Essentials Of Medical Pharmacy - Week 1 **printed**

Front 1

Scope of Pharmacology:
1) pharmacodynamics
2) pharmacokinetics
3) pharmacogenetics
4) pharmacognosy
5) pharmacotherapeutics
6) toxicology

Back 1

1) pharmacodynamics: what the drug does to the body
2) pharmacokinetics: what the body does to the drug
3) pharmacogenetics: unusual response to drugs due to genetics
4) pharmacognosy: drugs derived from herbal and natural resources
5) pharmacotherapeutics: how drug may best be used in therapy
6) toxicology: the study of poisons

Front 2

What is the therapeutic importance of drugs?

Back 2

It is the primary mean for prevention and alleviation of disease

Front 3

What is the difference between signs and symptoms?

Back 3

signs: objective measurement, lab findings

symptoms: subjective events described by the patient

Front 4

What are the factors important for maximizing the beneficial effect of drugs?

Back 4

* maintain a positive, supportive relationship with patient
* avoid drug interactions by obtaining a careful drug history
* monitoring changes and change regimen if necessary (ensure patient compliance)
* provide adequate information about good and adverse effects

Front 5

How many names does a drug have?

Back 5

1) chemical name
2) generic or nonproprietary name
3) brand or proprietary name (patented)

Front 6

Pregnancy Categories

Back 6

A: no increased risk
B: no adequate studies in pregnant women and animal studies show no risk OR studies in pregnant women have not shown risks but animal studies have
C: no adequate studies in pregnant women but animal studies have shown risk OR no adequate studies in pregnant women or animals
D: studies in pregnant women show risk, use only when benefit outweigh risks
X: studies in pregnant women show risk, not to be used!

Front 7

Drug Schedules

Back 7

I: high potential for abuse, NO accepted medical use (ie. ecstacy, heroin, canabis)
II: high potential for abuse, an accepted medical use (ie. cocaine, morphine)
III: potential for abuse, an accepted medical use (ie. vicodin)
IV: low potential for abuse with accepted medical use
V: even lower risk for abuse

Front 8

Drug Units

Back 8

* mole: Avogadros # = 6.022*10^23 entitites

*molar (M): unit of concentration (1mol/L)

* weight/volume percent (g/mL)

* cubic centimeter = 1 mL

* international unit (IU)

Front 9

Sources of Drugs

Back 9

* inorganic material (ie. metals for chemotherapy)

* living organisms (ie. hormones, alkaloids, vaccines, antibodies)

* synthetic or semisynthetic

* genetic engineering (ie. recombinant insulin)

Front 10

What is the difference between potency and efficacy?

Back 10

potency: refers to the amount of drug necessary to elicit a response

efficacy: a drugs ability to produce the maximal desired response

Which is more important?? EFFICACY

Front 11

What is the difference between a specialized and generalized receptor?

Back 11

receptor = site of drug action

generalized receptor: biological molecules (ie. enzymes, lipids, nucleic acid)

specialized receptor: ion channels and proteins in the plasma membrane (targets for neurotransmitters, hormones, cytokines, and autocoids)

**drugs and receptors interact via chemical bonds**

Front 12

Define:
affinity
specificity
stereoselectivity

Back 12

affinity: ...of the drug for the receptor
-binding constant of the drug for the receptor protein

specificity: ...of drug action
-depends on receptor and their distribution

stereoselectivity:
-size, shape and charge of a receptor
-chirality matters because less active isomer may not be able to orient all binding areas to the receptor surface

Front 13

What are the three modulators?

Back 13

Agonist: bind receptor and activates it

Antagonist: bind receptor and does NOT activate it

Allosteric modulator: binds at a separate allosteric site and either increases or decreases the response of natural agonist

Front 14

How many receptor superfamilies are there?

Back 14

1) ligand-gated ion channel
2) G-Protein-Coupled receptor (four families of G-proteins with purpose to carry G-protein couple receptor into cell; majority of drugs target)
3) receptor tyrosine kinase
4) nuclear hormone receptor (binds ligand in cytosol and translocates to the nucleus)

Front 15

Concentration/Response relationships

Back 15

* quantification of the amount of drug necessary to produce a given response
* ligand-receptor interactions produces, in most cases, a reversible bimolecular reaction

Front 16

Graded vs. Quantal Response

Back 16

Graded Response: vary from minimum to maximum response; increases continuously with increasing drug concentration

Quantal Response: all-or-none response to drugs; requires the use of populations of subjects; few at low doses, most at intermediate dose, and few at high doses

Front 17

Competitive vs. Noncompetitive Antagonists

Back 17

Competitive: competes at same site; reversible blockage; parallel right shift; most drugs

Noncompetitive: compete at same site; irreversible alkylating agent; forms covalent bonds; decreases receptors and maximum response

Front 18

Partial Agonist

Back 18

Partial agonists have a dual activity:
-only partly able to shift the receptor to its activated conformational shape
-inhibits the action of a full agonist down to the level of its own maximal effect

**partial agonists can sometimes act as an antagonist in the presence of a full agonist

Front 19

Absorption and Distribution:
transport of drugs across membranes

Back 19

*lipid bilayer are extremely hydrophobic
*most drugs must have some hydrophilicity to dissolve and be transported
*most transports across membrane are by simple passive diffusion

Front 20

Absorption and Distribution:
factors that favor the ability of a drug to cross a membrane

Back 20

*low molecular weight
*uncharged
*non-polar
*high lipid solubility
*oil/water equilibrium partition coefficient measures of lipid solubility or hydrophobicity
(the larger the partition coefficient, the greater the lipid solubility)

Front 21

Absorption and Distribution:
influence of pH

Back 21

*passive diffusion of a drug is a function of the pKa of the drug and the pH of the two compartments
*only the uncharged form of the drug can diffuse across membranes
(stronger acids have lower pKa values)

Front 22

Calculations:
degree of ionization

Back 22

pH-pKa = log [A-]/[HA]

Using pKa value of specific drug and pH of specific location (ie. stomach, blood, intestine), you can calculate the degree of ionization for the drug.

*ionized/charged form = [A-]
*[HA] = 1.0
*the bigger the [A-] value, the more ionized the drug is

Front 23

Type of Drug Transports

Back 23

**most drugs are transported via simple passive diffusion**
*active transport:
-specific carrier molecules
-use energy (ATP)
-saturable
-independent of concentration gradient
-in renal tubule cells, biliary tract, blood-brain barrier, GI tract
*facilitated diffusion:
-operates passively via a carrier
-glucose, amino acids
*endocytosis: a few substances are so large or impermeable that they can only enter by being engulfed

Front 24

Distribution to Special Organs and Tissues:
rate of blood flow

Back 24

Rate of blood flow determines maximum amount of drug delivered per minute.
-highly perfused: heart, brain, kidneys
-poorly perfused: bone, fat

Front 25

Distribution to Special Organs and Tissues:
blood-brain barrier

Back 25

The blood-brain barrier hinders transport of drugs and other material from blood into brain
-found throughout brain and spinal chord (except for the floor of the hypothalamus and the area postrema)
-tight junctions are present in brain capillaries
-only highly lipid-soluble drugs cross the blood-brain barrier
-may be compromised in infants and elderly

**intrathecal: route directly into brain (needed when treating meningitis with antibiotics)

Front 26

Metabolism of Drugs:

Back 26

*generally involves conversion of nonpolar, lipid-soluble compound to a more polar form
-converts prodrug to active drug

*most reactions can be categorized into four types:
1) oxidation
2) reduction
3) hydrolysis (phase I)
4) conjugation (phase II)

Front 27

Phase I

Back 27

Oxidation, Reduction and Hydrolysis (table 4-1)
*Oxidation: can take place at many different sites on a drug molecule
-an oxygen molecule may be inserted
-cytochrome P450-dependent mixed-function oxidase system
- >50 isofrosm of human P450 exist
-common feature of P450 substrates is their lipid solubility
*Reduction and Hydrolysis:
DH + NAD(P)H + H+ + O2 => DOH + NAD(P)+ + H2O

Front 28

Phase II

Back 28

Conjugation:
*couples the drug molecule to an endogenous substituent group
-resulting product will have greater water solubility
-enhanced renal and biliary elimination
-ATP-dependent
*common substituent groups:
-glucuronate
-glycine
-acetate
-sulfate

Front 29

Phase I and Phase II Reaction Sequence:

Back 29

1) Absorption
-Phase I (oxidation, reduction and hydrolysis)
2) Metabolism
-Phase II (conjugation)
3) Elimination
*drug changes from being lipophilic to hydrophilic through reaction
*does not need to go in sequence of phases

Front 30

Enzyme Inhibition and Induction:

Back 30

(tables 4-2, 4-5, and 4-6)

*different drugs may be substrates for the same metabolizing enzyme
-can competitively inhibit each other's metabolism

*many drugs, environmental chemicals and air pollutants can stimulate synthesis of drug-metabolizing enzymes
-inducers are also substrates for the enzyme they induce
-generally nonspecific and result in increases in metabolism of many substrates

Front 31

How is Tylenol metabolized?

Back 31

Acetaminophen is metabolized via the cytochrome P450 enzymes into a deleterious product, an unstable intermediate, which cases abnormal derivatives of protein, lipid, RNA and DNA, causing destruction of these compounds.
Because the liver has high levels of cytochrome P450 enzymes, it is the major organ affected by acetaminophen overdose.

Front 32

Zero-Order and First-Order Kinetics:

Back 32

*First-Order kinetic enzymes are operating at concentration levels far below saturation
-for nearly all drugs
-a constant fraction of drug is metabolized per unit time

*Zero-Order kinetic enzymes are operating at concentration levels near saturation
-a constant amount of drug is metabolized per unit time
-elimination rates no longer depend on dose or blood concentration

Front 33

Half-Life (t 1/2)

Back 33

*The time it takes for the drug concentration to decrease by half
*Accumulation and elimination rates are the same:
1 half-life = 50% of steady-state concentration is reached or lost
2 half-lives = 75% of steady-state concentration is reached or lost
4 half-lives = >90% of steady-state concentration is reached or lost
*Rule of Thumb: four half-lives must elapse after starting a drug-dosing regimen before full effects will be seen

Front 34

Hepatic and Biliary Clearance

Back 34

*enterohepatic cycling occurs when the drug is reabsorbed from the GI tracts and returned to the systemic circulation
*results in a measurable increase in the plasma concentration of drug several half-lives after the drug was originally administered

Front 35

Renal Elimination of Drugs

Back 35

(manipulation of urine pH)
*renal clearance of drugs takes place via glomerular filtration, tubular secretion, and tubular reabsorption
*In drug overdose, the manipulation of urine pH is sometimes used to prevent reabsorption
-ammonium chloride acidifies urine
-sodium bicarbonate alkalinizes urine
**bases clear rapidly by making urine more acidic
**acids clear rapidly by making urine more alkaline

Front 36

Clinical Pharmacokinetics:
Main routes of drug administration

Back 36

*enteral: drugs entering body via GI tracts
*parenteral: drugs entering body via injection
*per os: drugs entering body via mouth
-sublingual: under tongue
-oral: swallowed
-buccal: in cheek pouch
*pulmonary
*rectal
*topical
*injection
-intravenous (IV), subcutaneous (SC), intraarterial (IA), intrathecal (into subarachnoid space)

Front 37

Therapeutic Index

Back 37

*a measure of drug safety margin
TI = LD50/ED50
-LD50: median lethal dose (kills half of the subjects)
-ED50: median effective dose (produces desired effects in 50% of subjects)
*high TI = large margin of safety (safer)
*low TI (<3) = need therapeutic drug monitoring (unsafe)

Front 38

Ocular Routes of Administration

Back 38

*for ophthalmic drugs to be effective, they must reach the ocular tissue in high concentrations
*depending on the specific diagnostic or therapeutic objectives, ophthalmic drugs may be administered by:
-topical -oral
-parenteral -periocular
-intracameral
-intravitreal

Front 39

Inactive Ingredients

Back 39

*preservatives: destroy or inhibit multiplication of microorganisms
*viscosity-increasing agents: increase retention time
*antioxidants: delay deterioration of product by oxygen
*wetting agents: allow drug solution to spread
*buffers: maintain pH of 6-8
*tonicity agents: optimize isotonicity with tear film

Front 40

Ophthalmic Dosage Forms

Back 40

*Solutions and Suspensions:
-most are in this form
-applied directly into eye from bottle
-don't touch tip of dropper
-resuspend suspension by shaking solution to ensure accurate dosage of drug
*gel
*spray

Front 41

Ophthalmic Devices

Back 41

*scrubs (Ocusoft)
*contact lenses (promote time-release of solutions or suspensions; corneal shield)
*cotton pledgets
*filter strips
*artificial tears inserts (Lacrisert)

Front 42

Ophthalmic Routes of Administration

Back 42

*Oral administration
*Perioculuar/Peribulbar administration
*Intracameral administration
*intravitreal administration

Front 43

Ophthalmic Routes of Administration:
Oral Administration

Back 43

*most ocular disease responds to topical therapy, but some disorders require systemic drug administration
-carbonic anhydrase inhibitors for glaucoma
-antibody therapy of preseptal cellulitis
-antihistamine therapy for acute allergic edema of the eyelids

Front 44

Ophthalmic Routes of Administration:
Perioculuar/Peribulbar

Back 44

*when higher concentration of drugs are required, drugs can be injected locally into the periocular tissues
*periocular drug administration includes subconjunctiva, sub-Tenon's, retrobulbar
*corticosteroids, antibiotics, local anesthetics

Front 45

Ophthalmic Routes of Administration:
Intracameral

Back 45

*administering drug directly into anterior chamber of eye
*a viscoelastic substance is injected into the anterior chamber to protect corneal endothelium

Front 46

Ophthalmic Routes of Administration:
Intravitreal

Back 46

*severe, acute, or chronic intraocular inflammation or eyes failed with conservative therapy
*intravitreal antibiotics: endophthalmitis
*intravitreal ganciclovir: cytomegalovirus retinitis
*pegaptanib (Macugen): neovascular ARMD

Front 47

Slow-Release Intravitreal Inserts

Back 47

*a ganciclovir implant (Vitrasert) is available that delivers the antiviral agent continuously to the vitreous and retina for periods of 4-6 months
*intravitreal fluocinolone is available as an implant (Retisert) to deliver steroid at a constant rate to the posterior segment of the eye for 2-3 years

Front 48

Prescription Content:

Back 48

*physicians name, address and office telephone number
*date
*patients name, age, and current address
*name and dosage of drug
*how drug is to be taken (directions to both pharmacist and patient)
*refill and safety cap information
*prescriber's signature
*expiration date
*supplemental information (ie. shake well before using, keep refrigerated, for the eye)

Front 49

Telephone Orders and Standing Orders

Back 49

Telephone Orders:
*a physician may telephone a pharmacist an rx
*asap, write drug order and send to pharmacist
*fax copy can confirm oral order but not legally acceptable because signature must be original

Standing Orders:
*written orders left by a physician as an on-going prescription in a hospital, nursing home or residential care setting
*properly dated, written and signed

Front 50

E-Prescribing

Back 50

*about 3 billion rx written annually
*allows an accurate, error-free and understandable rx directly to a pharmacy from the point of care
*involved e-prescribing software and a transmission network that links participating pharmacies
*if pt doesn't want rx electronically, physician can print a copy

Front 51

Generic Substitution

Back 51

*generic products tested by the FDA and determined to be therapeutic equivalents are listed in the FDA orange book
*these products contain the same active ingredients as their brand name counterparts and also meet bioequivalence standards within certain tolerances

Front 52

Why would you not want to prescribe generics for some drugs?

Back 52

*some drugs contain either unique chemicals or exhibit bioavailability characteristics that differ from those of generic products
*In addition, there are drugs with narrow therapeutic indices (eg. warfarin and carbamazepine) where small changes in bioavailability can lead to increased adverse effects