Exam 1 Flashcards
Preclinical Stage of Drug Development
Identification and animal testing
Clinical Stage of Drug Development
Establish safety and effectiveness in humans
Phase I Clinical Trials
Healthy patients; safe dose and pharmacokinetics
Phase II Clinical Trials
Treat disease in small number of patients
Phase III Clinical Trials
Compare new drug to standard therapy in large number of patients
Graded Drug Response
Can be measured continually up to max response; e.g. numerics like BP or HR
Quantal Drug Response
Effect is either present or absent
Drug Potency
How much drug is required to produce a desired effect
Drug Efficacy
Maximum effect a drug can produce
Drug Selectivity
Ratio of desired response dose to dose that produces undesired effects
Therapeutic Index
Ratio of lethal dose to therapeutic dose of drug
Therapeutic Index of:
2 compared to 10
TI of 2 means double the therapeutic dose is lethal where TI of 10 means ten times the therapeutic dose is lethal
Ion Channel Receptors
Increase flow of Ions altering electric potential.
Rapid Onset and short duration
ACh; GABA; Excitatory AA
GPCR
Work through secondary messengers (cAMP, CA++, IP, DAG)
Available GPCR decreases when stimulated
Risk for rebound when drugs are d/c
Transmembrane Receptors
Hormone binding; phosphorylates tyrosine
Insulin
Partial Agonist
Bind to receptor sites but don’t activate every receptor
Max response is lower than full agonist
Bioavailability
Percentage of the administered drug that is absorbed into central circulation
Ion Trapping
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
Protein Binding
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
P-glycoprotein
Efflux transporter
MRP1
Efflux transporter
BRCA1
Efflux transporter
Phase 1 Metabolism
Redox reaction
CYP450
Can inactivate or activate a drug
Phase 2 Metabolism
Conjugation Reactions
Generally inactivate a drug and make it more hydrophilic for easy excretion
Breakdown CYP3A4*1
3-Family
A-Subfamily
4-Individual Enzyme
*1-Mutation from wild type
First-Order Metabolism
Fixed fraction of a drug is metabolized per hour
Half-life metabolism
Half-Life Metabolism
1st-50%
2nd-75%
3rd-87.5%
4th-93.75%
Drugs are usually dosed at their half life time
Zero Order Metabolism
Constant amount of drug is metabolized each hour
Enzyme Induction
Increased expression of drug metabolizing enzymes that can speed up or decrease metabolism.
Glomerular Filtration
Small unprotein bound drug molecules are filtered into lumen of nephron
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
WHO’s 6 step model for drug prescribing
Define patient’s problem
Specify therapeutic objective
Choose treatment
Start Treatment
Educate the patient
Monitor Effectiveness
I Can PresCribE A Drug
Indication
Contraindications
Precautions
Cost/Compliance
Efficacy
Adverse effects
Dose/Duration/Direction
Legend Drugs
Contain “Federal law prohibits dispensing without a prescription” label
Schedule I
No Legal Use
Heroin, LSD, mescaline, Illegal Fentanyl
Schedule II
No Refills
Narcotics
Stimulants
Barbitals
Schedule III
Max 5 refills or 6 months
Narcotics mixed with nonnarcotics
Steroids, testosterone
Schedule IV
Benzodiazepines
Schedule V
Loperamide
Cough medications
Pharmacological ADR
Intrinsic; Predictable based on MOA
Idiosyncratic ADR
Unpredictable;
Can be Immune response, receptor mutation, drug-drug, biological system variation
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
Type I Immune ADR
IgE mediated; immediate hypersensitivity
Type II Immune ADR
Antibody dependent cytotoxicity
E.g. Drug induced thrombocytopenia
Type III Immune ADR
Immune complex hypersensitivity; IgG and IgM; Week or longer
Arthus reaction to Td Vaccine presents as severe vasculitis
Type IV ADR
Delayed type hypersensitivity; Not antibody mediated; Contact dermatitis
Rapid Reaction ADR
Immediately after med admin
First dose ADR
Reaction is unlikely to persist with repeated exposure
Early ADR
Develop early and generally do not require discontinuation
Slow drug titration can help
Intermediate ADR
Occur after repeated exposures
Late ADR
Prolonged exposure; generally predictable as known side effect of medications
Genetic Polymorphism
Differences of a DNA sequence found in at least 1% of the population
Genomics
Study of the complete set of genetic information present in an organism
Pharmacogenomics
Study of the genetic differences between people and the impact that has on the response to pharmaceuticals
Poor Metabolizers
Lack a working enzyme
Intermediate Metabolizers
Heterogenous for one working wild type allele and one variant allele
Extensive Metabolizers
Two standard functioning alleles
Ultrarapid Metabolizers
More than one functioning copy of a given enzyme
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
CYP2C9 and Warfarin
*2 and *3 are PM and resulted in reduced maintenance dosing requirements
Herbal Remedies for GI Disorders
Caraway
Carob
Psyllium
Senna
Triphala
Herbal Immune Boosters
Echinacea
Ginseng
Herbals For Men’s Health
Ashwagandha
Gokshura
Hory Goat Weed
Maca
Saw Palmetto
Yohimbine
Herbals for Women’s Heatlh
Cranberry
Dong Quai
Raspberry
Shatavari
Herbals for Mental Health
DHEA
Ginkgo
Kava
Melatonin
SAM-e
St John’s Wort
Valerian
Herbals for Pain
Chondroitin
Feverfew
Turmeric
While Willow Bark
Wintergreen
Entheogens
Psychedelics
Direct Cost
Directly attributed to the disease in question
Indirect Cost
Costs associated with loss of function or premature death d/t disease
Intangible Cost
Value place on QOL
Cost-Minimization
Outcome is clinically identical
Cost-effectiveness
Different clinical outcome
Justifying of increased cost for incremental outcome improvements
Cost-benefit
Expressing clinical outcome in monetary units
Cost-Utility
Cost of treatment compared to outcome of QALY. Year at full health is 1 QALY
Quality adjusted life years
____ increases peristaltic action of the lower bowel. Can be overused and create dependency
Senna
____ used to support the immune system, brain function, and memory
Lion’s Mane
____ Ayurvedic herb known to increase stamina, libido, and sexual function in men
Gokshura
____ is a Peruvian herb used to improve sexual behavior
Maca
____ is known to decrease symptoms of an enlarged prostate due to benign prostatic hyperplasia
Saw Palmetto
____ is generally believed to enhance the central sexual impulse by blocking the alpha-2 adrenoceptors in the locus coeruleus in the brain
Yohimbe
____ relieve symptoms of menstrual pain, premenstrual syndrome, infrequent periods, recovery from childbirth, menopause, and fatigue/low vitality
Dong Quai
Raspberry Leaf
Relieves morning sickness and uterine relaxant
____ 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
____ used to treat anxiety disorders, fatigue, and insomnia. Like benzodiazepines, ____ has been used in the treatment of seizure activity and for sedation
Kava
Kava is used to treat ____, ____ , and ____ . Like benzodiazepines, Kava has been used in the treatment of seizure activity and for sedation
Anxiety, fatigue, insomnia
____ has drug interactions with SSRIs, cyclosporins, BC pills, antidepressants, warfarin, oxycodone and digoxin
St John’s Wort
____ is extracted from the cartilage of cow trachea and is often combined with glucosamine for the treatment of pain. May potentiate anticoagulants.
Chondroitin
____ 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
Feverfew most common adverse reactions were mouth ulcerations, hypersensitivity, and a ____ characterized by moderate to severe pain and joint and muscle stiffness
Withdrawal syndrome
____ is often combined with chondroitin for the treatment of OA and is thought to stimulate cartilage production and enhance rebuilding of damaged cartilage.
Glucosamine
____ promising effects have been observed in patients with various pro-inflammatory diseases. Reduced GI effects compared to ____
Turmeric; NSAIDs
____ 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
____ 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
____ can be used for indigestion, flatulence, constipation, and menstrual cramps
Caraway
____ is often used in combination with a hydrating solution such as Pedialyte to treat diarrhea
Carob Powder
____ 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
____ 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
___ 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
___ improves fertility and increases sexual drive. Symptoms of tachyarrhythmias, aggressive behavior, and irritability have been noted in older patients
Horny Goat Weed
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
___ 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
___ 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
