Quiz 1 Flashcards
Schedule II controlled substances
Very high abuse potential, high dependence
No refills or phone ins, some states require triplicate Rx, expires 7 days-6 months
Ex. Morphine, amphetamines
Schedule I controlled substances
No medical use, very high abuse potential
Ex. Pcp, marijuana, ecstasy, heroin
Schedule III controlled substances
Moderate abuse potential, mod-low physiological dependence, but high psych dependence.
Max 5 refills/6 months
Ex. Usually mix of substances- hydrocodone and acetaminophen, some stimulants
Schedule IV controlled substances
Low abuse potential, low physio dependence, may cause psych dependence.
Max 5 refills/6 months
Ex. Benzos, sleep-aids, weak barbiturates
Schedule V controlled substances
Very low abuse potential, contains small quantities of the substance.
Max 5 refills/6 months
Ex. Lomotil, codeine in antitussives
Inscription
Name of med (generic vs. brand) and dose
Subscription
Medication formulation and number to be dispensed.
Instructions for pharmacist
Superscription
Rx
Sig/signa
Directions to patient
1 tsp = ? ml
5 ml
Write using ml, not tsp
1 tbsp = ? ml
15 ml
Write using ml, not tbsp
Pharmacology
Study of drug actions
Pharmacy
Safe practice of compounding, utilizing, and dispensing medicines
Pharmacotherapeutics
Study of therapeutic use and effects of medications
Pharmacogenomics
Study of relationship of patients genetic makeup to specific medications
PharmacoDynamics
What the drug does to the body
Pharmacokinetics
What the BODY does to the drug:
Through absorption, metabolism (bioavailability), distribution, elimination.
What property is required for a drug to move through the body? A. A negative electric charge B. transport protein C. Ability to cross membranes D. Selective affinity
C. Ability to cross membranes
When ordering an oral medication, you know that only a portion of the does actually reaches systemic circulation because of what process? A. Hepatic first pass B. renal bio transformation C. Protein binding D. Receptor affinity
A. Hepatic first pass
A patient reports becoming “immune” to a medication because it no longer works to alleviate symptoms. You recognize that this decreased effectiveness is likely caused by
Desensitization of receptor sites by continual exposure to the drug
The components of the cell or organism that the medication binds with to achieve its therapeutic effect
Receptor
What determines the medication dose or concentration?
Receptors’ affinity.
Affinity
The strength of attraction between the receptor and medication
The stronger the affinity, the stronger the response, the smaller needed dose
Higher affinity can cause more side-effects, though
Intrinsic activity
Ability of the medication to bind to the receptor
Receptor sensitivity
Receptors response to medication, altered by other medications and electrolytes (hypokalemia effects digoxin toxicity)
Receptor Selectivity
Medications ability to prefer one receptor over the other
Want medication to be highly selective and specific
Receptor specificity
Medications ability to bind with only one receptor
Want medication to be highly selective, highly specific
Agonist
Medication that binds to naturally occurring receptor and activates receptor
Ex. Albuterol
Antagonist
A medication that binds to a receptor and blocks stimulation from another medication or naturally occurring substance
Ex. Narcan
Competitive
Noncompetitive
Chemical-meds bind to other meds and inactivate
Physiological-cause physio effect opposite of that med
Desensitization
Receptors become less responsive over time
Inactivation
Receptor loses function
Up-regulation
Number of cell receptors may increase, may result from prolonged antagonism
Down-regulation
Number of cell receptors may decrease, usually related to prolonged stimulation
Why chronic medication doses increase over time
Goal of prescribing medications is to administer at same rate as..
Same rate as excretion of the drug
Tachphylaxis
Rapid tolerance and decrease benefit to medication
Absorption
The movement of the medication from its site of administration into the blood stream
By- passive diffusion, facilitated diffusion, filtration, or active transport
Passive diffusion
Movement from higher concentration to lower
Lipophilic, hydrophilic
Requires no energy
Lipophilic
Lipid-soluble, non-ionized, moves through phospholipid bilayer easier and faster than hydrophilic
Hydrophilic
Water-soluble, ionized, moves through plasma easier
Facilitated diffusion
Medication combines with another molecule to facilitate absorption
Requires no energy
Filtration
Medication passes through pores in membranes
Smaller molecules
Affected by concentration gradient
No energy required
Active transport
Medication moved against gradient USING ATP/energy, usually by a protein
Larger molecules
Bioavailability
Amount of unchanged medication that enters systemic circulation
Determines the medication’s ability to have a therapeutic benefit
Iv meds are 100% bioavailable
Low bioavailability means goes through a lot of first pass and decrease of the amount of drug absorbed
Distribution
How the medication is transported throughout the body to the cells
Affected by similar factors that affect absorption
Lipophilic are faster and easier to move across membrane
Total med level=
Bound level + Free level
The more the medication is bound to proteins, the less it’s available for distribution, metabolism, and elimination.
The free medication is what is available to be used
Albumin
Transport protein used in distribution, acidic medications bind strongly to
Hypoalbumenemia could lead to a transient increase in free drug level and risk of toxicity, why important to think about nutrition status
Ex.warfarin
Higher binding potential makes medication more unstable and more likely to have complications
Alpha 1-acid glycoproteins
Lipoprotein that is used in distribution, basic medications bind strongly to
Ex. Propranolol
Higher binding potential makes medication more unstable and more likely to have complications
Depot storage
Lipophilic medications accumulate in adipose tissue.
More fat, require more medication
Calcium binding medication accumulate in bones and teeth
Watch in pregnancy
Volume of distribution
A calculated value that defines the distribution of the medication throughout the body.
Theoretical value of how well drugs distribute through the body. Cardiac, liver, adipose all effect absorption
Defines where the drug likes to be.
Large Vd
Widely distributed-vascular and extra vascular
Lipophilic, neutrally charged and not tightly bound
Can cross blood brain barrier if needed
Removed in a steady state
High Vd-higher dose to get to target plasma concentration
Small Vd
Minimally distributed throughout the body:mainly contained in vascular space
Tightly bound to proteins and highly water-soluble (hydrophilic)
Can’t cross over membranes
Not distributed well
Need small dose to obtain target plasma concentration
Metabolism
(Bio transformation)
Changes that occur to the administered active medication that lead to less-active metabolites, active metabolites, or changes in a pro-drug into an active drug
First pass metabolism
Metabolism of the drug before it reaches the systemic circulation
All enteral meds will go through
Increase first pass, decrease plasma concentration of drug
Through GI tract (acidic environment) and/or through liver via portal vein
Eventually all medication go through hepatic metabolism via hepatic artery, some just go through body first.
Phase I of hepatic biotransformation
(Nonsynthetic) Uses enzyme cytochrome p450 (cyp 450) to oxidize, reduce, or hydrolyze to form a more polar charge so that it can tx through membrane and be eliminated. Lipophilic-easier to absorb, more water soluble-easier to excrete
Phase II of hepatic transformation
(Synthetic) (non-microsomal), conjugation reactions to attach medication with a polar group to facilitate elimination through kidneys
To be excreted by the kidneys, does the molecule need to be polar or nonpolar?
Must be polar, have a charge to go through tubules
And hydrophilic
Do all medications go through phase I AND phase II of hepatic biotransformation?
All meds must go through hepatic biotransformation, but the phases are not sequential or necessary for all medications
Glucuronidation
Addition of glucuronic acid to drug to make more acid and able to be eliminated
Cytochrome P450
Located mainly in endoplasmic reticulum of hepatocytes
Responsible for the non synthetic, microsomal phase of hepatic biotransformation
A patient has liver failure. How does this effect his ability to metabolize medications?
It decreases his ability to metabolize a medication. It also increases his chances of toxicity.
Inducers
A medication or chemical that increases activity and/production of CYP.
Results in decrease in amount of the medication and sub therapeutic levels
Ex. Smoking, phenytoin, alcohol, benzos
If a patient smokes, is he at risk for subtherapeutic or supertherapeutic drug levels?
Subtherapeutic, because it induces CYP, which increases metabolism.
Inhibitors
A medication or chemical that decreases activity and/or production of CYP
Results in an increased amount of the medication and risk for toxicity
Ex. Grapefruit juice, birth control, allopurinol
Liver failure, heart failure can cause decrease perfusion and decrease metabolism too
Why do you instruct patients to not drink grapefruit juice while taking some medications?
Because it is an inhibitor of CYP, that is responsible for phase one of hepatic biotransformation. A decrease in this enzyme will decrease metabolism of a medications and cause an excess or toxic level
Enterohepatic recirculation
Some medications are reabsorbed into the small intestine and subsequently retained in the portal and then systemic circulation
Ex. Steroids, digoxin and some cancer agents
What main organ is responsible for elimination?
Kidney
A medication has a high Vd. What would you expect the half-life and clearance to be?
Shorter half-life, faster clearance
A medication has a low Vd. What would you expect the half-life and clearance to be?
Longer half-life, slow clearance. RISK for TOXICITY. Smaller amount of drug needed for therapeutic effect.
What lab should you evaluate in determining renal function and dosing of medication?
Creatinine clearance
Why should you not just rely on serum creatinine?
Normal is 0.75-1.2
Will not elevate until there is a 60% decrease in renal function
Effected by muscle mass-smaller muscle mass causes lower creatinine
How do you obtain creatinine clearance and what does it represent?
Obtained by a 24-hour urine test, use to evaluate Rx, estimates GFR, normal 110-120 ml/min for healthy adult-decreases 1ml/min per year after age 40. Not a concern until gets below 50
Formula for creatinine clearance
CrCl= (UrVolume in ml/min x UrCr in mg/dL) / Serum Cr in mg/dL
If 24 hour urine is not obtained, how else can you get creatinine clearance?
Crockcroft-Gault formula
CrCl= [(140-age in years) x (wt kg)] / 72 x Serum Cr in mg/dL
** multiply total by 85% if female **
Lbs to kilograms
kg = lbs/2.2
Creatinine clearance general guidelines
> 50 = little to no change in therapy
25-49 = moderate decrease in dose or frequency
< 25 = significant dose decrease and frequency
What is better absorbed-pills or liquids?
Liquids
Solutions
2 or more dissolved substances
Aromatic waters
Water based solution with volatile substance
Extracts
Very concentrated medication in alcohol and water
Tinctures
Alcohol based extracts
Elixirs
Alcohol, water, sugar, and flavoring in a solution
Syrups
Sugar and water
Emulsions
Oil and water
Liniments
Alcohol, oil or soap
Suspensions
Solid in liquid that does not dissolve
How would an abrasion effect a topical medication?
Would increase absorption
Do medications administered by an epidural go through hepatic biotransformation?
No, epidural medications are local and not absorbed. Do not enter systemic circulation.
Intranasal
Absorbed as fast as iv. If need med and no iv present. Systemically absorbed
Dose
Amount given each time
Dosage
Overall amount of drug given per course of therapy
Onset of action
Time it takes for medication to cause its desired effect
Minimum effective concentration
Minimum concentration at which medication causes its desired effect.
Must give dose at at least this concentration to have effect.
Shorter the half-life, the faster you will reach this goal.
Steady state concentration
Time the medication stays at constant concentration in regards to a single administration (plateau)
Typically takes 4-5 half lives to acheive
Goal - Amount administered equal to amount eliminated
Therapeutic Index
Measure of the medications safety.
Margin between the lethal dose and effective dose.
The wider the TI, the safer the medication
Ex. Digoxin has a narrow TI
Peak
High point of concentration after administration.
Highest risk for toxicity at this point.
Trough
The low point of concentration after administration
Little to no therapeutic effect
Half Life
Amount of time it takes for the medication concentration to decrease by 50% after the medication is discontinued.
Normally takes 4-5 half lives to reach steady state
Normally takes 3-4 half lives to eliminate 90% of medication once it is stopped
Very dependent on hepatic and renal function
Does half life change by route?
No- half life is independent of route. Same iv or po.
Zero order medications
Doesn’t matter the concentration of medication. Metabolizes at same rate.
First order medications
Increase in concentration causes and increase in metabolism and eliminatio
Most drugs act this way
If Levaquin has a half life of 6-8 hours, how often would you give the medication?
You would give once daily. Half life of 6-8 hours, usually takes 4-5 half lives to reach therapeutic level, so 6 x 4= 24 hours
After discontinuation of Levaquin, half life of 6-8 hours, how long does it stay in circulation?
Takes 18 hours to decrease by 90%. Takes 3-4 half lives.
Duration of action
The time the medication has a desired effect.
The amount of time the drug is effective
Short duration, give at regular intervals
Same as half life?
Maximum efficacy
The degree to which the medication causes its maximum therapeutic effect
Ex. 100 mcg of fentanyl may have top benefit. 200 mcg will not make more effective than that dose for that patient
How effective is the drug?
Potency
The amount of medication needed to produce 50% of the maximum response.
Used to compare same class drugs Ex. Dilaudid is more potent than morphine because it takes less of the drug to have effect. Both are effective, but dilaudid is more potent.
Considered potent when has a high intrinsic activity at a low dose, meaning higher affinity to receptors
Addition interaction
2 or more meds have a combined benefit
1+1=2
Synergistic interaction
2 or more meds have a greater response when combined, than given separately
1+1=3
Increased reaction
Potentiation interaction
Separately the meds are weak or ineffective, but given together they are more effective.
0+2=2
Antagonism interaction
One med inhibits or blocks the other med
1+1=0
A 56 year old man has chronic kidney disease. Will metabolism be effected?
No, elimination will be effected
A 76 year old has an elevated temperature. Will this effect metabolism?
Yes, there will be an increase in metabolism, no effect on elimination
Why is metabolism decreased in an infant?
Liver is still developing
The ACNP is reviewing an older adult patient's chart before ordering medications. Which is of most concern? A. Chronic constipation B. Increased body fat C. Low serum albumin D. Low serum creatinine
C. Low serum albumin-transport binding competition
Increased body fat would increase storage of drug, not as concerned with creatinine. Decreased in older adults and dependent on muscle mass.
When is the highest risk of teratogen-induced gross malformations during pregnancy?
During the first trimester, first three months
Can bound drugs cross the placental membrane?
No, only free drugs can cross the placental membrane.
Lipophilic, nonpolar drugs cross the membrane
Category A
Safe, well controlled studies, no risk
Category B
Animal studies show that they are safe, but no human studies done
Category C
Studies are unavailable or studies show could be harmful.
Not recommended, but use if potential benefit justifies risk
Category D
Known fetal risk. Do not use unless life-threatening for mother. Will effect baby.
Category X
Known fetal risk, no benefit
How long should a lactating mother wait between breast feeding and taking medication?
3-4 hours before.
What is the only process that will no change dramatically due to age?
Absorption
Distributive changes seen in elderly
Decrease in body water and muscle mass Increase Vd and prolong half life Increase in body fat Increase Vd and prolong half life Decreased albumin levels Increased glycoprotein levels
Metabolism changes in elderly
Without liver disease, there is usually no major decline in function. Some phase I slowed
With age, liver recovers slower.
Top 10 Drugs to Avoid in Elderly
- NSAIDS- increase risk for ulcers and bleeding
- Digoxin- easier toxicity d/t decreased kidney function
- Sulfonylureas- severe decrease in BG
- Muscle Relaxants- over sedation leading to falls, cause constipation
- Benzos and sleep aids- over sedation leading to falls
- Anticholinergics- ex. Elavil, urinary retention, hypovolemia, constipation
- Demerol/Meperidine- seizures
- Antihistamines- same as anticholinergics
- Antipsychotics- avoid 1st generations (ex. Haldol), increase risk of stroke and falls
- Estrogen- increase risk of cancer
