RXRS 200 Midterm 1

Pharmacology

the study of drugs and their interactions with living systems

Pharmacy

the science of the preparation of drugs

therapeutics

the treatment of disease with drugs and by other means

drug

A chemical substance that is taken to cause changes in a person's body or behavior

Sources of drugs

plants, animals, synthetic chemicals, genetically engineered chemicals, minerals

The Yellow Emperors' Inner Classic

Ancient Chinese document and discussion of yin-yang and acupuncture; the first Chinese manual on pharmacology

Ebers Papyrus

An ancient document dating to 1550 BCE that contains around 700 formulae and remedies that demonstrate Egypt's advanced understanding of anatomy and pathology.

Al-Hawi

20 volume medical book written by the ancient Iranian physician, Al-Razi

the first antibiotic

discovered by Alexandrias Fleming in 1928 when he noticed that the fungus, penicillium, killed disease causing bacteria

Harvoni (ledipasvir/sofosbuvir)

first combination pill approved to treat Hepatitis C

Types of drug interactions

-Drug-Drug
-Drug-Nutrition
-Drug-Disease

Polymedicine

the use of many drugs to treat multiple health problems for older adults

curative

cures or treats a problem

prophylactic

prevents a problem

diagnostic

helps diagnose a disease or condition

palliative

relieving or soothing the symptoms of a disease or disorder without effecting a cure

replacement

replaces a missing substance

destructive

destroys tumors and/or microbes

How are drugs named?

<Brand Name> (<Generic Name>)

chemical name

Precise description of a drug's chemical composition and molecular structure.

generic name

a shorter name that is derived from the chemical name which is more commonly used

brand name

the name that goes along with the generic name; protects the name of the drug for advertising purposes

What are the variables of drugs?

- physical nature (state of matter)
- size
-reactivity
-drug-receptor bonds, shape

capsule

powdered or solid medication enclosed in a dissolvable cylindrical gelatin shell

tablet

solid medication particles bound into a shape designed to dissolve or be swallowed

powder

small particles of medication designed to be dissolved or mixed into a solution or liquid

drops

Sterile solution that contains medication intended to be delivered directly into the area to be treated

skin preparation

Gel, ointment, or paste substance designed to permit transdermal absorption

suppository

a waxlike medication that dissolves in the rectum or other body cavity

liquid (drug form)

medication dissolved or suspended in liquid intended for oral consumption

inhaler/spray

Medication in gas or fine liquid form intended for inhalation and absorption through the lungs, airway, or oral tissues

What is the drug cycle?

- Administration
- Ingestion
- Absorption
- Distribution
- Metabolism
- Excretion

How can drugs be administered?

- Enterally
- Parenterally
- Topically

enteral drug administration

The delivery of any medication that is absorbed through the gastrointestinal tract

parenteral drug administration

drug administered by means other than through the GI tract, such as infusion or injection

topical drug administration

applied directly to the site of desired effect

pharmacokinetics

what the body does to the drug

Absorption

process by which a substance moves into the bloodstream from the site where it was administered

distribution

delivery of a drug to the appropriate site after the drug has been absorbed into the bloodstream

metabolism

the drug is chemically transformed

excretion

the drugs and their transformed products are removed and do not build up in the body

pharmacodynamics

what the drug does to the body

mechanism of action

how a drug produces its physiological effect in the body

therapeutic effect

The desired or intended effect of a particular medication

side effect

an unwanted physical or mental effect caused by a drug when administered at the normal dose

adverse effect

Unintended, undesirable, often unpredictable effect; can cause severe harm or death

toxic effect

may develop after prolonged intake or accumulation of drug in the blood due to impaired metabolism or excretion

drug receptors

any portion of a tissue or cell which a drug can bind and initiate its effects; proteins that are inside or on the surface of a cell that mediate the drug activity

ligand-gated ion channels

membrane ion channels operated by the binding of specific molecules to channel proteins

Enzyme-linked receptors

participate in cell signaling through extracellular ligand binding and initiation of second messenger cascades

intracellular receptors

drug receptors located inside the cell rather than on its cell membrane

dose

a quantity of a medicine or drug taken or recommended to be taken at a particular time.

concentration

amount of a drug in a given volume of blood plasma, measured as the number of micrograms per milliliter

EC50

Concentration of the drug that produces 50% of maximal effect

ED50

The drug dose that produces 50% of a maximal effect

TD50

the dose producing a toxic effect in 50% of the population

LD50

the dose producing a lethal effect in 50% of the population

specificity

when a drug is able to bind with a specific cell site, either on its cell membrane or within the cell

potency

describes the amount of a drug required for a given response; the more potent a drug is, the lower the ED50

efficacy

extent to which a drug can produce a response when all available receptors or binding sites are occupied (the Emax on the dose-response curve)

Agonist

a molecule that, by binding to a receptor site, stimulates a response

Antagonist

a molecule that, by binding to a receptor site, inhibits or blocks a response

full agonist

Ability of a drug to produce 100% of the maximum response regardless of the potency

partial agonist

results in less than a maximal response even when the drug occupies all of the receptors

reversible competitive antagonism

inhibition that can be overcome by increasing the concentration of the agonist; rightward shift of the cone-effect curve with no effect to the Emax or EC50

Irreversible competitive antagonism

competition between agonist and antagonist for the same receptors, but stronger binding forces prevent the effect of the antagonist being fully reversed, even at high agonist concentrations; right shift of the cons-effect curve, generally displaying a decreased slop and Emax

noncompetitive antagonist

inhibits agonist activity by blocking the function of the receptor at a different site

signal transduction

A series of molecular changes that converts a signal on a target cell's surface to a specific response inside the cell

What makes up a signal transduction pathway?

- proteins
- lipids
- small molecules
- ions

endocrine signaling

Specialized cells release hormone molecules into vessels of the circulatory system, by which they travel to target cells in other parts of the body

paracrine signaling

a cell releases hormones that will activate cell-surface receptors on a cell nearby

autocrine signaling

cell secretes a hormone that will activate receptors on that same cell

What are the stages of cell signaling?

1. Reception
2. Transduction
3. Response

reception

The target cell's detection of a signal molecule coming from outside the cell

transduction

receptor confirmation change initiates the process of transduction

response

the signal triggers a specific cellular response

signal amplification

increasing a signal so that minimal receptor occupation by small amounts of neurotransmitters in the synapse produces significant cellular response

types of signals

- light
- mechanical stress
- gases
- small molecules
- amino acids
- lipids
- steroids
- proteins

first messengers

the ligand is the first messenger; can be antagonist or agonist

second messenger

molecules that transmit signals received at receptors

GPCRs

G-protein coupled receptors
- Can activate enzymes
- regulators of nerve activity in the CNS
- have 7 transmembrane domains
- haloperidol, atropine, propanolol, dobutamine

enzyme-linked receptor

- ligand regulated transmembrane enzymes
- polypeptides cross the plasma membrane
- consists of an extracellular hormone binding domain and a cytoplasmic enzyme domain
- the enzymatic domain may be tyrosine, a serine kinase, or a guanylyl cyclase

intracellular receptors

- receptors located inside the cell rather than on its cell membrane
- the effects of these agents can persist for hours or days after the agonist is no longer present
- typically found in the cytosol that binds onto biological compounds
- binds to promoters to stimulate transcription of genes, thus termed "gene active"
- bad because the response may take 30 mins to hours, the time required for protein synthesis
- includes: estrogen binding receptors, translocation to nucleus, estrogen response elements binding

ion channel receptors

Channel proteins that allow ions to enter or leave a cell
- transmit their signals by increasing the flow of relevant ions and altering the electrical potential across the membrane
- time between binding and response can be measured in milliseconds
- examples of transmitters: GABA, Glutamate, Achetylcholine

drug affinity

strength of binding between a drug and its receptor

desensitization

repeated exposure to the same concentration of a drug leads to the dose being ineffective

Cmax

Maximum plasma concentration of a drug

T1/2

half-life; time taken for the concentration to decrease by 50%

Tmax

time of peak plasma concentration on a measuring curve

area under the curve (AUC)

a measure of drug concentration in the blood; measures the total drug exposure

routes of drug delivery

- Parenteral (IV, SM)
- Transdermal
- Oral
- Rectal
- Topical

infusion

starts at a low concentration, which gradually increases over time until elimination=input

bolus injection

A single dose of medication administered all at one time; Cmax reached at time 0

What happens as the rate of absorption slows down?

- Tmax occurs later
- Cmax is lower
- Duration of the drug in the body is longer

Therapeutic Drug Monitoring (TDM)

determination of plasma concentrations to optimize a patient's drug therapy

How are drugs transported?

- Passive diffusion
- facilitated diffusion (carrier mediated, no energy input)
- Active transport (carrier mediated, with energy input)

factors affecting oral absorption

1. disintegration/dissolution of dosage form
2. food
3. blood flow in GI
4. GI motility/emptying
5. drug stability vs. enzymes/pH

What determines drug distribution?

- Physiological volumes of body tissues and fluids
- binding to tissue components
- binding to blood components

Vd

volume of fluid required to contain the total amount of drug in the body at the same concentration as that in the plasma; = amount of drug in body/plasma concentration

What kind of plasma proteins can drugs bind to?

- Albumin
- Alpha-I acid glycoprotein
- Lipoproteins
- Globulins