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Intro to Pharmaceuticals > Test 5 Review > Flashcards

Test 5 Review Flashcards

(110 cards)

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0
Q

Intrapatient therapeutic variability

A

Different response in the same patient at different times

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1
Q

Interpatient therapeutic variability

A

Different response between different people

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2
Q

Pharmacokinetic variability

A

Varying of delivery, removal, efficacy, and toxicity of drug (body does to drug)
-dangerous to drugs with a narrow therapeutic index (more likely to be fatal)

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3
Q

What plays a vital role in pharmacokinetic variability?

A

Genetic effect

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4
Q

Why is body weight and composition a source of pharmacokinetic variability?

A

Obese person has a higher volume of distribution for lipophilic drugs (dissolve in fat and spread farther) so they need a smaller dose

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5
Q

How to find dose required?

A

(Avg dose/70kg) x weight in kg

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6
Q

Why is age a source of pharmacokinetic variability?

A

Very young or old people have a worse immune system and enzymes are too weak to absorb the medication correctly

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7
Q

Why are infants and children at higher risk of greater bioavailability?

A

They have increased permeability of membranes such as the BBB, they have increased water content, decreased blood flow, metabolism, and renal clearance

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8
Q

Why do the elderly have risk of greater bioavailability?

A

Decreased liver and kidney function and a higher plasma concentration (liver can’t metabolize well and kidney can’t eliminate well)

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9
Q

Why is sex a source of pharmacokinetic variability?

A

Women have higher fat content, therefore more volume of distribution for lipophilic drugs

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10
Q

Why does pregnancy and lactation affect pharmacokinetic variability?

A

Teratogenicity (drugs crossing placenta and affecting fetus) and it is unknown how some drugs will affect a pregnancy

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11
Q

Fetal Alcohol Syndrome-FAS

A

Woman either drinks during pregnancy or takes a drug that affects the child, resulting in a malformed face “teratogenic effect”

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12
Q

Why does health and disease affect pharmacokinetic variability?

A

Kidney and liver disease will affect variability, dehydration, malnutrition, etc

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13
Q

Pharmacodynamic variability

A

What the drug does to the body

-variable drug effects due to difference in structure and function of target organs or patient disease

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14
Q

Why is sex a source of pharmacodynamic variability?

A

Females are more responsive to pain medications

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15
Q

Why is idiosyncrasy a source of pharmacodynamic variability?

A

Idiosyncrasy is an unpredictable and unusual response that is undocumented, usually a genetic predisposition, so it can affect what the drug does to the body

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16
Q

Why are circadian rhythms a source of pharmacodynamic variability?

A

Because chemicals like histamine and sex hormones are highest at night, and cortisol is highest in the morning so they can affect what the drug does to the body

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17
Q

Why does drug tolerance a source of pharmacodynamic variability?

A

If someone is tolerant to a drug they need more and more, so an increased dose can affect what the drug does to the body

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18
Q

Tachyphylaxis

A

Rapidly increasing response to a drug after administering a few doses

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19
Q

Why is receptor regulation by drugs a source of pharmacodynamic variability?

A

It can result in either tolerance or a more pronounced effect, so it can influence what the drug does to the body
-receptor up and receptor down regulation

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20
Q

Receptor up regulation

A

Number of receptors increase with continuous administration of drug, resulting in too many places for the drug to attach, causing a rebound (more pronounced) drug effect

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21
Q

Receptor down regulation

A

Number of receptors decrease with continuous administration, results in not enough places for the drug to attach leading to tolerance

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22
Q

Why is drug resistance a source of pharmacodynamic variability?

A

Because 3 types of resistance lead to absorption and elimination problems, affecting what the drug does to the body

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23
Q

Intrinsic resistance

A

Resistance to causing activity when attached to a receptor, leads to decreased absorption or increased elimination, and decreased response to the drug

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24
Acquired genetic resistance
Resistance that is acquired through a person's genetics
25
Cross resistance
Resistance to one drug causes resistance to similar drugs that use the same enzyme system (multiple drug resistance) -must change the resistant drug to find another drug
26
Drug allergy
Adverse side effect that can cause rashes, itchy eyes, swollen face, or anaphylactic shock
27
Mechanism of drug allergy
B lymphocytes activate antibodies that attach to the mast cell, and upon second exposure the mast cell releases histamine that causes the allergic reaction
28
Drug compliance
Willingness and ability to stick to correct doses
29
Causes of non-compliance
Too many medications, cost, side effects, lack of understanding MOST COMMON CAUSE IS SIDE EFFECTS
30
FDA
Food and drug administration
31
What does the FDA do?
Regulates development of new drug products and marketing
32
What are the FDA's functions?
1. Promote and protect public health 2. Monitor product after it is in use 3. Regulates products (food products, tissues of transplantation, cosmetics, electronic devices that emit radiation)
33
Federal Food, Drug, and Cosmetic Act of 1938
Single most important act related to the FDA, gave authority to the FDA for them to regulate food, drugs, and cosmetics
34
Steps of new drug development
- Select the lead compound and check for affinity, efficacy, early ADME, toxicity - preclinical testing (on animals, checks for efficacy, toxicology, ADME processes then move to humans) - investigational new drug (IND, must be approved by the IRB) - clinical trials on humans with the disease
35
Institutional review board
IRB Reviews and approves research on a drug before it is classified as an investigational new drug and proceeds to clinical trials
36
4 Phases of Drug Trials
1. Small number of healthy volunteers-safety, toxicology, and pharmacokinetics (is it safe?) 2. Small number of people with disease-efficacy, dosing, and adverse effects (does it work?) 3. Larger number of sick patients-compare to current treatment (is it better?) 4. Post marker surveillance of drug's effects-detects adverse effects (can it stay?)---can result in removal of a drug from the market and is completely voluntary, people must report side effects to the FDA
37
How long does the process take for drug research and approval?
It can take 10+ years
38
What happens between phases 3 and 4 of drug trials?
A 1-4 year period elapses between those stages where the drug is approved for sale on the market
39
polypharmacy
giving multiple drugs for multiple conditions, or multiple drugs to manage one condition
40
3 types of reactions
pharmaceutical, pharmacokinetic, and pharmacodynamic
41
pharmaceutical reactions
drugs reacting chemically or physically during administration or absorption, altering the variability of one or both drugs--chelation, adsorption, altering gastric pH, and incompatibilities
42
chelation
agents (chelating agents) bind to a drug forming an insoluble complex that is poorly absorbed ex) tetracycline and ciprofloxacin (antibiotics)=insoluble complex
43
adsorption
physical binding of a drug with other solids, leading to increased absorption ex) antacids adsorb and decrease absorption of iron
44
alteration of gastric pH
some drugs are used to increase pH, and may affect drugs that absorb better at a low pH ex) omeprazole increases gastric pH, and decreases absorption of ampicilin
45
incompatibilities
some drugs can decrease the effects of other drugs | ex) when IV fluids are mixed together they may be incompatible and decrease their effects
46
what happens when meds are taken on an empty stomach?
the plasma concentration is very high since there is nothing else to absorb
47
why should you not take meds with milk?
the medicine binds to the milk and forms an insoluble complex--this delays absorption and reduces effect
48
what should you take medications with?
water
49
pharmacokinetic interactions
changes to the ADME processes of another drug (what the body does to the drug - account for the most drug interactions - ADME processes, distribution interactions, excretion interactions, biotransformation interactions, enzyme induction and inhibition
50
gastric motility and emptying time
low gastric emptying time-higher bioavailability, increased absorption from small intestine high gastric emptying time-low bioavailability, decreased absorption and stays in stomach longer
51
what is the normal gastric emptying time?
90 minutes
52
intestinal flora
bacteria in the large intestine that help absorb drugs-if there are less bacteria, it leads to less metabolism and a high concentration b/c the medicine isn't absorbed fast enough
53
saturation of carrier mediated absorption
all receptor are occupied and the drugs can't reach the target--low bioavailability and absorption
54
distribution interactions
displaces the drug from the transporter, resulting in an increased plasma concentration and increased metabolism and excretion
55
excretion interactions
changes urinary pH-increased urinary pH leads to decreased excretion of bases, increased excretion of acids (acids are 0-6 on scale, bases are 8-14)
56
alteration of tubular secretion
tubular secretion is active transport with a specific transporter for acids and bases, and competition b/w these results in decreased secretion and clearance
57
biotransformation interactions
affects metabolism of other drugs, and if a drug stays in the stomach too long it is less available for absorption
58
enzyme induction
potentiated effect | ex) St. John's wort induces CYP3A, and when given with other drugs it causes faster elimination
59
enzyme inhibition
another drug is inhibited ex) CYP3A is inhibited by grapefruit juice, increasing the bioavailability of the drug it is given with, leading to toxicity
60
most important enzyme in the liver?
CYP3A, most often responsible for life threatening drug reactions and metabolized 55% of all drugs
61
pharmacodynamic drug interactions
one drug changes the pharmacological effect of another (drug does to body, molecular and chem. interactions) -additive, synergistic, and antagonistic reactions
62
additive reaction
something is added - most common type of pharmacodynamic reaction - 1+1=2
63
synergistic reaction
combined effect of the medications is greater than either of their individual effects -1+1=3
64
antagonistic reaction
results in inhibition | -classified as competitive, noncompetitive, etc
65
tyramine
compound in cheese that causes hypertensive crisis if given with antidepressants, because it increases availability (toxicity) of the compound
66
why can warfarin not be taken with greens?
greens have vitamin K, warfarin is an anti-vitamin K drug and an anticoagulant, so it renders warfarin ineffective
67
what can replace the friendly bacteria killed by antibiotics?
compounds in yogurt
68
why can drugs not be taken with alcohol?
alcohol has depressive properties and either an additive or synergistic reaction, so it leads to high blood pressure
69
what happens when alcohol is taken with tylenol?
it produces a higher level of toxic metabolites, affecting the liver
70
why is grapefruit juice bad for medications?
it binds to CYP3A, inhibiting it, increasing the toxicity and effect of the drug. also causes decreased metabolism
71
what happens if herbal tea is taken with estrogen?
it leads to increased estrogen amounts
72
what happens when St. John's wort is given with the majority of medications?
it causes nausea, weakness, and fatigue
73
what does warfarin do with some medications?
its effect as an anticoagulant is decreased causing increased bleeding and bruising
74
pharmacogenetics
study of genetically determined variability in response of people to drugs -studies specific differences
75
pharmacogenomics
study of effect of person's genetic inheritance on body's response to drugs by studying multiple genes and alleles -uses a genome wide approach, more broad than pharmacogenetics
76
DNA
codes for producing genetic chemicals
77
RNA
messenger, carries info through cytoplasm
78
transcription
DNA->mRNA | takes place in the nucleus, a DNA strand untwists to form two single-strand mRNA molecules
79
translation
mRNA->proteins takes place in the ribosomes, the mRNA formed from transcription carries the message through the cytoplasm to the ribosomes to carry out translation
80
how many chromosomes do humans have, and what are they called?
``` 46 total (23 from sperm, 23 from egg) 22 pairs are called autosomes, and 23rd pair are the sex chromosomes (XX or XY) ```
81
gene
sequence of DNA that encodes a particular trait
82
complementary base pairs of DNA
adenine-thymine | guanine-cytosine
83
2 alternative forms (alleles) of genes
homozygous-two same alleles (SS) | heterozygous-two different alleles (Sc)
84
how many known genes are in the human genome?
30,000
85
genotype
how genes are arranged--genetic makeup
86
phenotype
physical expression of the genotype
87
gene expression
manifestation of genotype into the phenotype
88
mutation
occurs in less than 1% of population | permanent change or structural alteration of DNA
89
germline mutation or hereditary mutation
mutation transmitted through germ cells (sex cells) through the generations
90
acquired mutation
acquired through exposure to toxins (radiation, smoke, etc) that occurs in a single cell after conception and it spreads to all cells that multiply from it
91
polymorphism
mutation that occurs in over 1% of population
92
most common type of polymorphism
single nucleotide polymorphism--one of the nucleotides in the A-T G-C base pairs is replaced
93
sickle cell anemia
a single amino acid changes in the hemoglobin, causing a RBC to form into a sickle shape and can't function correctly
94
glucose 6 phosphate dehydrogenase deficiency (G6PD)
most common enzyme deficiency, certain medications cause hemolysis (rupture of RBC) -there are no obvious signs, and it is more common in males and african americans
95
monogenic disease
1 gene is involved | -cystic fibrosis, huntington's, sickle cell anemia
96
polygenic disease
more than 1 gene is involved | -asthma, heart disease, Alzheimers
97
gene deletion
leads to enzyme deficiency, leads to slow metabolizers--toxicity
98
gene amplification
increased gene expression, leads to more enzyme and fast metabolizers (if the drug is eliminated too fast it can cause resistance)
99
hyporesponsers
receptors are under-responding, some may be inactive and this leads to a low availability of the drug
100
hyper-responders
receptors are over-responding, so a small dose could cause a large response
101
variation can change the availability of drug transporters
decreased transporters=low availability, drug doesn't reach target so no response increased transporters=too much drug reached the target and causes too much of a response
102
those that are slow metabolizers probably have a what?
genetic problem
103
clinical applications of pharmacogenomics
help identify a group that will benefit from a drug and the group that will experience toxicity, so a drug can still be marketed
104
benefits of pharmacogenomics on drug therapy
advanced disease screenings (people know their risks so make better lifestyle choices), drugs with more specific targets, choice of drugs and dose, and more universal drugs
105
genetics
identification of disease susceptibility in genes and gene variants by studying patients
106
genomics
identification of genes and gene families as drug targets based on sequence similarities
107
functional genomics
understanding function of gene and variants
108
identifying drug compound
finding compound that interacts appropriately with the target
109
compound optimization
alteration of compound structure to optimize pharmacokinetic(ADME) and pharmacodynamic (drug to body, chemical reactions) properties

Intro to Pharmaceuticals (10 decks)

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