Exam 3 General Info Flashcards
What is onset?
The time form when a drug is introduced into the body to when it begins to show a therapeutic effect
What is duration?
The total time where a drug is displaying a therapeutic effect
What is intensity?
The Cmax of the drug or a point in time where the drug is displaying the greatest amount of effect
What are reasons why less than 100% of a drug may not reach the site of action.
Excretion and Degradation
Define pharmacokinetics
The study of absorption, distribution, biotransformation, and elimination of xenobiotics
Define pharmacodynamics
The study of molecular, biochemical, and physiologic effects of xenobiotics and their mechanisms of action.
Biopharmaceutics is…..
The pathway of the drug from the mouth all the way until it gets absorbed
What is drug disposition?
The fate of a drug after it has entered the systemic circulation
What do pathophysiology, pharmacodynamics and pharmacokinetics add up to?
Pharmacotherapeutics
What percent of drugs currently fail clinical trails due to problems with ADME
Less than 10%
Which route of administration will give the most rapid effect based on onset
Intravenously - entered the bloodstream and can bypass physiological barriers
Which route of administration will give the least amount of onset? (usually)
Orally - has to go through many physiological barriers before causing an effect
What is special about intramuscular dosing?
Can be specially made to have a very long lasting duration
The 4 major routes of administration are?
Ingestion (orally)
Inhalation (pretty quick)
Dermal (hard to administer drugs this way)
Parenteral (injections such as intravenous, subcutaneous, intramuscular, intraperitoneal)
A reduction in the extent of absorption will impact which pharmacological effect?
Intensity (but it may also effect the others)
A reduction in the speed of entry will impact which pharmacological effect?
Onset
Whats the difference between fexofenadine and diphenhydramine?
diphenhydramine can cause drowsiness while fexofenadine has an added structure which provides the same effect but it dose not provide sleepiness.
What are the four potential consequences of drug metabolism (biotransformation)?
- Active drug to inactive metabolite (phenobarbital - hydroxylation - hydoxyphenobarbital)
- Active drug to active metabolite (Procainamide - acetylation - N-acetylprocainamide)
- Inactive drug to active metabolite (Codeine - demethylation - morphine)
- Active drug to reactive metabolite (acetaminophen - reactive metabolite / liver toxicity)
What does absorption mean?
Anytime a drug has to pass a biological membrane
Which route of administration goes right into the systemic system?
Intravenously
Which route of administration avoids the need to cross a biological membrane in order to reach the CNS?
NONE
The six factors that determine movement of a drug across membranes?
- Characteristics of the membrane
- Mechanism of passage across membrane
- Dwell time of drug-membrane interface
- Physiochemical characteristics of the drug
- pH of the microenvironment
- Surface area of absorptive surface
Where does most drug absorption occur?
In the small intestine / microvilli and vili and its increased surface area (EVEN if it gets favored in the stomach)
What impact would a drug that speeds up stomach emptying have on the time to peak concentration for acetaminophen?
It will be higher because it will be absorbed more quickly
What is passive diffusion
Where drugs can passively diffuse through aqueous channels in the intercellular junctions or through lipid cell membranes
What is active diffusion
Where drugs can pass through but they need energy either through carriers or by membrane limited vesicles in or out of the cell
What is the driving force for movement of a drug across membranes via transcellular or paracellular diffusion?
Will always move with the concentration gradient (high to low)
What % of drugs use transcellular diffusion?
95%
Transceullar diffusion
passive diffusion across membrane is dependent on compound pKa and solution pH
How can you increase transcellular permeability?
- remove ionized groups
- increase lipophilicity
- reduce the size
paracellular diffusion
not a lot of drugs can do this, has to be super small to pass through, but toxins are being explored to be able to open these tight junctions to make bigger molecules fit.
The rate of diffusion is impacted by…….
diffusion coefficient, partition coefficient, membrane thickness, surface area of membrane
Saturation point
There is a fixed point where even if you add more drug it will not show more effect
Carrier mediated transport?
In contrast to simple diffusion, carrier mediated transport is both saturable and subject to competitive inhibition
As you increase the dose of riboflavin the amount decreases as the dose gets higher because it is totally saturable.
yup
What happens when you take food with medication?
The GI slows down causing the drug to be more actively absorbed.
Carrier mediated transport mechanisms
Facilitated diffusion (concentration gradient only), Active transport (may go against the concentration gradient but needs energy)
Efflux transporters are
transporters are doing the opposite of the transporter they remove drugs out of the cell, one of the major causes of drug resistance and antibacterial resistance.
Efflux transporters - p-glycoprotein
- can limit drug absorption
2.can enhance drug elimination - limited distribution (brain or testes, or maternal blood)
What is the main efflux transporter?
PGP
How are nanoparticles able to enter the cell and cross the membrane?
This happens by endocytosis
perfusion rate limited
involved in the movement of blood to the tissue and once it reaches it destination it can easily move through the membrane
permeability rate limited
Once the drug moves through the blood to the tissue it takes longer to pass through the membrane because of its charge
will perfusion rate limited or permeability rate limited show lower tissue distribution?
permeability rate limited will have slower tissue diffusion
What is convection?
the movement of molecule by pressure
What is diffusion?
the movement by concentration gradients
Is diffusion or convection (transvascular - movement across the endothelial cell) likely to be more important to monoclonal antibodies?
Convection because its so big and wont be able to enter from diffusion so it needs the pressure
what is pharmacologically active?
only the free drug
What 3 ways does the blood brain barrier keep drugs out of the brain
- Tight junctions (almost no paraceulluar diffusion)
- Negative lipid head groups
- A high concentration of PGP - high efflux activity
What are the four mechanisms that drugs can get into the CNS?
- They have the correct physiochemical properties
- Direct administration into the cerebral spinal fluid
- They utilize existing transporters
- Disruption of the BBB
What can happen to some drugs that can cross the BBB but they don’t aren’t seen?
The efflux transporters are working efficiently at keeping the drugs out of the brain that you cannot tell
would a mother want to be on heparin or warfarin
heparin because it wont be able to cross through the placenta to get into the child
What are the 2 main routes of excretion?
Renal - kidneys (most primary)
Biliary - feces
What are 3 secondary routes of excretion?
Pulmonary
Salivary
Mammary
Why do some labels tell us to drink plenty of water with the medication?
Some medication is poorly soluble and can precipitate out of the tubule and cause damage to the kidneys
Why should you not take a lot of vitamin C?
The more you take the more just gets reabsorbed and produces no effect. renal tubular reabsorption
where does filtration happen in the kindeys?
Glomerulus in bowmans capsule
where does active tubular secretion happen in the kindeys?
In the proximal tubule
where does active tubular reabsorption happen in the kidneys?
In the distal tubule
Whats the molecular weight that isnt able to be filtered through kidneys
greater than 5000
What are factors that can influence filtration?
- # of functional nephrons (decrease as you get older)
- molecular size / weight 5000
- protein binding
- renal blood flow
Urinary excretion rate and dose
The secretion rate would saturate at some point of the dose because all of the excretion receptors are occupied meaning there will be a fixed number getting secreted
how much urine actually gets secreted and not reabsorbed?
1%
What is the hepatic elimination split up by?
metabolism
feces or biliary
which way does bile move in the liver?
moves from the inner portion to the outside and drains into the bile ducts
where does blood move in the liver?
moves form the portal vein on the outside to the inside central canal
what get moved in hapatocytes?
stuff can move in or out of hapatocytes
for drugs that are getting excreted in the bile ducts whats the most optimal molecular weight?
500-600 because the lower molecular weight will get passively reabsorbed before entering the bile ducts
what is dose dumping?
When you get a bump in dose when you eat in the morning because the gallbladder got emptied.
what are two reasons why drug metabolism is important to adverse reactions?
- Change the pharmacological activity
- Change elimination
what is the main organ involved in drug metabolism
the liver
what is the second most important organ for drug metabolism
the GI tract
name two ways the metabolism of a drug metabolized by p450 can be decreased?
decrease NADPH or inhibit the CYP450 reductase
What is phase 1 drug metabolism
A chemical modification (biotransformation) which adds a functional group.
What is phase 2 drug metabolism
Conjugation of polar group with a drug
do inducers or inhibitors cause more interactions
inducers cause more interactions
autoinduction is…..
when you take the dose so many times that the amount you put in the body is the amount youre outputting. this will lead to breakthroughs as the medication isnt providing its full effect
which CYP2 is the most important
CYP2C9 because of its bigger active site
CYP2D6 metabolizes what % of all clinically important drugs?
20%
If a molecule inhibits CYP2D6 will they try to make a different drug that dosent inhibit this enxyme?
Yes, because it metabolizes so many drugs that its important to not inhibit this CYP
CYP3A4 substrates ….
midazolam and indinavir
CYP3A4 inhibitors ….
ritonavir and ketoconazole
CYP3A4 inducers ….
rifampin and St. Johns Wort
CYP2D6 substrates ….
codeine and fluoxetine
CYP2D6 inhibitors ….
fluoxetine and quinidine
CYP2D6 inducers ….
??? clinical relevance ???
CYP2C9 substrates ….
S-warfarin and ibuprofen
CYP2C9 inhibitors ….
fluconazole and amiodarone
CYP2C9 inducers ….
rifampin and secobarbital
Does phase 1 or phase 2 mostly inactive drugs?
Phase 2
