Pharm Flashcards
multidrug-resistant TB
TB resistant to INH and RIF
high risk for treatment failure and further acquired drug resistance
refer them to ID specialists and state health departments
extensive drug resistant TB
MDR (INH and RIF) plus resistance to FQN and at least one other injectable (amikacin, kanamycin, capreomycin)
relatively rare
cell wall comparison
inner leaflet of outer membrane composed of arabinogalactan and mycolic acids
outer leaflet is composed of extractable phospholipids
principles for TB treatment
use multiple drugs
prolonged treatment required for successful eradication
patients must be followed closely
therapeutic failure
positive sputum cultures after 4 months compliant therapy
goals of TB treatment
convert sputum cultures to negative
prevent the emergence of resistance
assure a complete cure without relapse
MOA rifampin
inhibits DNA dependent RNAP
suppression of initiation of chain formation in RNA synthesis
bactericidal-kills within macrophages and in caseating granulomas
synergism for rifampin
isoniazid
shortens course of therapy
distribution of rifampin
widely distributed
excellent tissue distribution
metabolism of rifampin
metabolized by deacetylation
autoinduction of metabolism occurs-maximum at 6 doses
adverse effects of rifampin
transient elevation in serum transaminases
hepatotoxicity (higher risk in alcoholics)
GI upset
hypersensitivity
discoloration of bodily fluids
drug interactions for rifampin
increase in P450 increased metabolism of warfarin theophylline narcotics oral hypoglycemics steroids (oral contraceptives)
place of rifampin in therapy
treatment of active TB
2nd line for preventative therapy
mechanism of action isoniazid
inhibits synthesis of mycolic acid
transported into bacterium-kills actively growing in extracellular, inhibits dormant organisms in macrophages and caseating granulomas
metabolism isoniazid
primarily by acetylation
monoacetyl hydrazine-important metabolite
source of hepatotoxic effects in isoniazid
hydroxylated to an electrophilic intermediate
rates of acetylation of isoniazid
slow or rapid acetylators
slow-higher chance of adverse reactions
Egyptians-slow
Eskimos and Japanese-rapid
elimination of isoniazid
elimination dependent on acetylator phenotype
adverse effects of isoniazid
transient elevation in serum transaminases
hepatotoxicity
neurotoxicity
hypersensitivity
avoiding neurotoxicity from isoniazid
pyridoxine (B6) to reduce incidence
particularly important in alcoholics, children, malnourished, slow acetylators
use of isoniazid in therapy
treatment of active TB
preventative therapy for patients with +PPD
mechanism of action for pyrazinamide
not documented
bactericidal toward dormant organisms in acidic environment within macrophages
metabolism of pyrazinamide
hydrolyzed in liver to active pyrazinoic acid
elimination of pyrazinamide
5-hydroxypyrazinoic acid excreted by kidneys
adverse effects of pyrazinamide
hepatotoxicity
hyperuricemia (decreased renal excretion)
GI upset
hypersensitivity (photosensitivity, rash)
mechanism of action for ethambutol
bacteriostatic
elimination of ethambutol
elimination of parent compound+inactive metabolite excreted in urine
adverse effects ethambutol
optic neuritis (decreased red-green acuity)
monitor every 4-6 weeks
use caution in young children
mechanism of action for streptomycin
aminoglycoside antibiotic
bactericidal through protein inhibition
inactive against intracellular organism
alternative to ethambutol
absorption of streptomycin
poorly absorbed in GI tract
administer IV or IM
adverse effects for streptomycin
nephrotoxicity (less than other aminoglycosides)
impairment of 8th cranial nerve function (vertigo>hearing)
pain on injection
second line agents
para-aminosalicylate ethionamide cycloserine capreomycin kanamycin amikacin
rifabutin
rifamycin derivative
used in TB patients who have experienced intolerance to rifampin or experiencing interactions
more active against MAC
adverse reactions to rifabutin
rash GI arthralgias myalgias discoloration of urine/sweat/tears neutropenia hepatotoxicity
requirements for rifapentine
with INH in continuation phase
must be HIV negative
must have non-cavitary, drug susceptible pulmonary TB with negative sputum smears at completion of initial phase of treatment
mechanism of action clofazamine
causes inhibition of transcription
used as an antileprosy agent
clofazamine adverse reactions
GI upset
severe and life threatening abdominal pain and organ damage from crystal deposition
discoloration of skin and eyes
macrolides in TB
unlikely to be effective against TB
clarithromycin and azithromycin against MAC
quinolones in TB
ciprofloxacin and ofloxacin effective against TB
RIPE or RIPS
use if >4% resistance
6 months for general TB treatment
avoid in renal failure
avoid streptomycin, kanamycin, and capreomycin
avoid in children
avoid ethambutol
suspected treatment failure
add >2 new TB agents
lepromatous leprosy
loss of specific cell mediated immunity
tuberculoid leprosy
strong cell mediated immunity
diagnosis of leprosy
acid-fast stain and cytologic examination of skin
response to lepromin skin test
treatment of leprosy
dapsone/rifampin/clofazimine
duration for 3-5 years
mechanism of action dapsone
competitive inhibitor of folic acid synthesis
inhibition of dihydropteroate synthase which prevents utilization of PABA
bacteriostatic
adverse reactions to dapsone
hemolytic anemia
hypersensitivity
MAI
symptoms usually when CD4 <100
prophylaxis at <50
fever, night sweats, weight loss, anemia
macrolides in MAC
clarithromycin better than azithromycin
usually one with ethambutol
inflammatory mechanism of asthma
increase mast cells, eosinophils, Th2 cells
increase histamine, D4, D2 in airway
inflammatory mechanism of COPD
increase neutrophils, macrophages, CD8T cells
role of space chamber
increase proportion of drug entering airway
used to decrease oropharyngeal deposition of inhaled corticosteroids
albuterol, levalbuterol
B2 agonist with quick onset
used to reverse asthma/bronchospasm
adverse effects of albuterol, levalbuterol
overuse indicates worsening asthma
airway tolerance
tremor, restlessness, tachycardia, hypokalemia
epinephrine MOA
A1, A2, B1, B2 agonist
adverse effects of epinephrine
palpitations, pale complexion, sweating, tremor, anxiety
adverse effects isoproterenol
cardiac stimulation
non-selective B agonist not used in US
salmeterol, formoterol, indacterol
long acting B2 agonists
uses for LABA
prophylaxis
not used in acute asthma attack
have to be given with inhaled corticosteroid
combination inhalers
more effective than corticosteroids or LABA alone
increase B2 receptor numbers
ipratropium, tiotropium
muscarinic receptor antagonists
do not cross BBB (quaternary amines)
ipra 4x, tio 2x
adverse effects ipratropium, tiotropium
bitter taste dry mouth glaucoma urinary retention paradoxical bronchospasm
methacholine
agonist that is used to diagnose bronchial airway hyperactivity in patients that have asthma
theophylline
weak inhibitor of PDE isoforms, bronchodilator, anti-inflammatory activity, inhibits A1
metabolism of theophylline
metabolized by p450
large variations in clearance (intra and inter-individual variability)
toxicity of theophylline
headache, nausea, vomiting and restlessness at low dose toxicity
high concentration-cardiac arrhythmias (PDE3), seizurs (A1)
beclomethasone, flunisolide, fluticasone, mometasone, triaminolone
maximal benefit may take weeks
front line therapy for asthma
local effects of corticosteroids
dysphonia, cough, oropharyngeal candidiasis
spacer decreases local adverse effects
leukotriene inhibitors
cysteinyl leukotrienes are produced during asthma
zafirlukast, montelukast, pranlukast
selective leukotriene receptor antagonist (C4/D4/E4)
zileuton
inhibits 5-lipoxygenase (rate limiting enzyme in leukotriene biosynthesis)
use of leukotriene inhibitors
reduce occurrence of bronchospasm in response to allergens, cold air, and exercise
timing of leukotriene antagonists
monte 1x
zafir 2x
frequency for zileuton
4x/day
adverse effects leukotriene inhibitors
hepatic toxicity
HA in zafirlukast
fever and chills in Zileuton
MOA cromolyn and nedocromil
mast cell stabilizers
inhibit mast cell degranulation and histamine release
use of cromolyn
asthma and allergic rhinitis
MOA omalizumab
anti-IgE
inhibits binding of IgE to IgE receptors on mast cells
adverse effects omalizumab
anaphylaxis
use omalizumab
severe asthma not controlled by corticosteroids
use alpha-1-proteinase inhibitor
used to inhibit the activity of elastase (due to alpha-1-antitrypsin deficiency)
leads to early onset emphysema
opioids for cough
bind mu, suppress in medullary cough center to suppress cough
adverse effects from opioids
sedation, constipation, opioid-induced respiratory depression could be troublesome in asthma
dextromethorphan MOA
centrally active N-methyl-D-aspartate antagonist
acts in medullary cough center to suppress cough
adverse effects dextromethrophan
hallucinations at high concentrations
MOA benzonatate
acts peripherally by inhibiting stretch receptors in respiratory passages and lungs to suppress cough
adverse effects benzonatate
dizziness
MOA guaifenesin
increase volume and reducing viscosity of secretions in trachea and bronchi
adverse guaifenesin
nausea
MOA N-acetylcysteine
free sulfhydryl group opens disulfide bond in mucus proteins and lowers mucus viscosity
use N-acetylcysteine
acetaminophen overdose
COPD, CF
MOA dornase alpha
DNAse that reduces viscoelasticity of sputum in patients with CF by breaking long extracellular DNA molecules into smaller fragments
adverse effects dornase alpha
dyspnea
first generation anti-histamines
diphenhydramine, brompheniramine, chlorphenamine
second generation anti-histamines
loratidine, cetirizine
uses for anti-histamines
allergic rhinitis, sleep aid, urticaria, motion sickness
adverse effects for anti-histamines
dizziness, sedation
use of diphenhydramine
sleep aid and motion sickness
nasal spray ipratropium
rhinorrhea, allergic rhinitis
oxymetazoline
alpha1 agonist
phenylephrine
selective alpha1 agonist
pseudoephedrine
alpha and beta agonist that may also enhance release of norepinephrine
indications for adrenergic agonists
decongestants
adverse effects of adrenergic agonists
rebound nasal congestion
hypertension
ischemia, peripheral ischemia, angina
synthesis of histamine
from histidine by histidine decarboxylase
basophils with histamine
blood
mast cells with histamine
skin
intestinal mucosa
lung
around blood vessels and nerves
non-mast cells with histamine
gastric enterochromaffin cells
epidermis
CNS neurons
complex with histamine
heparin chondroitin sulfate eosinophilic chemotactic factor neutrophilic factor proteases
metabolism of histamine
methylation to from N-methylhistamine
converted to N-methylimidazoleacetic acid by MAO
oxidative deamination by diamine oxidase to imidazole acetic acid
metabolites of histamine
imidazole acetic acid
N-methylhistamine
substances that release histamine from mast cells
curare
morphine
venoms
inflammatory mediators
histamine from gastric ECL cells
released by acetylcholine and gastrin
H1 receptor
smooth muscle, endothelium, brain
Gq
chlorpheniramine antagonist
H2 receptor
gastric mucosa, cardiac muscle, mast cells, brain
Gs
ranitidine antagonist
H3 receptor
presynaptic brain, myenteric plexus
Gi
thioperamide, clobenpropit antagonist
H4 receptor
eosinophils, neutrophils, CD4 T cells
Gi
thioperamide
result of histamine in blood vessels
vasodilation-flushing, decrease BP
indirect-release of NO and PGI2
result of histamine in capillary permeability
increase permeability leading to edema
responsible for urticaria
result of histamine in heart
increase rate and force of contraction
result of histamine in lungs
bronchoconstriction
result of histamine in gastric mucosa
increase acid secretion from parietal cells
result of histamine from nerve endings
pruritis from epidermis
pain and itching from dermis
result of histamine from CNS
increased wakefulness and suppresses appetite
triple response
red spot-vasodialtion
wheal-increase capillary permeability
flare-axon reflex leading to vasodilation
metabolism of loratadine
cyp3A4
duration of anti-histamines
second generation longer acting
active metabolites of older drugs
prolonged duration of action and excreted unchanged
effects of H1 antagonism
reversible competitive little effect on bronchoconstriction vasoconstriction no permeabiltiy decreased HR suppresses flare some relief of atopic dermatitis and contact dermatitis
strongest muscarinic effect
promethazine
muscarinic effect of second generation
none
adverse reactions to antihistamines
CNS stimulation seen in poisoning
depression seen in first generation (potentiated by alcohol and CNS depressants)
antimuscarinic effects for 1st generation
GI for 1st generation
uses of antihistamines
exudative allergy-rhinitis, urticaria, conjunctivitis
bronchial asthma
systemic anaphylaxis
prevent motion sickness
promethazine
H2 receptor antagonists
cimetidine
ranitidine
famotidine
effects of H2 antagonists
decrease gastric acid secretion
adverse effects of H2 antagonists
HA
GI
fatigue, drowsiness
pharmacokinetics H2 antagonists
renal excretion
drug interactions from Cimetidine (inhibits p450)
use H2 antagonists
promote healing of peptic or duodenal ulcer
uncomplicated GERD
prophylaxis of stress ulcers
use H2 antagonists
promote healing of peptic or duodenal ulcer
uncomplicated GERD
prophylaxis of stress ulcers
tidal volume
volume of air inspired and expired during normal quiet breathing
inspiratory reserve volume
maximum amount of air that can be inahled after a normal tidal volume inspiration
expiratory reserve volume
maximum amount of air that can be exhaled from the resting expiratory level
residual volume
volume of air remaining in the lungs at the end of maximum expiration
vital capacity
volume of air that can be exhaled from lungs after a maximum inspiration
VC=IRV+TV+ERV
inspiratory capacity
maximum amount of air that can be inhaled from the end of a tidal volume
IC=IRV+TV
functional residual capacity
volume of air in lungs at the end of TV expiration
elastic force of chest wall balanced by elastic force of lungs
FRC=ERV+RV
total lung capacity
volume of air in lungs after maximum inspiration
TLC=IRV+TV+ERV+RV
kussals
rapid shallow breathing
emaciation cachectic
malignancy
TB
pulmonary cachexia syndrome
obese
sleep apnea syndrome
clubbing
widening of AP and lateral diameter of terminal portion of fingers
angle between the nail and skin is greater than 180
periungual skin is stretched and shiny
causes of clubbing
intrathoracic malignancy (lung, pleural, mediastinal) suppurative lung disease (abscess, bronchiectasis, empyema) interstitial fibrosis (alveolar capillary block syndrome)
atelectasis shift
towards affected side
plerual effusion shift
to unaffected side
pneumothorax shift
to unaffected side
asymmetrical chest expansion
abnormal side expands less
lags behind the normal side
vocal fremitus increased
alveolar consolidation
vocal fremitus decreased
increased distance between lung and chest wall
pneumothorax, pleural effusion
increased dullness
atelectasis, alveolar filling/consolidation, pleural effusion, fibrosis
hyperresonance
hyperinflation, pneumothorax
normal inspiration:expiration ratio
3:1
rhonchi
obstruction to airways
diffuse-asthma or COPD
crackles
sound generated from collapsed state
chronic bronchitis, pneumonia, CHF, atelectasis
on inspiration-secretions in bronchi
wheezes
correspond to degree of airway obstruction
extrathoracic lesion stridor
on inspiration
laryngomalacia/vocal cord lesions/edema after extubations
intrathoracic lesion stridor
on expiration
tracheomalacia/bronchomalacia/extrinsic compression
fixed lesions stridor
croup
paralysis of both vocal cords
laryngeal mass or webs (like Plummer-Vinson?)
obstructive ratio
decreased
DLCO may be normal
TLC and RV might be high
restrictive ratio
normal
decreased DLCO