Advanced Pharmacology: Pharmokinetics

aqueous preparations include what?

syrup, suspensions, solutions, emulsions

tablet preparations

powders that are compressed into convenient form

capsules

gelatin reservoir used to administer powders or liquids

Delayed-release

tablets or capsules with special formulations/coatings that dissolve at different rates/areas

enteric coated

acid resistant coating that allows coating to dissolve in basic environment

suppositories

varied excipients but dissolve once inserted

transdermal

bandage or patch system administers drug, provides continuous release

parenteral

injection by needle and syringe

what are some common routes of parenteral injections?

subcutaneous (SQ), intramuscular (IM), intravenous (IV)

oral route onset

30-60 minutes

rectal route onset

15-30 minutes

intravenous onset

within 1 minute

Things to consider when picking preparations for medications

who can receive, administration requirements, how quickly effect is achieved

What does ADME stand for in kinetics?

absorption, distribution, metabolism, excretion

absorption

how does the body change the drug

distribution

where does the drug go in the body

metabolism

how does the body change the drug

excretion

how does the drug leave the body

speed of absorption depends on what three factors?

preparation, route, concentration

Passive diffusion is NOT ________

saturable

___________ mediated processes are saturable

carrier

____________ drugs cross membranes easily

non-ionized

__________ drugs are less likely to cross membrane

ionized

Ionized drugs are water __________

soluble

a base in a base

unionized drug

an acid in an acid

unionized drug

an acid in a base

ionized drug

a base in an acid

ionized drug

Acidic drugs are ionized in _______ environments

basic

Acidic drugs are unionized in ________ environments

acidic

Basic drugs are ionized in _______ environments

acidic

Basic drugs are unionized in ___________ environments

basic

What are some of the factors that affect gastrointestinal function that can affect drug absorption?

transit time (too fast vs too slow), absorptive surface area (surgery), food (can bind drug), drug interactions (bind with other drugs)

extent to which a drug is absorbed into systemic circulation

bioavailability

Above what percent is considered highly bioavailable?

70

Extended release/controlled release drugs can NOT be _______

crushed

First pass effecy

the liver biotransforms the drug before it reaches systemic circulation or the liver extracts the drug into the bile before it reaches systemic circulation

Net effect of the first pass effect

absorbed drug never makes it past the liver

Most aborption in the small intestine occurs in the first ______ meters

two

the small intestine has a large......

absorptive surface area

Does blood supply near anus go to liver?

NO

When would you use a per rectum drug?

unconscious patient, vomiting patient, infants

Does the rectum have a first pass effect?

No

What does PGP do?

takes absorbed drug from the blood and throws it back into lumen, decreasing drug absorption

Cheeking can be a major problem in what patients?

psychiatric, problem patients, kids

What are factors controlling absorption when giving SQ/IM?

vehicle, volume, surface area and site of administration

Intrathecal absorption

drug is placed inside meninges

In intrathecal absorption, it MUST be.....

preservative free

Is intravenous/intra-arterial reversible?

No

What percent bioavailability is intravenous/intra-arterial?

100%

When can you have increased permeability in topical absorption?

burns and rashes

Inhalation has good absorptive capacity in _________ spaces

alveolar

Greater than what percent is considered highly protein bound?

90%

If an unbound drug is active, it can

distribute

If a bound drug is inactive, it.....

stays in vasculature

highly protein bound drug will have increased effect in _______ albumin

low

an organ that receives more blood can receive more _____

drug

The brain is composed of _______

lipids

__________ soluble drugs readily penetrate the brain

lipid

what are ways in which we can overcome the blood brain barrier?

increase concentrations, give lipophilic drugs, give medication locally

What is volume of distribution?

size of an area in the body the drug distributes to

Less than 70L volume of distribution

Drug primarily distributes to small area (vasculature)

Greater than 70L volume of distribution

Drug distributes to large area (everywhere)

What occurs in phase I of metabolism?

dramatically alters the biological properties, making metabolites and inactivating the drug (except for prodrugs)

_____ enzymes perform Phase I

CYP

Induction of CYP

decreases concentrations of active drug by increasing deactivation

Inhibition of CYP

concentrations of drugs may be prolonged by decreasing deactivation

CYP inducer examples

carbamazepine, oxcarbazepine, phenytoin, phenobarbitol, rifampin, St. johns wort

CYP inhibitor examples

anti-infectives (macrolide except azithromycin, azoles), amiodarone, protease inhibitors (navir's), cyclosporine, cimetidine

Pro-drug

a medication that is inactive upon administration and is then metabolized into an active drug, undergoes bioactivation

Phase II of metabolism

conjugation adds sulfate, glucuronic acid, and glutathione (to make it more water soluble)

What plays into renal clearance?

size, charge, shape

Ionized drugs are ______ likely to leave compartment

less

GFR

glomerular filtration rate, the flow of blood through kidney

Creatinine clearance

volume of plasma that is filtered of creatinine per unit of time

creatinine

product of muscle metabolism excreted by the kidneys

If actual weight is less than idea, use _______

actual

If actual weight is greater than idea, use ________

ideal

Unlike creatinine, __________ __ levels are less affected by muscle mass, age, sex, or diet

Cystatin C

Cystatin C is used to

estimate glomerular filtration rate (eGFR)

Clinical use of cysteine C

sometimes used instead of or in addition to serum creatinine for kidney assessment, helps refine drug dosing for medications cleared by kidneys

How is bile excreted

into the GI tract and released as stool

enterohepatic recycling

Liver to bile to intestine to blood to liver, Drug stays in circulation longer

Half life

time required for concentrations of the drug to fall to half of its original level

_________ determines dosing interval/how often you give a drug

half life

How many half lifes are required to eliminate greater than 95% of the drug?

5

5 classes of drugs in sports testing

stimulants, narcotic analgesics, diuretics, anabolic agents, peptide hormones

beta blockers improve performance in anaerobic events that require

steadiness and control

Steady state is reached when

drug absorption equals elimination

____ _____ determines steady state

half life

Loading dose

rapidly obtains therapeutic concentrations, specifically drugs that have half lives that are longer than the frequency of administration

zero per order kinetics

amount per unit time, unusual

In zero order kinetics, rate is constant and _________ of drug

independent

Zero order is often seen in _________ use

alcohol

First order kinetics

fractions per unit in time, rate is in proportion to the amount of drug in the body by percent, typical