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Pharmaceutics Exam 3
ADME, Routes of Administration, Solubility, Distribution, Solutions
173
Pharmacology
Professional
10/04/2011

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Cards

Term
Define ADME
Definition
Absorption, distribution, metabolism, excretion

What happens to a drug when it enters the body
Term
What are the two routes of drug administration?
Definition
Extravascular and intravascular
Term
What are the two ways for intravascular drug administration?
Definition
Intravenous and intra-arterial
Term
What is a benefit to intravascular drug administration?
Definition
100% of drug is available to the circulatory system
Term
List examples of extravascular drug administration
Definition
Oral, transdermal, suppositories, sublingual, subcutaneous, intramuscular, hypodermic
Term
If a drug is injected, is it 100% available to the circulatory system?
Definition
No, not necessarily. Intramuscular injection is not 100% absorbed.
Term
What is Cmax?
Definition
The peak concentration of drug in the body
Term
Will a drug concentration ever reach zero?
Definition

No, due to half life, it theoretically never reaches zero.

 

After a while (4 half lives or so) we just pretend that it is zero.

Term
Describe the graph for an intravascular drug concentration in the body
Definition
Starts at Cmax and then approaches zero
Term
Describe the graph for an extravascular drug concentration in the body
Definition
Slowly increases as drug is absorbed to Cpeak (at Tmax) then reduces to approach zero
Term
What is Cpeak? When does Cpeak happen?
Definition
Cpeak is when an extravascular drug is at its highest blood concentration. The time this occurs is called Tmax
Term
What are the steps of oral absorption?
Definition
Drug in stomach:
1. Disintegration
2. Dissolution (going into solution)
Then a percentage passes epithelium into circulation
Term
What factors affect absorption through GI epithelium?
Definition

1. MW (lower, <500, is easier absorbed)

2. pKa

3. Solubility

4. Dosage form (liquid faster than tablet)

5. Anatomy and physiology of gut

Term
Define distribution
Definition
Various transport processes that take the drug from the site of absorption to general circulation
Term
What is the medium through which the drug distributes?
Definition
Blood
Term
List some factors that affect drug distribution
Definition
Body tissue characteristics, disease state, lipid solubility, regional pH differences, extend of drug protein binding
Term
What are some organs highly perfused with blood? What are some areas poorly perfused?
Definition
High- heart, liver, lungs, kidneys
Medium- skeletal muscle
Low- fat tissue, brain, bone
Term
How would disease state affect drug distribution?
Definition
If there is a disease that affects blood perfusion, such as heart failure, drugs are less/slower distributed
Term
What form of a drug is more lipid/membrane soluble?
Definition
Unionized
Term
What drug form is less fat soluble?
Definition
Polar, hydrophyllic, ionized

Ex. Aminoglycosides
Term
Give an example of how regional differences in pH can trap a drug in a tissue
Definition
Some drugs are unionized at 7.4 and pass into breast tissue. Once inside, they ionize due to acidic pH and become trapped.

Another example- urine
Term
List some common binding proteins found in the blood. How do they affect drug distribution?
Definition
Albumin, α-acid glycoprotein, and lipoprotein

Bound drugs don't pass through membranes
Term
What is another term for metabolism?
Definition
Biotransformation
Term
Define metabolism
Definition
When drugs are acted on by liver enzymes and converted to metabolites (therapeutically inactive products)
Term
What is phase I of metabolic processes?
Definition
Oxidation, reduction, and hydrolysis
Term
What is phase II of metabolic processes?
Definition
Conjugation (something added to the drug, often gluconic acid) to increase polarity

aka synthetic reactions
Term
What is the overall goal of metabolism?
Definition
To render a drug inactive and to make it more hydrophillic (polar) to be excreted in the urine
Term
Define elimination
Definition
The sum of metabolic and excretion processes in the body
Term
Renal excretion is the sum of what three kidney mechanisms?
Definition
1. Glomerular filtration
2. Tubular secretion
3. Tubular reabsorption
Term
What is the most common mode of drug administration?
Definition
Oral (po)
Term
What are downsides to oral drug administration?
Definition
Some is lost in degradation, drug absorbed in an unpredictable manner, drugs can't be given to patients with nausea, GI intolerance, or unconsciousness
Term
Other than urine, what ways can drugs be excreted?
Definition
Bile, sweat, breast milk
Term
Define parenteral
Definition
Any route other than the GI tract (usually means injection)

para=outside enteron=intestine
Term
What is a requirement for parenteral drug formulations?
Definition
Sterlization
Term
List the parenteral needle routes from shortest needle to longest needle
Definition
Intradermal, subcutaneous, intravenous, intramuscular
Term
Define intravascular
Definition
Intravenous and (less commonly) intratria, introduction of drug directly into vasculature
Term
What are benefits to intravascular administration?
Definition
Bypasses absorption, rapid and complete drug availability in systemic circulation, good for emergencies
Term
What are downsides to intravascular administration?
Definition
Painful, infection risk, requires skill and training to administer
Term
Define intramuscular
Definition
Administration into muscle tissue
Term
Where are the common sites of intramuscular injection?
Definition
Deltoid, vastus lateralis, gluteus
Term
When would intramuscular administration be used?
Definition
When a predictable and uniform absorption is desired over immediate effect
Term
What are downsides to intramuscular administration?
Definition
Slower, irritation around injection site, painful, requires skill/training to administer
Term
Define subcutaneous administration
Definition
Drug is injected into the connective tissue below the skin
Term
Why would subcutaneous injection be chosen?
Definition
If a slower rate of absorption is desired; to avoid an intense, short, frequent dosage
Term
What are classic examples of subcutaneous injections?
Definition
Insulin, sodium heparin (can't be oral and need to be absorbed slowly over hours)
Term
What is a benefit of subcutaneous over iv or im?
Definition
Subcutaneous doesn't require medical supervision and can be self administered
Term
Define intradermal
Definition
Drug is injected into a skin layer, uncommon
Term
When would intradermal be used?
Definition
Usually for diagnostic and test procedures, such as allergy testing or PPD testing
Term
Define intrathecal administration
Definition
Drug is injected into spinal canal
Term
When is intrathecal administration used?
Definition
Spinal anesthesia, chemotherapy, or pain management
Term
Define intraperitoneal administration
Definition
Drug is injected into the peritoneum (aka paritoneal cavity), a serous membrane which forms the lining of abdominal cavity
Term
When would intraperitoneal administration be used?
Definition
When large amounts of blood replacement fluids or needed; when low blood pressure prevents use of suitable iv
Term
When would topical drug administration be used?
Definition
When localized effects are required
Term
What are the three categories of drug administration?
Definition
Oral, parenteral, topical
Term
Define inhalation administration
Definition
Nose/lung delivery system
Term
When would a nose inhalation administration be used?
Definition
If the drug is a decongestant
Term
When would a lung inhalation administration be used?
Definition
Anti-asthmatic or to manage COPDs with bronchiodialators, corticosteroids

(Side note- Nebulizers are used if the patient cannot take a deep enough breath for a metered dose inhaler)
Term
Define dermal drug administration
Definition
Drug is applied directly on the intended region to treat skin disorders

Also, transdermal administration is when drug is introduced into circulation after application to the skin
Term
Give an example of a disease requiring dermal topical administered drug
Definition
Eczema, pruritis
Term
Give an example of a transdermal topical administered drug
Definition
Scoplamine patch for motion sickness
Term
Define oral mucosal administration
Definition
Drug is administered in the form of gel or paste in the mouth for localized effect
Term
Give an example of a complaint requiring oral mucosal topical administered drug
Definition
Mouth ulcers
Term
What form are rectal/vaginal administered drugs in?
Definition
Suppositories, ointments, or creams
Term
What sorts of diseases would require rectal/vaginal drug administration
Definition
(I'm sure we all just got some lovely mental images)

Localized infection, hemorrhoids, inflammation
Term
Define intraocular
Definition
Topical drug administration in the form of solution to treat various eye infections or to manage post operative eye
Term
Define intravitreal
Definition
Injection into the vitreous of the eye
Term
Define intracardiac
Definition
Injection directly into the heart. Rare. example: epinephrine in cardiac arrest
Term
Define intracavernosal
Definition
Penile injection, often used to treat erectile dysfunction (phenylephrine)
Term
Define solution
Definition
A homogenous molecular dispersion of two or more components
Term
Define solubility
Definition
The concentration of solute dissolved in a unit of solvent in equilibrium at a certain temperature
Term
How is solublilization related to precipitation?
Definition
They are in equilibrium and can shift to either side
Term
Define solubility constant Ksolubility
Definition
Ksolubility= solubilization rate/precipitation rate
Term
What are the three work-requiring steps of dissolution?
Definition
1. Molecular breakdown of solute
2. Creation of molecular space for solute molecules
3. Integration of solute molecules
Term
Define heat of solution (ΔHsolution)
Definition
The heat absorbed per mole when a small quantity of solute is added to a large quantity of solution
Term
Give the formula for heat of solution (ΔHsolution)
Definition
ΔHsolution = ΔH sublimation + ΔH hydration
Term
Define ΔH sublimation
Definition
Energy required to separate 1 mole of solute into its ions in gaseous states
Term
Define ΔH hydration
Definition
Heat liberation when one mole of gaseous ions are hydrated
Term
How are ΔH solution and solubility related?
Definition
The lower the ΔH solution, the more soluble (inversely related)
Term
Define solubility product
Definition

A property of only slightly soluble electrolytes

 

AaBb  ↔ aA+ + bB-

Term
Define K'sp
Definition

K'sp= [A+]a[B-]b

Make sure you know how to solve. For example, moles need to be doubled if 2 are produced in solution, then squared as indicated by the ^a and ^b above

 

Has the ' because it is not ideal mathematically

Term
When will a solution precipitate (based on ion product and solubility product)?
Definition
Precipitation will occur if ionic product > solubility product
Term
What happens if a common ion is added to a solution?
Definition
It shifts the equilibrium to the left (reducing solubility) because it increases ionic product
Term
What happens if an indifferent ion is added to a solution?
Definition
Equilibrium is shifted towards the right (increasing solubility)
Term
Why does an indifferent electrolyte increase solubility?
Definition
From his notes: Because it increases ionic strength, which reduces the "activity coefficient" of the sparingly soluble salt From what I understand: Because the indifferent ions will bind to the solute ions, reducing common ion availability and forming more soluble products
Term
Define activity coefficient
Definition

A function of the work of solubilization and the volumes of solute and solvent

 

Xideal x γ = X real

 

Relates real and ideal work of solubilization

Term
How does addition of an indifferent electrolyte decrease γ ?
Definition

Ideal Ksp = γAB x [A+][B-]

 

So Ideal Ksp = γAB x Apparent Ksp

 

 

Apparent Ksp = Ideal Ksp / γAB

 

AB  and Apparent Ksp are inversely related)

Term
Give an example of a clinical discovery where an indifferent ion was added into a solution
Definition
Oral or iv administration of phosphate salts lowers serum calcium concentration in hypercalemic human subjects.

Once calcium was precipitated as CaHPO4, it could be eliminated
Term
Why does heating enhance solubility in liquids (most of the time)?
Definition
Because of LeChatlier's principle. Solubilization is usually endothermic, by adding heat the reaction can shift to lead to more solubilization
Term
How do cosolvents aid solubility?
Definition
Cosolvents aid in dissolving unionized molecules, especially if the solute is nonpolar
Term
When do cosolvents decrease solubility?
Definition
If the solute is polar

(water is already polar so adding a nonpolar cosolvent would decrease solubility)
Term
List some common co-solvents
Definition
Glycerin, ethyl alcohol, propylene glycol, polyethylene glycol
Term
How does pH assist solubility?
Definition
Adding an acid or base promotes ionization, ionized solutes have strong ion-dipole interactions with water
Term
What is another way to represent HA ↔ H+ + A- ?
Definition
S= So + Si

So is unionized
Si is ionized
Term
Give the Henderson-Hasselbach equation for solubility
Definition
ph= pKa + log (S-So/So)

For weak acid

ph= 14- pKa + log (So/S-So)

For weak base
Term
What happens when alcohol is added to an aqueous solution of weak electrolytes?
Definition
Increases the solubility of un-ionized species

Decreases solubility by raising pKa
Term
How do surfactants influence solubility?
Definition
Increases:
Ionized drug remains in the water phase, unionized are allowed to reside in the hydrophobic core of micelles
Term
Describe complexation
Definition
Enhances solubility to a maximum level before saturation; works through relatively weak forces such as hiding hydrophobicity
Term
Give some examples of complexing agents
Definition
Ammonia, caffeine, phenols, EDTA (chelation), cyclodextrins, molecular complexes PEG, PVP, methyl cellulose
Term
What are cyclodextrins?
Definition
Cycles of glucose (with a cavity) that increase solubility of hydrophobic drugs through complexation (hiding hydrophobic groups in core)
Term
Define prodrug strategy
Definition
Modifying a drug so it is more soluble for transport across the membrane. After transport, metabolism turns it back into the active drug.
Term
Give an example of prodrug strategy
Definition
Methyldopa (active drug) is converted to methyldopate ester (prodrug) and solublized as hydrochloric salt for preparation of iv injection
Term
How does mitrometrics influence solubility
Definition
All he wants us to know is that decreasing particle size or asymmetry increases solubility
Term
List the steps of phase-solubility analysis
Definition
1. Mix in increasing amount of solvent at constant temp and pressure
2. Separate undissolved solution and estimate dissolved solute
3. Plot solution concentration vs system concentration
Term
What is Gibb's phase rule
Definition
F=C-P+2

Degrees of freedom= #components - #phases + 2
Term
When calculating degrees of freedom, what are the degrees used?
Definition
1. Concentration
2. Temperature
3. Pressure

Subtract them if they are constant!
Term
What do miscibility of liquids depend on?
Definition
Internal pressures (ex. polarity is a high internal pressure)
Term
Define complete miscibility
Definition
Solvents are miscible in any proportion
Term
If a solute is added to a binary liquid-liquid system, what happens?
Definition

It is now a ternary system

 

A) If solute is only soluble in liquid, miscibility is decreased

B) If solute is equally soluble in both liquids, miscibility is increased (blending)

Term
Define blending
Definition
Increased miscibility in a liquid-liquid system due to addition of a solute that is equally soluble in both liquids
Term
What happens when a solute is added to immiscible solvents?
Definition
The solute distributes itself between two layers in a definite ratio, K (distribution/partition coefficient) K= C1(oil)/C2(water) or K= C1(water)/C2(alcohol)
Term
If a solute is ionizing in one of the solvents, what happens to the distribution coefficient?
Definition
It is now K' and you add the unionized form of the solute to the concentration where it is dissociating
Term
*I just want to include a note here that I did not attempt to make flashcards for the equation manipulations for the "distribution" notes. It is math rearrangement that does not translate well to flashcards.
Definition
Term
What is required for preservatives to work?
Definition
They need to partition into microbes to work

ex. Benzoic acid needs to be in [HA], water phase
Term
Define octanol-water partician coefficient
Definition
An indication of lipophilicity or hydrophilicity of a drug. A drug with higher coefficient is stronger and longer lasting
Term
What is the octanol/water coefficient required for oral administration?
Definition
Log of the partition coefficient must be <5
Term
What are Lipinski's rule for oral administration?
Definition
An orally active drug has no more than one violation of the following criteria:

1. Not more than 5 hydrogen bond donors (nitrogen or oxygen atoms with one or more hydrogen atoms)
2. Not more than 10 hydrogen bond acceptors (nitrogen or oxygen atoms)
3. A molecular mass not greater than 500 daltons
4. An octanol-water partition coefficient[3] log P not greater than 5

Notice all the rules have multiples of 5 in them!
Term
What are benefits to oral solutions over oral tablets/capsules?
Definition
-Better for infants, pediatrics, geriatic, psychiatric
-Therapeutically effective and diverse
-Minimizes "cheeking"
Term
What are disadvantages to oral solutions over oral tablets/capsules?
Definition
-Less stable
-Some drugs are not soluble
-Must mask taste
-Bulky, hard to transport
-Requires patient measurement
Term
What are the three phase types of solutions?
Definition
Solids in liquids, liquids in liquids, gases in liquids
Term
What solutes, other than the drug, are often added to solutions?
Definition
Color, flavor, sweetness, stability, buffering salts, preservatives
Term
What is a consideration when adding dye to solutions?
Definition
The pH needs to be watched because the dye might precipitate out
Term
Give two examples of official aqueous saturated solutions
Definition
CaOH topical, KI oral
Term
List three auxiliary solvents
Definition
Alcohol, glycerin, propylene glycol
Term
What is a recent concern of using propylene glycol as a solvent?
Definition
The WHO recently established a maximum daily intake (though there is no known toxicity dose)

Concerns of lethargy, apnea, and metabolic acidosis in pediatrics
Term
What are the three ways to get purified water?
Definition
Distillation, ion exchange treatment, or reverse osmosis
Term
What is the definition of a purified water?
Definition
When evaporated, it must not yield more than 0.001% residue (100x more pure than tap water)
Term
What are four types of USP waters?
Definition
1. Purified water

2.Water for injection (most widely used)

3. sterile water for injection (packaged in single dose containers)

4. Bacteriostatic water for injection (contains antimicrobial agents)
Term
Describe alcohol, USP
Definition
Ethanol, ethyl alcohol 95-96%
Term
Describe dehydrated alcohol, USP
Definition
No less than 99.5% ethanol

Used where a water-free alcohol is desired
Term
Describe diluted alcohol, USP
Definition
Useful mix of alcohol and purified water

49%
Term
Describe rubbing alcohol
Definition
70% ethyl alcohol with water, denaturants, color/purfume, stabilizer

Denaturants discourage consumption
Term
Describe isopropyl rubbing alcohol
Definition
70% or 91% isopropyl alcohol

With water, color/purfume, stabilizers

Used for hypodermic injections and disinfecting skin
Term
What is the first step in making a drug solution?
Definition
Check the solubility of the drug

Remington's or Merck Index
Term
What units are solubility given in
Definition
Grams of solute per mL of solvent
Term
Define stress testing
Definition
A way to test if a drug will still be soluble under storage at non-standard temperatures

Solutions are subject to temperature elevations in 10 degree Celsius
Term
When heating a solution to dissolve a drug, what is important to remember?
Definition
Do not use concentrations higher than the solubility at room temperature
Term
In liquids, which three solvent combinations are miscible?
Definition
1. Alcohol and water
2. Glycerin and water
3. Glycerin and alcohol
Term
What is the main concern of stability of solutions?
Definition
Precipitation
Term
Define adjuvant
Definition
a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself
Term
Define dry mixtures for reconstitution
Definition
Include everything besides the solvent (usually distilled water)
Term
Describe rehydration solutions
Definition
Things like pedialyte with lots of electrolytes, liquid and powder, should not be mixed with electrolyte containing liquids
Term
Define oral colonic lavage solution
Definition
An osmotic laxative, has electolytes with polyethylene glycol

240mL every 10 minutes until 4L consumed
Term
Define magnesium citrate oral solution
Definition
A saline cathartic with citric acid, lemon oil, syrup, and carbonation
Term
Define sodium citrate and citric acid oral solution
Definition
Used to alleviate gout or uric acid by being an alkalinizer
Term
Describe syrup
Definition
Sugared vehicles (little or no alcohol), pH varies, must be preserved against bacteria unless sucrose is greater than 65%w/w or 85%w/v
Term
What are the three types of syrup
Definition
Simple, flavoring, and medicinal
Term
Describe simple syrup
Definition
850g sucrose and 450mL water/L

Concentrated, but not saturated. Must make sure it is stable at the temperature needed.
Term
Do syrups have a higher or lower solvent power than water?
Definition
Lower (they are worse solvents) because there is already bonding between syrup and water
Term
What can replace sugar in syrups?
Definition
Methylcellulose or hydroxyethylcellulose (important for diabetic patients

Cellulose (to increase viscocity) and artificial sweetener
Term
List some antimicrobial preservatives
Definition
Benzoic acid, sodium benzoate, methylparaben, polyparaben, alcohol, sorbic acid
Term
Describe flavorants
Definition
Must be water soluble, synthetic or naturally occurring

Ex. orange oil, vanillin
Term
What are the three ways to preserve syrups
Definition
Solution with heat, agitation without heat, percolation
Term
Define inversion (in a syrup)
Definition
Under heat, sucrose is hydrolyzed into dextrose and fructose (sweeter and darker)

Overheating causes caramelization (more susceptible to decomposition)
Term
Define percolation
Definition
Forming an extract of sucrose to prepare a syrup

Uncommon
Term
Describe elixers
Definition
Clear, sweetened hydroalcoholic solutions

Alcohol 5-40%

Less effective in masking taste than syrups

Glycerin is often added to enhance solvent and act as preservative
Term
What are some advantages and disadvantages of elixers?
Definition
Advantage: flexibility and ease of dosing

Disadvantage: alcohol content
Term
Define tincture
Definition
Alcoholic or hydroalcoholic solutions prepared from vegetable or chemical substances (Nonvolatile)

Alcohol from 15-80%

Can't be mixed in diverse liquids, precipitation is common

Poor taste
Term
If a patient is on metronidazole or chloropropamide, what should they not have?
Definition
Alcohol-containing substances

Disulfurrin reaction, very bad
Term
Define spray
Definition
Aqueous or aleaginous solutions in the form of course droplets or as finely divided solids to be applied topically
Term
Define NaCl equivalent
Definition
The amount of NaCl that is osmotically equivalent to 1g of the drug
Term
Describe aluminum acetate topical solution
Definition
Applied topically as an astringent wash; used in various types of dermatologic lotions/creams/pastes
Term
What is another term for CaOH topical solution?
Definition
Limewater
Term
Define Coal Tar topical solution?
Definition
An alcoholic solution containing 20% coal tar and 5% polysorbate 80 (a nonionic surfactant)
Term
Define hydrogen peroxide topical solution
Definition
Local anti-infective for use topically on the skin
Term
Can you use ear products in the eye? Can you use eye products in the ear?
Definition
You can use eye products in the ear, but not the other way around
Term
Define chlorhexidine gluconate solution
Definition
Broad spectrum antiseptic, used as a surgical scrub and skin cleanser
Term
Define thimerosal topical solution
Definition
Water-soluble mercurial antibacterial and mild antifungal agent, also used as a preservative
Term
Define retention enemas
Definition
Solutions administered rectally for local effects (hydrocortisone) or for systemic absorption (aminophylline)
Term
What are two examples of topical tinctures
Definition
Iodine tincture, compound benzoin tincture (prepared by maceration)
Term
Define maceration
Definition
"to soak", a properly comminuted drug is permitted to soak in the menstuum until the soluble constituents are dissolved
Term
Define spirits (essences)
Definition
Alcoholic solutions (>60%) of volatile substances

Separate from water, used as a flavoring agent, may be taken orally, topically, or inhaled
Term
Define liniments
Definition
Alcoholic or oleaginous solutions or emulsions of various medicinal substances intended to be rubbed on the skin
Term
Define collodions
Definition
Liquid preparations composed of pyroxylin dissolved in a solvent mixture

Usually composed of alcohol and ether with or without medicinal substances
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