage Form Considerations

A
  1. Indication
  2. Efficacy
  3. Safety
  4. Convenience
45
Q

Dosage Form Indication

A

life-threatening indications: drug must work quickly and be able to be administered by healthcare professional

46
Q

Dosage Form Efficacy

A

ability of drug to cross membranes and reach correct site of action
affected by:
- solubility
- polarity
- lipophilicity
- pH

47
Q

Dosage Form Safety

A

narrow therapeutic index: infusion, CR formulations, injection depots
- SQ/IM limited volume for dilution
- cannot inject homogenous lipids -> emulsification can reduce toxicity

48
Q

Dosage Form Convenience

A

ability to be administered by the pt
- pt preference
- dosing frequency
- storage
-cost

49
Q

Volume of Distribution

A

how far the drug is distributed out
- large VD = large reach around body
- small VD = less stretch across tissues

50
Q

Factors Affecting Distribution

A
  1. cardiac output
  2. regional blood flow
  3. tissue volume
  4. pH partitioning
  5. protein binding
51
Q

Why enzymes in metabolism?

A

enzymatic alteration occurs in metabolism to alter the drug’s original structure to a metabolite that can be excreted
why?
- the ability to eliminate xenobiotics allows animals to adapt to environmental changes in habitat and food supplies
- ensures survival of the species

52
Q

Metabolism Process of Drugs

A
  • occurs mostly in the liver
  • occurs in phases (1&2)
  • goal is to make more water-soluble for excretion via the kidney
53
Q

Metabolism: Phase 1 Enzymes

A

primary enzyme involved is cytochrome P450 system aka CYP P450
- superfamily of enzymes responsible for metabolizing xenobiotics
- grouped into families–named for family/subfamily:
a. 12 CYPs responsible for most pharmaceutical metabolism
b. CYP2C9, CYP2C19 CYP2D6, CYP3A4 are most common
- these enzymes are nonspecific:
a. able to metabolize many diverse compounds
b. rate is slower compared to enzymes with high specificity
c. many drugs are metabolized by multiple CYPs
d. major contributor to drug-drug interactions
- some other enzymes involved in phase 1: oxidation, hydrolysis of epoxide rings
- deactivates most drugs
- sometimes activates them in cases of very specific drugs

54
Q

What is biggest system of enzymes in metabolism phase 1?

A

Cytochrome P450 (CYP P450)

55
Q

Metabolism Phase 2 Enzymes

A

Transferases:
- sulfation
- glucoronidation
- addition of glutathione, methyl groups, acetyl groups
Other Enzymes:
- alcohol dehydrogenase
- aldehyde dehydrogenase

56
Q

Methods of Elimination of Drugs

A
  • renal excretion (majority of elimination)
  • breast milk
  • bile
  • lungs
  • sweat
    -saliva
57
Q

Renal Elimination Things to Know

A
  • drugs are filtered from the plasma at the glomerulus
  • renal function is important for drug dosing, affects serum concentrations and duration
  • some drugs can cause renal injury
  • some drugs are secreted into renal tubules or reabsorbed into systemic circulation from renal tubules (but not always only excreted)
58
Q

Estimates of Glomerular Filtration Rate (GFR)

A

A. Creatinine Clearance (CrCl) - mL/min
- calculated by Cockcroft-Gault or 24 hour urine collection
- the lower the CrCl, the worse the renal function
B. eGFR - mL/min
- modified diet in renal disease equation (MDRD)
- CKD-Epi creatinine equation (21’)
**both are used and values aren’t often too different
** smaller values = worse renal function
** most drugs based on CrCl not eGFR

59
Q

Serum Concentrations

A

measuring the amount of drug in the blood (used interchangeably with term “plasma levels”)
- done to estimate the amount of drug at the site of action
- correlation between drug response and serum concentration

60
Q

First-Order Kinetics for Drugs

A

drug metabolized per unit of time is a percentage of serum concentration

61
Q

Zero-Order Kinetics for Drugs

A

drug metabolized per unit of time is constant

62
Q

Zero-Order Elimination

A

a constant amount of drug (mg) is removed per unit of time
- rate of drug elimination per hour is “independent” of drug concentration (the same amount of drug is eliminated per hour regardless of how much of drug is in the body)
- examples: aspirin, ethanol

63
Q

First-Order Elimination

A

a constant percent of drug is removed per unit of time
- rate of drug elimination per hour is “dependent” on drug concentration (the more drug in the body, the more that is eliminated per hour)
- half-lives

64
Q

Half-Life (t^1/2)

A

time required for the amount of drug in the body to decline by 50%
- longer half life = longer time to leave the body/longer time in the body

65
Q

Steady State Concentration

A

drug infusion and elimination are occurring at the same rate
- not often doing continuous infusions though

66
Q

Bolus Dosing Steady State

A

usually around 5 half-lives and where the drug is hitting steady up and down flow of concentration w/doses

67
Q

Pharmacodynamics

A

the study of the biochemical, cellular, and physiological effects of drugs and their mechanisms of action

68
Q

Drug Targets

A
  • enzymes & cell receptors (most common)
  • ion channels (when you wanna change a charge, think anti-seizure meds, pain meds, some cardiac meds)
  • carrier proteins (anti-depressant SSRIs)
  • structural proteins and nucleic acids (usually on bacteria, antibiotics
69
Q

Drugs Can Affect Ligand-Gated Ion Channels

A

some receptors when bound to a drug will cause an action potential, leading to systemic action downstream from that binding drug
- very fast, within milliseconds

70
Q

Drugs Can Affect G-Protein Coupled Receptors

A

drugs binding to a g-protein receptor will lead to a domino effect of things happening for something to happen at the end of the chain of events
- reasonably fast, within seconds

71
Q

Drugs can Affect Kinase-Linked Receptors

A

steps of things occurring w/phosphorylation to get rxn to occur
- slower, within hours

72
Q

Drugs Can Affect Nuclear Receptors

A

drug enacts change in nucleus of cell and changes genes to alter protein synthesis
- slow acting, within hours

73
Q

Actions at Receptors

A
  1. agonism
  2. partial agonism
  3. antagonism
  4. modulation at an allosteric site
74
Q

Agonism

A

binding causes a physiologic effect

75
Q

Partial Agonism

A

binding causes a physiologic effect but it is not as big of an effect as full agonism

76
Q

Antagonism

A

binding does NOT cause a physiological effect and blocks agonist from binding to start a physiological effect
- might bind where endogenous ligand normally binds or at an allosteric site to cause this

77
Q

Modulation at an Allosteric Site

A

binding changes the physiologic effect of the endogenous ligand
- changes receptor so against can’t bind OR changes receptor so agonist can bind better

78
Q

Efficacy

A

the ability of a drug to produce a defined effect under ideal and controlled circumstances
- only in research
- effectiveness would be in clinical setting

79
Q

Potency

A

the concentration of a drug needed to produce a defined effect

80
Q

Dose-Response Curve

A

shows that eventually, even as concentration of drug increases, the maximal response does not anymore eventually

81
Q

Initial Dose

A

“starting dose”
- sometimes not even therapeutic dose but used so that pt can get used to drug

82
Q

Intermediate Doses

A

“typical” doses
- titrate up based on response or clinical guidelines
- generally, increase dose to increase response

83
Q

Maximum Dose

A

largest effect the drug can produce
- no additional response w/dosage increase
- no increase will affect efficacy

84
Q

Mechanisms of Drug Interactions

A

a. pharmacodynamic interactions
b. pharmacokinetic interactions

85
Q

Pharmacodynamic Drug Interactions

A
  • interaction of therapeutic actions: drugs w/similar or opposite effects
  • binding the same receptor
86
Q

Pharmacokinetic Drug Interactions

A

a. absorption:
- chelation (binds w/supplements, which inactivates the drug)
- binding
- changes to GI pH
b. distribution
- changes in protein binding d/t physiological state or competition from other drugs
c. metabolism
- if multiple drugs are metabolized by p450, then may not be able to metabolize all at once if not enough of enzyme and too much of multiple drugs

87
Q

Classifications of Drug Interactions

A

A. Antagonism
B. Synergystic
C. Potentiation
D. Additive

88
Q

Antagonism Drug Interaction

A

one drug makes another drug less effective when taken together

89
Q

Synergistic Drug Interaction

A

drugs work together to be more effective and each becomes more effective when used together

90
Q

Potentiation Drug Interaction

A

one drug makes another drug more effective but it still stays at the same potency

91
Q

Additive Drug Interaction

A

(most common) where both stay at the same effect but are added together and don’t negatively or positively impact one another

Foundations of Medicine PA S1 (13 decks)

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