NR PHARMACOLOGY INTRODUCTION TO PHARMACOTHERAPEUTI CSINTRO TO PHARMACOTHERAPEUTICS
Prescription Writing
Need at least 2 patient identifiers: Name, DOB,
... [Show More] Address, Date of Rx, Prescriber name, address, license number, DEA number if applicable, Info for supervising MD,
Drug: name/strength/dose/route/QTY/refills, Signature
• U: write out “unit”
•
IU: write out “international units”
JC “Do Not Use” List
• Q.D., Q.O.D.: write out daily or every other day
• Trailing/leading zeros
• MS, MSO4, MgSO4: write morphine sulfate or magnesium sulfate
•
µg: write mcg
ANTIBIOTICS
Class
PCN:
1st
Gen
PCN:
2nd
Gen
PCN:
3rd
Gen
PCN:
4th
Gen
Cephalosporin:
1st
Gen
Cephalosporins:
2nd
Gen
Cephalosporins:
3rd
Gen
Cephalosporins:
4th
Gen
Cephalosporins:
5th
Gen
Carbapenems
Monobactam
Drug
Pen G (IV)
Benzathine penicillin (IM)
Pen VK (PO)
Nafcillin (IM/IV)
Cloxacillin (PO)
Dicloxacillin (PO)
Ampicillin (PO)
Amoxicillin (PO)
Augmentin
(amox + clavulanate)
Zosyn (piperacillin +
tazobactam) (IV)
Cefazolin (IM, IV)
Cephalexin (PO)
Cefaclor
Cefuroxime (IM, IV, PO)
Ceftriaxone (IM, IV)
Cefotaxime (IM, IV)
Cefixime (PO)
Cefepime (IM/IV)
Ceftaroline (IV)
Doripenem
Ertapenem
Imipenem & cilastatin
Meropenem
Inhibit cell wall
synthesis
Inhibit cell wall
synthesis, Bactericidal
MOA
Uses/Coverage
Pneumococcal pneumonia
Syphilis, strep throat
Gram + coverage and Treponema pallidum
Antistaphylococcal, MSSA
Extended-spectrum: G(+) PLUS some G(-);
OM, URI
Diarrhea, Good for beta-lactamase: H.Flu,
M.Cat
Broad spectrum, covers Pseudomonas, many
G(-)
good Gram + coverage, NO MRSA coverage
Not as good G+ but some G(-); OM, Strep
pharyngitis
better G- but lower G+ coverage, High risk w/
some for ESBL resistance
Good G+ and G- coverage, Covers
Pseudomonas
G- as 3rd
Inhibit cell wall
synthesis
Aztreonam:
IM, IV, inhale Inhibit cell wall
-gen plus MRSA coverage
Broader than other BL-abx
All IV, IM, saved for very broad coverage
G- ONLY, Covers Pseudomonas
May have cross-sensitivity
to PCNs
Ertapenem: not good
Pseudomonas coverage
Never use for empiric tx,
1
Cross-sensitivity with PCNs
Ceftriaxone good for
gonorrhea d/t single dose
ADR/DDI
Education/Other
• H.S.: write half-strength or at bedtime
• T.I.W.: write three times weekly or 3 times weekly
•
S.C. or S.Q.: write Sub-Q or subQ or subcutaneously
• D/C: write discharge
•
c.c.: write mL
• AS, AD, AU, OS, OD, OU: write out, e.g., both eyes or left earsynthesis
Good for PCN-allergic
Vancomycin IV
Vancomycin PO
Telavancin
Macrolides
Erythromycin
Clarithromycin
Azithromycin
Doxycycline
Tetracyclines
Minocycline
Tigecycline IV
Amikacin
Aminoglycoside
Gentamicin
Tobramycin
Clindamycin
Linezolid (Zyvox)
Ciprofloxacin
Levofloxacin
Fluoroquinolones
Moxifloxacin
Others
Folate Antagonist
Miscellaneous
Metronidazole
Nitrofurantoin
unclear, thought to
inhibit several enzyme
pathways and possibly
TMP-SMX
(Bactrim, Septra)
Inhibit cell wall
synthesis
Inhibit cell wall
synthesis
Inhibit protein
synthesis, bind to 50s
ribosomal subunit
Inhibit protein
synthesis, bind to 30s
ribosomal subunit
Derivative of
minocycline
Inhibit protein
synthesis, bind to 30s
ribosomal subunit
Inhibit protein
synthesis, bind to 50s
ribosomal subunit
Inhibit protein
synthesis, bind to 50s
ribosomal subunit
Inhibit nucleic acid
synthesis – inhibit
topoisomerase
Mainly for G+ and MRSA IV
For C. diff. colitis
Alternative to vancomycin
Covers G+ and MRSA
G+, G-, and atypicals, Often used to treat G+
in pen-allergic patients;
Enzyme inhibitor: E > C >> A
Must watch with: CBZ, warfarin, statins, etc.
Coverage very broad: G+, G-,aerobic and
anaerobic, spirochetes, mycoplasmas,
rickettsiae, chlamydiae, some protozoa, MRSA
PO
MRSA, MDRSp, VRE, ESBL-producing G-,
many anaerobes, NOT for Pseudomonas; for
Complicated SSTIs, intraabdominal ifxn, CAP
G- including Pseudomonas
Mainly for anaerobic coverage
PO or IV and in some topicals, MRSA PO
PO & IV
Use for resistant organisms: MRSA, VRSA,
VRE, penicillin-resistant Strep. pneumo
UTI, GI, Pseudomonas
Monitor renal function and serum drug levels!
ADR: ototoxicity, nephrotoxicity
ADR: rashes and high rate of C.diff.
Caution for Serotonin
Syndrome
UTI, GI, LRI, URI, skin
LRI, URI, GI, skin (no
UTI!!)
PO, otic, ophthalmic
broad G-,
respiratory FQs
with improved G+
coverage
Broad with G+ and G-, NO Pseudomonas
Common for UTI, MRSA PO
Covers protozoa, anaerobes
**DOC: C.diff. colitis
Trichomoniasis; Various infections of: skin,
bone, CNS, GYN, GI, LRI, endocarditis
Use in simple UTI treatment and prophylaxis
NOT pyelonephritis or complicated cystitis
Might offer benefit when
transitioning to outpatient
ADR: C.diff colitis!! CNS: seizure, dizziness; Cardiac: QT
prolong; MS: tendon, cartilage; Endo: glycemic control;
Skin: photosensitivity, rash
DDI: antacids, Fe, Ca, Zn
ADRs: rash (simple to SJS),
photosensitivity, crystalluria
(need to counsel)
Dose based on TMP (more
important in PO liquid)
ADR: Avoid with EtOH. Metallic taste
CI: ClCr <60 mL/min; Do not use in renal impairment
Warnings/Caution: Hepatic disease, Elderly
2
ADR: dose-related
ototoxicity &
nephrotoxicity; Red man
(infusion NOT allergy)
ADR: Teratogenic and QT
prolongation
Allergic reactions are rare!
ADR: n/v, metallic taste
Dose for renal fxn, monitor
serum levels
No drug monitoring
Improved H.Flu vs. E-mycin
Long 1/2 life, good for
Chlamydia, other atypicals
High levels of resistance
CI: Avoid with chelating agents (MVI, antacid, milk, iron),
Avoid in pregnancy and small children (<8) – Binds Ca and
will stain teeth
ADR: n/v, liver disease, phototoxicitycell wall synthesis
3PHARM FALL 2013 BLOCK I: DERM & EENT
INTRODUCTION TO DERMATOLOGIC PRODUCTS
Determinant of
Pharmacologic
Response
1. Permeability and penetration – hydrated > dehydrated, thin > thick, trauma > no trauma
2. Concentration gradient – greater concentration greater amount per unit time (threshold may exist)
3. Dosing – time left on skin, frequency, quantity; dermis acts as barrier and can effect duration
4. Vehicle – cream, ointment, liquid, solution
5. Occlusion – maximizes efficacy, increases absorption, protection
Emulsions – drug particle contained w/in vehicle/base; Indication for different types of products (dry/wet, sensitivity/pain, size, location, acute/chronic)
Creams – most common vehicle, no occlusion
Drug Delivery
Systems
Ointments – common, good for dry lesions due to occlusive properties; NOT for intertriginous areas; can be cosmetically unpleasing
Gels – clear, non-greasy, non-staining, non-occlusive, quick drying; can sting on application and be drying (due to EtOH)
Solutions – evaporate quickly (drying), used in acute/weeping/oozing wounds
o Tinctures – alcohol-based solution, used for extreme drying properties
Aerosols – advantage for painful skin, but expensive and not efficient dosage form
Lotions – good for tender areas, spreads easily, evaporates quickly, good for large areas
Powders – used to absorb moisture/friction; caution w/ very wet lesions due to crusting
Choosing
Which Drug
Delivery System
to Use
DRY wet lesions and WET dry lesions **more liquid agents dry better
Acute inflammation (oozing/weeping/vesication/edema/pruritis) aqueous vehicles, powders, lotions, sprays, aerosols
Subacute inflammation (crusting/oozing/pruritis) creams, gels
Chronic inflammation (lichenification/dryness/erythema/pruritis/scaling) ointments
Cream
Pharmacological
Advantage
Advantages for
Patient
Locations on Body
Disadvantages
Occlusion
Drug
Minoxidil
MOA
Leaves concentrated drug at skin
surface
Spreads and removes easily,
no greasy feel
Most locations
Needs preservatives
Low
Vehicles for Topically Applied Drugs
Ointment
Protective oil film on skin
Spreads easily, slows water evaporation,
gives cooling effect
Avoid intertriginous areas*
Greasy to very greasy, stains clothes
Moderate to high, increases skin
moisture
ANDROGENIC ALOPECIA Tx goal: reduce loss and maintain existing hair **If you stop therapy, hair loss WILL return!
Indication
ADRs/DDI/CI
Changes follicle size & growth cycle of
hair to f hair & thicker/longer shaft
Finasteride Type II 5-alpha-reductase inhibitor,
Topical formulation only to limit and
contain ADR (BP); OTC, 1st
line M & F
ADR: local irritation, undesirable
growth if inappropriately use **well-
tolerated
PO (tablet) formation that only grows *CI: pregnancy
Specific Education/Other
Wash hands after application,
treatment must be continuous
Caution in women of child-bearing
4
Gel/Foam
Concentrates drug at surface after
evaporation
Non-staining, grease-less, clear
appearance
Foams well for scalp and other
hairy locations
Needs preservatives, high alcohol
can be drying
Low residue on scalp
Solutions and foams are well
accepted on scalp
Lotion/Solution/Foaminhibits conversion of testosterone to
dihydrotestosterone (reverse loss)
Class
Drug
Amphotericin B
(“Amphoterrible”)
Fluconazole
(Diflucan)
Azoles
Itraconazole
Voriconazole
Posaconazol
e
Echinocandins
disrupts cell wall structure
formation by inhibiting β-
glucan synthase
disrupts cell wall formation
via pyrimidine analog
Flucytosine
MOA
binds to ergosterol and
alters permeability; large
spectrum of activity
inhibit synthesis of
ergosterol by blocking
demethylation of lanosterol
hair at vertex/frontal scalp; first line
for men, second line for women
ADR: libido, erectile dysfunction,
ejaculation disorder, ejaculation vol
SYSTEMIC ANTIFUNGALS
Indication
IV; only used in infectious disease with high
resistance *lipid formations are less toxic, but still
not good
IV and PO; Important treatment for infections due
to Candida; drug of choice for vaginal yeast
infections
IV and PO *bioavailability varies, PO solution
achieves higher serum concentrations; Used for
fungal nail infections
IV and PO; Broad spectrum triazole used for
serious infections, first line for aspergillosis
PO suspension
Broad-spectrum triazole, but can cause many DDIs
IV only; used to treat significant fungal infection –
integral component of Aspergillus and Candida cell
wall
PO only, rarely used as monotherapy due to rapid
resistance development
Spectrum: Cryptococcus spp, Candida spp; used to
treat cryptococcal meningitis in combination w/
AmB
Key Points of Systemic Antifungals
Always consider hepatic function (liver disease, heavy EtOH use, etc.)
Review patient’s medical history to avoid DDIs
Generally well tolerated
(but expensive)
ADR: visual abnormality
*Enhanced w/ high-fat meal,
splitting dose in fasting
*more common/better
tolerated/less DDIs than azole
Can cause liver problems – must
get liver enzymes checked every 4-
6 weeks
ADRs/DDI/CI
ADRs: EXTREMELY TOXIC
(nephrotoxicity, infusion-
related toxicity)
age, wash hands/gloves, treatment
must be continuous
Specific Education/Other
Systemic –azole agents in primary care are mainly used for skin/nail disorders, vaginal yeast infections (fluconazole)
TOPICAL ANTIFUNGALS
Class
Topical
Azoles
Topical
Allylamines,
Butylamine
Topical
Polyene
Other
Naftifine
Terbinafine
(Lamisil)
Butenafine
Nystatin
Drug
MOA
Block biosynthesis of ergosterol
inhibit squalene epoxidase (key enzyme in
ergosterol biosynthesis pathway)
Bind to ergosterol in fungal cell membrane,
changes membrane permeability
Selenium exerts a cytostatic effect of cell of epidermis
Indication
Tinea pedis/cruris/corporis, tinea versicolor,
cutaneous candidiasis, vaginal candidiasis
Tinea pedis/cruris/corporis, tinea versicolor
Specific Education/Other
*Most effective topical antifungal for
treatment of dermatophytes
**Terbinafine = tx for nail fungus
cutaneous infections caused by Candida
albicans, other Candida spp
tinea versicolor
*not useful against dermatophytes
*highly toxic systemically
Lotion, Shampoo formulations OTC (well-
5Sulfide
Tolnaftate
Ciclopirox
and follicular epithelium
tolerated)
Distorts the hyphae and stunts mycelial
growth of fungal species
alters integrity of fungal cell membrane
Tinea pedis/cruris/corporis, tinea versicolor
skin, superficial nail infections; tinea
pedis/cruris/corporis, tinea versicolor *activity
against Candida
*Fluconazole
Indicated for candidiasis
*yeast/vaginal infections
Single dose is used for treatment
Itraconazole
Systemic Agents for Superficial Infections
Ketoconazole
Indicated for candidiasis,
dermatophytes (tineas),
onychomycosis (nail fungus)
Multiple DDIs – Inhibited CYP3A4
Indicated for candidiasis,
dermatophytes
Multiple DDIs, potential
hepatotoxicity *only last line in
life-threatening infection
(Tinactin) *tough-actin tinactin; Cream,
solution, powder, spray, gel forumations OTC
Cream, lotion, nail laquer (Penlac)
formulations
Terbinafine
Griseofulvin
PO and topical available
Indicated for candidiasis,
dermatophytes, onychomycosis
Potential hepatotoxicity –
monitor liver enzymes
Inhibits mitosis, rarely used
Indicated for dermatophytes and
onychomycosis
*Pulse Therapy (Terbinafine and Itraconazole): Used in onychomycosis treatment, has some evidence for less toxicity (dosed daily 1 week, off 3 weeks) to decrease ADRs, DDIs
DRUG ERUPTIONS
Types of Drug Eruptions
General Approach to
Drug Reactions
Reaction
Acneiform Reactions
Photosensitivity
Reactions
Allergic Contact
Dermatitis
Erythema Multiforme
Stevens-Johnson
Syndrome (SJS)
Topical Epidermal
Necrosis (TEN)
Erythema Nodosum
Drug Hypersensitivity
Reaction
Fixed Drug Eruption
Maculopapular
Mild rash, itching, dry skin severe, potentially life-threatening conditions)
SJS, TEN, Angioedema, Vasculitis, Coagulent-induced skin necrosis
(1) Recognize that problem may be drug-related Identify agent (2) STOP OFFENDING AGENT (3) Determine severity (i.e. triage situation) (4) Treat
sequelae **Don’t forget to EDUCATE PATIENT
Characteristics
Common Offenders
Differ from true acne: no comedone, uniform appearance of lesions, location,
age, recent drug exposure
Phototoxic reactions – exaggerated sunburn or increased sensitivity to light;
UVA causes alteration of drug to toxic form (>common)
Photoallergic reactions – manifests in bullae, urticaria, sunburn; UVA alters
drug to antigen and leads to allergic response ( [Show Less]