Basic Concepts Flashcards
What is the difference between chemical and brand names of drugs?
- Chemical name refers to compound’s structure
- Brand name is the proprietary name
What is a generic drug?
- Non-proprietary drug name that may be less well recognized
What type of medication does not require a prescription to be purchased by the consumer?
Over the Counter (OTC)
Why may a drug be sold OTC?
It is deemed safe without direct medical supervision
Can OTC drugs be involved in significant drug interactions?
Yes.
Whose authorization is required for a prescription medication?
Licensed Health Care Provider (HCP)
What is the purpose of drug scheduling?
- Organize drugs on their potential for abuse
- Used for prosecution
What level of government sets the standards for drug scheduling?
- Federal
What schedule of drug has a currently accepted medical use in the US, but has a high potential for abuse that may lead to severe psychological or physical dependence?
Schedule II
What schedule of drug has a low potential for abuse, but may be sold in limited amounts without a prescription at the discretion of a pharmacist?
Schedule V
What schedules of drugs have a medically accepted use?
Schedules II - V
What schedule of drugs may lead to a moderate or low physical dependence or high psychological dependence if abused?
Schedule III.
What schedule of drugs may lead to a limited physical or psychological dependence if abused>
Schedule IV.
What are 8 sources of drug information?
- E-facts and comparisons
- Clinical Pharamacology
- Lexi-comp
- Micromedex
- Product package insert
- National guidelines
- Primary literature
- www.dailymed.nlm.nih.gov
- URI library
What are 4 sources of new drug material?
- Plants/ natural products
- Synthesized in lab
- Human pooled blood products
- Animal products
What was the original birth control drug synthesized from?
- Conjugated estrogen from horse urine
What is the 7 step process of new drug testing?
- Compound discovery and “bench” testing/ evaluation
- Animal phase of testing
- Human phase I
- Human phase II
- Human phase III
- FDA approval with patent
- Human phase IV/ post marketing phase
Why are small animals used to test drugs?
- Save space and money
- Enough similarity with people that results are applicable
- Condense lifespan
- Genetically malleable
- Can look at different models
What is being examined during each stage of human phase drug testing?
I: Dosing safety
II: Efficacy
III: Clinical trials, large double blind/ single blind studies; (larger versions of 1 and 2
IV: Monitoring markets for adverse drug effects on a more diverse population
Who mandates the length of each stage of drug testing?
The FDA
Why do more adverse drug effects present themselves once human phase IV drug testing occurs?
- Larger, and more diverse population
- Prescription is more liberal, and/ or off-labeling
What is the major difference between all 4 stages of human phase drug testing?
- Sample size; form very small to very large
What is the pharmaceutical portion of drug administration?
- Disintegration of the “hard” drug to pharmaceutical form
What is pharmacokinetics? What are the 4 components?
- How the body acts on the drug
- Absorption
- Distribution
- Metabolism
- Excretion
What is pharmacodynamics?
- Biochemical and physiological effects of drugs and their mechanism of action
What are some preparations of drugs?
- Aqueous
- Alcohol
- Solid
- Powder
- Tablet
- Lozenge
- Capsule
- Delayed-release
- Suppositories
- etc…
What are the 2 general routes of drug administration?
- Parenteral
- Enteral
What is a parenteral drug administration? What are some examples?
- By any route that does not involve the GI tract
- Injections
- Transdermal patches
- IV
- Sprays/ inhalers
- Cream
- Suppository
What is an enteral drug administration? What are some examples?
- Drug travels directly to the gut by the small or large intestines
- Oral/ PO (Per os)
What is ADME?
- Absorption
- Distribution
- Metabolism
- Excretion
What is drug absorption?
- Entrance of drug into blood stream
What 2 factors affect the speed of drug absorption?
- Properties of drug
- Properties of environment
What are the 5 drug properties that affect absorption?
- Dosage form
- Drug water solubility
- Drug lipid solubility
- Drug particle size
- Drug concentration
What body structure acts as barriers to drug absorption?
- Membranes
What is the common cell membrane barrier? What is it impermeable to?
- Phospholipid bilayer
- Impermeable to water
What types of particles easily cross the phospholipid bilayer, and what types of particles cannot pass through the membrane?
- Small, uncharged particles pass through
- Large uncharged and/or small charged ions cannot pass through
What properties of the phospholipid bilayer make it impermeable to water or other charged particles?
- Hydrophilic heads
- Hydrophobic tails
How does the extracellular enviornment affect absorption of ASA?
- Basic environments ionize ASA making it difficult to pass through the plasma membrane
What is bioavailability?
- The percentage of the administered dose that is absorbed into systemic circulation
What are 3 factors that can influence bioavailability?
- Administration
- Target environment/ tissue
- Properties of a drug
What is drug distribution?
- Drug distribution to the organs and tissues of the body after it has been absorbed into the blood stream
What are the 4 main factors affecting drug distribution?
- Physical properties of the drug
- Lipid solubility
- Affinity/ receptors
- Drug protein complex
What are 4 special anatomical barriers to drug distribution?
- Blood brain barrier
- Plasma protein binding
- Blood flow
- Fetal-placental barrier
What is the blood brain barrier?
- An additional lipid barrier that protects the brain by restricting the passage of electrolytes and similar water soluble substances
What property must a drug possess to pass through the blood brain barrier?
- Lipid solubility
What type of cells make up the lipid coating of the blood brain barrier?
Glial
Drugs possessing what 3 properties have the best chance of passing the blood brain barrier?
- Small
- Unionized
- Lipophyllic
What property of the blood brain barrier prevents inionized substances from passing through?
- Tight junctions
How can the blood brain barrier become damaged?
- Immature children have a leaky or under-developed barrier
- Sepsis/ septic shock/ burn related encephalopathy
- TBI
What type of protein produces a large amount of protein binding?
Albumin
What do plasma proteins normally bind to?
- Hormones and vitamins
What is the effect of plasma protein binding in drugs?
- Bound drugs are not active pharmacologically
What 4 organs receive the largest amount of blood? What is the effect of this?
- Liver
- Kidneys
- Heart
- Brain
- Exposed to the largest amounts of drugs
What is the Volume of Distribution?
- The theroretical volume that the toatl amount of administered drug would have to occupy if it were uniformly distributed to provide the same concentration as it presently has in blood plasma
- A greater Vd means it is more diluted in the blood plasma
- Size of the compartment necessary to account for the total amount of drug in the body if it were present throughout the same concentration found in plasma
What is the formula for Volume of Distribution (Vd)?
Amount of drug administered/ plasma concentration of drug
What is the goal of drug metabolism?
- Convert the drug to a form that is easily excreted
- Which is usually ionized, and wter soluble
What organ tends to process drugs, and is the most critical organ of metabolism?
The liver
Which organ tends to excrete drugs?
The kidney
What is another function of drug metabolism besides excretion?
- Activate the drug
What is biotransformation?
- Chemical alteration of drugs and foreign compounds in the body
What enzyme family is plentiful in the liver?
- CYP450
What are some other organs besides the liver that metabolize drugs?
- Kidneys
- Lung
- GI tract
- Skin
What are 3 examples of biochemical reactions?
- Hydrolysis
- Oxidation
- REduction
What is the main function of the DMMS?
- Take lipid soluble drugs and prepare them for excretion via the renal system
What is a phase 1 reaction?
- Hepatic/ liver reaction; Liver creates the enzyme that clears the compound
What is a phase 2 reaction?
- Conjugation reactions; add another element so that the renal system can clear it faster
What is the first-pass effect?
- Drugs pass through the liver before they are distributed to the body, and are many drugs are inactivated by the liver reducing the amount of active drug that reaches general circulation
What are 2 methods of bypassing the first-pass effect?
- Consider a parenteral delivery system
- Administer a higher dose
What is enzyme induction/ drug disposition?
- If a drug is used repetitively, it may increase enzyme activity leading to a faster metabolism of the drug, and a shorter duration of drug action
What is enzyme inhibition?
- Some drugs can inhibit enzymes, slowing the metabolism of other drugs metabolized by the enzyme system, increasing duration and intensity of drug effects.
Besides drugs, what else can cause enzyme inhibition?
Food
Which type of enzyme effect is more dangerous, induction or inhibition?
Inhibition
Which enzyme effect optimizes the enzyme system?
Enzyme induction/ drug disposition
How can an enzyme system be optimized?
- pH or temperature increase
What are the 3 common pathways of drug excretion?
- Kidney/ renal
- Liver/ hepatic
- Lungs/ pulmonary
What is clearance?
- The ability of the body to remove drug from the blood or plasma
How is clearance measured in terms of units?
- Volume per unit time (mL/min)
What other factor besides clearance affects the amount of drug removed?
- Plasma concentration
What is entero-hepatic recirculation?
- Drug secreted into bile (may go into feces OR drug may be reabsorbed)
What type of drug can remain in circulation for a long time after it is absorbed? Why?
- Highly lipphyllic drugs may remain in circulation due to entero-hepatic recirculation
During what phases of ADME do plasma levels increase?
- During absorption and distribution
During what phases of ADME do plasma levels fall?
- During Metabolism and Excretion
What is the minimum effect concentration?
- The level of the drug in the blood at which it is effective
What is the therapeutic range?
- The range in which the drug will be effective
What is the toxic concentration of a drug?
- The level of the drug in the blood at which it will have harmful effects
What is the plasma half-life of a drug?
- The time required for the plasma concentraiton of a given drug to fall to half of its original level
Upon what 2 factors does half-life depend?
- Clearance and Vd
What is a loading dose?
- The dose required to get the blood plasma level of the drug into therapeutic range
What is a maintenance dose?
Retaining a drug in its therapeutic range
What is a median effective dose?
- Dose required to produce a specific therapeutic response in 50 % of a group of patients
What is a median lethal dose?
- Dose that causes death in 50 % of a group of animals
What is the formula for the therapeutic index?
median lethal dose/ median effective dose
Should a therapeutic index be high or low for safety’s sake?
High to separate lethal dose from effective dose
What is the abbreviation for median effective dose?
ED50
What is the abbreviation for median lethal dose?
LD50
What is the dose response relationship?
- A given response for a given dose
What is potency in terms of dose response?
- How strong is the drug
- Greater effect at lower doses
What is efficacy in terms of dose response?
- How well does it work, and what is its effect
- Increased maximum response
What are receptors?
- Specific molecules that interact with drugs and control the action of cells and tissues
What is an agonist?
- A drug with affinity (attraction to receptors) and efficacy (change in the function of the cell)
What is an antagonist?
- A drug with affinity, but no efficacy.
Often acts as a blocker
What is another name for an agonist drug?
- Mimic-er
What is competetive inhibition?
- Drug occupies activation site, and blocks cell/ reaction from happening
What are the 2 types of competitive antagonists?
- Reversible
- Irreversible
What is a non-competitive antagonist?
- Binds elsewhere onto the same receptor blocking biologic signalling
Are non-competitive antagonists reversible?
Sometimes
What are examples of personal factors that affect variation in drug response?
- Age
- Weight
- Gender
- Percent body fat
- Genetics
- Emotional state
- Placebo effect
- Presence of disease
- Patient compliance
Which is the most common reason for variation in drug response?
- Patient compliance
What is a teratogen?
- Drugs taken by mother that are harmful to the developing fetus
Is the placenta a drug barrier?
No
What is it called when a drug is passed from mother to child through breast milk?
- Passive exposure
Which trimesters of pregnancy are most affected by teratogens?
1st and 2nd
What characteristics infants and children differ from adults, affecting ADME?
- Thinner skin
- Less skeletal muscle
- High percentage body water
- Lower body fat
- High percentage of unbound drug due to reduced plasma proteins
What are 4 physiologic changes due to aging?
- Cardic Output decreases
- Blood blow decreases secondary to CO decrease
- Reduced gastric acid secretion, motility and intestinal absorption
- Lean body mass and total body water decrease with age while percent body fat increases
How is the rate of drug metabolism affected with aging?
- Decreases
Which enzyme system is most affected by age?
- Mixed-function oxidase system
How is renal blood flow affected by aging?
- Decreases
How is bioavailability of oral drugs affected by aging?
- Increases
What is the overall effect of aging on drug effects?
- Increased duration
- Decreased metabolism
What are 4 other special populations?
- Patients taking numerous medications
- Acute or chronic illness
- Patients in drug/ alcohol recovery
- Known or suspected alterations in drug metabolism (genetic or otherwise)
