Intro Pharm Sci Exam 2

What is BCS?

Biopharmaceutics Classification System; measures how well a drug will be orally absorbed via solubility and permeability

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 absorption?

Disintegrate the solid dosage form

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

Ileum (~60% of length)

How does systemic drug admin differ from local?

Drug gets into the blood stream

How are ionized drugs brought into cells?

Ion trapping

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?

Larger surface area due to villi

If a concentration gradient is increased what occurs to the rate of passive diffusion?

Increases

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 factors impact rate of carrier-mediated transport?

Vmax, Affinity of drug for transporter, Conc. gradient

What does the kinetics graph of a immediate-release tablet look like?

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

What is a Class I drug?

High solubility and permeability

What is a Class II drug?

Low solubility, High permeability

What is a Class III drug?

High solubility, Low permeability

What is 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 IM drug admin?

Injection into muscle (90*), Near 100% systemic absorption

What are the characteristics of SC drug admin?

Injection into subcutaneous tissue (45*), High systemic absorption

What are the characteristics of ID drug admin?

Injection into dermis (10-15*), Low-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 conc.

What are the disadvantages of Parenteral drug admin?

Increased admin and personnel cost, Risk of adverse effects, Inconvenient to pts

What are the advantages of Rectal drug admin?

Alt oral route, High % dose absorption, Avoids 1st pass effect

What are the disadvantages of Rectal drug admin?

Awkward/ less preferred by pts, Often less stable formulation

What are the advantages of Buccal/ Sublingual drug admin?

Rapid absorption, Avoids first pass effect, More convenient that 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 pts, adds cost for the pt

What are the advantages of Transdermal drug admin?

Relativly constant drug level in blood, Convenient, Non-invasive, Higher adherence

What are the disadvantages of Transdermal drug admin?

Environ changes may impact drug delivery (sweat, extreme temp), May cause irritation at admin site

What are the advantages of Pulmonary drug admin?

Rapid-acting, Ideal for local treatment of resp 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 admin?

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 pts

What is Delayed release?

Delays release to usually protect drug from stomach acid

What is Sustained release?

The rate of released drug matches rate of elimination

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 a specific target

What is Biological targeted delivery?

Targeting a 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 anticoags

What is 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 .01mg/mL, what would happen to the % bound if the drug concentration increases?

Stays the same

2 MULTIPLE CHOICE OPTIONS

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

What is a common property of drugs with low Vd?

High % protein binding, Hydrophilic or large molec,

What is a common property of drugs with high Vd?

Low % protein binding, Lipophilic or small molec

An IV bolus of 50mg is administered to a pt. Blood conc was taken and measured to be 1.0mg/L. What is the Vd?

Vd = 50 L

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 hydroxylases 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/or 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 in half-life, Increased polarity, Inactivation (most of the time)

What enzyme and cofactor is responsible for Glucuronidation?

Glucuronosyltransferase (UGT), UDPGA

What is Glucuronidation?

Most common Phase II rxn; 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 rxn; 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 rxn; Acetyl group from Acetyl-CoA is attached to an amine (favors primary), doesn't change sol/polarity but does often remove activity,

What enzyme and cofactor is responsible for Glutathione (GSH) Conjugation?

Glutathione-S-transferase (GST), GSH

What is Glutathione (GSH) Conjugation?

Important Phase II rxn; Activated, nucleophilic GSH neutralizes electrophilic toxins, over reliance causes added toxicity due to loss of GSH reserves

What causes an Acetaminophen (APAP) overdose to be deadly?

Build-up of the toxic metabolite NAPQI that depletes GSH reserves and causes liver damage

What rxns are MAO enzymes responsible for?

Oxidation rxns

What does CYP2D6 mean?

CYP (CYP450 superfamily), 2 (CYP2 family), D (CYP2D subfamily), 6 (specific isoform in the CYP2D subfamily)

What are the most common CYP450 isoforms?

CYP2C9, CYP2D6, CYP3A4/5 (CYP3A)

What are the types of Enzyme inhibition?

Competitive and Irreversible inhibition

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, Why?

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

3 MULTIPLE CHOICE OPTIONS

A pt (25 M) 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 as a line cook. Pt reports increase in nausea, dizziness, and headaches. Being a good pharmacist you know Drug A is broken down into an 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

3 MULTIPLE CHOICE OPTIONS

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 conc of statin to dangerous levels (increased risk of rhabdomyolysis)

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 feeing into the nephrons

What is the efferent renal arteriole?

Arteriole transporting filtered blood back to the body

What is the glomerulus?

The location in the nephron in which filtration actually occurs

What are the Peritubular 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 a measure of?

How efficiently kidneys clear drug activity from the blood

What is the difference between Excretion and Clearance?

Excretion is the mass of drug removed from the body (mg/Hr), Clearance is the volume of blood filtered to achieve the delta [drug-blood]

What are the most common routes of drug excretion?

Urine and feces

How does the kidneys excrete dugs?

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 Renal drug Excretion?

% ionization (prevents reabsorption), Increases polarity, Size (