INTRODUCTION

PHARMACOLOGY- Gk “pharmakon/φάρμακον” (drug) & “-logia/λογία” (study)

- how drugs interact w/biological systems to affect fx
- study of interaction between living org & exogenous chemicals that alter
Sources of Drug Information
normal biochemical fx
- Pharmacopoeia; Formulary, Nursing Textbook, Package Insert
DRUG- substance/mixture for diagnosis, cure, treatment, disease prevention - Reference: PDR, Drug fact/comparison; nsg drug guide/handbook
PHARMACODYNAMICS- study of drug biochemical & physiological effects - Journal: medical letter; American Journal of Nursing - Internet
- mechanism of action; WHAT DRUG DOES TO BODY
PHARMACOKINETICS- study of absorption, distribution, biotransformation(metabolism) Nursing Process in Pharmacology
& excretion; WHAT BODY DOES TO DRUG ASSESSMENT- basis care is planned, implemented, evaluated
PHARMACOTHERAPEUTICS - assess: findings/cues; drug history
- study of how drugs may best be used in treatment; CHOOSING THE BEST DRUG Drug History- evaluate med needs; obtain current & past med use (OTC, prescribed,
 which drug would be most/ least appropriate to use for specific disease herbal, illicit)
 what dose would be required - identify problems r/t drug therapy; identify risk factors in drug therapy
PHARMACOGNOSY- study of drugs derived from herbal & natural resources DIAGNOSIS- based on assessment; actual/potential
TOXICOLOGY- study of poisons & poisonings; toxic effects on living organism ex: Knowledge Deficit r/t lack of experience w/medication regimen & second grade reading
level as adult as evidenced by inability to perform return demonstration & inability to
Sources of Drugs state adverse effects to report to prescriber
PLANTS- digitalis (purple foxglove); vincristine (periwinkle); morphine (opium) risk for injury r/t forgetfulness
ANIMALS- Insulin (pigs & cows); Vaccine (killed/attenuated microorg from horses) Ineffective therapeutic regimen management r/t lack of finances
SYNTHETICS- genetic engineering to alter bacteria for therapeutic & effective chemicals PLANNING- characterized by goal setting/expected outcome representing nsg care
INORGANIC COMPOUNDS- salts of various elements (have therapeutic effects in body) effectiveness (px goal, state of desired px behavior/response
- aluminum (antacid for hyperacidity); fluoride (dental carries & osteoporosis)
include: identification of therapeutic intent for every med
Drug Classifications side effect to be expected/reported
identification of recommended dosage & route of administration
PRESCRIPTION- written order by qualified health prof to a pharmacist/ therapist for a
scheduling of med administration
specific treatment for px
teach px to keep written records of his responses
Components: - date & time drug was written - drug name - drug dosage additional teaching (administration technique, proper storage)
- route of administration - administration frequency & duration
- physician signature IMPLEMENTATION- nsg action to achieve outcome; in/de/interdependent
include: client teaching/educ  drug administration; drug effectiveness assessment; self-
NON-PRESCRIPTION- OTC medications administration; diet; side effect; cultural consideration
INVESTIGATIONAL- subjected to clinical studies to evaluate usefulness
ILLICIT/STREET- illegal; non-medical, alter mood/feeling (heroin, nubain, Cytotec) EVALUATION- ongoing assessment for:
ORPHAN- for rare disease (affect < 200,000 in US) - med effectiveness; recurring illness signs observation; side effect dev’t; health teaching
- neglected bc sales profit may not be enough to cover costs of dev’t effectiveness

Pregnancy Categories
Categor Description
y
- controlled studies in women can’t show risk to fetus in 1st trimester (no
A evidence of risk in later trimester); SAFE
- fetal harm possibility is remote
- animal studies didn’t show fetal risk but no controlled studies in
pregnant women
B - animal reproduction studies show adverse effect (other than decreased
fertility) but unconfirmed in women 1st trimester (no risk in later
trimesters)
- animal study revealed adverse effect on fetus (teratogenic/
C embryological); no controlled study in women; BENEFIT OUTWEIGH RISK
- given only when potential benefit justifies potential risk to fetus
- positive evidence of human fetal risk but benefits is acceptable for
D pregnant women for life-threatening situation where other drugs are Factors Influencing Drug Action
ineffective) Age- extremes most sensitive (newborn, infant, elderly)
- animal/human study showed fetal abnormalities; TERATOGENIC Body Wt- ↑ dosage = overweight; ↓ dos = underwt (pediatrics use mg/kg)
X - drug risk in pregnant women outweighs any possible benefit Metabolism/Genetics- susceptibilities metabolize meds differently
- contraindicated in women who are/may be pregnant - lack enzymes prolong plasma level & ↑ toxicity risk
Drug Names - pharmacogenomics (how drugs interacts w/inherited genes)
CHEMICAL- systemically derived name showing Illness- pathologic condition alter rate of absorption, distribution, metabolism, excretion
chem structure; chem constitution; exact atoms placing - short gut syndrome (↓ absorption capacity)
- N-Acetyl-para-aminophenol Psychological- attitude/expectation; willingness to take meds (compliance)
GENERIC- given before drug turns official; reflect important Dependence/Addiction/Habituation- withdrawal (physical); emotional attachment
pharmacological/chem characteristic; acetaminophen Tolerance- ↑ dose needed to produce same effect lower doses once provided
BRAND- followed by ®; name is registered; its use is - may be caused by psycho dependence
restricted to drug owner (manufacturer); Tylenol Cumulative Effect- if next doses are administered before previous dose is fully metabolized
- result to drug toxicity; consumption rate exceeds metabolism rate

Drug Interactions
ADDITIVE- 2 drugs w/similar effect  double effect (1+1 = 2)
SYNERGISTIC- combined effect of 2 drugs ≥ sum of effect of each drug given alone
- ampicillin + sulbactam = prolonged antibiotic action
ANTAGONISTIC- 1 drug interferes w/action of another
- tetracycline + antacid = ↓ tetracycline absorption)
INTERFERENCE- 1 drug inhibits met/excretion of 2nd drug  ↑ activity of 2nd drug
- probenecid + spectinomycin = prolonged spectinomycin antibacterial
 activity d/t blocking renal excretion by probenecid 2. Erroneous
INCOMPATIBILITY- not mixed together/administered at same site - brand name precedes generic name - generic name is inside parenthesis
- haziness, precipitate, change of solution color when mixed - brand name isn’t in parenthesis - > 1 drug prescribed on 1 prescription form
- ampicillin + gentamicin = amp inactivates gentamicin
DESIRED ACTION- expected response 3. Impossible
SIDE EFFECT- d/t pharmacological effect; when meds is administered regardless of dose - only generic name is written but not legible
ADVERSE EFFECT- undesirable event at normal dose/correct administration - generic name doesn’t correspond to brand name
TOXICITY- severe adverse effect/poisonous - generic & brand names aren’t legible - drug prescribed isn’t registered w/BFAD
CARCINOGENICITY- induce cells to mutate & become malignant Rx components
TERATOGENICITY- induce birth defect
Reaction to Drug
PHOTOSENSITIVITY- skin, eyes
HYPERSENSITIVITY- exaggerated immunologic response to drug considered as foreign
IDIOSYNCRATIC- during 1st intake (d/t metabolism differences)
- does not occur at any dose in most patients and develop mostly unpredictable
in susceptible individuals only
Principles of Drug Actions
1. Drug don’t create new cellular fx but only alter
- antibiotic slows growth/reproduction of microbial organism
- drug action is relative to physiological state when drug was administered
2. Drug may interact w/body in many ways
- alter body fluid chem composition
PHASES OF DRUG THERAPY
- accumulate in tissues bc affinity for tissue component (form chem bond w/receptors) I. PHARMACEUTIC
Disintegration - breakdown of a tablet into smaller particle
3. Drug response/effect strength depend on drug molecule’s fit in receptor site
Dissolution - Dissolving process of smaller particles in GIT fluid prior to absorption
- precise fit  strong effect loose fit  weak effect
factor: Rate limiting- time for drug to disintegrate, dissolve, available to be absorbed
4. Agonist-Antagonist drug exert both agonist & antagonist response
Excipients- Fillers (inert substances/additives) allow drug turn to size & shape
- agonist (produce response); antagonist (counter/depress response; in antidote therapy)
- enhances drug dissolution; ↑ drug absorbability
- ex: Potassium  Penicillin potassium; Sodium  Penicillin G sodium
Phases of Clinical Trials
PHASE SUBJECT DESCRIPTION
NORMAL HUMAN - determine dose-response relationship &
VOLUNTEERS pharmacokinetics of new drug (except CANCER DRUG)
I
- dosage effect observed to know significant
response/toxic effect
SMALL # OF SICK PX - effect compared w/placebo drug/agent (know if
II W/TARGET DISEASE agent has desired effect)
(VOLUNTEERS)
MANY HUMAN - same above but w/double-blind studies
VOLUNTEERS SICK - effect is compared to standard/previous treatment
III
W/TARGET DISEASE strategy II. PHARMACOKINETICS
(6000 CASES) - drug movement to achieve drug action
ALL PX SICK - post-marketing surveillance
processes:
IV W/TARGET DISEASE - detect toxicity early to prevent major therapeutic
(AS PRESCRIBED) disaster 1. ABSORPTION- from GI tract to body fluids by passive/active absorp/ pinocytosis
Passive - higher to lover concentration w/o requiring energy
Guiding Principles Active - uses energy to actively move a molecule across a cell membrane
C- heck why meds is given & know drug classification - Pinocytosis (Cell Drinking) - engulfing drug particles
H – ow to know if med is effective? Assessment parameters in monitoring effects? factors
E- xactly what time should med be given o Blood flow o Pain o Stress & food o Exercise
C – lient teaching tips. What therapeutic & side effects o Drug solubility o pH o Drug concentration o Dosage form
K – eys to giving it safely. Identify interv to counteract adverse effects o Nature of absorbing surface- single cell layer faster than multi-layered skin
- respiratory epithelium (steroids); intestinal epithelium (carb)
o Hepatic first-pass effect- drug inactivation by hepatic enzymes before drug reaches
THE PRESCRIPTION systematic circulation for distribution
- written order/instruction of valid physician/dentist/veterinarian for specific drug use - bioavailability: % administered drug dose reaching sys circu
- doctor’s order on px chart for use of specific drug o Enterohepatic recycling- absorption from bile to small bowel then into circulating sys
- basis: Rules & Regulations to Implement Prescribing Requirement under Generics Act ofo Route of administration- linked to blood supply (vascularity)
1988 (RA 6675) Factors affecting Absorption
Legal Basis Intravenous blood volume (vascularity)
GENERIC NAME Intramuscular & Subcutaneous perfusion, fat content, temp
1. all prescriptions Oral stomach activity; time length in stomach,
- generic name of active ingredient as prescription: for drugs w/single active ingredient bloodflow to GIT, presence of interacting
- “ determined by BFAD “ “ : for drugs w/2 or more active ingredients food/drug
2. written in full but salt/chemical form abbreviated Mucous Membrane perfusion, integrity, food presence, smoking,
3. clearly written on prescription immediately after Rx/order chart time length in area
4. brand name + generic name may be used
- if written on prescription pad; brand name in parenthesis written below generic name 2. DISTRIBUTION- drug becomes available to body fluids & body tissues
- “ “ px chart, “ “ “ after generic name Factors: Blood flow, Affinity to body tissues; Protein-binding effect
PRESCRIPTIONS NOT ALLOWED Manner
1. Violative Protein-binding- protein REGULATE drug; bind w/specific protein components such as:
- generic name isn’t written - generic name not legible; legible brand name is written Bound portion is inactive (doesn’t exert pharmacologic response)
- brand name is indicated & instructions added (“no substitution”) which obstruct/ Unbound portion is active (free drug)
hinder/ prevent generic dispensing Toxicity: excess free-circulating drug (when 2 highly-protein bound drugs are
given to px w/liver disease/low albumin)
Blood-brain Barrier- protective sys (keep foreign invaders/poisons away from CNS)
Highly lipid-soluble drugs
Antibiotics can’t pass through
CNS effects by med result from indirect processes & not by actual CNS to drug
Placenta & Breastmilk- drugs readily pass through (can affect developing fetus)
- Secreted into breastmilk ANTIMICROBIALS & ANTIBACTERIALS
ANTIMICROBIALS – inhibit growth of/ kill bacteria outright
Category A NO RISK evident ANTIBACTERIAL/ANTIBIOTIC–specifically kills bacteria; destructive/inhibiting bact growth
B NO RISK in human/animal studies
C RISK can’t be ruled out Pharmacokinetics
D + evidence of risk • only penetrate bacterial cell wall in sufficient conc; must have affinity to binding sites
X CONTRAINDICATED in pregnancy • TIME drug remains at binding site = INCREASE EFFECT;
• Controlled by DISTRIBUTION, HALF-LIFE, ELIMINATION
• Most aren’t highly CHON bound = longer HALF-LIFE greater conc at binding sites; mostly
3. METABOLISM- chem changes substance undergo in body (by enzymatic action)
eliminated through URINE after 7th half-life
- Drugs are metabolized in GI tract & liver
- most drugs inactivated by liver enzymes & converted into water-soluble Resistance to Antibacterials
substances (for renal excretion)
INHERENT / NATURAL – occur w/o previous exposure to antibacterial drug
Half-life (t ½) -time for ½ of drug concentration to be eliminated ACQUIRED - caused by PRIOR exposure to antibacterial
- decrease drug into half through time - Responsible for causing Penicillin resistance = PENICILLINASE
- First order: proportional rate of elimination to concentration (metabolize PenG = drug is ineffective)
- Zero order: constant rate of elimination regardless of conc - cause: mutant bacteria (grown a thicker cell wall)
T½ TIME ELAPSED DOSAGE (at 20mg start) PERCENTAGE LEFT transfer of genetic instruction to another bacterial species
1 2 hrs 10 mg 50%
2 4 hrs 5 mg 25% to beat the problem
3 6 hrs 2.5 mg 12.5% • New antibiotics are developed
4 8 hrs 1.25 mg 6.25% • Dev’t of ANTIBIOTIC RESISTANT DISABLERS (disable antibiotic-resistant mechanism in bact)
• Bacterial Vaccines (e.g. DPT, Flu Vaccine, TT)
4. EXCRETION • Prevent antibiotic abuse
- by organs/tissues (part of natural metabolic activity) • COMPLIANCE & MULTI ANTIBIOTIC THERAPY
• Kidneys (main route; [free, water-soluble, unbound drugs])
• Urine pH (influences drug excretion) Antibiotic Combination
Acidic (for weak base drugs) ADDITIVE EFFECT - equal to SUM of effects of 2 antibiotics
Alkaline (for weak acid drugs) POTENTIATIVE (SYNERGISTIC)- 1 antibiotic potentiates 2nd antibiotic’s effect
• Others (bile, feces, lungs, saliva, sweat, breastmilk) ANTAGONISTIC- drug combo that’s BACTERICIDAL PENICILLIN + BACTERIOSTATIC,
TETRACYCLINE drug = desired effect may be reduced
Spectrum
NARROW - against 1 type of organism (Penicillin & Erythromycin – for gram (+) bacteria)
BROAD- against gram (+) & gram (-) (Tetracyline & Cephalosporins)
General Adverse Reaction
1) HYPERSENSITIVITY – rash, pruritus, hives; severe anaphylactic shock
III. PHARMACODYNAMICS- Study of drug conc & its effects on body TX: antihistamine, epinephrine, bronchodilators
drug response cause: primary physiologic effect (desirable) secondary (un/desirable) 2) SUPERINFECTION – secondary infection d/t disturbed normal flora; occur w/use of broad
ex: Diphenhydramine HCL (1st generation antihistamine) spectrum antibiotics
Treats allergies (primary); CNS depression (secondary)
3) ORGAN TOXICITY – damage to organs involved in drug metabolism & excretion (liver &
Receptor Theory- drugs act on receptors by binding to receptor to produce kidneys) (aminoglycosides = OTOTOXIC & NEPHROTOXIC)
(initiate)/block (prevent) a response
Drug Actions- replace/act as substitutes for missing chemicals Nsg Consideration
- Increase/stimulate certain cellular activities • Monitor for superinfections
- Depress/slow cellular activities • Evaluate renal [BUN & creatinine] & liver [AST,ALT] functions
- Interfere w/functioning of foreign cells (invading microorganisms) • Diarrhea r/t superinfections (mgt: take yogurt, more fluids)
• Inform physician before taking other meds • Cultures- prior to 1st dose
Onset of Action- Time to reach min effective concentration (MEC) after drug is administered
• Alcohol is OUT! / ask about allergies • Take full course of meds
Peak of Action- Condition when drug reaches its highest blood/plasma conc
• Evaluate cultures, WBC, C&S
Duration of Action- length of time drug exerts a pharmacological effect
Agonists- Drugs that produce a response
Antagonists- block a response AMINOGLYCOSIDES
Therapeutic Index- Measures margin of safety of drug Mode of Antibacterial Action
- narrow MOS (low therapeutic index) wide MOS (high therapeutic index) • Multiple daily dosage regimens are traditionally used
- closer ratio is to “1” = greater toxicity danger - maintain serum conc above minimum inhibitory concentration (MIC)
Therapeutic Range (therapeutic window)- between min effective conc in plasma & min - Min inhibitory concentrations (MICs) (lowest conc of antimicrobial inhibiting microorg
toxic conc visible growth after overnight incubation
- ex: Paracetamol (10 mg to 15 mg /kg) • As plasma levels ↑= aminoglycosides kill ↑proportion of bacteria at more rapid rate
Peak Drug Level- Highest drug plasma concentration at a specific time - Same w/penicillins & cephalosporins
Trough Level- lowest drug plasma conc & measure rate where drug is eliminated - time-dependent killing (longer drugs are maintained above MIC= more bacteria killed =
- Indicates rate of drug elimination drug becomes independent of conc, where it’ll still have same effect even at ↓ conc)
• Aminoglycosides have post-antibiotic effect
- Killing action continues even after plasma levels have declined below measurable levels
• Aminoglycosides have greater efficacy in large single dose (than multiple smaller doses)
- Toxicity depends on actual increased plasma conc & duration level is exceeded
- Leads to: once daily dosing = more advantageous

Pharmacokinetics
• Structurally related amino sugars attached by glycosidic linkages
• Must be given thru IM/IV (for systemic effect)
- Not absorbed well through oral (limited tissue penetration in CNS)
• Undergoes renal excretion (plasma levels are greatly affected by renal function)
- Excretion is proportional to creatinine clearance - half-lives 30 min- 1 hour
- Dosage adjustments needed in renal dysfunction  Procaine & Benzathine have longer half-lives (given IM  active drug has slow
release into bloodstream)
 most penicillins can cross blood-brain barrier only when meninges are inflamed
Mechanism of Action Mechanism of Action: BACTERICIDAL
• Aminoglycosides are bactericidal inhibitors of protein synthesis - inhibit cell wall synthesis by:
• enhanced by bacterial cell wall synthesis inhibitors • Drug binds to specific enzymes (penicillin-binding proteins [PBPs] located in bacterial
• Binds to 30s ribosomal subunit & interfere w/ protein synthesis in 3 ways: cytoplasmic membrane
- Block formation of initiation complex - Cause misreading of code in mRNA template • Inhibition of transpeptidation reaction crosslinking linear cell wall peptidoglycan chain
- Inhibit translocation • Activation of autolytic enzymes that cause lesions in bacterial cell wall
- disrupt polysomal structure  non-functional monosome (possible 4th MOAas proposed)
Resistance
Mechanism of Resistance - Enzymatic hydrolysis of beta-lactam ring  loss of antibacterial activity
• Streptococci (S pneumoniae) & Enterococci = relatively resistant (due to drug’s inability - major cause: Formation of beta-lactamases (penicillinases) by staphylococci & gram (-)
to penetrate their cell walls) - to combat, bacterial enzyme inhibitors are used w/penicillins to prevent inactivation
1. Clavulanic acid 2. Tazobactam 3. Sulbactam
Clinical Use
- in MRSA: structural change in target PBPs (& in resistance to penicillin G in pneumococci)
• Main differences d/t activities against specific microorganisms: gram (-) rods
- in some gram (-) rods (pseudomonas), changes in outer cell wall porin structures
• Gentamicin, Tobramycin, Amikacin (serious infections of aerobic gram (-) bacteria
contribute resistance (prevents penicillins from accessing & binding to PBPs)
(E. coli, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, Serratia)
- alternative meds for: H. influenzae, M. catarrhalis, Shigella spp Clinical Use
• ineffective for gram (+) cocci (instead, combined w/cell wall inhibitors e.g. penicillin) NARROW SPECTRUM PENICILLINASE (Susceptible)
• Streptomycin for:: Penicillin G
- Enterococcal carditis (Infective endocarditis): heart valves/endocardium infection - Prototype of penicillins subclass w/ limited spectrum of antibacterial activity (susceptible
- Plague: contagious; characterized by fever & delirium, buboes formation (bubonic plague to beta-lactamases)
& lung infection (pneumonic plague) - against common streptococci, meningococci, gram-positive bacilli, spirochetes
- Tularemia - many strains of pneumococci are now resistant to penicillins (PRSP)
- Pulmonary tuberculosis (if resistant to streptomycin, use amikacin instead) - most strains of S. aureus & N. gonorrhea are resistant d/t beta-lactamase production
• Spectinomycin administered thru IM - no longer DOC for gonorrhea, but still for syphilis
- Single dose for gonorrhea - enhanced by co-administration of aminoglycosides
- not an aminoglycoside but a related drug (aminocyclitol) Penicillin V
- for oropharyngeal infections (given orally)
Toxicity
OTOTOXICITY VERY NARROW SPECTRUM PENICILLINASE (Resistant)
- main possible conditions: Auditory damage (amikacin & kanamycin) Methicillin- prototype, rarely used due to its nephrotoxic potential
Vestibular damage (gentamicin & tobramycin) Nafcillin
 IRREVERSIBLE (decreased w/loop diuretics) Oxacillin
- Contraindicated in pregnancy (damage to fetus hearing after exposure; unless potential • Primary use: staphylococcal infections
benefits outweigh risks)  MRSA & MRSE (S. epidermidis) = resistant to all penicillins & most multiple antimicrobials
NEPHROTOXICITY WIDER SPECTRUM PENICILLINASE (Susceptible)
- Acute tubular necrosis (reversible but more common in: Ampicillin & Amoxicillin:
 Elderly - wider antibacterial activity than penicillin G (but still susceptible to penicillinase)
 Taking other med (amphotericin B, cephalosporins, vancomycin) - for Enterococci, L. monocytogenes, E. coli, P. mirabilis, H. influenzae, and M. catarrhalis
- Most nephrotoxic: gentamicin & tobramycin (Some resistant strains have developed)
NEUROMUSCULAR BLOCKADE - activity is enhanced when used w/ penicillinase inhibitors (clavulanic acid 🡪 Co-Amoxiclav)
- Rare, may result in respiratory paralysis - Reversible: calcium and neostigmine - Synergistic w/aminoglycosides in enterococcal & listerial infections (ampicillin)
- May require a mechanical ventilator Piperacillin & Ticarcillin:
SKIN REACTIONS - against gram (-) rods: Pseudomonas, Enterobacter. Klebsiella
- caused by: Neomycin (Allergic skin reactions, Contact dermatitis) - used w/penicillinase inhibitors (tazobactam & clavulanic acid) to enhance activity

Nsg Responsibilities Toxicity

• Monitor periodical audiogram, BUN/creatinine & vestibule fx study over 10 days therapyALLERIGC REACTION
• Adjust for renal insufficiency • Monitor VS, peak and serum levels - Urticaria, severe pruritus, fever, joint swelling, hemolytic anemia, nephritis, anaphylaxis
• For IV admin., dilute and administer slowly to prevent toxicity - occur if given penicillin again (in 5-10% of persons)
• Monitor I & O, hydrate well before & during therapy (flush in between) - Maculopapular skin rash (but mimics an allergic reaction) (ampicillin)
• SFF meals (anorexia/nausea) • Establish plan for safely if vestibular nerve effects occur.GASTROINTESTINAL DISTURBANCE
• Administer other antibiotics 1 hr before/after amino - Nausea & diarrhea (oral penicillins)
• Recommend using sunblock & protective clothing when exposed to the sun - d/t direct irritation/by overgrowth of gram (+) organisms/yeasts
- Pseudomembranous colitis (ampicillin)
MISCELLANEOUS: Neutropenia (nafcillin); Interstitial nephritis (methicillin)

BETA-LACTAM ANTIBIOTICS II. CEPHALOSPORINS

I. PENICILLIN - Derivatives of 7-aminocephalosporanic acid & has beta-lactam ring structure
- Derivatives of 6-aminopenicillanic acid - many are in clinical use (vary in antimicrobial activity & designated acc to generations: in
- has beta-lactam ring (for antibacterial activity/antibiotic effect) order of their introduction into clinical use)
- has additional chemical substituents which confer differences (antimicrobial activity,
susceptibility to acid, enzymatic hydrolysis, biodisposition) Pharmacokinetics
- many are available for oral use (mostly parenteral)
pharmacokinetics - those w/sidechains undergo hepatic metabolism; majority undergo renal excretion via
- vary in resistance to gastric acid (variable bioavailability) active tubular secretion (only Cefoperazone & Ceftriaxone are excreted mainly in bile)
- not metabolized extensively (excreted unchanged in urine via glomerular filtration &
- most don’t enter cerebrospinal fluid even when meninges are inflamed
tubular secretion, latter is inhibited by probenecid
- Nafcillin (excreted mainly in bile) Mechanism of Action
- Ampicillin (undergoes enterohepatic recycling) - bind to penicillin-binding proteins to inhibit bacterial cell wall synthesis (like penicillins)
(bactericidal)
- some structural differences make it less susceptible to penicillinase made by staphylococci
- all are active against P. aeruginosa & acinetobacter spp, (except for ertapenem)
 often paired w/ aminoglycoside if used against pseudomonas
- Given parenterally; against microbes resistant to other antibiotics (except MRSA)
- Co-drugs of choice for: Enterobacter, citrobacter, serratia spp
Resistance • Imipenem- rapid inactivation by renal dehydropeptidase I
- some bacteria can produce beta-lactamases inactivating cephalosporins - administered in fixed combo w/cilastatin (dehydropeptidase I inhibitor)
- from decreases in membrane permeability to cephalosporins/changes in PBPs - Increases its half-life & inhibits metabolite formation toxic to kidneys
– MRSA is resistant  other carbapenems are not significantly degraded by kidneys
 Imipenem-Cilastatin: Partial cross-allergenicity w/penicillins
1ST GENERATION
- Adverse effects: GI distress, skin rash; CNS toxicity (confusion,
Cefazolin (parenteral) & Cephalexin (oral)
encephalopathy, seizures (at very high plasma levels)
- active against gram (+) cocci (staphylococcus, common streptococci)
- against many strains of E. coli & K. pneumoniae • Meropenem- not metabolized by renal dehydropeptidases; less likely to cause seizures
– used as surgical prophylaxis • Ertapenem- long half-life but less active against enterococci & pseudomonas
– Minimal activity against: Gram (-) cocci, Enterococci, MRSA, most gram (-) rods - IM route causes pain & irritation
2ND GENERATION
BETA-LACTAMASE INHIBITORS (Clavulanic acid, Sulbactam, Tazobactam)
- Lesser activity against gram (+) microbes vs 1st gen
- used in fixed combo w/certain hydrolyzable penicillins
 But have extended gram (-) coverage - most active against plasmid-encoded beta-lactamases (by gonococci, streptococci, E.
 Marked differences between usefulness between drugs in group coli, H. influenzae)
ex: Bacteroides fragilis (cefotetan & cefoxitin)
- not for enterobacter, pseudomonas, serratia (type of beta-lactamase is chromosomal,
Sinus, ear, respiratory infections by H. influenzae/M. catarrhalis (cefamandole,
not plasmid-encoded)
cefuroxime, cefaclor)
3RD GENERATION Other Cell Wall/Membrane-Active Agents
• ↑ activity against gram (-) microbes resistant to other beta-lactam medications VANCOMYCIN
– can penetrate blood-brain barrier (except for cefoperazone & cefixime) - transglycosylation: Prevents peptidoglycan chain elongation & interferes w/cross-linking
• Most active against: Providencia, serratia marcescens, beta-lactamase-producing strains of Resistance d/t decreased affinity for binding site
H. influenzae & Neiserria - Narrow spectrum of activity:
• Less active against: Enterobacter strains producing extended-spectrum beta-lactamases  Used for serious infections caused by drug-resistant gram (+) organisms
• reserved for serious infections: Pseudomonas  cefoperazone, ceftazidime Methicillin-resistant staphylococci (MRSA)
B. fragilis cetizoxime Penicillin-resistant pneumococi (PRSP) combined w/ 3rd gen cephalosporin
• except for: ceftriaxone (parenteral) & cefixime (oral) for gonorrhea (ceftriaxone)
TH Backup drug for Clostridium difficile infection
4 GENERATION
- Not absorbed in GI tract (given orally for bacterial enterocolitis)
Cefepime- more resistant to beta-lactamases by gram-negative: Enterobacter, haemophilus,
- parenteral, penetrates most tissues & eliminated unchanged in urine
neisseria, some penicillinase-resistant pneumococci
- dosage modification is mandatory in renal failure patients
– combines: Gram (+) activity of 1st generation
- toxicity: Chills, fever, phlebitis, ototoxicity, nephrotoxicity
Wider gram (-) spectrum of 3rd gen
TH
Rapid intravenous infusion Red Man Syndrome (d/t histamine release)
5 GENERATION
• for treating bacteria resistant to commonly used antibiotics FOSFOMYCIN
Ceftaroline – broad spectrum activitiy against MRSA (others: MRSE, VRE) - Antimetabolite inhibitor of cytosolic enolpyruvate transferase
- ineffective against Pseudomonas  Prevents N-acetylmuramic acid formation (precursor for peptidoglycan chain formation)
Ceftobiprole- aka 5th gen cephalosporin (term not universally accepted)  Resistance: ↓ drug intracellular accumulation
- powerful antipseudomonal activity; binds strongly to PBP 2a - Excreted by kidney in urinary levels higher than min inhibitory conc (MIC) (against UTI)
- has activity against MRS, S. pneumonia, enterococci - diarrhea when multiple dosing
- newer meds used for healthcare-associated pneumonia (HCAP)/HAP - synergistic w/beta-lactam & quinolone antibiotics in some infections

Toxicity BACITRACIN
ALLERGY- skin rashes to anaphylactic shock - Peptide antibiotic interfering w/ late stage in cell wall synthesis in gram (+) organisms
- between cephalosporins is complete (100%) - Limited to topical use bc of marked nephrotoxicity
- “ cephalosporin & penicillin is incomplete (5-10%)
CYCLOSERINE
ADVERSE EFFECTS
- Antimetabolite blocking amino acids incorporation into peptidoglycan side chain
- pain at IM injections (phlebitis if given IV)
- Highly neurotoxic (tremors, seizures, and psychosis)
- ↑ nephrotoxicity of aminoglycosides (if given together)
 Limited use to tuberculosis that is resistant to first-line antituberculosis drugs
- hypoprothrombinemia & disulfiram-like actions w/ ethanol (cefamandole,
cefoperazone, cefotetan) DAPTOMYCIN
 d/t methylthiotetrazole group - Novel cyclic lipopeptide w/spectrum like vancomycin (against vancomycin-resistant
 Disulfuram-like action: alcohol reaction leading to nausea, vomiting, strains of enterococci & staphylococci)
flushing, dizziness, throbbing headache,
- Eliminated via kidney
chest/abdominal discomfort, general hangover-
- Monitor creatinine since it causes myopathy
like symptoms
Other Beta-Lactam Drugs
AZTREONAM
- monobactam resistant to beta-lactamases by some gram (-) rods (Klebsiella,
pseudomonas, serratia); No activity against gram (+) bacteria/ anaerobes
- Cell wall synthesis inhibitor (preferentially binds w/penicillin-binding protein (PBP3)
- Synergistic w/ aminoglycosides
- IV route; eliminated via renal tubular secretion
- Half-life is prolonged in renal failure
- adverse effects: GI upset w/ superinfection, vertigo, headache, rarely hepatotoxicity
Skin rash may occur but there is no cross-allergenicity w/ penicillins
CARBAPENEMS (Imipenem, Doripenem, Meropenem, Ertapenem)
- chemically different from penicillins but retain beta-lactam ring structure
- low susceptibility to beta-lactamases, making it useful against: Gram (+) cocci, Gram (-)
rods, anaerobes
 ANTI-HYPERTENSIVES Nsg Consideration
- Encourage implement lifestyle changes
Drugs Affecting Cardiovascular System - Administer on an empty stomach
Antihypertensives - Alert if px is for surgery/ dialysis / situations which may drop fluid volume
- ACE inhibitors - Angiotensin II receptor blocker - Calcium Channel Blocker - Parenteral form ONLY if oral form is not available
- Symphatolytics, - Vasodilators - Adjust dose if w/ renal failure
Diuretics: - Thiazide - Loop - Osmotic - Potassium-sparing - Don’t give if BP is below 90/70, monitor BP for 2 hours after first dose (hypotension)
Anti-Anginal: - Nitrates - Non-nitrates - Avoid ambulation (dizziness)
- Report cough / angioedema
Cardiac Glycosides
- Report dysgeusia if more than 1 month
Drugs affecting Blood: Anticoagulants, Throbolytics, Hemostatics
BLOOD PRESSURE- measurement of force applied to artery walls ANGIOTENSIN II RECEPTOR ANTAGONIST (“- sartan”)
- determinants: cardiac output, peripheral vascular resistance - selectively bind angiotensin II receptors in blood vessels & adrenal cortex
- baroreceptors/pressure receptors: specialized cells in aortic arch ex: telmisartan (Micardis) candesartan (Blopress)
- Renin-Angiotensin Aldosterone System (RAAS: compensatory mechanism losartan (Diovan) valsartan (Cozaar)
when BP in kidneys fall irbesartan (Aprovel) eprosartan (Teveten)
use: when ACE inhibitors aren’t tolerated
SE: HA, diarrhea, dyspepsia, cramps
AE: angioedema, hyperkalemia
CI: nephron dysfunction, CHF, pregnancy
Nsg Consideration: - ensure female px is NOT PREGNANT
- take w/o regard to food

CALCIUM CHANNEL BLOCKERS

MOA: prevents movement of Ca ions in myocardium & vascular smooth muscles.
Normally: Ca inc muscle contractility, peripheral resistance & BP
Ex: amlodipine ( Norvasc) nimodipine (Nimotopp) diltiazem (Cardizem)
felondipine (Plendil) nicardipine ( Cardene) nifedipine (Procardia)
verapamil ( Calan)
USES: Angina, hypertension, atrial fibrillation
SE/AD: HA, dizziness, hypotension, syncope, reflex tachycardia, constipation, AV block,
bradycardia, peripheral edema
Nsg Consideration: - Monitor ECG, CR, BP
- Have “E” cart available with IV administration
- Position to decrease peripheral edema
- Protect drug from light & moisture
- ↑ OFI and fiber in the diet
- Avoid overexertion when anginal pain is relieved
- May give paracetamol if with HA
HYPERTENSION- “silent killer”; when BP is above normal for sustained period - Take with meals/ milk
- types: Primary, Secondary - No not chew or crush sustained released
Stepped Care Approach
1. Lifestyle modification- wt reduction; ↓ Na intake, moderate alcohol intake, smoking
cessation, ↑physical exercise
2. + Drug
Health Teaching
P- ressure blood monitor
R- ise slowly
E- ating must be considered
S- tay on meds
S- kipping/abrupt stopping is a NO
U- ndesirable response
R- emind to exercise, decrease alcohol
E- liminate smoking
VASODILATORS
ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (“- pril”) MoA: relax blood vessel (artery) smooth muscle; promote ↑blood flow to brain & kidney
MoA: blocks angiotensin I conversion to angiotensin II Ex: hydralazine (Apresoline) minoxidil (Loniten) diazoxide ( Hyperstat)
use: hypertension, MI nitroprusside ( Nitropress)
ex: Benazepril (Lotesin) Quinapril (Accupril) Perindopril (Aceon) USES: severe hypertension, emergencies
Captopril (Capoten) Fosinopril (Prinivil) Lisinopril
SE / AE:
Enalapril maleate (Vasotec) Moexipril (Univasc) Ramipril Trandorapril
- hydralazine: tachycardia (beta blockers), palpitations, edema (diuretics), HA, dizziness,
SE: cough, hypotension, HA, dysgeusia (perversion of taste perception), insomnia, N/V, GI bleed, lupus like and neurologic symptoms
diarrhea
- minoxidil: similar effects, excess hair growth, precipitates angina
AE: reflex tachycardia, chestpain, angina, CHF, cardiac arrhythmias, ulcer, liver/renal - Nitroprusside & diazoxide (hyperglycemia): similar
problem, photosensitivity, hyperkalemia, neutropenia, angioedema
CI: allergy, pregnancy, lactation, cerebral insufficiency
DI: + probenecid = ↓ elimination DI: + other antihypertensive drugs = additive effect
+ potassium supplement & diuretics = hyperkalemia (K+ above normal)
Nsg Consideration: D – irectly acts on vascular smooth muscle
+ NSAIDS = ↓hypotensive effect
I – ncrease renal and cerebral blood flow
+ Antacids = ↓absorption
L - upus like reaction (fever, face rash, muscle/joint pain, spleenomegaly)
+ tetracycline = ↓ tetra absorption
A – ssess peripheral edema
CI: renal disease, sever Na depletion, CHF, pregnant & lactating women
 T – ake with food Minipress SINS (undesirable effects of Alpha Adrenergic Blockers
O – ther side effects (headache, dizziness, anorexia, Inc. Cardiac, ↓BP S-yncope & Sexual dysfunction
R – eview BP (orthostatic hypotension), blood glucose I- ncreased drowsiness, orthostatic hypotension, HR
N- eed to be recumbent for 3-4 hours after initial dose
SYMPATHOLYTICS
- Beta-blockers (“- olol”) CENTRALLY ACTING ALPHA 2 AGONIST
BETA-ADRENERGIC BLOCKERS MOA: - ↓ sympathetic response from brainstem to peripheral vessels;  ↓peripheral
MoA: block beta 1 (Cardiac) / beta 2 (lungs) adrenergic receptor sites; ↓SNS effects by vascular resistance & BP
blocking release of catecholamines, decreasing HR & BP - Stimulate alpha2 receptors: ↓sympathetic activity
 Beta 1 receptors- in HEART & KIDNEYS ↑vagus nerve
- when stimulated, they ↑HR, AV conduction, automaticity ↓epinephrine, norepinephrine, renin release
 Beta 1 blockers- ↓HR, BP, myocardial contractility, myocardial O2 consumption SE/ AE: drowsiness, HA, dry mouth, dizziness, bradycardia, constipation, hypotension,
occasional edema, wt gain
 Beta 2 receptors- in LUNGS, GI tract, liver, uterus, vascular smooth muscle, skeletal muscle
- dilate bronchial & vascular smooth muscle DI: + propranolol = paradoxical hypertension
 Beta 2 receptor blockade- inhibit smooth muscle relaxation in blood vessel, bronchi, Ex: Methyldopa (Aldomet) - chronic hypertension/pregnancy induced hypertension (PIH)
GI sys, genitourinary tract Clonidine (Catapres)
Uses: hypertension, dysrhythmia, angina pectoris  both drugs cause Na & water retention (usually given w/diuretics)
AE: rebound hypertension
Nsg Considerations:
- Monitor baseline VS (q30 mins until stable during initial therapy) & weight ( refer: wt
Main contraindication: Asthma Diabetes Mellitus gain > 4 lbs/ week)
Block (heart block) Electrolyte Imbalance (hyperkalemia) - Abrupt D/C = hypertensive crisis ( restlessness, tachycardia, tremors, HA, ↑BP), compliance
COPD - Taper dose gradually over more than 1 week
DI: + antacids = delayed drug absorption - Recommend last dose of the day to be taken at bed time
+ lidocaine =↑plasma level of lidocaine - Sugarless gum, sips of tepid water may relieve dry mouth
+ insulin/ Oral Hypoglycemic Agent (OHA) = hypo/ hyperglycemia
+ cardiac glycosides= additive bradycardia ADRENERGIC NEURON BLOCKERS (Peripherally Acting Sympatholytics)
+ calcium channel blockers= ↑pharmacologic and toxic effects of both MOA: block norepinephrine release from sympathetic nerve endings  ↓ BP
+ cimetidine= ↓ metabolism of beta blockers SE: orthostatic hypotension, Na & water retention; vivid dreams, nightmares, suicidal
+ theophylline = impaired bronchodilating effect intention (reserpine)
Ex: Nonselective Beta Blockers: Carvedilol (Coreg) Nadolol (Corgard) Ex: reserpine (Serpasil); guanethidine monosulfate (Ismelin)
Propranolol (Inderal) Timolol ( Blocadren) Nsg Considerations: - Take with meals, no alcohol
Pindolol ( Visken)
Cadioselective Beta Blockers (B1): acebutolol (Sectral) atenolol ( Tenormin) ALPHA 1 & BETA 1 ADRENERGIC BLOCKERS
betaxolol (Kerlone) bisoprolol (Zebeta) MOA: blocks alpha1 & beta1 receptor sites; ↓ BP & moderately ↓PR
esmolol (Brevibloc) metoprolol (Betaloc, Cardiostat) SE: orthostatic hypotension, GI disturbances, nervousness, dry mouth, fatigue
Nsg Consideration: - Lifestyle modification; Compliance (rebound hypertension) AE: heart block
- Monitor blood sugar with diabetics CI: large doses could block bete2 receptors = ↑ airway resistance in patients w/asthma
- Monitor triglycerides and cholesterol level (LDL) Ex: labetalol (Normodyne); carteolol (Cartrol)
- Monitor BP & pulse before and after
- Withhold if pulse is < 60 or SBP < 90 SYMPATHOMIMETICS & SYMPATHOLYTICS
- Monitor any change in the rhythm/signs of CHF  REFER TO SEPARATE HANDOUT!!!
Undesirable Effect: B -radycardia
L- ipidemia increases /- ibido decreases CHOLINERGICS & BLOCKERS
br O-nchospasm  REFER TO SEPARATE HANDOUT!!!
C- HF (chronic heart faliure) / - onduction abnormalities
K- onstriction (peripheral and vascular)
E- xhaustion / - motional depression
R- educes recognition of hypoglycemia CARDIAC GLYCOSIDES / ANTIAGINAL DRUGS
ALPHA-ADRENERGIC BLOCKERS (“-sin”) Congestive Heart Failure (CHF)- heart fails to effectively pump blood d/t damaged/
MOA: - blocks alpha 1 adrenergic receptors  vasodilation of arteries & veins overworked heart muscle
- ↓peripheral resistance; relaxes smooth muscle of bladder / prostate - cause: coronary artery disease, cardiomyopathy, hypertension, valvular heart dis
- ↓ VLDL & LDL = ↓ fat deposits ; ↑ HDL
- Doesn’t affect glucose metabolism & respiratory function
- Causes Na & H2O retention with edema; given with diuretics
WARNINGS: renal disease, elderly more sensitive
Ex:
Potent Alpha Blockers: hypertensive crisis & severe hypertension from catecholamine
secreting tumors of the adrenal medulla (pheochromocytoma)
- Phentolamine - Phenoxybenzamine - tolazoline
Prazosin ( Minipress) = CHF (Chonic Heart Failure)
Doxazosin (Cardura) = BPH (Benign Prostatic Hyperplasia)
Terazosin (Hytrin) = BPH
SE: orthostatic hypotension (dizziness, faintness, ↑HR)
- 1st dose syncope (hypotension with loss of consciousness)
- Nausea, drowsiness, nasal congestion, weaknes, loss of libido
- Phentolamine: reflex tachycardia
DI: + other antihypertensive, alcohol, nitrates= ↑ hypotensive effects
Prazosin + anti-inflammatory drug = peripheral edema
Prazosin & nitroglycerin = syncope
Nsg Interv: - Monitor BP frequently - Protect from falling / injury
- Assess BP & HR before each dose
- If dose is during the day, client must remain recumbent for 3-4 ˚
- Assist with ambulating if client is dizzy
- EDUC: Implement safety precautions
Report if edema is present
Sugarless gum, sips of tepid H2O, etc. may relieve dry mouth
CARDIAC GLYCOSIDE- originally derived from poisonous fox-glove/digitalis plant NITRATES
- used by William Withering of England to alleviate dropsy (edema of MOA: vein dilation = less blood return to heart (decrease preload)
extremities d/t cardiac & kidney insufficiency secondary to CHF) artery “ = less vasoconstriction & resistance (decrease afterload)
- ex: digoxin (Lanoxin, Lanoxicaps)- PO, IV Uses: treatment & prevention of angina, dec BP
MOA: inhibits Na- K pump which ↑intracellular Ca & allow more Ca to enter myocardial SE: HA (most common), dizziness, hypotension, reflex tachycardia, decrease CR, GI distress,
cells during depolarization causing: flushing
 (+) inotropic action (↑ myocardial contraction) AE: some degree of hepato / nephrotoxicity
 (-) chronotropic action (↓ heart rate) Nsg Consideration
 (-) dromotropic action (↓conduction velocity) - Assess chest pain: Precipitating factors Radiation Time
 ↑cardiac output & renal perfusion Quality Severity/ symptoms
USES: CHF, AF, A flutter - PO: take on empty stomach; undergoes hepatic first pass effect
rapid onset, excreted thru kidney, has NARROW MARGIN OF SAFETY - SL: every 5 min X 3 doses; effect lasts for 10 minutes
: store in dry & dark bottle
Digitalis toxicity: anorexia, diarrhea, N/V, bradycardia, cardiac dysrhythmias, HA, : check expiration date (up to 6 months only)
malaise, blurred vision, visual illusions (white, green, yellow halos : take sips of water BEFORE administration
around objects), confusion, delirium : allow drug to dissolve before taking anything PO
Antidote: digoxin immune Fab (intoxication with serum level of > 10ng/mL) : burning / stinging sensation means the drug is potent
 Binds w/ digoxin to form complex molecules that can be excreted in urine - Buccal: place drug between upper lip & gum/between cheek & gum
CI: hypersensitivity, ventricular tachycardia and fibrillation, heart block, MI, renal - IV infusion: dilute drug in glass IVF bottles via infusion pump, onset 1-3 min same w/SL
insufficiency, electrolyte imbalance ( inc Ca, dec K & Mg) - Topical Ointment: remove previous application
DI: + verapamil, quinidine, quinine, erythromycin, tetracycline, cyclosporine = ↑toxic effect : spread drug over a 6x6 in area on chest, back, upper arm; cover w/ a
+ loop diuretics/ hydrochlorothiazide = HYPOKALEMIA (↑effect at its myocardial cell plastic wrap
action site) : rotate site, avoid touching the ointment
+ cortisone preparations = sodium retention & potassium excretion - Patch: water proof; apply wearing gloves at Anterior Chest Wall, non-hairy portion
+ thyroid hormones, metoclopramide = less effective : remove previous patch, rotate sites
+ antacids =↓digitalis absorption : remove after 12 hours to prevent tolerance
: do not apply defibrillator paddles over drug, may cause burn
Nsg Consideration:
- Spray: lift tongue then spray, avoid inhaling drug
- Consult prescriber about loading dose
- General: withhold: BP < 90/60, HR <60, acetaminophen for HA, reassess chest pain
- Monitor apical pulse in 1 full minute, monitor for quality & rhythm
after 2-5 minutes (SL, spray, except PO)
- Check dosage & preparation carefully
- Check pediatric dose with extreme care
- Follow dilution carefully for IV preparation
- Administer IV dose very slow over at least 5 minutes
- Weigh patient
ANTI-ARRHYTHMIC DRUGS
- Avoid administering oral drug w/ food or antacid
conduction sys
- Maintain emergency equipment on standby = lidocaine (arrhythmias), phenytoin
(seizure), atropine SO4 (to ↑cardiac rate), cardiac monitor
- Monitor therapeutic level of digoxin (0.5 – 2 ng/ mL) , digoxin toxicity
K-rich food: banana, avocado, broccoli, dried fruit, orange, nuts, potato, prunes, tomato
Na-rich “ : buttermilk, margarine, canned/processed/preserved food, fast foods, ketchup

ANTI-AGINALS
Coronary Artery Disease (CAD) – lumen of blood vessels turn narrow,  blood is no
longer able to flow freely to muscles
Angina Pectoris – “suffocation of chest”; when myocardial demand for O2 can’t met by
narrowed blood vessels
Anginal pain- chest tightness, pressure in the center of the chest, and pain radiating
down the neck and left arm.
Myocardial Infarction (MI) – when coronary vessels is completely occluded & cells that
depend on vessels for O2 become ischemic, then necrotic & die
Types of Angina:
Classic (stable) – occurs w/stress exertion
Preinfarction (Unstable) - occurs frequently over course of day w/ progressive severity
Variant (Prinzmetal, vasospastic) - occurs during rest

Types of Anginal Drugs:

1. Non- nitrates (beta blockers, calcium channel blockers)
2. Nitrates- isosorbide mononitrate (Imdur, isoket, isordil);
nitroglycerin (Deponit, Nitrostat)
ECG Waves
1. P-WAVES- Atrial depolarization (if formed as impulse originating in SA node)
2. QRS COMPLEX- Depolarization of Bundle of His (Q); Depolarization (RS)
3. T- WAVE- Represents repolarization of ventricles
4. PR- INTERVAL- AV conduction time 2. PHASE 1- very short period where Na ion conc equalize inside and outside the cell.
5. QT INTERVAL- Reflects ventricular action potential duration 3. PHASE 2- Plateau stage; occur as cell membrane becomes less permeable to Na, Ca
slowly enters cell, causing potassium to leave cell.
- cell membrane is trying to return to its resting phase (REPOLARIZATION)
4. PHASE 3-time of rapid repolarization as Na gates are closed & K flows out the cell.
5. PHASE 4- when cell comes to rest.
- sodium-potassium pump returns to membrane to its resting potential (Na
outside cell-K inside cell).
- Spontaneous depolarization begin again.

Cardiac Dysrhythmia/Cardiac Arrhythmia- deviation from normal rate/heartbeat pattern

- bradycardia/tachycardia
Anti-Arrhythmic Drugs
- affects action potential of cardiac cells, altering their automaticity, conductivity, or both
- used in emergency situation; produce new arrhythmia (PROARRHYTHMIC)
I. CLASS I ANTI-ARRHYTHMICS- block Na channel in cell membrane during action potential
- depressing phase 0 action potential
subtypes: (Classes 1a, 1b, 1c)
CLASS 1A
MOA: Depress phase 0 action potential & prolong action potential duration.
Slows down conduction and prolongs repolarization
Ex: DISOPYRAMIDE (Norpace) MORICIZINE (Ethmozine) PROCAINAMIDE (Pronestyl)
QUINIDINE (Cardioquin)
Therapeutic indication: ventricular arrhythmias
Undesirable Effect: CNS- Dizziness, Drowsiness, Fatigue, Twitching, Mouth numbness
Slurred speech, vision changes, tremors
GIT- Altered taste, nausea, vomiting
CVD- Arrhythmias, hypotension, cardiac arrest
Others: respiratory arrest
Nsg Consideration
- Monitor ECG, VS, serum electrolytes, CBC, kidney & liver function
- Maintain life support equipment
- Give parenteral form only if oral form is not feasible
- Titrate dose to achieve control of arrhythmia
- Establish safety precaution
- Lifestyle modification

II. CLASS II ANTI-ARRHYTHMICS

- beta-adrenergic blockers
MOA: Reduce Ca entry, decreases conduction velocity; automaticity, recovery period.
Blocks beta receptors, causing depression of phase 4 of action potential.
Ex: Acebutolol (Sectral) Esmolol (Brevibloc) Propranolol (Inderal) Sotalol (Betapace)
Therapeutic Indications: Supraventricular tachycardia; PVC’s
Contraindication: Sinus bradycardia (<45bpm); AV blocks, Cardiogenic shock, CHF , Asthma
Respiratory depression
DI: Verapamil= synergestic Insulin= hypoglycemia
Undesirable effect: same w/Class 1; loss of libido

III. CLASS III ANTI-ARRHYTHMICS/POTASSIUM CHANNEL BLOCKERS

MOA: Prolong repolarization during ventricular dysrhythmia
“ action potential duration.
Blocks K channel & slow outward movement of K during phase 3 of action potential
Ex: Amiodarone (Cordarone) Bretylium Ibutilide (Corvert) Dofetilide (Tikosyn)
Sotalol (Betapace)
TI: Ventricular arrhythmias, Atrial fibrillation, Atrial Flutter
CI: none; AV block: Ibutilide & Dofetilide
Automaticity of Heart UE: liver toxicity (amiodarone)
Automaticity- ability of pale/P-cells to generate action potential/electrical impulse w/o DI: Digoxin & Quinidine = toxicity
being excited to do so by external stimuli
5 phases of Action Potential IV. CLASS IV ANTI-ARRHYTHMICS
1. PHASE O- when cell reaches point of stimulation. - Ca channel blockers
- Na gates are open along cell membrane, Na rushes into cell then causing MOA: Blocks Ca movement across cell membrane, depressing generation of action
DEPOLARIZATION potentials, delaying phase 1 & 2 repolarization, & slowing conduction thru the AV node.
TI: Supraventricular tachycardia
Ex: Diltiazem (Cardizem); Verapamil ( Calan)
CI: Allergy, Heart blocks, Pregnancy & lactation, CHF/hypotension
DI: Beta-blockers = cardiac depression digoxin = additive AV slowing
digoxin, Prazosin, Quinidine = toxicity
Other drugs: Adenosine (Adenogard)- slows conduction through AV node; IV T- ake time to check VS
Digoxin H- yperglycemia, hypokalemia, hyperuricemia monitoring
I- nstruct to weigh in daily
A- void sudden position changes
DIURETICS Z- ugar monitoring
I- &O (intake & output) monitoring -
Food Sources D- iuresis is expected: I&O
 K-rich: banana, avocado, broccoli, dried fruits, orange, nuts, potato, prunes, tomato E- at potassium rich foods
 Na-rich: buttermilk, margarine, canned/ processed/fast/preserved foods, ketchup
 Ca-rich: broccoli, dairy & milk products, seafoods, spinach
II. LOOP DIURETICS
Kidney Fx MOA: inhibits Na & Cl absorption from Loop of Henle & distal tubules, causes rapid
Nephrons- functional unit of kidneys diuresis, little effect on glucose
3 processes to produce urine: USES: HPN, edema associated with CHF, cirrhosis with ascites, hypercalcemia
1. FILTRATION- water & solutes movement: plasma in glomerulus  glomerular capsule DI: (same w/thiazides)
membrane  capsular space of Bowman’s capsule
SE/AE: hypokalemia, hyponatremia, hypocalcemia, hypomagnesemia, hypochloremia,
2. REABSORPTION- molecule movement out of tubule into peritubular blood hyperuricemia, orthostatic hypotension, constipation, N/V, ↓platelet, ototoxicity
- 80% water, Na, K, Cl, most substances are reabsorbed (IV bumetanide), dehydration, photosensitivity, thiamine deficiency,
- 20% of glomerular filtrate enter Loop of Henle hyperglycemia (glycogenolysis), elevated BUN & creatitine
 Descending loop of Henle >> water is reabsorbed; Ex: furosemide (Lasix) torsemide (Demadex) ethacrynic acid (Edecrin)
 Ascending limb >> sodium is reabsorbed. bumetanide (Bumex)
 Distal Tubule >> sodium is reabsorbed
Nsg Responsibility
 Final reabsorption of water >> distal tubule & small collecting tubules.
 remaining water & solutes are now appropriately called URINE. - Monitor VS, edema, urine output, serum K. Na, Ca, Cl, thiamine, blood glucose & platelet
levels, Mx of digoxin & lithium toxictiy
3. SECRETION- molecule movement out of peritubular blood into tubule for excretion - Potassium rich foods
- proximal tubule: uric acid, creatinine, H ions, ammonia are secreted - Give slow IVTT (2 mins) to prevent hearing loss
- distal tubule: K ions, H ions, ammonia are secreted - With food, in AM
C- heck for weight gain
DIURETICS- produces increased urine flow by Na & water reabsorption from tubules E- nsure VS prior to administration
  - 2 main purposes: To ↓ hypertension & to ↓ edema I - & O monitoring
indication: - Congestive heart failure (CHF) - Pulmonary edema - Renal disease L - aboratory values assessment
- Liver failure & cirrhosis - Hypertension (HPN) - Glaucoma I - nstruct to rise slowly
Contraindication: - Allergy - Fluid & electrolyte imbalances - DM N- octuria prevention:
- Severe renal diseases - Systemic Lupus Erythematous (SLE) G - ive it with meals

III. OSMOTIC DIURETICS

MOA: increase osmotic pressure in the glomerular filtrate, preventing reabsorption of
water & electrolyes
USES: ↑ ICP, edema, prevention of renal failure, oliguria, inducing diuresis during
chemotherapy
CI: anuria
DI: ↑hypokalemia which may ↑digoxin toxicity
SE/AE: pulmonary edema d/T rapid fluid shifting, NV, tachycarida, ↓ Na, K, Cl, Ca,
dehydration
ex: mannitol (Osmitrol) urea (Ureaphil) glycerin (Osmoglyn) = dec IOP
isosorbide (Ismotic)
Nsg Responsibilities:
- Monitor VS, wt, urine output, serum, NA, K, Cl, Ca
- Watch for rapid ↑BP & rapid sympathetic overactivity (↑HR, tremor, agitation)
I. THIAZIDE DIURETICS - Assess lung & heart sounds
- Check skin turgor, LOC, Mx of dec ICP
MOA: ↑Na & water excretion by inhibiting Na reabsorption in distal tubule
- Mannitol: check bottle or vial for crytallization, warm bottle & shake vigorously to
 not effective for immediate diuresis
dissolve crystals, if it doesn’t dissolve= DO NOT administer
Uses: mild- moderate HPN, edema associated w/ CHF, cirrhosis w/ ascites : use IV line with filter
Warning: ↓K, renal/ hepatic dysfunction, gout : infuse for 30- 60 minutes
DI: + lithium = lithium toxicity O- liguria, edema, inc. ICP (indication)
+ digoxin = digoxin toxicity (bradycardia, N/V, visual changes) S- tops reabsoprtion of water
+ corticosteroids, amphotericin, ticarcillin = Hypokalemia M- annitol
+ sulfonamides = Cross sensitivity O- utput of urine, electrolytes - monitor
SE/ AE: hypokalemia, hyponatremia, hypomagnesemia, hypotension, bicarnonate loss, T-issue dehydration UE
hypercalcemia, hyperglycemia, hyperuricemia, N/V, constipation, rashes, dizziness, I-ncreased frequency/volume of urination
weakness, increase LDL, photosensitivity, H/A, dehydration, blood dyscrasias C-irculatory overload UE

Ex: chlorothiazide (Diuril) chlorthalidone (Thalitone) hydrochlorothiazide (Hydrodiuril)

IV. POTASSIUM SPARING DIURETICS
indapamide (Lozol) metolazone (Zaroxolyn)
MOA: acts on the distal tubule to promote Na and water excretion & prevent potassium
Nsg responsibility excretion; AKA: Aldosterone antagonist
- Monitor BP, wt OD, urine output, edema
USES: HPN, edema = CHF, nephrotic syndrome to counteract hypokalemia caused by
- Monitor K, Na, Ca, blood glucose, LDL, triglycerides
other diuretics
- Change position slowly
CI: severe renal disease, severe hyperkalemia
- No alcohol
- Take with meals preferably in AM DI: + lithium = lithium toxicity
- K-rich food (banana, avocado, broccoli, dried fruit, orange, nuts, potato, prune, tomato) + ACE inhibitor = hyperkalemia
- Manage photosensitivity + digoxin = digoxin toxicity
- Signs of hypokalemia (muscle weakness, cardiac dysrhythmias, cramps, dizziness, N/V, + K supplements (kalium durule) = hyperkalemia
tingling sensation, “U” wave on ECG (3.5 – 5.1 mEq/L)
SE/AE: hyperkalemia, N/V, diarrhea, dry mouth, rash, dizziness, weakness, bluish colored
urine (triamterene) hypotension, increase potassium level result in peaked T wave
on ECG
AE: HA, photosensitivity, anemia, ↓ platelet
Ex: spironolactone (Aldactone) amiloride (Midamor) triamterene (Dyrenium)
Nsg Responsibilities:
- Monitor VS, urine output, serum K level
- Inform client that hypotensive effects may not be seen for 2 weeks
- Avoid potassium rich foods
- Manage photosensitivity
- Avoid salt substitutes
- Take with meals
- Bluish colored urine is harmless
- Administer in Am

Interventions for Diuretics

D-iet: ↓sodium intake T-ake early in day; w/meals
I-ntake & output monitoring I- nteractions; digoxin
U-ndesirable effects C- ause / aggravate diabetes
R-eduction of edema S- ensitivity to sunlight
E-lectrolytes review