KK's Exam Study

what is the definition for BCS

Biopharmaceutics classification system; measures how well a drug will be orally absorbed via solubility and permeability

how does systemic drug admin differ from local drug admin

drug gets into blood stream

how are ionized drugs brought to cells

ion trapping

what is the First Pass Effect

the elimination of drugs via the liver prior to acting on the body

what is the role of the stomach in drug absopriton

disintegrate the solid dosage form

which section of the small intestine are majority of drugs absorbed (longest)

ileum (60% of length)

an increase in what results in slower passive diffusion

increase in membrane thickness

why is the small intestine favored over the large intestine for drug absorption

large surface area due to villi

if a concentration gradient is increased, what occurs to the rate of passive diffusion

inceases

theoretically, the rate of passive diffusion will continuously increase with concentration gradient. is this true for carrier-mediated transport, if so why?

the rate of mediated transport maxes out when the carrier proteins are saturated

what factor impacts the rate of carrier-mediated transport

Max, affinity of drug for transporter, concentration gradient

what does the kinetics graph of an immediate-release tablet look like

quick increase in plasma drug level, rapid drop to a slower rate of excretion

what are characteristics of a Class I drug

high solubility and permeability

what are characteristics of a Class II drug

low solubility, high permeability

what are characteristics of a Class III drug

high solubility, low permeability

what are characteristics of a Class IV drug

low solubility and permeability

what does ID mean

intradermal

what does IP mean

intraperitoneal

what are the characteristics of an IV drug admin

injection into vein, 100% systemic absorption

what are the characteristics of an IM drug admin?

injection into muscle (90 degrees), near 100% systemic absorption

what are the characteristics of SC drug admin

injection into subcutaneous tissue (45 degrees), high systemic absorption

what are the characteristics of ID drug admin

injection into dermis (10-15 degrees), low to no systemic absorption, uncommon

what are the advantages of parenteral drug admin

bypass oral barriers, rapid onset of action, less variability in amount of drug reaching sys circulation, may achieve higher tissue concentration

what are the disadvantages of parenteral drug administration

increased admin and personal cost, risk of adverse effects, inconvenient for patients

what are the advantages of rectal drug administration

alt oral route, high % dose absorption, avoids first pass effect

what are the disadvantages of rectal drug absorption

awkward/less preferred by patients, often less stable formulation

what are the advantages of buccal/sublingual drug admin

rapid absorption, avoids first pass effect, more convenient than other alts (IV) to oral delivery, avoids acidic pH of stomach

what are the disadvantages of buccal/sublingual drug admin

taste/discomfort may be barrier for some, adds cost for the patient

what are the advantages of transdermal drug admin

relatively constant drug level in blood, convenient, non-invasive, higher adherence

what are the disadvantages of transdermal drug admin

environment changes may impact drug delivery (sweat, extreme temp) may cause irritation at administration site

what are the advantages of pulmonary drug admin

rapid acting, ideal for local treatment of respiratory disease

what are the disadvantages of pulmonary drug admin

nebulizer can be tedious, difficult to achieve systemic absorption (except for anesthetic)

what are the advantages of nasal drug administration

high drug absorption, convenient, useful for drugs that are degraded in GI

what are the disadvantages of nasal drug admin

low surface area making delivery of an effective dose difficult, nasal tissue is sensitive, not appealing to most

what is delayed release

delays release to protect drug from stomach acid

what is sustained release

the rate of released drug matches rate of elimintation

what is targeted drug delivery

drug delivered to specific anatomical area

what is physical targeted delivery

admin to specific site, avoiding systemic exposure

what is chemical targeted delivery

uses SAR to make drug more selective for specific target

what is biological targeted delivery

targeting drug to a bio marker present only in disease state

what is ADME

absorption, distribution, metabolism, excretion

what does the kinetics graph of an IV bolus look like

max drug conc. followed by a rapid decrease (distribution) to a slower decrease (elimination)

what is drug distribution

reversible transfer of drug between vascular (blood) and extravascular space

how is serum produced

clotted blood is spun and the liquid is collected, lacks clotting factors but is more stable for long term storage

how is plasma produced

liquid blood is spun and the “clear” liquid is collected, contains clotting factors and

what is the volume of distribution (Vd)

the apparent volume in which a drug is dissolved to reach a certain concentration

how does the circulatory system effect capillary exchange

arterioles push blood into the tissues, venules pull blood into the capillaries

lipophilic drugs favor which type of passive diffusion

transcellular, paracellular

hydrophilic drugs favor which type of passive diffusion

paracellular

if a drug is 50% bound to protein at a blood concentration of .01 mg/mL what would happen to the % bound if the drug concentration increases

stays the same

what proteins bind to drugs most commonly

albumin (lipid transporter), alpha-1-acid glycoprotein

how does protein binding affect drug distribution

prevents diffusion across the cell membrane

how would you explain Vd to a health care professional

Vd is a measurement of how well a drug can distribute through the body, it also is used to determine the size of a dose required to reach a desired initial blood concentration

how would you explain Vd to a layman

Vd is the amount of fluid a drug would have to be dissolved in to achieve a desired initial concentration of drug

what are common properties of drugs with low Vd

high % protein binding, hydrophilic, large molecules

what are common properties of drugs with high Vd

low % protein binding, lipophilic, small molecules

an IV bolus of 50mg is administered to a pt. blood concentration was taken and measured to be 1.0 mg/L. what is the Vd?

(Vd =) 50L

what is CYP450

a superfamily of oxidative enzymes responsible for phase 1 metabolism

what is dealkylation Rxn

removal of an alkyl group from a N, O, S. O-dealkylation leads to COOH formation

what is aliphatic hydroxylation

addition of a hydroxyl group to an aliphatic group, can be metabolized to COOH in some drugs

what is aromatic hydroxylation

Addition of a hydroxyl to an aromatic ring

what is alkene hydroxylation

insertion of an O into a C=C resulting in a ketone or an epoxide

what is epoxide hydrolysis

epoxide hydrolase forming a diol from an epoxide

what is ester hydrolysis

ester hydroxylates cleaving an ester forming an OH on the drug

why do some drugs cause toxicity even though they seem to initially work

they form toxic metabolites

how do phase I and phase II differ

phase I tends to make drugs smaller and more polar. phase II tends to make drugs larger, more polar, and detoxifies them

what is the difference between drug metabolism and excretion

metabolism is the enzymatic breakdown of drugs whereas excretion is physically removing the drug from tissue/the body

what are potential outcomes of drug metabolism

increase/decrease half life, increased p

what enzyme and cofactor is responsible for glucuronidation

glucoronosyltransferase (UGT), UDPGA

what is glucoronidation

most common phase II reaction, glucuronide metabolite is added to OH or N increasing polarity and size, this enhances renal and hepatic excretion

what enzyme and cofactor is responsible for sulfate conjugation

sulfotransferase (SULT), PAPS

what is sulfate conjugation

phase II reaction, sulfate replaces OH favoring aromatic C, increases polarity

what enzyme and cofactor is responsible for acetylation

N-acetyltransferase, acetyl-CoA

what is acetylation

rare phase II reaction, acetyl group from acetyl-CoA is attached to an amine (favors primary), doesn’t change sol/polarity but removes activity

what enzyme and cofactor is responsible for glutathione (GSH) conjugation

glutathione-s-transferase (GST), GSH

what is glutathione conduction (GSH)

important phase II reaction; activated, nucleophilic GSH neutralizes electrophilic toxins, over reliance causes added toxicity due to loss of GSH reserves

what causes acetaminophen (APAP) overdose to be deadly

build up of toxic metabolite NAPQI that depletes GSH reserves and causes liver damage

what rxns are MAO enzymes responsible form

oxidation reactions

what does CYP2D6 mean

CRP - CRYP450 superfamily, 2-CYP2 family, D-CYP2D subfamily, 6-specific isoform in the CYP2D subfamily

what are the most common CYP450 isoforms

CYP2C9, CYP2D6, CYP3A

what are the types of enzyme inhibition

competitive and irreversible

A pt is on Drug A to decrease BP by diluting urine. Upon doing research, you find it is metabolized by CYP5B7. if the pt starts taking Drug B a known inhibitor of CYP5A1, should we be concerned about Drug A toxicity (if so why)

No, the inhibited enzyme is in a different subfamily so there will be no drug interactions

a pt (25M) has been taking Drug A for 5 years to deal with chronic illness X. upon doing research, you find Drug A is metabolized by CYP1A2. recently, the pt reports they have begun smoking to help with the stress of their job. Pt reports increase in nausea, dizziness, and headaches. being a pharmacist, you know Drug A is broken down in the active metabolite with side effects including those reported by pt. Why might the pt be experiencing these worsened side effects?

smoking acts as an inducer of the enzyme resulting in a more rapid metabolism

what is PK boosting

combination of meds to increase effectiveness without unintended side effects

why might it be dangerous to combine a CYP450 inhibitor with Statin

increases the concentration of statin to dangerous levels (increased risk of rnhabdomylosis)

what is a nephron

functional unit of the kidney responsible for the filtration of blood to produce urine

what is the afferent renal arteriole

arteriole feeling into the nephrons

what is the glomerulus

the location in the nephron in which filtration actually occurs

what are the pertubular capillaries

capillaries wrapped around the renal tubule allowing for secretion and reabsorption of drugs, ions, and other molecules

what is tubular secretion

active transport of drug into the urine against the gradient

what is tubular reabsorption

passive diffusion of unionized drug from the filtrate back into the blood

what is enterohepatic recycling

reactivation of drugs via excretion in bile followed by reactivation by GI flora

what is clearance of measure of

how efficiently kidneys clear drug activity from the blood

what is the difference between excretion and clearance

excretion is the mass amount of drug removed from the body (mg/Hr), clearance is the volume of blood filtered to achieve the delta (drug in blood)

what are the most common routes of drug excretion

urine and feces

how do the kidneys excrete drugs

drugs are initially filtered at the glomerulus, along the renal tubules drugs are passively and actively transported into the urine to be excreted

how does the liver excrete drugs

adds the drugs to bile to be removed via feces

why is enterohepatic recycling important to drug therapy

drugs can stay active in the body for longer, if not taken into account this can result in a toxic build-up of drug

what characteristics impact enterohepatic excretion

drugs > 500MW are always added to bile (phase II often does this)

how does a low urine pH affect reabsorption of WA drugs

enhances reabsorption due to low % ionization