Exam Two Flashcards

Pharmacology

scientific study of drug actions and their effects on living organisms

Pharmacokinetics

movement of drugs through the body

the study of what the body does to drugs

how drugs are handled by the body

Pharmacodynamics

study of what the drug does to the body

Factors that Influence Pharmacokinetics

route of administration

absorption

distribution

metabolism

excretion/elimiation

Distribution

passage of drug from bloodstream into organs

Individual Differences that Affect Pharmacokinetics

gender

race/ethnicity/genetics

age

body weight/size/fat content/health/prior experience

Absorption

movement of a drug from the site of administration (external world) into the blood stream

Passive Diffusion

molecules passing through a semipermeable membrane from high concentration to low concentration

Oral Administration

drug is absorbed through the gastrointestinal system

Per Os (P.O.)

Latin for by mouth

seen on doctor’s prescription for oral administration

Small Intestines

where most drugs are absorbed into the blood stream in the G.I. system

lots of surface area and lots of places for drugs to be absorbed

drugs stay in here for a long time

pH in neutral and drugs become unionized

Absorption Rate of Orally Administered Drugs

20-30 minutes to reach brain

75% of lipid soluble psychoactive drugs absorbed in 1-3 hours

total absorption in 6-8 hours

Reasons to Take Drugs With or Without Food

food slows absorption and gastric emptying

buffers G.I. system from drugs that irritate it

some foods deactivate some drugs

some foods influence rate by changing G.I. activity

Advantages of Oral Administration

relatively safe

relatively slow absorption

easy

self-administered

painless

ecominical

Disadvantages of Oral Administration

relatively slow

not soluble and stable in stomach

cannot pass from G.I. track into circulatory system

bad taste, vomiting, stomach distress

highly variable and unpredictable absorption

cannot use in certain situations

First Pass Metabolism

orally administered drugs are metabolized by G.I. and liver enzymes before they reach their target

other routes of administration bypass this

reduces bioavailability

Buspirone

antianxiety drug that has few drug interactions and side effects but only about 5% gets to the brain because an enzyme breaks it down

taking it with grapefruit juice can inhibit the enzyme and allow more to get to the brain

evidence suggests higher effectiveness but also more side effects

Rectal Administration

form of mucous membrane administration

suppository form

used when a person is vomiting, unconscious, unable to swallow, or is an infant

absorption is irregular, unpredictable, and incomplete

relatively slow absorption 

Eye and Ear Administration

a form of mucous membrane administration

typically used for local effects

Administration by Inhalation

absorbed through mucous membranes in lungs

quickest onset and fastest to get drug out (10 sec faster than IV)

Reasons Absorption by Inhalation is so Fast

lungs have large surface area, lots of blood flow, and are specialized for exchange of gas

drug also has less physical space to cover

Forms of Inhalation

gaseous vapor/huffing

smoking

powder inhalation

Advantages of Inhalation

rapid onset and offset

good control of how much is in the body and when

Disadvantages of Inhalation

rapid onset and offset can make it trickier to control

damage to lungs, particularly when smoking

general problems associated with smoking

gas vapors may not be mixed with enough oxygen

smoking generally not a prescribed method

Electronic Cigarettes

battery operated devices designed to deliver nicotine with flavorings and other chemicals to users in vapor instead of smoke

other ingredients not well regulated

usually does not work as a smoking cessation therapy

Sublingual Adminitration

a way of administering through the mucus membranes of the mouth

administered under the tongue

Buccal Administration

a way of administering through the mucus membranes of mouth

administered in the cheek

Intranasal Administration/Snorting

administering drugs through mucus lining of nose

avoids G.I. track and may bypass blood brain barrier

Transdermal/Topical Administration

across the skin in the form of creams or patches

especially for lipid soluble drugs

controlled, sustained delivery at a programmed rate

avoids first pass metabolism

potential for skin irritation

Sites for Injection of Drugs

veins

muscles

under skin

brain (rare)

Intravenous Injection (IV)

injection in veins

Acute Injection

quick and at once

rush for recreational users

Slow Injection

IV bag used to slowly administer drug

Advantages of Intravenous Injection

can be speedy in emergencies or slow by IV bag

precise dosage and timing

dilute and administer large volumes of drugs

Disadvantages of Intravenous Injection

little ability to recall in instances of overdose or allergic reaction (speed)

not suitable for oily substances or insoluble substances (blood clots, embolisms)

insoluble filler materials in recreational drugs can cause health problems

requires sterile techniques to reduce risk of infectious diseases (hepatitis, HIV)

expensive (IV bags, hospital)

Intramuscular Injection (IM)

injection into muscle

rate depends on blood flow to muscles

slower absorption than IV but faster than oral (10-30 min)

even absorption over time

can be irritating and cause discomfort

can be dissolved in aqueous or oily solution

Depot Injections

intramuscular injection of drug dissolved in oily substance

slow onset and prolonged action

compliance, ease, not easily reversible

Subcutaneous Administration (SC, Sub-Q)

administered under the skin

can be injected or implanted

Subcutaneous Injection

injected under the skin

also known as skin popping

absorption is slow and steady

many drugs irritate skin

not good for large volumes

Subcutaneous Implants

implanted under the skin

can last a long time

seen with birth control

Other Injection Methods

spinally/epidural injection

intracranial injection

intraperitoneal injection

Factors that Influence a Drug’s Ability to Cross Membranes

solubility (more lipid soluble is more likely to cross)

ionization (not ionized is more likely to cross)

size (small molecules more likely to cross)

Ionization

molecules becoming charged, especially when dissolved in a water medium

depends on pH and pKa

Curare

poison used in Central and South America vis dart or arrows to paralyze and kill game

blocks acetylcholine receptors at neuromuscular junction

it is safe to eat the meat because it stays highly ionized in the GI tract and does not enter the blood, making it safe to ingest

Blood Brain Barrier (BBB)

capillaries in brain do not have gaps and astrocytes act as a second layer

allows small lipid soluble molecules to pass and some others by active transport but keeps harmful substances out

important because the brain has a weaker immune system than the rest of the body in order to protect neurons

Circumventricular Organs

places where the blood brain barrier is weakened so the brain has an idea of what is going on in the blood

important for things like hormone sensing and vomiting reflex

Neurotrophic Factors

important for the developing brain to help neurons grow and make connections

cannot cross the blood brain barrier, making it difficult to use them for therapies

Glymphatic System

lymphatic vessels in central nervous system that remove potentially toxic protein waste and biological debris

system works better at night

Sundowner’s Syndrome

people with dementia lose quality of function in the evening

may be because of protein buildup during the day that is then cleared out at night

Placental Barrier

barrier between blood circulation of pregnant mother and her fetus

differ in drug sensitivity

will cross if the substance can cross the blood brain barrier

fetus relies on mother to break down drugs

Teratogens

agents that induce developmental abnormalities in a fetus

effect can depend on drug, time of exposure, and extent of exposure

Where Most Drugs Are Found

heart, brain, kidneys, liver

where there is a lot of blood flow and where drugs are metabolized and excreted from

Depot Binding

binding of a drug to inactive sites

common places are plasma proteins (blood), muscles, and fat

the extent of this binding can effect the drug and its effects (magnitude and duration)

variability can be a source of individual variability in drug response

Depot Binding Influences

initial effect at site of action (speed and magnitude)

continued effects after drug is redistributed

availability to metabolize

Termination of Action

generally a two step process involving metabolism and excretion

some drugs will get excreted without getting metabolized

Metabolism

conversion of fat soluble drugs into more water soluble and larger molecules

predominantly occurs in the liver via liver enzymes

there are some enzymes in the GI tract and other areas

less capable of being reabsorbed by the kidneys

Advantages of Drugs Excreted Unchanged

good for those with liver disease, fast metabolizers, or drug has heavily indiced enzymes

Metabolite

byproduct of metabolism

Inactive Metabolite

byproduct of metabolism that does not do anything

Active Metabolite

byproduct of metabolism that is active

can be more active, less active, or have different effects

in some case, this has been turned into a drug because of different kinetics

Consequences of Active Metabolites

longer lasting effects

potentially causes unwanted effects (less likely)

Pro Drug

drug administered in an inactive or significantly less active form and then biotransformed into an active metabolite

may circumvent GI problems and improve bioavailability

examples: L-dopa, codeine, lisdexamfetamine

Cytochrome P450 Enzyme Family

all-purpose family of metabolizing enzymes (lack specificity)

involved in the metabolism of food and drugs

three subfamilies are involved in 70-80% of drug metabolism

Genetic Polymorphism

multiple enzyme (gene) forms (alleles)

Factors Influencing Metabolism

genetics

age

gender/sex

physiological factors (enzyme induction and inhibition)

drug competition

Enzyme Induction

enzymes become more efficient or greater in number when the drug they metabolize is present

contributes to tolerance

Cross Tolerance

tolerance developing in one drug produces tolerance in another similar drug

less sensitive to effects of drug

seen with heroine and morphine

Enzyme Inhibition

drug will cause enzymes to work poorly or decrease in number

more sensitive to effects of drug

common with SSRIs

Drug Competition

simultaneous administration of drugs metabolized by a limited number of enzymes

can lead to dangerous drug interactions (alcohol and barbiturates) 

Routes of Excretion

most common: renal (kidneys) via urine

others: lungs, skin, bile, breast milk

Excretion Half-Life (t½)

time for plasma level of a drug to fall by 50%

First-Order Kinetics

drug clearance most often occurs exponentially

more drug, more rapid clearance

initial rapid fall due to redistribution

slower prolonged drop due to metabolism

Zero-Order Kinetics

constant rate regardless of concentration

example: alcohol

Steady-State Concentration

level of drug achieved in the blood with repeated regular interval dosing

achieved when the amount administered per unit time equals the amount eliminated per unit time

about 5-6x a drug’s elimination half-life

Goals/Reasons for Therapeutic Blood Monitoring

is patient taking the drug as prescribed

avoid toxicity

enhance therapeutic response

test for atypical metabolizers

save money