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ANAP 500 - Physiology 1 - Lancaster > Test 3 > Flashcards

Test 3 Flashcards

1
Q

What is pharmacology?

A

Pharmacology is the study of how drugs interact with the body to produce therapeutic effects.

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2
Q

What is pharmacy?

A

Pharmacy is the practice of compounding and dispensing medicines

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3
Q

What are pharmacotherapeutics?

A

Pharmacotherapeutics are the EDUCATED applications of drugs for the treatment of diseases as associated with patient care.

IE - Appropriate drug, appropriate dose, for the appropriate disease, for the appropriate patient.

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4
Q

What are pharmacodynamics?

A

Pharmacodynamics are the effects of a drug on a physiologic or biochemical function of the body: “What a drug does to the body”

REMEMBER - drug has effect on body at the SAME time the body has an effect on the drug.

pharmaco Dynamics = what the Drug does to the body

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5
Q

What are pharmacokinetics?

A
  • Effects of the body on a drug (What the body does to a drug)
  • Fate of a drug during its course in the body: absorption, distribution, metabolism, and elimination/excretion.

“Kinetics makes me think of motion, and our bodies are constantly in motion, thus kinetics = body in motion = what the body in motion does to the drug”

An example being: Drug concentrations in body fluids and tissues and how they vary with time due to what the body is doing to the drug through absorption, distribution, metabolism, excretion, etc.

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6
Q

Name the listed drug components that are active ingredients (5)

A
  1. Alkaloids (atropine)
  2. Glycosides (digitalis)
  3. Polypeptides (insulin) (long chain of amino acids)
  4. Salts (morphine, potassium chloride)
  5. Steroids (cortisone, estrogen, progesterone, testosterone, aldosterone)
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7
Q

Name the listed drug components that are additives (inactive) -

A 
Blinders
Diluents
Disintegrators
dyes
flavorings
fillers
lubricants
vehicles
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8
Q

True or False - A drug additive should NOT effect the active ingredient within the drug.

A

True

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9
Q

True or False - Drug companies must always use the same ADDITIVES for a drug when making a generic version of the drug.

A

False - Different companies may use different additives for drugs, so a drug from one company to another may not be equivalent to a trade name or to another generic form from a different company.

Also, the desired effects can be changed, IE - blood levels of a drug and the side effects can both be effected.

Ex: Cyclosporine - one formulated by one company can have a different interactions than from another company. They MUST NOT switch companies of a medication… must ALWAYS get the same medication from the same company.

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10
Q

Routes of drug administration

A 
Enteral (by mouth through the GI tract)
Subligual (under the tongue)
Buccal (in gums and cheeks)
Rectal (in the bum)
Parenteral (IV, IM, SQ)
Inhalation (respiratory system)
Topical (on the skin or eyes)
Intrathecal (Subarachnoid space in brain)
Epidural (Epidural space in spinal cord)
Intranasal (Nasal mucosa)
Transdermal (SLOW specific administration through the skin.
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11
Q

Enteral administration

A

Most common form of administration

ORAL - through the GI tract.

  • passes from mouth to stomach. Some drugs absorbed here, most drugs are absorbed in the SMALL INTESTINE (duodenum)
  • drugs must be able to permeate the gut lining.
  • drugs hit portal circulation first (hepatic first pass metabolism)
  • after the liver, drugs enter systemic circulation.

Include Feeding/Gastric tubes.

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12
Q

Sublingual administration (SL)

A

Absorbed through capillary bed under the tongue to systemic circulation.
NO HEPATIC FIRST PASS - (but will hit liver later on)

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13
Q

Buccal administration

A

Absorbed through capillary bed of buccal mucosa (between gums and cheeks) into systemic circulation.
NO HEPATIC FIRST PASS

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14
Q

Rectal administration (PR “per rectum”)

A

absorbed from rectal capillaries into BOTH SYSTEMIC AND PORTAL CIRCULATIONS.
-Degree of intestinal metabolism and/or Hepatic first pass effect varies depending on how far the medication is inserted into the rectum.
Rate of absorption is inconsistent “because everyone’s ‘finger of administration’ is a different length”

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15
Q

What is parenteral administration?

A

IV, IM, SQ.

Bypass the GI tract straight into systemic circulation, so NO hepatic first pass effect.

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16
Q

IV drugs are injected directly….

A

into the blood or systemic circulation. Rapid onset of action. 100% bioavailability

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17
Q

IM injections are injected…

A

directly into muscular tissue from where it is absorbed into capillaries and systemic circulation.
Rate of absorption depends on whether drug is aqueous (water) based and rapidly absorbed OR oil-based and slowly absorbed.
Also depends on rate of blood flow to site of injection.

HIGHER BLOOD FLOW = HIGH RATE OF ABSORPTON

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18
Q

Subcutaneous injections are injected where?

A

Subcutaneous tissue from where it is absorbed into capillaries and systemic circulation.

Rate is affected by same factors as IM, oil/water base, rate of blood flow to injection site.

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19
Q

Inhalation

A
  • Drug absorbed from mucosa of respiratory system where it may have local effect and/or be absorbed into capillaries and systemic circulation.
  • No hepatic first-pass effect.
  • Often delivered in metered-dose devices or by aerosolization.
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20
Q

Topical Administration

A

(THINK LOCAL)
Drug usually in cream, ointment, or liquid form, applied to skin or eyes for local effect.

-Usually LITTLE systemic absorption, but can be increased by using on extensive parts of the skin, long term use, skin excoriation (torn or worn skin), and the individual pharmacology of the drug.

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21
Q

Intrathecal

A
  • Drug administered into subarachnoid space surrounding spinal cord and brain.
  • Used for drugs that cannot cross the blood-brain barrier when given systemically and that are required to treat conditions of the central nervous system.
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22
Q

Epidural

A
  • Drug administered into epidural space surrounding the spinal cord (between the dura mater and the ligamenta flava [the ligaments that join adjacent vertebral laminae]).
  • Used for administration of analgesics and anesthetics.
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23
Q

Intranasal

A
  • Drug, usually in liquid or powder form, applied to nasal mucosa from where it has local effects and/or absorbed into capillaries and systemic circulation for systemic effects.
  • No hepatic first-pass effect.
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24
Q

Transdermal

A
  • Patch containing a special formulation of a drug is applied to the skin.
  • The drug is slowly absorbed through the skin into the capillaries and systemic circulation.
  • No hepatic first-pass effect.
  • Requires adequate amount of adipose tissue for adequate absorption.
  • Much more absorption into systemic circulation than from a simple topical drug application.
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25
Q

Drugs that are NOT administered via the GI tract / absorbed into portal circulation / transported to the liver where hepatic first-pass effect metabolism occurs will AT SOME POINT be transported to the liver via the hepatic __; then these drugs will be metabolized in the liver (but this is not hepatic first-pass effect/metabolism).

A

hepatic artery

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26
Q
  • Most drugs exert their actions on cells by first binding with cell receptors – either body cell receptors or microorganism cell receptors.
  • The receptors are proteins that may be membrane-bound (part of the cell membrane) or intracellular (in the cytoplasm or in the nucleus).
  • Each cell has only a certain number of receptors; therefore, they can become __.
A

saturated

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27
Q

-When a drug binds with a cell receptor, several outcomes are possible:
1- Opening or closing of ion channels in the cell membrane, which alters the membrane potential and the cell’s activities; leads to rapid target cell response.
2- Activation or inhibition of intracellular enzymes, G-proteins, second messengers (e.g., cAMP, cGMP, calcium-calmodulin, inositol phosphate, many others). The second messenger then activates or inhibits intracellular protein kinases (enzymes) or various chemical reactions to bring about the cell response to the drug.
3- Increased nuclear DNA transcription to mRNA, and increased ribosomal protein synthesis, which then brings about a cell response; target cell response takes hours to days to weeks.
4- Inhibition of DNA synthesis, ribosomal protein synthesis, and/or bacterial cell wall production.

A

1- ion channels (rapid)
2- secondary messengers and kinases
3- increase DNA transcription (hours to weeks)
4- inhibit DNA, protein, or cell wall synthesis

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28
Q

Inhalation administration

A

Drug absorbed from mucosa of respiratory system where it may have local effect and/or be absorbed into capillaries and systemic circulation.
NO HEPATIC FIRST-PASS EFFECT

Ex: nebulizers
Often delivered in metered-dose devices or by aerosolization

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29
Q

Each cell has only a certain # of receptors which means…

A

it can become SATURATED.

  • maximal effect is reached when receptors are saturated.
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30
Q

Intrathecal (Brain/Spinal cord) administration

A

Drug administered into the subarachnoid space surrounding the spinal cord and brain.
-used for drugs that CANNOT cross the blood-brain barrier when given systemically and that are required to treat conditions of the CNS.

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31
Q

Where are enteral drugs primarily absorbed?

A

The small intestine, the duodenum particularly. The duodenum has a large surface area is why the most absorption of oral meds occurs here.

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32
Q

Epidural

A

Drug administered into epidural space surrounding spinal cord (between the dura mater and the ligamenta flava (the ligaments that join adjacent vertebral laminae)).

-used for admin of analgesics and anesthetics

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33
Q

Getting excess amounts of any kind of agent can lead to what?

A

receptor DOWN-regulation (a protective mechanism to protect cells from excess stimulation by an agent)

Ex: too much chronic oxycodone creates “tolerance”(down-regulation)

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34
Q

Transdermal

A

(THINK SYSTEMIC)
DIFFERENT THAN TOPICAL - is specifically formulated to SLOWLY absorb into the SYSTEMIC circulation.

  • requires adequate amount of adipose tissue contact for adequate absorption.
  • NO hepatic first effect.
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35
Q
  • Number of receptors on target cells may increase in number (up-regulate) over time and thus become more responsive to endogenous or exogenous agents OR
  • May decrease in number (down-regulate) over time and thus become less responsive to endogenous or exogenous agents.
  • Binding of an endogenous or exogenous agent with receptors often causes receptor __-regulation to protect target cells from excess stimulation by the agent.
  • Deficiency of an endogenous agent may cause receptor __-regulation to increase target cells’ responsiveness to the agent.
A

down-regulation

up-regulation

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36
Q

Affinity is the strength of binding/affinity between a drug and its receptor.
-The __ the affinity of a drug and its receptors, the __ the target cell response.

A

greater the affinity the greater the response

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37
Q

What about this whole hepatic first - pass thing? What if drugs DON’T have it?

A

Drugs that are not administered via the GI tract and then absorbed into portal circulation to be transported to the liver where hepatic first-pass effect/metabolism occurs
- WILL at some point be transported to the liver via the hepatic artery; then these drugs will be metabolized in the liver (but this is NOT HEPATIC FIRST-PASS EFFECT/metabolism)

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38
Q

An agonist is a drug that binds to the same cell receptor as an endogenous agent and brings about the __ change in the function of the cell as the endogenous agent.

A

same

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39
Q

the LOADING DOSE is an __ dose of a drug, higher than subsequent doses, to achieve a rapid therapeutic plasma concentration.

A

first or initial

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40
Q

a PARTIAL AGONIST does not produce maximal effects even when bound with __ cell receptors.
-EXAMPLE: Buprenorphine (used to treat opioid addiction and to treat acute and chronic pain) is a partial agonist for µ-opioid receptors.

A

all

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41
Q

an ANTAGONIST is a drug that__ the effects of an endogenous agent on the function of a cell; also blocks effects of an agonist drug on a cell.

A

inhibits or blocks

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42
Q

with a Competitive antagonist, the degree of inhibition produced depends on the __ of antagonist: as the __ of the antagonist increases the degree of inhibition increases.

  • In addition, clinical response depends on the concentration of an agonist that is competing for binding to receptors. As the concentration of agonist increases, the concentration of antagonist needed for inhibition also increases.
  • EXAMPLE: The beta receptor antagonists such as propranolol, metoprolol, and atenolol
A

concentration

concentration

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43
Q

An Irreversible antagonist is an antagonist that binds __ and tightly with receptors so that the receptors are completely unavailable for binding of agonist.
- EXAMPLE: Phenoxybenzamine (used to treat pheochromocytoma [excess norepinephrine and epinephrine produced by a adrenal medulla tumor])

A

irreversibly

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44
Q

What is an Antagonist?

A

A drug that inhibits (blocks) effects of an endogenous agent on the function of a cell; also blocking effects of an agonist drug on a cell.

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45
Q

the DOSE is the __ of drug administered at one time (e.g., 500 mg; 40 Units; 5 mcg/kg

A

amount

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46
Q

the DOSAGE is the overall drug regimen, including the amount per dose, the frequency of dosing, and the total length of the drug regimen (e.g., 500 mg four times a day for 10 days).

A

dosage = amount, frequency, and length (or “age”) of regimen

the dose”age”

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47
Q

the LOADING DOSE is an __ dose of a drug, higher than subsequent doses, to achieve a rapid therapeutic plasma concentration.

A

first or initial

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48
Q

the MAINTENANCE DOSES are the doses of a drug, following a loading dose, to maintain a steady-state therapeutic plasma concentration. To maintain a steady-state plasma concentration, the maintenance dosage regimen must equal the rate of drug metabolism and elimination from the body.
-Dosing Rate = Clearance (i.e., rate of elimination from the body) X Desired Plasma Concentration of the Drug

A

clearance x desired plasma concentration = dosing rate

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49
Q

the ONSET OF ACTION is the Time it takes for a drug dose to begin to have a therapeutic __.

A

effect

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50
Q

the HALF-LIFE is the amount of time for the plasma concentration of a drug to decrease by __% after discontinuation of the drug; related to volume of distribution (see below) and clearance/elimination rate of the drug (see below).

A

50%

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51
Q

Maintenance dose

A

Doses of a drug following a loading dose, to maintain a STEADY state therapeutic plasma concentration.

To maintain a steady-state plasma concentration, the maintenance dose must EQUAL the rate of drug metabolism and elimination from the body!!!

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52
Q

What is the dosing rate?

A

Should equal the clearance rate from the body times the desired plasma concentration of the drug.
DR = CxPc (don’t need to compute)

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53
Q

the THERAPEUTIC INDEX is a measure of drug safety.

the Formula is: __50/__50

A

LD50/ED50

think “LED”, not “EDLD”

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54
Q

the MARGIN OF SAFETY is based on the therapeutic index.

  • The __ the therapeutic index, the __ the margin of safety and the safer the drug is to administer without causing side effects.
  • a Therapeutic Index less than or equal to 2.0 is difficult to use without the patient developing toxicity (e.g., digoxin, TI = 2.0).
A

higher

higher

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55
Q

STEADY-STATE CONCENTRATION is the time the (therapeutic) plasma concentration of a drug remains relatively __ (i.e., remains at a plateau).

A

constant

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56
Q

the PEAK is when drugs are administered (other than by continuous IV infusion), the plasma concentration of the drug increases immediately after the drug is administered and then decreases several hours after the drug is administered.

  • The PEAK is the high point of fluctuation of a plasma drug concentration.
  • Toxic effects are __ likely during the peak.
A

most

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57
Q

the TROUGH is the low point of fluctuation of a plasma drug concentration.
-Drug effects are __ during the trough.

A

unlikely

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58
Q

the HALF-LIFE is the amount of time for the plasma concentration of a drug to decrease by __% after discontinuation of the drug; related to volume of distribution (see below) and clearance/elimination rate of the drug (see below).

A

50%

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59
Q

What are drug receptors?

A

Proteins that may be membrane-bound (part of cell membrane) or intracellular (in the cytoplasm or nucleus).

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60
Q

with a CONTINUOUS IV INFUSION, plasma drug concentration rises rapidly.

  • Steady state plasma drug concentration reached after __ to __ half-lives; INCREASING rate of infusion increases the plasma drug concentration AFTER steady state is reached, but does not DECREASE the time to reach steady state.
  • Also requires same amount of time (4-5 half-lives) for clearance/elimination of 90-95% of the drug from the body.
A

4 to 5

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61
Q

Each cell has only a certain # of receptors which means…

A

it can become SATURATED.

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62
Q

When a drug binds with a cell receptor, what outcomes are possible? (4)

A
  1. Opening/closing of ion channels in cell membrane. Alters membrane potential and the cell’s activities; leads to RAPID TARGET CELL RESPONSE!!!
  2. Activate or inhibit intracellular enzymes, G-proteins, second messengers. The second messenger then activates or inhibits intracellular PROTEIN KINASES (enzymes) or various chemical reactions to bring about cell response.
  3. Increased nuclear DNA transcription to mRNA and increase ribosomal protein synthesis, which then brings about a cell response. THIS CAN TAKE A VERY LONG TIME, hours all the way even to weeks!
  4. Inhibition of DNA synthesis, ribosomal protein synthesis, and/or bacterial cell wall production.
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63
Q

What is receptor up-regulation?

A

Number of receptors on target cells increase in number (over time) and thus become MORE responsive to endogenous (made inside the body) or exogenous (made outside the body) agents.

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64
Q

What is receptor down-regulation?

A

Number of receptors on target cells decrease (over time) and thus become LESS responsive to agents.

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65
Q

Getting excess amounts of any kind of agent can lead to what?

A

receptor DOWN-regulation (a protective mechanism to protect cells from excess stimulation by an agent)

Too much chronic oxycodone creates “tolerance”(down-regulation)

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66
Q

PROTEIN BINDING COMPETITION- when one or more drugs __ for binding sites on plasma proteins.

  • Thus, one drug is unable to bind with its protein binding site, which may increase the concentration of that drug (at least transiently).
  • However, if the displaced drug is eliminated by the kidneys while in “limbo”, the concentration of the displaced drug will soon decrease, perhaps even to subtherapeutic levels.
A

compete

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67
Q

What is the affinity of drug receptors?

A

Is the strength of binding/affinity between a drug and its receptor.

The GREATER the affinity of a drug and its receptors, the GREATER the target cell RESPONSE.

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68
Q

A drug Agonist is what?

A

A drug that binds to the SAME cell receptor as an endogenous agent and brings about the SAME change in the function of the cell as the endogenous agent.

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69
Q

What is a STRONG (or full) Agonist drug?

A

A drug that produces maximal effects when bound with only a few receptors.

Ex - morphine, isoproterenol

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70
Q

What is a PARTIAL Agonist drug?

A

A drug that does NOT produce maximal effects even when bound with ALL cell receptors. (It produces a sub-maximal response)

Ex: - Buprenorphine - used to treat opioid addiction, is a partial agonist for u-opioid receptors.

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71
Q

ANTAGONISM is when one drug __ the effect of another drug (chemical antagonism) (1 + 1 = 0).

  • The antagonist may or may not have pharmacologic activity by itself.
  • E.G., naloxone antagonizes opioid analgesics.
  • E.G., protamine antagonizes heparin.
  • NOTE that both naloxone and protamine have pharmacologic effects of their own in addition to being antagonists for other drugs.
A

inhibits or stops

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72
Q

Only what form of a drug may leave the vasculature and hit the target cells?

A

Free form (when this happens, more of the BOUND form a drug is released into the blood)

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73
Q

Tissue reservoirs

A

Bones, adipose tissue.
Some drugs bind with the metals in bones - calcium
sometimes drug level in blood decreases, and then subsequently some of the drug is release from the reservoir. (depends on the nature of the drug and the receptor)

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74
Q

What is a major site of biotransformation of drugs?

A

Hepatic enzymes in Liver. - metabolites go back to the blood..

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75
Q

Excretion - what is major organ?

A

Kidneys -

Some of free form of drug and some metabolites (broken down parts of a drug) are excreted.

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76
Q

during the DISTRIBUTION PHASE of half life(t1/2 alpha) a RAPID decrease in the plasma drug concentration as a drug dose is __ throughout the body.

A

distributed

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77
Q

during the ELIMINATION PHASE of half life (t1/2 beta) a SLOW decrease in the plasma concentration of a drug because of its metabolism and __ from the body.

A

clearance/elimination

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78
Q

Rule of Thumb: It takes __ to __ half lives after starting a drug-dosing regimen for full effects to be seen.

A

4 to 5

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79
Q

It takes __ to __ half lives after stopping a drug for 90-95% of the drug to be cleared/eliminated and most of the drug effects to stop.

A

4 to 5

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80
Q

If the routes of drug clearance/elimination are altered, then it takes longer for a drug to be cleared/eliminated and its half-life is __. NOTE: This does NOT mean an increase in the NUMBER of half-lives, but an increase in the LENGTH or TIME of each half-life

A

lengthened or increased

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81
Q

the DRUG DOSE - TIME - RESPONSE CURVE is an individual’s response to __ doses of a given drug over time.
-Shown as a graph that compares the magnitude of drug actions with the concentration of the drug required to cause those actions, which are affected by everything you can imagine.

A

increasing

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82
Q

RED-MAN (RED-NECK) SYNDROME is related to __ IV infusion of vancomycin.

  • Characterized by fever, chills, paresthesias, vasodilatation, hypotension, and erythema at the base of the neck and upper back.
  • Usually resolves 15-20 minutes after infusion stopped.
  • After symptoms subside, restart the infusion at a SLOW rate.
A

rapid

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83
Q

a SINGLE DOSE exhibits __ plasma drug concentration rise and peak as the drug enters the bloodstream, and then fall rapidly as the drug is distributed from the blood to tissues, and then is biotransformed and eliminated/cleared.

A

one

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84
Q

INTERMITTENT DOSING leads to __ peaks and troughs of plasma drug concentration.

  • Drug must be administered for 4 – 5 half-lives of the drug before steady state is reached.
  • Also requires same amount of time (4-5 half-lives) for clearance/elimination of 90-95% of the drug from the body.
A

multiple

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85
Q

with a CONTINUOUS IV INFUSION, plasma drug concentration rises rapidly.

  • Steady state plasma drug concentration reached after __ to __ half-lives; INCREASING rate of infusion increases the plasma drug concentration AFTER steady state is reached, but does not DECREASE the time to reach steady state.
  • Also requires same amount of time (4-5 half-lives) for clearance/elimination of 90-95% of the drug from the body.
A

4 to 5

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86
Q

What is an Antagonist?

A

A drug that inhibits

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87
Q

EFFICACY is the degree to which a drug causes maximal effects, or the __ of a drug for treatment of a specific condition.

A

effectiveness

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88
Q

POTENCY is the amount of drug required to produce __% of the maximal response that the drug can cause.

  • Used to compare drugs within the same classification.
  • Cannot be used to compare drugs in different classes.
  • Example: 100 mg Drug X (an opioid analgesic) = 1 mg Drug Y (also an opioid analgesic).
  • So, Drug Y is 100 times more potent than Drug X in terms of their analgesic properties.
A

50%

89
Q

PLACEBO EFFECT is usually a beneficial therapeutic effect that apparently arises from __ factors.
-Effect is unpredictable.

A

psychological

90
Q

ALTERED ABSORPTION- when one drug __ the absorption of another drug.
-E.G., antacids decrease GI absorption of tetracycline and many other antimicrobials.

A

inhibits

91
Q

ALTERED BIOTRANSFORMATION/ METABOLISM- when one or more drugs induce or __ for metabolizing enzymes

A

compete

92
Q

PROTEIN BINDING COMPETITION- when one or more drugs __ for binding sites on plasma proteins.

  • Thus, one drug is unable to bind with its protein binding site, which may increase the concentration of that drug (at least transiently).
  • However, if the displaced drug is eliminated by the kidneys while in “limbo”, the concentration of the displaced drug will soon decrease, perhaps even to subtherapeutic levels.
A

compete

93
Q

ALTERED CLEARANCE/ELIMINATION is when one drug __ the renal clearance/elimination of another drug.

A

decreases

94
Q

ADDITION is when the response caused by using two or more drugs is __ the combined responses of the individual drugs (1 + 1 = 2).

A

EQUAL TO

95
Q

SYNERGISM is when the response caused by using two or more drugs is __ the combined responses of using the individual drugs separately (1 + 1 = 3).

A

GREATER THAN

96
Q

POTENTIATION is when one drug that has no effect by itself __ the effect of another drug (0 + 1 = 2).

A

enhances or potentiates

97
Q

ANTAGONISM is when one drug __ the effect of another drug (chemical antagonism) (1 + 1 = 0).

  • The antagonist may or may not have pharmacologic activity by itself.
  • E.G., naloxone antagonizes opioid analgesics.
  • E.G., protamine antagonizes heparin.
  • NOTE that both naloxone and protamine have pharmacologic effects of their own in addition to being antagonists for other drugs.
A

inhibits or stops

98
Q

Some undesired effects are PREDICTABLE. They are: side effects, toxic effects, and cumulative effects.

A

side, toxic, cumulative

all predictable undesired effects

99
Q

SIDE EFFECTS are effects of a drug in __ to the primary desired therapeutic effects

A

addition

100
Q

TOXIC EFFECTS are effects related to __ drug levels in a patient.
-Usually reversible, but may be lethal if not corrected early.

A

excessive

101
Q

CUMULATIVE EFFECTS are effects related to administration of a dose __ the previous dose has dissipated.
-the rate of administration exceeds rate of elimination/excretion; possibly due to liver and kidney failure, or just overdosing.

A

before

102
Q

There are three kinds of UNexpected UNpredictable drug effects. They are 1- allergy/ hypersensitivity, 2- idiosyncratic reaction, 3- red man/ red neck syndrome.

A

allergy, idiosyncratic, red neck

all UNpredictable undesired effects

103
Q

ALLERGY/HYPERSENSITIVITY is an __ response to a drug or one of its metabolites or one of its additives.
-The allergic response may be mild to severe to life-threatening.

A

immunologic

104
Q

A base drug is one that __ hydrogen ions/protons (H+) in a chemical reaction.

A

accepts

105
Q

SERUM SICKNESS is a drug reactions that involve __ and complement activation. Clinical manifestations include urticarial skin eruptions, arthralgias, lymphadenopathy, and fever. Usually last about 6-12 days and subside after offending drug is eliminated.

A

IgG for “G”radual

106
Q

Stevens-Johnson syndrome is a SEVERE, often FATAL, type of __ sickness that includes erythema multiforme, sloughing of the skin, arthritis, nephritis, central nervous system abnormalities, and myocarditis.

A

serum

107
Q

an IDIOSYNCRATIC REACTION is an __ drug response infrequently seen in most patients.
-Related to genetic differences in drug metabolism and genetic differences in immunologic mechanisms.

A

unusual

108
Q

RED-MAN (RED-NECK) SYNDROME is related to __ IV infusion of vancomycin.

  • Characterized by fever, chills, paresthesias, vasodilatation, hypotension, and erythema at the base of the neck and upper back.
  • Usually resolves 15-20 minutes after infusion stopped.
  • After symptoms subside, restart the infusion at a SLOW rate.
A

rapid

109
Q

CONTRAINDICATIONS are conditions, situations, or pathophysiologic entities in which a drug should __ be used as it is likely to lead to serious side effects.

A

NOT

110
Q

TOLERANCE is the __ response to a drug, usually related to increased metabolism of the drug or downregulation (decreased number and/or decreased responsiveness) of drug receptors.

A

decreased

111
Q

DEPENDENCE is related to a person requiring a drug to function “normally.”
-Cessation produces __ symptoms with physiologic and/or psychologic components.

A

withdrawal

112
Q

WITHDRAWAL- __ that occur when a drug is discontinued in a person who is dependent on the drug.

A

symptoms

113
Q

CROSS TOLERANCE/CROSS DEPENDENCE is tolerance or dependence that develops to drugs that are __ related.

A

chemically

114
Q

TACHYPHYLAXIS is the rapid __ /decreased therapeutic effect related to repeated administration of some drugs.

A

tolerance

115
Q

PLACEBO EFFECT is usually a beneficial therapeutic effect that apparently arises from __ factors.
-Effect is unpredictable.

A

psychological

116
Q

CONTRAINDICATIONS are conditions, situations, or pathophysiologic entities in which a drug should __ be used as it is likely to lead to serious side effects.

A

NOT

117
Q

TOLERANCE is the __ response to a drug, usually related to increased metabolism of the drug or downregulation (decreased number and/or decreased responsiveness) of drug receptors.

A

decreased

118
Q

DEPENDENCE is related to a person requiring a drug to function “normally.”
-Cessation produces __ symptoms with physiologic and/or psychologic components.

A

withdrawal

119
Q

WITHDRAWAL- __ that occur when a drug is discontinued in a person who is dependent on the drug.

A

symptoms

120
Q

CROSS TOLERANCE/CROSS DEPENDENCE is tolerance or dependence that develops to drugs that are __ related.

A

chemically

121
Q

TACHYPHYLAXIS is the rapid __ /decreased therapeutic effect related to repeated administration of some drugs.

A

tolerance

122
Q

PLACEBO EFFECT is usually a beneficial therapeutic effect that apparently arises from __ factors.
-Effect is unpredictable.

A

psychological

123
Q

What is a COMPETITIVE antagonist? What is clinical response dependent on?

A

Degree of inhibition depends on concentration of antagonist. (more drug = more block)

Clinical response DEPENDS on the concentration of an AGONIST that is COMPETING for binding receptors. (more agonist agent = MORE ANTAGONIST required for inhibition.

Ex - Beta blockers

124
Q

DRUG ABSORPTION is __ from site of administration into the blood.
-To be absorbed, the drug must cross various membranes (e.g., GI tract, oral mucosa, skin, alveoli, capillaries, cell membranes).

A

movement

125
Q

What are the three mechanisms for drug absorption? DFA

A

diffusion, filtration, active transport

126
Q

Diffusion is the most __ and most __ mechanism of drug absorption.
-Drugs diffuse across membranes from higher to lower concentrations of the drug, WITH the concentration gradient.

A

most common

most important

127
Q

Lipid-soluble (lipophilic), un-ionized drugs diffuse through phospholipid membranes __ than water-soluble (hydrophilic), ionized drugs.

A

faster

128
Q

Water-soluble, ionized drugs pass through watery environments, such as the plasma and interstitial fluid, more __ than lipid-soluble, un-ionized drugs.

A

readily

129
Q

In the body, a drug must pass through __ phospholipid cell membranes and watery environments, so a drug can be too lipid-soluble and un-ionized or too water-soluble and ionized, which would influence its ability to pass through either cell membranes or watery compartments.

A

both

130
Q

Filtration is the __ flow of both solvent and drug through pores in membranes.

  • Occurs more easily with small molecules, but to some extent with larger molecules such as some proteins.
  • The rate of filtration is affected by the concentration gradient of the drug; drug moves from higher to lower concentration, with the gradient.
A

bulk

131
Q

Active transport uses energy from ATP to transport a drug __ its concentration gradient.

A

AGAINST

132
Q

Three drug related factors that influence the rate of absorption
1- molecular __/__
2- water or lipid __
3- degree of __

A

1- molecular size and weight
2- water or lipid solubility
3- degree of ionization

133
Q

regarding MOLECULAR WEIGHT/SIZE

-Generally, __ molecules cross membranes by diffusion or filtration more readily than larger molecules.

A

small

134
Q

The Ionization constant (__) is the pH at which the ionized and un-ionized concentrations of a drug are equal.
-NOTE: __ is NOT the same as pH.

A

pKa

pKa

135
Q

An acid drug is one that __ hydrogen ions/protons (H+) in a chemical reaction.

A

donates

136
Q

Weak acid drugs form salts with __ (positively charged ions) such as Na+, Mg++, or Ca++.

  • Drug names that begin with a cation are weak acids.
  • E.G., Sodium thiopental; Magnesium gluconate; Calcium citrate
A

cations

137
Q

ACID DRUGS become more ionized in an environment with a pH > than the drug’s pKa and less ionized in an environment with a pH < the drug’s pKa

A

acid + acid = unionized

138
Q

A base drug is one that __ hydrogen ions/protons (H+) in a chemical reaction.

A

accepts

139
Q

What an Irreversible Antagonist?

A

An antagonist that BINDS SO TIGHTLY and IRREVERSIBLY with receptors so no agonist can bind.
Ex - Phenoxybenzamine (for pheochromocytoma)

there are not many of these

140
Q

What is a chemical antagonist?

A

Ignores cell receptors completely. drug to drug.
Ex - Protamine/Heparin

What if you give protamine by itself? Is an anticoagulant.

Neutralizes heparin on a weight bases. Need to know how much heparin has been given to find out how much you need to give.

141
Q

Dose

A

Amount of drug administered at ONE time

142
Q

Dosage

A

The overall drug regimen, including amount per dose, frequency of dosing, and the total length of the drug regimen.

143
Q

Loading Dose

A

Initial dose of drug higher than subsequent doses, helps achieve RAPID therapeutic plasma concentration.

144
Q

Maintenance dose

A

Doses of a drug following a loading dose, to maintain a STEADY state therapeutic plasma concentration.

To maintain a steady-state plasma concentration, the maintenance dose must EQUAL the rate of drug metabolism and elimination from the body.

145
Q

What is the dosing rate?

A

Should equal the clearance rate from the body times the desired plasma concentration of the drug.
DR = CxPc

146
Q

Onset of Action

A

Time it takes for a drug dose to begin to have a therapeutic effect.

147
Q

Minimum effective (Threshold concentration)

A

Plasma concentration of a drug BELOW which there is no therapeutic effect.

-not necessarily the same as the desired steady state.

148
Q

Lethal (Toxic) Dose

A

LD50 - concentration of a drug that causes death or toxicity in 50% of those administered.

149
Q

Therapeutic Index

A

Measure of how safe a drug is. LD50/ED50

150
Q

Margin of Safety

A

based on therapeutic index (usually between 1 and 10). The higher the margin of saftey, the safe the drug to administer without causing side effects.

TI < 2 is tough (ex - digoxin TI = 2.0)

151
Q

Steady-state concentration

A

the time the therapeutic plasma concentration of a drug remains relatively constant (plateau).

152
Q

Weak base drugs form salts with __ (negatively charged ions) such as chloride and sulfate.

  • Drug names that end with an anion are weak bases.
  • E.G., Drug X chloride; Drug Y sulfate; Lidocaine hydrochloride; Morphine sulfate.
A

anions

153
Q

BASE DRUGS become more ionized in an environment with a pH < than the drug’s pKa and less ionized in an environment with a pH > than the drug’s pKa

A

Base + base = more unionized

154
Q

Despite a drug’s state of ionization/un-ionization, most drug absorption occurs in the small intestine rather than the stomach, because the small intestine has a much, much greater surface area than the stomach.

A

THUS, THE SMALL INTESTINE IS THE PRIMARY SITE FOR DRUG ABSORPTION WHEN A DRUG IS ADMINISTERED VIA THE GI TRACT.

155
Q

ION TRAPPING occurs when pH is __ on two sides of a cell membrane.

A

different

156
Q

Most drugs are __ ionized in the plasma than at the administration site, which favors absorption from the administration site into the plasma and plasma trapping for distribution to site of action.

A

more

157
Q

Applications of ion trapping:

  • Excretion of drugs in the urine
  • Acid drugs are excreted faster in an __ urine because the drugs become more ionized, which makes the drugs more difficult to reabsorb.
  • Base drugs are excreted faster in an __ urine because the drugs become more ionized, which makes the drugs more difficult to reabsorb.
  • The concept of ion trapping also applies to anesthetic agents to help trap the drug in the body compartment where it has the greatest effect.
A

alkaline

acidic

158
Q

True or false, IV administered drugs are already in the blood so they do not need to be absorbed.

A

True

159
Q

True or false, Generally, IM and SC administered drugs are more readily absorbed than orally administered drugs.

A

True

160
Q

what are some CONDITIONS THAT AFFECT ABSORPTION FROM ITS SITE OF ADMINISTRATION

A

Food in GI tract, stomach acidity, blood flow to GI tract, blood flow to muscular/subcutaneous tissue and skin.

161
Q

BIOAVAILABILITY is the __ of a drug that enters the systemic circulation after administration by any route.
- A drug must be bioavailable to reach its site of action.

A

fraction

162
Q

Drugs given IV have __% bioavailability

A

100%

163
Q

For drugs administered orally, the __ is the fraction of a dose that enters the systemic circulation compared with the amount that enters when given __.

A

bioavailability

IV

164
Q

Oral bioavailability is decreased by:

A
  • Poor solubility.
  • Incomplete absorption from GI tract.
  • Intestinal enzyme metabolism to inactive metabolites.
  • Rapid hepatic first-pass effect (biotransformation/metabolism).
165
Q

DRUG DISTRIBUTION TO SITE OF ACTION is the __ by which a drug is transported through the blood and then leaves the blood and enters the interstitial/extracellular fluid and into cells to exert its effect.

A

process

166
Q

To effectively reach its site of action a drug must be able to cross all membranes from the blood to the site of the target cell receptors.
-At the site of the target organ/tissue, the drug must first cross __ membranes to move from the blood into the interstitial fluid, and then must cross __ cell membranes to move into cells (unless the drug exerts its effect on a receptor embedded in the cell membrane).

A

capillary membranes

phospholipid cell membranes

167
Q

Distribution is affected by many of same factors that influence rate of absorption.
name some

A
  • Concentration gradient
  • Molecular size.
  • Blood flow to various organs/tissues.
  • Lipid-solubility vs. water-solubility
  • Degree of drug ionization
  • Degree of protein binding
  • Amount of free drug
  • Other factors.
168
Q

Binding of a drug with plasma proteins __ the amount of free drug in the plasma.
-Protein binding is usually __.

A

reduces

reversible

169
Q

A drug must be __ to cross the capillary membrane to the interstitial fluid and then to target organs/tissues.

A

free

170
Q

Increased protein binding __ drug distribution, drug biotransformation, and renal drug excretion.

A

decreases

171
Q

Protein binding can __ drug interactions: multiple drugs competing for same binding sites on proteins can result in higher free blood levels of one of more of the drugs, which can lead to (transient) toxic effects.

A

increase

172
Q

Name two proteins that drugs bind primarily with

A

albumin and alpha-1 acid glycoprotein

173
Q

Does albumin bind with acidic or basic drugs?

A

acids, e.g., warfarin, penicillins, sulfonamides

174
Q

Does alpha-1 glycoprotein bind with acidic or basic drugs?

A

basic, e.g., quinidine, meperidine, imipramine, chlorpromazine

175
Q

Name two areas for depot storage

A

fat- for lipophilic drugs

bones and teeth- for calcium binding drugs

176
Q

VOLUME OF DISTRIBUTION (Vd) is a calculated value that describes drug distribution throughout the body: it is the __ that would be required to contain the administered dose if that dose were evenly distributed throughout the body in the same concentration as measured in the plasma. It is an apparent or conceptual volume into which a drug APPEARS to be distributed; it does not represent actual drug distribution.

A

volume

So if the Vd was 3 liters, imagine your body was only 3 liters in volume, but had equal concentrations of drug in every compartment and tissue.

If the Vd was 80 liters (the average 70kg person holds ~42 liters) imagine your body being twice as big or 140kg and the drug equally distributed in all tissues.

177
Q

Drugs that distribute extensively have a __ VD and drugs that distribute minimally have a __ VD.

A

large

small

178
Q

Total body water volume of 70 kg person ~ __ liters water

A

42 liters

179
Q

Extracellular volume ~ __ liters

extracellular volume is composed of the __ and __ fluid

A

15 liters
plasma
interstitial fluid

180
Q

Plasma volume ~ _ liters

A

3

plasma volume is 1/5 or 20% of the extracellular volume

181
Q

Interstitial volume ~ _ liters

A

12

interstitial volume is 4/5 or 80% of the extracellular volume

182
Q

Intracellular volume ~ __ liters

A

27

about twice the amount of volume compared to extracellular

183
Q

if the Vd </= 3 liters the drug distributed__

A

in plasma only and probably highly bound with plasma proteins.

184
Q

if the Vd 3 – 15 liters the drug is distributed in _

A

plasma and interstitial fluid.

185
Q

if the Vd 15 – 42 liters the drug is distributed in __

A

plasma, interstitial fluid, and intracellular fluid.

186
Q

if the Vd > 42 liters the drug is distributed __

A

throughout body and highly bound to tissues and/or sequestered in a depot.

187
Q

DRUG BIOTRANSFORMATION (METABOLISM) changes an active drug into an active, inactive, or less-active metabolite or changes a prodrug into an active drug.

A

active drug -> active/inactive/less active metabolite

prodrug -> active drug

188
Q

in the GASTROINTESTINAL TRACT, digestive enzymes and enzymes in the intestinal cells may __ some drugs to less active or more active metabolites.

A

metabolize

189
Q

explain hepatic first pass effect

A
  • Blood from most of the gastrointestinal tract circulates through the portal circulation to the liver before circulating to any other organs.
  • During this “first-pass” through the liver, some or all of an orally/enterally administered drug can be metabolized to an inactive, less active, or more active metabolite, or prodrugs can be activated to the active drug.
  • APPLIES ONLY TO DRUGS ABSORBED THROUGH STOMACH OR INTESTINES*
190
Q

In hepatic biotransformation/metabolism, PHASE I (NONSYNTHETIC) REACTIONS cause __ or __ of a drug to a more polar (charged) form.
-Drug metabolites may be renally excreted after undergoing Phase I reactions (because they become more charged), or they may proceed to Phase II reactions.

A

oxidation or reduction

191
Q

in hepatic biotransformation/metabolism, PHASE II (SYNTHETIC) REACTIONS: An endogenous polar group is __ with a drug, which makes the drug more polar (charged) and easier to excrete through the kidneys.

  • Drugs undergoing Phase II reactions usually (but not necessarily) have undergone Phase I reactions first.
  • Some drugs undergo Phase II reactions before undergoing Phase I reactions.
A

conjugated

192
Q

is cytochrome p450 associated with phase 1 or 2 biotransformation?

A

phase 1

193
Q

Cytochrome P450 uses an __ transport chain (donates and accepts protons [hydrogen ions]) to oxidize or reduce drugs in Phase 1 nonsynthetic biotransformation reactions

A

electron

194
Q

what enzyme is responsible for about 50% of cytochrome P450 hepatic drug biotransformation?

A

CYP 3A4

195
Q

What does “induced” mean when referring to enzymes?

A

increased activity
An induced enzyme metabolizes both the drug that induced the enzyme and any other drugs metabolized by that enzyme.
-The outcome is decreased concentration/activity of the drugs that are usually metabolized (substrates) by the enzyme that is induced.

196
Q

EXAMPLES OF P450 ENZYME INDUCERS

A

alcohol, smoking, phenobarbital, many tranquilizers-sedatives-hypnotics, phenytoin, rifampin.

197
Q

What does “inhibited” mean when referring to enzymes?

A

decreased activity
The inhibited enzyme has decreased effect on metabolizing drugs specific for that enzyme.
-The outcome is increased concentration/activity (possibly toxic levels) of the drugs that are usually metabolized (substrates) by the inhibited enzyme.

198
Q

EXAMPLES OF P450 ENZYME INHIBITORS

A

allopurinol, chloramphenicol, grapefruit juice, isoniazid, cimetidine, disulfiram, ketoconazole, nortriptyline, oral contraceptives.

199
Q

TOTAL DRUG ELIMINATION is the volume of fluid completely cleared of a drug per unit of time; __ be directly measured in the body.

A

cannot

200
Q

Total Drug Clearance = Renal clearance + Hepatic clearance + Lung clearance + Other routes of clearance

A

all routes of clearance combined = total drug clearance

201
Q

Most drugs are excreted __, but some are eliminated through the bile into the stool and a few are eliminated via the lungs.

A

renally in the urine

202
Q

Is there a way to clinically measure hepatic and lung elimination?

A

no

203
Q

Decreased renal function significantly decreases drug clearance/elimination, increases the __ of the drug, and can lead to toxic or lethal drug concentrations.

A

half life

204
Q

What number should we have tattooed on our foreheads? What is the normal range for that number?

A

baseline serum creatinine
normal 0.75-1.2 mg/dl

imagine people walking around with 0.75 and 1.2 tattooed on their foreheads

205
Q

Each time serum creatinine __ from a person’s baseline, that person’s kidney function has decreased by about 50%.

A

doubles

206
Q

Creatinine clearance is the rate at which kidneys clear creatinine from the plasma.

  • Estimates __
  • measured by a 24-hour urine collection
A

GFR- glomerular filtration rate

207
Q

How to calculate creatinine clearance

A

urine vol in ml’s per minute times the urine creatinine in mg/dl
divided by the plasma creatinine in mg/dl

so take the jug of 24 hour urine, figure out how many mils they average per minute, times it by the creatinine in the jug, then divide it by the creatinine in the blood.

pee jug blood “pee jugular blood”

208
Q

What is the normal creatinine clearance?

A

110-120 ml/min

imagine peeing a liter every 10 minutes

209
Q

what is the Cockcroft-Gault formula for estimating CrCl

A

(140 - age) x kg’s divided by
serum creat x 72

x 85% for females

210
Q

if your renal function is equal or greater than 50% of normal, how much dosage change is required?

A

none or small decrease in dosage

211
Q

if your renal function is 25-50% of normal, how much dosage change is required?

A

moderate decrease in dosage

212
Q

if your renal function is less than 25% of normal, how much dosage change is required?

A

significant decrease in dosage

213
Q

First order kinetics is a constant __ of drug eliminated per unit of time

A

fraction or percent, e.g., 2% per minute

-the total drug concentration will decrease by 50% per half-life time

214
Q

Zero order kinetics is a constant __ of drug eliminated per unit of time

A

amount, e.g., 10mg per minute

-occurs when elimination mechanisms are SATURATED.

215
Q

in pregnancy, category A is __

A

safe

human studies show no risk

216
Q

in pregnancy, category B is __

A

thought to be safe

animal studies show no risk, or risks shown in animals have not been shown in human in the 1st trimester

217
Q

in pregnancy, category C is __

A

risky, use only if benefit outweighs risk
no human or animal studies available, or animal studies show adverse affects and thus no human studies have been attempted.

218
Q

in pregnancy, category D is __

A

use only to save the life of the mother, severe fetal harm probable

219
Q

in pregnancy, category X is __

A

contraindicated in anyone pregnant or who may become pregnant

ANAP 500 - Physiology 1 - Lancaster (4 decks)

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