Lecture 1- pulm agents

metered dose inhaleres (MDI)

• hand held

• slow, deep inhalation

spacers

• attach to MDI to improve delivery to lungs

• reduce oropharyngeal deposition

• especially helpful for children or pts with poor coordination

dry powder inhalers (DPI)

• breath activated→ no need fro hand -breath coordination

• delivers dry, micronized powder directly into lungs

• generally easier to use than MDI

• higher lung deposition than MDI

• no spacer required

• requires adequate inspiratory flow

soft mist inhaler

• delivered in spray designed to be easier to inhale than MDI

nebulizer

• converts liquid into aerosol.mist

• less drug deposition in oropharynx

• increased drug delivery to the lungs

• useful fro children, elderly, or severely obstructed pts

FVC

• forced vital capacity

• maximum amnt of air exhaled after deep breath

FEV1

• forced expiratory vol in 1 second

• dx asthma: reversible decrease after bronchodialtors

FEV1/FVC

• ratio of how much air you can exhale in the first second compared to total capactiy

• normal = 0.7-0.8

• dx COPD: <0.7 post bronchodilators

types of inhaled medications

quick acting

• short acting beta agonist (SABA)

• short acting muscarinic antagonist (SAMA)

long acting

• long acting beta agonist (LABA)

• long acting muscarinic antagonist (LAMA)

• inhaled corticosteroids (ICS)

bronchodilators

B: B2 agonist (SABA + LABA)

A: anticholinergics (SAMA + LAMA)

M: methylxanthines (therophylline)

anti- inflammatory meds

S: steroids (ICS + oral)
L: leukotriene inhibitors (montelukast)
M: mast cell stabilizers (cromolyn)

pulmonary bronchodilators

• B2 adrenergic agonists agens

• anticholinergics (muscarinic antagonists)

• methylxanthines

B2 adrenergic agonists- MOA

• sympathomimetic drugs → activate B2 receptors in airway smooth muscle

• promote brinchoDILATION

• relieve bronchospasm

• suppress histamine release

B2 adrenergic agonists are most effective for:

• acute bronchospasm

• preventing exercise induced bronchospasm (EIB)

  • MC= albuterol

• NO inflammatory effect

short acting B2 adrenergic agonist (SABA)

• albuterol

• levalbuterol

SABA uses

• PRN for acute asthma attacks

• EIB prophylaxis

SABA pharmacokinetics

• onset: immediate 5-15 min

• peak effect: 30-60 minutes, relief up to 4-6 hours

long acting B2 adrenergic agonists (LABA)

• formoterol

• salmeterol

LABA uses

• longer duration of action at least 12 hrs

• monotherapy in asthma is contraindicated increased incidence of death when used alone

  • instead use (LABA + ICS)

ADE inhaled SABA

• generally well tolerated

• possible but minimal: tachycardia, angina, palpitations, tremor

ADE inhaled LABA

• similar ADE as SABA

• NO asthma monotherapy: increased risk of severe asthma events and asthma related death

• never use alone in asthma; most first line therapy

short acting muscarinic antagonists (SAMA) MOA

• block ACh at muscarinic receptors (M3) relaxes airway smooth muscle ad reduces mucus secretion

• block bronchoconstriction caused by activation of the parasympathetic nervous system

SAMA uses

• asthma: acute exacerbations

• COPD: maintenance. reduce air trappings and improve exercise tolerance

long acting muscarinic antagonists (LAMA)

• aclidinium

• tiotrapium

• umeclidnium

LAMA ADE

• minimal systemic absorption→ mostly local effects

• anticholinergic effects: dry mouth, blurred vision

• possible increased IOP

  • avoid in pts with glaucoma

SABA + SAMA

• albuterol/ ipratropium

LABA + LAMA

• formoterol/aclidinium

• formoterol/glycopyrrolate

methylxanthines

• theophylline

methylxanthines MOA

• relaxes airway smooth muscle→ bronchoDILATION

• admin oral or IV

DDI methylaxanthines

• increases levels of:

  • propanolol, cimetitine, cipro, OCPs, allopurinol

• decreases levels of:

  • phenytoin, carbamazepime, rifampin

ADE methylxanthines

THEOPH

T- tremor

H- heart (arrythmia)

E- electrolyte imbalance (hypokalemia)

O- oxidase inhibition (CYP)

P- pain in abdomen

H- head (headache, seizure)

ICS

• budesonide

• fluticasone propionate

ICS MOA

• suppress inflammation

• improve lung function, decrease bronchial hyperractivity, reduce daily sx and exacerbation frequency

• asthma: controller medications i

• COPD: esosinophil >150 better response

ICS ADE

• thrush

oral corticosterooids

• prednisone

• methylprednisolone

oral corticosteroid uses

• acute exacerbations of asthma or COPD

oral corticosteroids ADE

• long term/HIGH dose

• adrenal suppression

  • stress dose required during trauma, infection, or surgery

• hyperglycemia

• PUD

• growth suppression in children

ICS + LABA (asthma)

• budesonide/formoterol

• fluticasone/ salmeterol

ICS + LAMA + LABA

• fluticasone/umeclidinium/vilanterol

• budesonide/glycopyrrolate/formoterol

leukotriene modifiers

• montelukast

• zileuton

• zafirlukast

leukotriene modifiers uses

• ass on asthma maintenance, not acute attacks

• EIB

• aspirin exacerbated respiratory disease

leukotriene modifiers MOA

• Zileuton: inhibits leukotriene synthesis

• zafirlukast and motelukast: leukotrien receptors antagonists

leukotriene modifiers overall effects

• smooth muscle relaxation

• reduced airway edema

• decreased infalmmation/mucus

leukotriene modifiers ADE

• common: headache, URI, n/v/d, pancreatitis

• MSK: arthralgia, myalgia

• GI: hepatic toxicity- monitor labs/Sx

montelukast black box warning

• serious neuropsychitric events

leukotriene modifiers drug ineractions

• increases levels of theophylline, warfarin, and propanolol

mast cell stabilizers

cromolyn

mast cell stabilizers MOA

• prevents release of histamine and other inflammatory mediators

• suppresses airway inflammation

• no bronchodilation (not for acute attacks)

mast cell stabilizers uses

• prophylaxis fro mild asthma and EIB

• option if glucocorticoids are contraindicated or not tolerated

mast cell stabilizers ADE

• cough, bitter taste

omalizumab

• binds free IgE and prevents mast cells and basophil activation

• severe allergic asthma

• anaphylaxis

dupilimab

• blocks IL-4 adn IL-13 interaction

• severe eosinophilic asthma

benralizumab

• inhibits binding if IL-5 to receptor

• severe esoinophilic asthma

resilizumab

• bind directly to IL-5 and inhibit receptor binding

• severe esopsiniophilic asthma

• anaphylaxis

PDE-4 inhibitors

roflumilast

PDE-4 inhibitors MOA

• relax smooth muscle by inhibiting inflammatory cell activation and release by increasing cAMP

• no bronchodilation effects

PDE-4 inhibitors uses

• severe COPD, not for asthma

• chronic bronchitis

• severe airflow obstruction

abx for COPD

• azythromycin

abx for COPD- uses

• prophylaxis for COPD

• former smokers

• >65

• frequent exacerbations

abx for COPD- ADE

• hearing impairment

• QTc prolongation

• antimicrobial resistance

• GI sx

Beta-lactam antibiotics disrupt cell wall formation by interfering with which specific proteins?

Penicillin binding proteins (PBPs)

The inhibition of transpeptidation by beta-lactams leads to what outcome for the bacterial cell?

A weak cell wall and subsequent cell death.

To which antibiotic class do Penicillin G, Amoxicillin, and Ampicillin belong?

penicillins

Penicillins are highly active against which type of Gram (+) organisms?

Gram (+) cocci, such as Streptococci and Enterococci.

Which extended-spectrum penicillin adds coverage for Pseudomonas?

Piperacillin

What is the primary purpose of adding a beta-lactamase inhibitor to a penicillin?

To broaden coverage to include Staphylococcus aureus, Enterobacterales, and anaerobes.

Amoxicillin-clavulanate

A combination of a penicillin and a beta-lactamase inhibitor used to broaden antimicrobial coverage.

Cephalosporins generally show a progressive increase in activity against which type of bacteria across generations?

gram -negative

Which generation of cephalosporins is characterized by excellent Gram (+) activity but only modest Gram (−) activity?

first generation

Cephalexin and Cefazolin are examples of _____ cephalosporins.

first generation

What additional coverage do second-generation cephalosporins like Cefuroxime and Cefoxitin provide compared to the first generation?

Better Gram (−) activity and some anaerobic coverage

Third-generation cephalosporins such as Ceftriaxone exhibit strong activity against which bacterial group?

enterobacterales

Which specific third-generation cephalosporin adds coverage for Pseudomonas?

ceftazidime

Cefepime belongs to the _____ generation of cephalosporins and offers the broadest spectrum including Pseudomonas.

fourth

What is the unique antimicrobial target of the fifth-generation cephalosporin Ceftaroline?

MRSA

Which class of beta-lactams, including Meropenem and Imipenem, possesses the broadest spectrum of all beta-lactams?

carbapenems

Carbapenems are effective against MDR infections and active against which three categories of organisms?

Gram (+), Gram (−), and anaerobic organisms.

Vancomycin belongs to the _____ class of antibiotics.

glycopeptide

Vancomycin- MOA

Binds to peptidoglycan subunits to inhibit cell wall synthesis.

Vancomycin is primarily used to treat Gram (+) infections caused by _____.

MRSA

Aminoglycosides, such as Gentamycin and Amikacin, exert their effect by binding to the _____ ribosomal subunit.

30S

Aminoglycosides are primarily active against which type of bacilli?

Aerobic Gram (−) bacilli (e.g., Enterobacterales, Pseudomonas)

Tetracyclines inhibit protein synthesis by binding to the _____ ribosomal subunit.

30S

Doxycycline and Minocycline provide broad-spectrum activity against Gram (+), Gram (−), and which other distinct group?

Atypicals (e.g., Chlamydia, Mycoplasma, Rickettsia)

Macrolides, such as Azithromycin and Erythromycin, bind to the _____ ribosomal subunit.

50S

Macrolides are active against Streptococcus pneumoniae and which common atypicals?

Legionella, Chlamydia, and Mycoplasma.

Clindamycin is a member of the _____ antibiotic class.

lincosamide

The mechanism of action for Lincosamides involves binding to the _____ ribosomal subunit.

50S

While active against Gram (+) cocci and most anaerobes, Clindamycin notably lacks activity against _____.

enterococi

Oxazolidinones, such as Linezolid, inhibit protein synthesis by preventing _____ from binding to the ribosome.

tRNA

Linezolid and Tedizolid are specifically active against which resistant Gram (+) organisms?

MRSA and VRE (Vancomycin-resistant Enterococci)

Fluoroquinolones inhibit nucleic acid synthesis by targeting which two enzymes?

DNA gyrase and topoisomerase IV.

Levofloxacin and Moxifloxacin are predominantly active against _____.

Gram (+) organisms and atypicals

Which fluoroquinolone is specifically noted for its Gram (−) and Pseudomonas coverage?

ciprofloxacin

Rifamycins, like Rifampin, inhibit nucleic acid synthesis by targeting which enzyme?

RNA polymerase

Why are Rifamycins always used in combination therapy?

To prevent the rapid development of bacterial resistance.

Rifampin is highly active against Staphylococci, S. pneumoniae, N. meningitidis, and _____.

mycobacteria

Metronidazole belongs to the _____ antibiotic class.

nitroimidazole

What is the first-line antibiotic treatment for Clostridium difficile infections?

metronidazole

Metronidazole is active against which metabolic group of bacteria?

Obligate anaerobes (e.g., Bacteroides, Clostridium)