NURS 5334 Advanced Pharmacology Module 2 actual questions with 100% correct answers + detailed explanations

identification of teratogens

difficult to identify, 3 criteria must be met:

1. The agent must be present during the critical stage of development

2. The agent produces a particular pattern of birth defects in animal studies.

3. The agent crosses the placenta and there is a dose-response relationship.

3 stages of teratogenesis development

1. conception through week 2

2. embryonic period week 3-8 = gross malformations

3. fetal period week 9-delivery = functions disrupted w/ teratogen exposure

physiologic changes during pregnancy & drug impact

- 3rd trimester = renal blood doubles, renal excretion accelerated

- tone and mobility of bowel decreases -> prolongation of drug effects

placental drug transfer

all drugs can cross the placenta, some cross more easily than others

adverse reactions during pregnancy

can adversely affect both pregnant pt and fetus

- heparin -> osteoporosis

- prostaglandins -> stimulate uterine contraction

- some pain relievers can be used during delivery can cause respiratory depression in baby

teratogenesis birth defects

gross malformations = cleft palate, clubfoot, hydrocephalus

neurobehavioral & metabolic anomalies

responding to teratogen exposure

Determine when the drug was taken

Determine when the pregnancy began

-Weeks 3-8 (organogenesis) is most crucial time

Determine type of malformation expected

Conduct 2 US and consult FDA to determine severity

how to decrease risk of drug effects during breastfeeding

- take drugs immediately after breastfeeding

- avoid drugs w/ long half-lives

- choose drugs that tend to be excluded from milk, least likely to affect infant

- avoid hazardous drugs

pediatric response to drugs

- more sensitive to drugs

- greater individual variation

- sensitivity d/t organ system immaturity

- increased risk for adverse rxns

determining the intensity of duration of drug response in neonates & infants

- elevated drug levels = more intense response

- delayed elimination = prolonged response

- immaturity of organs = risk for both^

comparison of plasma drug levels in adults and infants

increased sensitivity in infants caused by immature state of...

absorption, protein binding of drugs, BBB, hepatic metabolism, renal drug excretion

infant absorption: oral administration

prolonged and irregular gastric

adult function at 6-8 months

infant absorption: gastric acidity

- very low 24 hours after birth

- does not reach adult values for 2 years

- low acidity = absorption of acid-labile drugs is increased

infant absorption: intramuscular admin

slow, erratic, delayed absorption as results of low blood flow in 1st few days of life

in early infancy, absorption of IM drugs more rapid than neonates & adults

infant absorption: transdermal

more rapid & complete for infants than older children & adults

- stratum corneum of infant's skin is thin

- blood flow to skin is greater in infants than older patients

- infants increased risk for toxicity from topical drugs

infant distribution: BBB

- not fully developed at birth

- drugs have easy access to CNS

- infants especially sensitive to drugs that affect CNS function

- dosage should be reduced for drug actions outside the CNS if those drugs are capable of producing toxicity as a side effect

infant hepatic metabolism

- drug-metabolizing capability of newborns is low

- liver's capability to metabolize drugs increases fast @ 1mo

- complete liver maturation occurs at 1yr

infant renal excretion

- low renal blood flow, glomerular filtration, & active tubular secretion

- drugs eliminated by renal excretion must have reduced dosing and/or longer dosing intervals

- adult level renal function occurs at 1yr

pharmacokinetics in children

metabolize drugs faster than adults till 2yrs, then gradual decline

sharp decline at puberty

may need to increase or decrease interval between doses

adverse drug reactions in children

- glucocorticoids -> growth suppression

- tetracyclines -> discoloring of teeth

- sulfonamides -> kernicterus

- fluoroquinolones -> musculoskeletal d/o's

- SSRIs - > black box increased SI

- OTC cough and cold meds not recommended in kids <2yrs

dosage determination in children

child's BSA x adult dosage/ 1.73m2 = child dose

older adults: altered pharmacokinetics

more sensitive to drugs than younger adults & w/ greater variation in pharmacokinetics

multiple & severity of illness, multiple pathologies

multiple-drug therapy (excessive prescribing)

poor adherence

older adults: absorption

- rate of absorption slows w/ age

- delayed gastric emptying & reduced splanchnic blood flow

older adults: distribution

- increased body fat % (storage depot for lipid-soluble drugs)

- decreased lean body mass %

- decreased total body water (distributed in smaller volume, concentration increased & effects more intense)

- reduced concentration of serum albumin -> decreased protein binding of drugs & increased levels of free drugs

older adults: metabolism

- hepatic metabolism declines

- reduced hepatic blood flow & liver mass

- decreased activity of hepatic enzymes

- half-life of some drugs may increase

- prolonged & enhanced drug responses

older adults: excretion

- decline in renal function, blood flow, GFR, active tubular secretion, # of nephrons

- drug accumulation d/t reduced renal excretion**

pharmacodynamic changes in older adult patients

- drugs w/ more intense effects

- beta blockers less effective, even in same concentrations

adverse drug reactions in older adults

7x more likely than adults

majority are dose related, not idiosyncratic

symptoms are often nonspecific

predisposing adverse reaction factors in older adults

- Drug accumulation secondary to reduced renal function

- Polypharmacy

- Greater severity of illness

- Multiple pathologies

- Greater use of drugs that have a low therapeutic index (e.g.,digoxin)

- Increased individual variations secondary to altered pharmacokinetics

- Inadequate supervision of long-term therapy

- Poor patient adherence

antimicrobials

used to treat infectious dx

significantly reduced morbidity and mortality from infection

classification of antibiotics

Drugs work on:

Cell wall synthesis

Cell membrane permeability

Protein synthesis (lethal)

Nonlethal inhibitors of protein synthesis

Synthesis of nucleic acids

Antimetabolites

Viral enzyme inhibitors

bactericidal

directly lethal to bacteria at achievable concentrations

bacteriostatic

slows bacterial growth but doesn't cause cell death

penicillin and cephalosporin MOA

inhibit cell wall synthesis-> bacterial lysis and death

___ MOA

increase cell membrane permeability -> leaking of ICF

aminoglycosides MOA

lethal inhibition of bacterial protein synthesis -> cell death

tetracyclines MOA

nonlethal inhibition of protein synthesis -> slow microbial growth (they do NOT kill bacteria)

rifampin, metronidazole, & fluroroquinolones MOA

binds to nucleic acids or interacts w/ enzymes required for nucleic acid synthesis -> inhibit bacterial synthesis of DNA and RNA or disrupt DNA function

antimetabolites (trimethoprim & sulfonamides) MOA

disrupt specific biochemical reactions -> decrease in synthesis of essential cell constituents or synthesis of nonfunctional analogs of metabolites

antiviral MOA

inhibit specific enzymes required for viral replication and infectivity

organisms w/ microbial drug resistance

Enterococcus faecium Staphylococcus aureus

Enterobacter species Klebsiella species

Pseudomonas aeruginosa

Acinetobacter baumannii

Clostridium difficile

4 basic microbial mechanisms of drug resistance

1. decrease concentration of drug @ site of action

2. inactivate drug

3. alter structure of drug target molecules

4. produce drug antagonist

NDM1 gene

can inactivate most all beta lactam abx

mechanisms for acquired resistance

-Spontaneous mutation (Random changes in a microbes DNA, resistance to one drug)

-Conjugation (extrachromosomal DNA is transferred from one bacterium to another, gram negative bacteria, multiple drug resistance)

which abx promote resistance?

broad-spectrum

more abx used, faster drug resistant organisms emerge

nosocomial infections

health care associated infections

superinfections

new infection appears during course of treatment for primary infection w/ drug resistant microbes

public health action plan to combat antimicrobial resistance

focus area 1 = surveillance

focus area 2 = prevention and control

focus area 3 = research

focus area 4 = product development

empiric therapy

abx therapy before causative organism is identified

prophylactic use of antimicrobials

surgery, bacterial endocarditis, neutropenia

penicllin structure

includes beta lactam ring

beta lactam family = cephalosporins, aztreonam, imipenem, meropenem, ertapenem

low toxicity

pencillins MOA

weaken cell wall -> cell rupture

bactericidal

3 mechanisms of bacterial resistance in penicillins

inability of penicillins to reach target

inactivation of penicillins by bacterial enzymes

production of penicillin binding proteins that have low affinity for penicillins

2 types of MRSA

health care associated MRSA

community associated MRSA

Penicillin G

bacterial to many gram positive & some gram negative prganisms

allergic reactions

Penicillin V

stable in stomach acid

replaced penicillin g for oral therapy

penicillinase resistant penicillins

Oxacillin, nafcillin, dicloxacillin

broad spectrum pencillins

ampicillin, amoxicillin

AE: rash, diarrhea

extended spectrum/antipseudomonal penicillins

Piperacillin

- broad spectrum, but penicillinase sensitive

- effective against organisms susceptible to aminopenicillins plus bacterial resistant antimicrobials

Beta-lactamase inhibitors

clavulanic acid, sulbactam, tazobactam

penicillin combinations

Extends antimicrobial spectrum when combined with penicillinase-sensitive antibiotics

- ampicillin/sulbactam (Unasyn)

- amoxicillin/clavulanic acid (Augmentin)

- piperacillin/taxobactam (Zosyn)

cephalosporins

most widely used abx group

beta lactam abx

bactericidal

low toxicity

cephalosporins MOA

B-lactam drugs that inhibit cell wall synthesis but less suspectible to penicillins -> cell lysis

1st generation cephalosporins

Cefazolin, cephalexin, Cefadroxil

2nd generation cephalosporins

Cefoxitin, cefaclor, cefuroxime, cefotetan, cefprozil, cefmetazole, cefonicid, loracarbef

3rd generation cephalosporins

cefotaxime, cefdinir, cefditoren, cefixime, cefpodoxime, cerazidime, cefibuten, ceftriaxone, cefoperazone, cefitzoxime

4th generation cephalosporins

Cefepime

5th generation cephalosporins

Ceftaroline

Ceftolozane

cefiderocol

new cephalosporin for MDR gram negative infections

used in adults w/ complicated UTIs and pyelo

cephalosporin drug interactions

Probenecid

Alcohol

Drugs that promote bleeding

Calcium and ceftriaxone

cephalosporin adverse effects

allergy, bleeding, thrombophlebitis

1st gen cephalosporin uses

prophylactically for surgery patients

2nd gen cephalosporin use

rarely used for active infections

3rd gen cephalosporin use

preferred therapy for several infections

highly active against gram-negative organisms

able to penetrate CSF

4th gen cephalosporin uses

HCA pneumonia including cause by pseudomonas aeruginosa

5th gen cephalosporin use

MRSA infection

carbapenems

Imipenem, Meropenem, Ertapenem, Doripenem

beta lactam abx

extremely broad spectrum

low toxicity

not active against MRSA

Imipenem

active against more bacterial pathogens & many resistant to other abx

highly effective against gram + cocci & omst gram - occi and bacilli

Vancomycin MOA, use

MOA = inhibit cell wall synthesis

use = serve infections, MRSA< staph, C diff

Vancomycin AE

ototoxicity, nephrotoxicity, red man syndrome, thrombophlebitis, thrombocytopenia

Telavancin

new class, lipoglycoproteins synthetic derivatives of vancomycin

effect only against gram +

AE: taste disturbance, NV, foamy urine, red man syndrome prolonged QT

BB warning! = HCA pneumonia w/ cr clearance <50

Monobactam

Aztrenonam

narrow spectrum

gram - aerobic only

Fosfomycin

singe dose therapy for uncomplicated UTI caused by e coli or enterococcus faecalis

AE = diarrhea, HA, vaginitis, nasuea

tetracyclines

tetracycline, doxycycline, minoocycline

MOA = inhibit protein synthesis, broad spectrum

use = infectious dx, acne, PUD, RA, mycoplasma pneumonia, lyme dx, anthrax, h pyylori

cant take w/ ca, iron, mg containing laxatives, antacids

AE = GI upset, bones & teeth, superinfection, hepatoxicity, renal toxicicty, photosensitivity

Macrolides

erythromycin, clarithromycin, azithromycin

MOA = inhibits protein synthesis, bacteriostatic can be bactericidal

active againt gram + and some gram -

use = whooping cough, chlamdia, m pneumonia, group A strep, if allgeric to penicillin

AE = GI upset, prolonged QT, cardiac death, superinfections, thrombophlebitits, transient hearring los

Clindamycin

MOA = inhibit protein synthesis, active against anaerobic bacteria (only certain ones outside CNS indicated)

can promote severe cdiff

AE = CDAD, hepatic toxicity, blood dyscrasias

Linezolid (Zyvox)

use = multi drug resistant gram + pathogens (VRE, MRSA)

MOA = inhibits protein synthesis, bacteriostatic

interacts w/ MAOIs

AE = NVD, HA

Telithromycin

use: Strep pneumonia

AE = severe liver injury, GI, visual changes, prlonged QT

Dalfopristin/Quinupristin

MOA = inhibits protein synthesis

use = VRE

AE = hepatotoxicity

CYP3A4 interaction

Chloramphenicol

MOA = inhibits protein synthesis

use = only life threatenning infection f nothing worked

AE = bone marrow depression, fatal aplastic anemia, gray syndrome, GI, peripheral neuropathy

aminoglycosides

Gemtamicin, tobramycin, amikacin, Neomycin, Kanamycin, Streptomycin, Paromomycin

narrow spectrum abx

bactericidal aerobic gram - bacilli

AE =nephrotoxicity, ototoxicity, neuromuscular blockade

Gemtamicin

used to treat infections caused by aeoribic gram - bacilli

pseudomonas aeruginosa

e coli

klebsiella

serratia

proteus mirabillis

AE = nephro & ototoxicity

sulfonamides

MOA = inhibit synthesis of folic acid

uses = UTI**, nocardiosis, chlamydia, UC, malaria

AE = stevens johnson syndrome, hematologic effects, kernicterus, renal damage from crystalluria

trimethoprim

MOA = inhibits dihydrofolate reductase -> supress DNA, RNA, protein synthesis

uses = acute and uncomplicated UTIs

AE = hematologic effects, hyperK, use in pregnancy and lactation

Trimethoprim/Sulfamethoxazole

MOA = inhibits bacterial folic acid synthesis powerfullly

use = UTI, OM, bronchitis, pneumonia, GI infection

AE = NV, rash, hyperK, stevens johnson, birth defects in first trimester

upper UTI

kidneys

acute pyelo

acute bacterial prostatitis

lower UTI

bladder & urethra

acute cystitis

acute urethral syndrome

organism that causes 80% uncomplicated community acquired UTIs

E coli

organism that causes most hosptial aquired UTIs

klebsiella

proteus

enterbacter

pseudomonas

staph

enterococci

e coli