Exam 1 Flashcards
1
Q
Preclinical Stage of Drug Development
A
Identification and animal testing
2
Q
Clinical Stage of Drug Development
A
Establish safety and effectiveness in humans
3
Q
Phase I Clinical Trials
A
Healthy patients; safe dose and pharmacokinetics
4
Q
Phase II Clinical Trials
A
Treat disease in small number of patients
5
Q
Phase III Clinical Trials
A
Compare new drug to standard therapy in large number of patients
6
Q
Graded Drug Response
A
Can be measured continually up to max response; e.g. numerics like BP or HR
7
Q
Quantal Drug Response
A
Effect is either present or absent
8
Q
Drug Potency
A
How much drug is required to produce a desired effect
9
Q
Drug Efficacy
A
Maximum effect a drug can produce
10
Q
Drug Selectivity
A
Ratio of desired response dose to dose that produces undesired effects
11
Q
Therapeutic Index
A
Ratio of lethal dose to therapeutic dose of drug
12
Q
Therapeutic Index of:
2 compared to 10
A
TI of 2 means double the therapeutic dose is lethal where TI of 10 means ten times the therapeutic dose is lethal
13
Q
Ion Channel Receptors
A
Increase flow of Ions altering electric potential.
Rapid Onset and short duration
ACh; GABA; Excitatory AA
14
Q
GPCR
A
Work through secondary messengers (cAMP, CA++, IP, DAG)
Available GPCR decreases when stimulated
Risk for rebound when drugs are d/c
15
Q
Transmembrane Receptors
A
Hormone binding; phosphorylates tyrosine
Insulin
16
Q
Partial Agonist
A
Bind to receptor sites but don’t activate every receptor
Max response is lower than full agonist
17
Q
Bioavailability
A
Percentage of the administered drug that is absorbed into central circulation
18
Q
Ion Trapping
A
Molecules exist as mixture of charged and uncharged ions depending on their pKa and the environmental pH
Only unionized molecules diffuse so an excess number of ionized drugs d/t pH will change distribution
19
Q
Protein Binding
A
Can increase drug in circulation keeping the drug from working at an active site
Deranged physio like low albumin will change drug concentrations and needs to be accounted for
20
Q
P-glycoprotein
A
Efflux transporter
21
Q
MRP1
A
Efflux transporter
22
Q
BRCA1
A
Efflux transporter
23
Q
Phase 1 Metabolism
A
Redox reaction
CYP450
Can inactivate or activate a drug
24
Q
Phase 2 Metabolism
A
Conjugation Reactions
Generally inactivate a drug and make it more hydrophilic for easy excretion
25
Breakdown CYP3A4*1
3-Family
A-Subfamily
4-Individual Enzyme
*1-Mutation from wild type
26
First-Order Metabolism
Fixed fraction of a drug is metabolized per hour
Half-life metabolism
27
Half-Life Metabolism
1st-50%
2nd-75%
3rd-87.5%
4th-93.75%
Drugs are usually dosed at their half life time
28
Zero Order Metabolism
Constant amount of drug is metabolized each hour
29
Enzyme Induction
Increased expression of drug metabolizing enzymes that can speed up or decrease metabolism.
30
Glomerular Filtration
Small unprotein bound drug molecules are filtered into lumen of nephron
31
Tubular Reabsorption and Secretion
Active and passive diffusion between the lumen of the nephron and the blood supply
Some drugs target active transporters here inhibiting movement of molecules
32
WHO's 6 step model for drug prescribing
Define patient's problem
Specify therapeutic objective
Choose treatment
Start Treatment
Educate the patient
Monitor Effectiveness
33
I Can PresCribE A Drug
Indication
Contraindications
Precautions
Cost/Compliance
Efficacy
Adverse effects
Dose/Duration/Direction
34
Legend Drugs
Contain "Federal law prohibits dispensing without a prescription" label
35
Schedule I
No Legal Use
Heroin, LSD, mescaline, Illegal Fentanyl
36
Schedule II
No Refills
Narcotics
Stimulants
Barbitals
37
Schedule III
Max 5 refills or 6 months
Narcotics mixed with nonnarcotics
Steroids, testosterone
38
Schedule IV
Benzodiazepines
39
Schedule V
Loperamide
Cough medications
40
Pharmacological ADR
Intrinsic; Predictable based on MOA
41
Idiosyncratic ADR
Unpredictable;
Can be Immune response, receptor mutation, drug-drug, biological system variation
42
Hapten Hypothesis
Drugs are LMW molecules that can bind to a protein causing an individuals metabolic pattern to generate reactive metabolites that elicit a reaction
43
Type I Immune ADR
IgE mediated; immediate hypersensitivity
44
Type II Immune ADR
Antibody dependent cytotoxicity
E.g. Drug induced thrombocytopenia
45
Type III Immune ADR
Immune complex hypersensitivity; IgG and IgM; Week or longer
Arthus reaction to Td Vaccine presents as severe vasculitis
46
Type IV ADR
Delayed type hypersensitivity; Not antibody mediated; Contact dermatitis
47
Rapid Reaction ADR
Immediately after med admin
48
First dose ADR
Reaction is unlikely to persist with repeated exposure
49
Early ADR
Develop early and generally do not require discontinuation
Slow drug titration can help
50
Intermediate ADR
Occur after repeated exposures
51
Late ADR
Prolonged exposure; generally predictable as known side effect of medications
52
Genetic Polymorphism
Differences of a DNA sequence found in at least 1% of the population
53
Genomics
Study of the complete set of genetic information present in an organism
54
Pharmacogenomics
Study of the genetic differences between people and the impact that has on the response to pharmaceuticals
55
Poor Metabolizers
Lack a working enzyme
56
Intermediate Metabolizers
Heterogenous for one working wild type allele and one variant allele
57
Extensive Metabolizers
Two standard functioning alleles
58
Ultrarapid Metabolizers
More than one functioning copy of a given enzyme
59
CYP2D6 and Codeine
CYP2D6 converts prodrug codeine into active metabolite morphine.
PM and UM may receive no benefit from codeine due to either not metabolizing it to active form or metabolizing too quickly
60
CYP2C9 and Warfarin
*2 and *3 are PM and resulted in reduced maintenance dosing requirements
61
Herbal Remedies for GI Disorders
Caraway
Carob
Psyllium
Senna
Triphala
62
Herbal Immune Boosters
Echinacea
Ginseng
63
Herbals For Men's Health
Ashwagandha
Gokshura
Hory Goat Weed
Maca
Saw Palmetto
Yohimbine
64
Herbals for Women's Heatlh
Cranberry
Dong Quai
Raspberry
Shatavari
65
Herbals for Mental Health
DHEA
Ginkgo
Kava
Melatonin
SAM-e
St John's Wort
Valerian
66
Herbals for Pain
Chondroitin
Feverfew
Turmeric
While Willow Bark
Wintergreen
67
Entheogens
Psychedelics
68
Direct Cost
Directly attributed to the disease in question
69
Indirect Cost
Costs associated with loss of function or premature death d/t disease
70
Intangible Cost
Value place on QOL
71
Cost-Minimization
Outcome is clinically identical
72
Cost-effectiveness
Different clinical outcome
Justifying of increased cost for incremental outcome improvements
73
Cost-benefit
Expressing clinical outcome in monetary units
74
Cost-Utility
Cost of treatment compared to outcome of QALY. Year at full health is 1 QALY
## Footnote
Quality adjusted life years
75
_\_\_\_ increases peristaltic action of the lower bowel. Can be overused and create dependency
Senna
76
_\_\_\_ used to support the immune system, brain function, and memory
Lion's Mane
77
_\_\_\_ Ayurvedic herb known to increase stamina, libido, and sexual function in men
Gokshura
78
_\_\_\_ is a Peruvian herb used to improve sexual behavior
Maca
79
_\_\_\_ is known to decrease symptoms of an enlarged prostate due to benign prostatic hyperplasia
Saw Palmetto
80
_\_\_\_ is generally believed to enhance the central sexual impulse by blocking the alpha-2 adrenoceptors in the locus coeruleus in the brain
Yohimbe
81
_\_\_\_ relieve symptoms of menstrual pain, premenstrual syndrome, infrequent periods, recovery from childbirth, menopause, and fatigue/low vitality
Dong Quai
82
Raspberry Leaf
Relieves morning sickness and uterine relaxant
83
_\_\_\_ is believed to stimulate prostaglandin synthesis and thereby cause vasodilation, increasing tissue perfusion and cerebral blood flow. It reduces platelet-activating factor and erythrocyte aggregation, it should not be taken with anticoagulants or antiplatelet medications.
Ginkgo
84
_\_\_\_ used to treat anxiety disorders, fatigue, and insomnia. Like benzodiazepines, _\_\_\_ has been used in the treatment of seizure activity and for sedation
Kava
85
Kava is used to treat _\_\_\_, _\_\_\_ , and _\_\_\_ . Like benzodiazepines, Kava has been used in the treatment of seizure activity and for sedation
Anxiety, fatigue, insomnia
86
_\_\_\_ has drug interactions with SSRIs, cyclosporins, BC pills, antidepressants, warfarin, oxycodone and digoxin
St John's Wort
87
_\_\_\_ is extracted from the cartilage of cow trachea and is often combined with glucosamine for the treatment of pain. May potentiate anticoagulants.
Chondroitin
88
_\_\_\_ is used most often to treat headache and migraines. It has also been used for toothache, joint pain, asthma, stomachache, menstrual problems, and threatening miscarriage. The assumed mechanism of action is the inhibition of _\_\_\_ release from platelets
Feverfew; Serotonin
89
Feverfew most common adverse reactions were mouth ulcerations, hypersensitivity, and a _\_\_\_ characterized by moderate to severe pain and joint and muscle stiffness
Withdrawal syndrome
90
_\_\_\_ is often combined with chondroitin for the treatment of OA and is thought to stimulate cartilage production and enhance rebuilding of damaged cartilage.
Glucosamine
91
_\_\_\_ promising effects have been observed in patients with various pro-inflammatory diseases. Reduced GI effects compared to _\_\_\_
Turmeric; NSAIDs
92
_\_\_\_ has been used for thousands of years as an anti-inflammatory, antipyretic, and analgesic. Has been associated with downregulation of inflammatory mediators
White Willow bark
93
_\_\_\_ thought effective in relieving pain from muscle strains, inflamed muscles, ligaments, and joints. Overgenerous application can result in _\_\_\_ poisoning from absorption into the bloodstream. Patients who are allergic to aspirin or who are taking _\_\_\_ should not use it.
Wintergreen Oil; salicylate; anticoagulants
94
_\_\_\_ can be used for indigestion, flatulence, constipation, and menstrual cramps
Caraway
95
_\_\_\_ is often used in combination with a hydrating solution such as Pedialyte to treat diarrhea
Carob Powder
96
_\_\_\_ has traditionally been used to treat GI disorders and restore bowel health. A 2007 study evaluated the inhibitory activities of _\_\_\_ against common bacterial isolates from patients with HIV and supported antibacterial activity by triphala against the isolates
Triphala
97
_\_\_\_ has been traditionally used as a general tonic and adaptogen, to improve one’s resistance to adverse conditions and enhance internal induction, phagocytosis, and natural killer, B, and T cells.
Ginseng
98
_\_\_ is used to strengthen the immune system, enhance stamina, and improve libido. _\_\_ found to have a GABA-mimetic effect and shown to promote formation of dendrites
Ashwagandha
99
_\_\_ improves fertility and increases sexual drive. Symptoms of tachyarrhythmias, aggressive behavior, and irritability have been noted in older patients
Horny Goat Weed
100
Evidence does support the benefit of _\_\_ use in patients with adrenal insufficiency; Patients with _\_\_-sensitive cancers should be discouraged from using _\_\_, as should pregnant and breastfeeding women.
DHEA; hormone; DHEA
101
_\_\_ is a chemical found naturally in the body produced from methionine, an amino acid found in foods. Used as antidepressant; some cases of mania have been reported in patients with bipolar disorder
SAME-e
102
_\_\_ seems to inhibit uptake and increase presynaptic release of GABA; however, it is not readily absorbed, is highly unstable, and quickly decomposes. Suggested for anxiety restlessness, and difficulty getting to sleep.
Valerian
