actions of the BODY on the DRUG

processes that determine the concentration of drugs in the body fluids and tissues over time

Drug absorption

distribution

biotransforamtion

excretion

how drug absorbed from the site of administration or indirectly into plasma

(injection, skin, oral)

distribute into the interstitial and intracellular fluids

(throughout the body to the target)

Actions of the DRUG on the BODY

Biochemical mechanisms:

receptors and signal transduction

Dose-response relationships:

Potency and Efficacy

receptors

signal transduction

Potency (concentration-related)

Efficacy (response-related)

application of drugs in Prevention, Cure, Alleviation, Treatment, or Diagnosis of disease

business end of pham

Treatment of diseases caused by parasitic or invading organisms

only situation in which give drug to kill off and destroy an organism or cancer

Chemical name

generic- used for class

Non-proprietary

official

proprietary

brand

Why aren't proprietary (brand/trade) names used in class?

Tablet- packed 

Capsule- usually in gelatin caplet that dissolves usually faster than a thick compressed tablet

 different rates of disintegration and dissolution may cause differences in bioavalability of drugs from different tablet formulations

enteric coating- coating to protect the stomach from the drug until it passes through or to keep the drug from being dissolved until it reaches the desired location

Sustained relaese (SR) or extended release (XR):

Controlled diffusion

controlled dissolution

osmotic pressure

the most common liquid pharmaceutical preparations

faster absorption than a tablet or capsule and is directly absorbed

oral

parenteral- other than enteral ( injection, topical, drops in eye, etc)

elixirs- contain alcohol used to dissolve the drug

syrups- contain sugar to make the drug more palatable

sterile solutions

skin patches- (nicotine, hormones) drug must be available for absorption through the skin parentral

aerosols- topical (sunscreen) inhaled (asthma)

ointments, creams, lotions- more messy than skin patch

suppositories- rectal

Risk/Benefit ratio

what are the benefits versus what are the risks

There are 4 phases

1) test on young normal males

2) test on diseased people well into disease state

3) if drug effective test again to make sure then released by FDA

4) post-marketing given out by docs and then company collects adverse rxn information to make sure drug still safe or pulled off the market

Dietary supplement health and education act of 1994

Not intended for the diagnosis, prevention, treatment, or cure of any disease.

no regulations or studies must be done before the drug is put on the market

each patient is differnt

therapy may be initiated without all the data

patient status may change

patient on multiple drugs

When a drug is administered where must it be moved into for passage throughout the body?

oral

sublingual- under the tongue

buccal- between cheeks and gums

rectal

intravascular- IV

intramuscular- IM

subcutaneous- SC

inhalation

inranasal

intrathecal- into the brain

intraventricular- into the ventricles of the brain

topical

transdermal

oral ingestion

interaction with food and gastric acid

food slows gastric emptying (less absorption)

intestinal transit- food, illness, blunt trauma

metabolism by the liver(first-pass) or gut enzymes/flora

physico-chemical properties of drug perparation

stomach v. duodenum- increased surface area and absorption in small intestine

can't use in comatose, sedated, or nauseous patients

bypasses GI tract and first-pass liver metabolism

requires low doses 

requires good solubility in water and lipid

as a suppository

drugs that are poorly absorbed in he GI

for unconscious or uncooperative patients

more rapid onset

absorption instantaneous

mainly for drugs in aqueous solutions or drugs not absorbed orally

cannot be recalled

chance of air emboli- gets stuck in the lungs causing pulmonary embolism

sepsis

dependent upon patient accessible veins

SC

suspension- not dissolved and part of the solution but remains in solid state

aqueous- dissolved in solution

SC

small pellet can also be implanted under the skin

blood flow to the muscle

exercise increases blood flow

blood brain barrier and blood CSF barrier impede entrance into the CNS

used to infections and tumor treatment

absorbed by the lungs which have large surface area for absorption which reaches the blood supply quickly and avoids first-pass metabolism

need to worry less about systemic effect and more about local effect

local effect desired

direct application and no need for needles

skin

eye

nasal

throat

vagina

urethra

few drugs penetrate the skin

absorption proportional to surface area

condition of the skin affects absorption

inflammation increases cutaneous blood flow and absorption 

enhanced by suspension in oily vehicle and rubbing into skin

phyisco-chemical properties of the barrier

• passive, facilitated, or active diffusion

physical properties of the system

• blood flow, surface area, contact time

physio-chemical properites of the drug

• molecular size, lipid solubility, ionization

smaller <200 MW 

not applicable to facilitated diffusion, active transport, or endocytosis

solubility of drug

chemical instability

formulation

first-pass hepatic metabolism

bioequivalent

only exists if the rates and extent of bioavailability of their active ingredients are not significantly different