Unit 1 Flashcards
Stage where drug is tested on animals for safety
Pre-clinical trials
Stage where drug is tested on healthy people in an inpatient setting
determine most effective administration routes and dosage ranges
Phase I
Stage where drug is tested on people with disease for which drug is intended in outpatient setting
Phase II
Stage where RCTs, double-blinded, and dose-ranging studies are performed
Phase III
Stage where post marketing data is collected
compare with other drugs on the market
long-term effects
analyze cost-effectiveness
Phase IV
At what point is a drug approved or rejected by the FDA
After Phase III
Cocaine and heroin schedule
I
Dilaudid schedule
II
Morphine schedule
II
amphetamines schedule
II
barbituates schedule
II
Methadone schedule
II
codeine schedule
3
cough medicine with codeine schedule
V
Percocet schedule
III
Benzos schedule
IV
How to write a prescription for schedule I and II drugs
paper, hand signed, specific number of pills, no refills
How to monitor adherence to therapy
lab testing
pill count
patient diary
How the body affects the drug
pharmacokinetics
How the drug affects the body
pharmacodynamics
4 phases of pharmacokinetics
- absorption
- distribution
- metabolism
- excretion
2 components of pharmacodynamics
- concentration of drug at site of action
- drug effect
therapeutic window
range of blood drug concentration that yields a sufficient therapeutic response without a toxic reaction
2 factors that affect absorption
GI motility and gastric emptying
5 factors that affect bioavailability
- first pass effect
- pro-drugs
- drug formulation (immediate vs extended release
- GI motility
- blood flow
the fraction or percentage of an administered dose of a drug that reaches the circulation in its unmetabolized form
bioavailability
250mg oral drug -> first pass-> 125mg enters blood = __ bioavailability
50%
How does gender affect pharmacokinetics
women have a high percentage of body fat which can alter the amount of drug at the site of action
hormones differ
first pass effect patho
oral drug absorbed through the alimentary canal, drugs go directly to the liver through the portal vein.
hepatic enzymes metabolize the drug, reducing the amount of active drug in the bloodstream
Pro-drugs
drugs that have no biologic activity itself, but once metabolized it becomes an active metabolite
precursor to the active drug
pro-drug
2 examples of pro-drugs
plavix and lovastatin
2 reasons for immediate release tab
quick onset
absorbs well in the acidic environment of stomach
2 reasons for enteric coating
slows drug to be dissolved in intestines rather than stomach
intestines have higher pH
helps preserve gastric mucosa
affinity
the attraction between a drug and a receptor
allosteric site
a binding site for substrates not active in initiating a response
biotransformation
metabolism or degradation of a drug from an active form to an inactive form
ligand
any chemical that interacts with a receptor
volume of distribution (Vd)
the extent of distribution of a drug in the body
high hepatic extraction ratio =>
low oral bioavailability
how does gastric emptying affect drug absorption
high rate of emptying hastens absorption and bioavailability in intestines
how does high fat meals and solid foods affect absorption
delays drugs initial delivery to intestinal absorption surfaces
how does decreased intestinal motility affect absorption and drug example
slowed peristalsis leads to greater absorption and bioavailability
prolongs contact time with intestinal surfaces (anticholinergics)
how does increased intestinal motility affect absorption and drug example
less absorption and bioavailability
shortens contact time with intestinal surfaces (laxatives)
how does blood flow affect pharmacokinetics
absorption and distribution
What route is affected by first pass effect
oral only
topical vs transdermal
topical is local absorption (does not cross the dermis)
transdermal is systemic delivery through the skin over time
examples of topical drugs
eye drops and topical steroids
3 things that affect distribution
blood flow to area
lipid vs water solubility
protein binding
protein binding pathophys
carrier proteins such as albumin bind to drug rendering it inactive or circulate unbound (free drug)
2 things that affect protein binding
affinity of drug for that protein and concentrations of both drug and protein
how does low albumin affect distribution
decreased protein binding, more free drug, higher activity of drug
drugs have higher and lower affinity for protein
drug with higher affinity may knock off a drug with lower affinity
why does INR increase when patients on coumadin take abx
abx have higher affinity for protein, knocks coumadin off protein, creating more free drug
lipid and water solubility affects
getting into the cell
phospholipid bilayer membrane acts as what
barriers, blocking or permitting the passage of various substances
Which type of compounds pass through a phospholipid bilayer readily and which has a harder time passing through?
- Hydrophobic (lipid soluble)
- Hydrophilic and ionized
4 other factors that affect distribution
- barrier integrity and strength
- size of drug molecule
- distance to travel from blood to cell
- pH
3 types of diffusion
Passive, facilitated, active
carrier proteins are utilized to transport larger molecules, from an area of higher concentration to lower
facilitated diffusion
requires energy, molecules move from lower concentration to higher concentration
active transport
metabolism
function of the body to change substances into water-soluble forms that will more readily be excreted
biotransformation of the drug from active form to inactive form
What organ is primarily responsible for metabolism
liver
phase one of metabolism
enzymatic processes that involve oxidation or reduction
drug is changed to form a more polar/water-soluble compound
hydrolysis
Phase two of metabolism
involves adding a conjugate to parent drug or phase 1 metabolized drug to further increase water solubility and enhance excretion
CVP how many enzymes are responsible for drug metabolism in 90% of cases
15
3 relationships drugs have with the CVP450 enzymatic system
substrate
inducer
inhibitor
CVP450 inducers meaning
stimulates the production of enzymes which increases the amount of enzymes available for metabolism
CYP450 inhibitors meaning
inhibits production of CYP enzymes, decreasing the metabolism of drugs and increasing circulating levels
3 drugs that induce CVP450
rifampin, phenytoin, st. johns wort
3 drugs that inhibit CVP450
grapefruit juice, azoles, protease inhibitors
3 factors that interfere with elimination
renal failure
hepatic failure
regular vs intermittent exercise
when is a drug considered fully cleared
after 4-5 half lives of the drug
how does renal failure interfere with elimination
increases the half life
how does hepatic disease interfere with elimination
impacts pro drugs and CVP450 enzymes, increases half live
how does regular vs intermittent exercise interfere with elimination
impacts blood flow, GI motility, and body temp
3 things that impact pharmacodynamics
receptor abundance (age-related)
receptor affinity (age-related)
post-receptor changes and sensitivities
4 involunatry function of ANS
thermoregulation
vascular contractility
heart and respiratory rates
digestion
2 voluntary function of SNS
movement and speech
sympathetic neurotransmitter
Norepinephrine
sympathetic receptors
Alpha 1&2
Beta 1&2
Alpha 1 receptor affects
smooth muscle
Alpha 2 receptor affects
brain, stem, spinal cord, and eye
Beta 1 receptor affects
myocardium
beta 2 receptor affects
lung
parasympathetic receptors
cholinergic and muscarinic receptors
parasympathetic neurotransmitter
ACH
What do ACH agonists do
cause contractions
increase secretions
what do anticholingercis do
block ACH
urinary retention
xerostomia
tachycardia
ED50 drug dose means
therapeutic effect in 50% of recipients
LD50 drug dose means
lethal dose in 50% of recipients
Therapeutic index =
LD50/ED50
type A adverse drug reaction
r/t pharmacologic action
side effects
mild hypersensitivity
type B adverse drug reaction
unusual or unanticipated action
hypersensitivity reaction