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920 Cards in this Set

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What characterizes the pharmacology of Heroin?
Very lipid soluble, short half-life, metabolized to 6-mono-acetyl morphine and subsequently to morphine
What process can be used for opioid detox?
Replace opioid with Methadone --> reduce Methadone dose --> discontinue Methadone --> help achieve abstinence with a long-acting opiate antagonist (e.g. Naltrexone) and social support
What drug can help alleviate the sympathetic effects of opioid/narcotic withdrawal?
Clonidine: α2-agonist
What characterizes the timeline of opioid withdrawal?
6-8hrs: drug seeking behavior, restless, anxious; 8-12hrs: pupils dilated/reactive to light, increased HR/BP, yawning, chills, rhinorrhea, lacrimation, piloerection, sweating, restless sleep; 48-72hrs: all previous plus weakness, aches, cramps, n/v/d, increased temp/RR/HR/BP, dehydration
What is the treatment of acute toxicity/overdose with opioids/narcotics?
Naloxone: opioid antagonist, used in life-threatening situations, given IV, short half-life;
Methadone: used in detoxification, causes less euphoria and less severe withdrawal
What are the effects of acute toxicity/overdose with opioids/narcotics?
Disruption of central control of peripheral sympathetic activity: respiratory/circulatory depression; also miosis, n/v, pulmonary edema, decreased reflexes, CNS depression (sedation, coma), convulsions, tissue toxicity (“heroin lung”, criminal behavior, violent death)
What are the effects of taking opioids/narcotics?
Desirable effects: euphoria, sedation, relief of anxiety, analgesia, depression of cough reflex*;
Subjective CNS effects: drowsiness, difficulty concentrating, apathy, decreased physical activity;
Undesirable effects: dysphoria, dizziness, n/v, constipation*, biliary tract spasm, urinary retention
What is an example of cross-dependence?
A heroin addict taking methadone as a substitute, in order to prevent a withdrawal syndrome
What are examples of opioids/narcotics used as drugs of abuse?
Morphine, Codeine, Meperidine, Methadone
What is an example of cross-tolerance?
A patient who has developed tolerance to barbiturates will also be tolerant to benzodiazepines
What characterizes alcohol withdrawal?
Symptoms begin within 6-48hrs and peak about 24-35 hrs after the last drink; symptoms incl. fever, rapid HR, changes in BP, extremely aggressive behavior, hallucination, mental disturbances, seizures (10% of cases), delirium tremens (5% of cases, develops after 2-4 days)
What are the acute effects of sedative hypnotics?
Euphoria, impaired judgment, loss of self-control, anterograde amnesic effects, physiological consequences similar to those of alcohol intoxication (though death is unlikely with pure benzodiazepines) – may also feel a remarkable capability for coping with stress/anxiety (due to disinhibitory effects)
What characterizes the tolerance effects of sedative hypnotics?
Tolerance occurs to a modest degree to the sedative effects, but not to the respiratory depressant effects (thus lethal overdose)
What are the mechanisms of action of alcohol?
NMDA antagonist, GABAA agonist, 5-HT3 antagonist, L-type calcium channel modulator
What are the treatment option for alcohol dependence?
Disulfiram (Antabuse), CCC (citrate calcium carbamate): both are acetaldehyde dehydrogenase blockers – can also call your local AAA (lol!!)
What is the treatment for alcohol withdrawal?
Benzodiazepines: relieve withdrawal symptoms, prevent progression to delirium tremens, reduce seizure risk – can be given PO/IV, not prescribed for more than 2wks or 3nights/wk
What characterizes delirium tremens?
Insomnia, tremulousness, REM rebound, high reflexes, weakness, anorexia, orthostatic hypotension, sweating, agitation, delirium, hallucinations, seizures (NMDA related), “status epilepticus”, disorientation, paranoid delusions, hyperthermia, dehydration, CV collapse, death
What drugs are used for detoxification or maintenance treatment with opioid/narcotic abuse?
Methadone: used for sequential detoxification and maintenance treatment;
LAAM: similar to Methadone but longer acting (“take home” medication);
Buprenorphine: partial opioid agonist which substitutes for low doses of opioids but antagonizes at high doses, can be taken sublingually as an alternative to Methadone
Naltrexone: causes precipitated abstinence, used for long-term maintenance of abstinence, long half-life, does not reduce “drug craving” sensations (social support needed)
What are the effects of alcohol overdose?
Slowed/slurred speech, ataxia, nystagmus, drowsiness, coma, confusion, decreased reflexes, respiratory depression, apnea, low BP, death
What is the mechanism of action of opioids on the mesolimbic DA system (VTA)?
Disinhibition (i.e. inhibition of GABA) of DA release, thus increasing DA activity – chronic exposure causes deficient VTA-NAC function
What are the uses of anxiolytics/hypnotics?
Flurazepam: sleeping pills; Flunitrazepam: “date rape drug”; Diazepam: tranquilizer; Chlordiazepoxide: tranquilizer; Clonazepam: anticonvulsant – all cause sedation/muscle relaxation, induce sleep; abuse may cause benzodiazepine-induced aggression
What is the treatment for sedative hypnotic withdrawal?
Slowly taper off drug; Stabilization with Diazepam, Chlordiazepoxide, Phenobarbital;
Can give Propranolol or Clonidine for v/n, tremor/twitching
What withdrawal symptoms of sedative hypnotics are a threat to life?
Hyperthermia, dehydration, electrolyte imbalance, exhaustion, CV collapse
What are the withdrawal symptoms of sedative hypnotics?
Minor: tremors, insomnia, high fever, clonic blink, anxiety, dysphoria, sleep disturbances;
12-16hrs: abd. cramps, n/v, orthostatic hypotension, increased DTR, hyperreflexia;
24hrs: pronounced weakness, course tremors (“the shakes”), hallucinations, hyperpyrexia;
48-72hrs: convulsive seizures (“rum fits”), vivid hallucination (“the horrors”), formication, agitation, disorientation, delirium, paranoid delusions
What is the treatment for sedative hypnotic overdose?
Flumazenil (benzodiazepine receptor blocker); no treatment for barbiturates
What are the signs/symptoms of acute overdose on sedative hypnotics?
Pupils are normal, BP/respiration depressed, nystagmus on lateral gaze, tendon reflexes depressed, ataxia, slurred speech, confusion, coma, shock, risk of death (esp. with barbiturates)
What characterizes Methaqualone?
“Downer”, works as Diazepam, seriously abused, very addictive
What are the negative symptoms of schizophrenia?
Flat affect, poverty of speech, attention impairment
What is the prototype drug of high potency antipsychotic?
Haloperidol: lower incidence of anticholinergic/antihistaminic/antiadrenergic effects,
higher incidence of extrapyramidal side effects
What are the correlations between the locations and effects of dopaminergic antagonism associated with low potency antipsychotics?
Mesolimbic/mesocortical: therapeutic effects; Nigrostriatal: extrapyramidal side effects;
Chemoreceptor regions: antiemetic effects; Posterior pituitary: increased prolactin secretion
What mechanisms of action are associated with first generation antipsychotics?
Antagonism of D2-dopaminergic receptors (therapeutic effects), α-adrenergic receptors (orthostatic hypotension, sedation), muscarinic-cholinergic receptors (dry mouth, blurred vision, urinary retention, constipation, confusion), histamine receptors (sedation)
What is the prototype drug of low potency first generation antipsychotics?
Chlorpromazine
What are the two general classes of drugs used in the treatment of schizophrenia?
First generation antipsychotics, second generation antipsychotics
What are the cognitive symptoms of schizophrenia?
Impaired though process, looseness of association, circular thought, neologisms
What are antipsychotics used for?
Symptomatic treatment of thought disorders, hallucinations, bizarre behavior, agitation, hyperactivity; Disease treatment of schizophrenia, schizoaffective/schizophreniform disorders, delusional disorders, acute mania, depressive psychosis, drug-induced psychosis
What are the positive symptoms of schizophrenia?
Hallucination, delusions
What are the anatomical features of schizophrenia?
Enlarged cerebral ventricles, hypofrontality, inferred dopaminergic dysfunction (increased)
What characterizes the pharmacokinetics of antipsychotics?
Generally well absorbed, highly lipophilic, half life of 20-40 hours, metabolized by CYP enzymes and conjugation reactions, excreted in urine and bile (less so), poor correlation between plasma concentrations and clinical response
What adverse effects are seen with second generation antipsychotics?
Metabolic syndrome: weight gain (significant, not dose-dependent, hard to lose), hyperglycemia, hyperlipidemia (elevated LDL, triglycerides)
Which side effects are reduced with second generation antipsychotics when compared to first generation drugs?
Acute extrapyramidal, tardive dyskinesia, autonomic effects, hyperprolactinemia
What characterizes the second generation antipsychotics?
Lower incidence of extrapyramidal effects, somewhat better effects of negative/cognitive symptoms, distinct receptor pharmacology (antagonize dopaminergic and 5-HT2 receptors)
What are the second generation antipsychotics?
Clozapine is the prototype drug – more recently developed drug incl. Olanzapine, Risperidone, Quetiapine, Ziprasidone, Aripiprazole
What drug interactions are seen with antipsychotics?
CNS depressants, alcohol, epinephrine (tachycardia, hypotension), L-dopa
What contraindications are associated with antipsychotics?
Parkinson’s disease, severe CNS depression, cardiac disease (caution)
What describes the extrapyramidal side effects of antipsychotics?
Early onset --> Acute dystonia: more prevalent with high potency drugs, treat with antiparkinsonian agents/anticholinergic drugs; Parkinsonism: sometimes mistaken for depression, treat with antiparkinsonian agents/anticholinergic drugs; Akathisia: feeling of restlessness, mistaken for agitation, treated by increasing dose/anxiolytics/Propranolol –
Late onset --> Perioral tremor: “rabbit syndrome”, treated with anticholinergics;
Tardive dyskinesia: involuntary movement of mouth/tongue, may involve limb movement (seen in 80% of older patients), symptoms worsen with drug withdrawal, prevention is best strategy
What other adverse effects are seen with antipsychotics?
Reduced seizure threshold, sexual dysfunction
What characterizes neuroleptic malignant syndrome?
Life-threatening side effect that can occur with all types of antipsychotics (more common with high potency drugs): catatonia, stupor, fever, unstable BP, myoglobinemia – treated by stopping antipsychotic, providing supportive treatment, and possibly Dantrolene/Bromocriptine
What characterizes Risperidone?
Resembles high potency first generation drugs: lower doses exhibit reduced extrapyramidal effects, orthostatic hypotension does occur; Affinity for D2, 5-HT2, muscarinic/histamine/α-adrenergic receptors
What characterizes the difference in symptomatic response with antipsychotics?
Better: agitation, hostility, hallucination; Lesser: motivation, cognitive function
What is drug selection based on when deciding on an antipsychotic?
Minimize acute extrapyramidal effects: second generation antipsychotics; Avoid sedative effects: high potency antipsychotics; If sedation is beneficial: low potency antipsychotics;
Elderly patients: low dose of high potency antipsychotic
What are the adverse effects of second generation antipsychotics?
Some sedation and extrapyramidal effects; generally lower incidence/severity
What characterizes Aripiprazole?
Partial agonist at D2 and 5-HT1A receptors, antagonist at 5-HT2A receptor, moderate affinity for histamine/α1-adrenergic receptors; also used for treatment of acute manic episodes, generally has low extrapyramidal side effects (except for a high incidence of akathisia)
What characterizes Ziprasidone?
Affinity for dopamine, 5-HT, α1-adrenergic receptors; Modest inhibition of 5-HT/NE reuptake; Has minimal weight gain, not associated with metabolic syndrome, less orthostatic hypotension, may affect symptoms of depression, QT prolongation
What characterizes Quetiapine?
Relatively low affinity for D2/5-HT2 receptors, moderate affinity for histamine/α-adrenergic receptors; Can see weight gain, metabolic syndrome, sedation
What are contraindications and caution associated with Clozapine and Ziprasidone?
Clozapine: CI with blood dyscrasias, caution with seizure disorders;
Ziprasidone: caution with cardiac disease
What characterizes Olanzapine?
Affinity for D1/D4 receptors, muscarinic/histamine/α-adrenergic receptors
What characterizes Clozapine?
Usually reserved for patients who failed to respond to other antipsychotics, can cause life-threatening agranulocytosis; Relatively low affinity for D2 receptors, higher affinity for D4 receptors (limbic/cortical areas), affinity for muscarinic/histamine/α-adrenergic receptors
What are complications associated with Otitis media?
Otitis Media with Effusion, hearing loss, perforation, Chronic suppurative OM with mastoiditis, Acquired Cholesteotoma, Mastoiditis, Facial paralysis, meningitis, lateral vein thrombosis
How is the clinical diagnosis of acute sinusitis made?
14-21 days symptoms of URI, facial pain, nighttime cough, Nose may very congested, can’t breathe through their nose. Normal colds usually last 3-7 days get better by 10 days if no improvement is when you think of sinusitis
What is the treatment for OM?
Amoxicillin, b-lactam antibiotic
What are the other less common pathogens that cause OM?
Streptococcus pyogenes (GAS), Staphylococcus aureus
What are the 3 main pathogens that cause OM?
Streptococcus pneumoniae, non-typable Haemophius influenzae, Moraxella catarralis
Why is Hearing Loss associated w/ OM a problem?
If children are at developmental stage of beginning to talk they could have a speech delay
What is Otitis Media with Effusion and how is it treated?
It is a malingering effusion in the ear, usually following an ear infection, the infection clears but you are left with fluid in the ear, child will have decreased hearing in the affected ear,
The ear is not draining, which creates a nice, rich medium for bacteria to go back in there and cause another OM; Starting counting from the day the infection clears for how long that effusion lasts, if it is longer than 3 months than you think about putting an ear tube in and send them to ENT; problem is that in b/w those 3 months they may get another infection and you have to start counting all over again
What is the most common reason for antibiotic treatment in children?
Otitis media
What the common risk factors for Otitis media?
young age (<2 years), smoking (passive), bottle use (esp after 12 months age), pacifier use, daycare, family history, cranial facial abnormalities (ex. Down’s syndrome)
What is a common complication following URI (eustachian tube dysfunction), especially in young aged children?
Otitis media
What other diagnostic tools beyond clinical examination can be used for diagnosis of acute sinusitis?
Sinus X-rays: Water’s view: mucosal thickening > 4mm, air fluid level, complete opacification diagnostic; CT scan: more sensitive diagnostic indicator of sinus disease, More expensive, harder to get; not practical, more radiation; Antral puncture for bacterial culture: NOT routinely done
In what age does Pertussis present?
The disease may occur at any age, but it manifests most severely in infants and young children, in whom it is potentially life-threatening. In adolescents and adults, pertussis may be mild or cause moderate to severe symptoms; the only symptoms may be those of a minor, nonspecific upper respiratory tract infection. Diagnosis is thus difficult in this age group.
How is pertussis transmitted?
It is one of the most highly communicable of all infectious diseases, easily transmitted from one person to another via coughed aerosolized droplets.
What is Pertussis?
Pertussis, or whooping cough, is a highly contagious acute RI, caused by Bordetella pertussis, a gram (-) aerobic bacillus.
What is the etiology of sinusitis?
Same as AOM except possible role of anaerobes; Strep pneumo, non-typeable h. influ, m. cat, the streps (pyrodines, pyogenes) move higher up on this list; anaerobes play a role b/c they get in the sinus cavities and thrive, not usually the only ones there but they go along for the ride
What are the Complications of sinusitis?
Chronic sinusitis, brain abscess, lateral vein thrombosis, nasal polyps; Rare but they do occur
What is the treatment for Sinusitis
Antimicrobials: 10-21 days, if they have had sinus infections in the past you ask how long did it take to clear up previously, treat them until they are better the drainage, and cough has stopped, and then an additional 5 days on top of that, may take them up to 2 weeks to feel better/clearing up; Topical steroids, neosynephrine: use briefly to help open things up
What are the risk factors for acute sinusitis?
Allergies, Cystic Fibrosis, Anatomic Abnormality, Smoking, Family history
What is the Paroxysmal phase of pertussis?
In the 2nd , paroxysmal stage, the cough becomes more severe. The pt has bouts of numerous, rapid coughs. At the end of each paroxysm, a long inspiratory effort is usually accompanied by a characteristic, high-pitched whoop. The pt may become cyanotic during these episodes & often appears very ill & distressed. Vomiting & exhaustion commonly follow each episode. This stage usually lasts for 1-6 wks, but can continue for up to 10 wks.
What are the major complications associated with Pertussis?
Major complications of pertussis include pneumonia & neurologic complications, such as seizures & acute encephalopathy. These complications are serious & sometimes fatal, occurring most often in children aged <6 months.
What are the diagnostic tests used for Pertussis?
Samples taken from nasal discharge or by swabbing the throat and tonsils are inadequate.; PCR is emerging as the diagnostic method of choice on the basis of studies showing it to be more specific & sensitive than culture. Serologic testing is not standardized & b/c of a lack of association b/w antibody levels & immunity to pertussis, results are difficult to interpret.; Direct fluorescent antibody (DFA) can yield rapid results but has disadvantages of variable sensitivity and specificity
What is the best site to obtain an appropriate clinical specimen for diagnostic testing of Pertussis?
the posterior nasopharynx, either by aspiration of nasopharyngeal secretions or by insertion of a swab applicator into the posterior nasopharynx.
How is Lymphocytosis used for the laboratory diagnosis of pertussis?
Lymphocytosis: Absolute lymphocytosis is a strong indicator of pertussis (lower chart in graph). It is usually present during the paroxysmal stage and persists for 3 to 4 weeks, a period when culture may be negative. However, lymphocytosis may not occur in infants and in patients who are partially immune as a result of previous immunization.
How is a culture used for the laboratory diagnosis of pertussis?
Culture: Isolation of the organism by culture is the standard lab test used in Dx. However, fastidious growth requirements make it difficult to isolate B pertussis. Organisms can be detected in the nasopharynx in the early, catarrhal stage of the illness when Sx are similar to those of the common cold; culture is significantly less likely to yield organisms if specimen collection is delayed beyond the 1st 3 wks of illness. By the time severe cough appears in the paroxysmal stage, the number of organisms has typically decreased; and by the convalescent stage, the organism has disappeared.
What is the Convalescent phase of pertussis?
The third, convalescent stage is characterized by gradual recovery over several wks.
The coughs subside but may recur for many months with subsequent respiratory infections.
Who acts as the reservoir for pertussis that likely causes infections in infants and young children?
Infected adolescents and adults with mild disease constitute the reservoir for infection in infants and young children.
What is the Catarrhal phase of pertussis?
The initial, catarrhal stage is insidious in onset,& similar to the common cold.
It is characterized by coryza, sneezing, low-grade fever, & a mild, occasional cough, lasts 1-2 wks.
What are the three phases of Pertussis Infection?
Catarrhal phase: Begins with URI phase (lasts 3-7 days)..if treated, prevent progression to other stages; Paroxysmal stage: Progresses to severe coughing often with characteristic resp whoop, followed by vomiting (lasts 3-6 wks)… if treated, only prevention contagiousness; Convalescent stage: Symptoms gradually wane (lasts 2-4 wks)
Why are cases of Pertussis under reported?
Because adolescents & adults often lack typical Sx, the incidence of pertussis tends to be underreported in these age groups. Reasons for underreporting include atypical forms of the disease, wide variability of Sx, lack of consultation by primary-care practitioners, difficulty of diagnosis, low level of awareness among physicians, and inconsistency in case definitions.
What is the strategy of Adult/Adolescent vaccination against Pertussis in the US?
Adolescents & adults are vulnerable to pertussis infection b/c immunity offered by their baby shots has now waned. So they are the prime reservoirs for transmission to infants, who are not yet fully immunized against pertussis disease. Universal immunization of adolescents age 11-18 years. Targeted immunization for household & close contacts of newborns, daycare workers, & health-care personnel. Adult vaccination every 10 years, and wound management (the new vaccine could substitute tetanus shots that are currently in routine use)
What is the Incubation period for Pertussis?
6- 20 days, Most contagious during catarrhal stage, may persist for 3 wks after onset cough
How is pertussis transmitted?
Transmission by resp secretions; 90% of nonimmune household contacts acquire disease; no carriers
What is the only host of B pertussis?
Humans
What can untreated patients with Group A Streptococcal Acute Pharyngitis/Tonsillitis develop?
Untreated patients may develop suppurative complication: otitis media, sinusitis, peritonsillar or retropharyngeal abscess (medical emergency), suppurative cervical adenitis
When is GAS pharyngitis transmission most common?
GAS pharyngitis more common in fall, winter, spring in temperate climates…closer contact to facilitate spread
What is impetigo?
Impetigo is a superficial infection from staph aureus or group A strep; not systemically ill, usually only seen here is in the summer because kids are wearing shorts and get trauma to the skin, it is more common in tropical climates (?related to minor skin trauma & insect bites)
What age is GAS pharyngitis common in?
GAS pharyngitis..any age but most common in school-agel Unusual in toddlers (1 to 3 years old) unless household contact…rheumatic fever is uncommon at this age
What is the epidemiology of Group A Streptococcal Acute Pharyngitis/Tonsillitis?
Pharyngitis results from contact with a person GAS pharyngitis (respiratory secretions); Fomites and household pets (i.e. dogs) are not the vectors; Associated with crowding, poor socioeconomic conditions; Close contact in schools & military recruits facilitate spread Food-borne outbreak associated human contamination & improper refrigeration
What is the Acute nonsuppurative sequelae caused by Group A Streptococcal Acute Pharyngitis/Tonsillitis?
rheumatic fever & acute glomerulonephritis
What is Scarlet fever and what is it associated with?
Scarlet fever associated with pharyngitis (occas. with pyoderma), it is no different than those with just pharyngitis except sandpaper rash (produces a erythrogenic exotoxin)
What is Group A ß-hemolytic streptococci (Streptococcus pyogenes)?
Gram positive cocci: typically in pairs & chains; More than 80 distinct M-protein types have been identified ; Association between certain serotypes (eg, types 1,3,5,6,18,19,24) & Rheumatic Fever (RF) but “rheumatogenic” factor not identified
What is the most common clinical illness?
Group A Streptococcal Acute Pharyngitis/Tonsillitis
What are three types of Strep Syndromes?
Streptococcal pharyngitis, Scarlet fever, Severe Invasive Strep Syndrome
What are complications of GAS pharyngitis?
Peritonsillar abscess, Parapharyngeal abscess, post-strep GN, ARF
What are other causes of a sore throat caused by nonexudative pharyngitis?
sinusitis, allergic rhinitis, viral URI
What are other causes of a sore throat caused by Exudative pharyngitis?
adenovirus (esp in young children); EBV; coxsackie (hand, foot, & mouth disease), N. gonorrhea (sexually active ppl); Non-Gp A strep pharyngitis
Why does Pneumonia present with Fever, Abdominal Pain & Vomiting?
Belly pain and vomiting w/ lobar bacterial pneumoina because get diaphragm is right between chest and stomach, and you get diaphragmatic irritation, get an ileus in the intestinal tract; pain (caused by RL or LL lung lobes) and child interprets it as belly pain;
What are the 3 most common pediatric causes of Fever, Abdominal Pain & Vomiting?
Viral Gastroenteritis, Pneumonia, Group A Streptococcal (GAS) tonsillitis/ pharyngitis
What is the presentation of a Parapharyngeal abscess?
May have trismus à cant open their mouth, because it hurts;, Less obvious, because you can see the tonsils and they may be red, will not move their neck because it is deeper in the neck, so it hurts so bad, they refuse to move their neck, considered a medical emergency
What is the presentation of a Peritonsillar abscess?
May have trismus à cant open their mouth, because it hurts , Usually can more their neck around, but they don’t want to open their mouth, if you see tonsillar asymmetry (One tonsil is big and beefy red but the other one is HUGE), suspect abscess either in their tonsil or behind it
When is GAS pharyngitis most contagious?
Communicability highest during acute infection, in untreated: diminishes over a period of weeks
When is GAS pharyngitis no longer contagious?
after 24 hours of appropriate antimicrobial Rx
How long is the incubation period of GAS pharyngitis?
2-5 days
Of those swabbed, how many adults actually have streptococcal pharyngitis?
In adults less than 1 out 10 will have strep because adults carry strep much less commonly
What is the treatment of Severe Invasive Strep Syndrome?
Treatment- Clindamycin +/- Pen G
What is Severe Invasive Strep Syndrome?
Severe Acute Infection, Resemble Toxic Shock (occurs w/ both Staph Aureus & GAS), presents with fever, erythroderma, multiple organ damage, positive blood culture, Usually with preceding musculoskeletal trauma
What are the Suppurative complications of GAS?
peritonsillar abscess, retro pharyngeal abscess/ cellulitis
How & Why do we Treat GAS?
Penicillin VK is drug of choice: narrow spectrum, cheap, effective, BID dosing, must treat 10 days, Macrolide resistance reported (recent Pittsburgh outbreak of Azithromycin-R GAS strain), Get better faster (? about 1 day); disease is self limited even without treatment: majority is self-limiting, Suppurative complications, Diminish contagiousness, Prevent Rheumatic Fever
How is the diagnosis of GAS pharyngitis made?
Clinical suspicion of GAS pharyngitis, No evidence of scarlet fever, Rapid antigen swab of tonsillar papillae & posterior pharynx (Sensitivity 60-90%), Bacterial throat swab (back-up the rapid strep test w/ this), (+) Rapid strep in 10 minutes
What is the sensitivity of the Rapid Strep test?
rapid stress test is only 60% sensitive; so there could still be strep there even w/ a negative RST;
What are the signs and symptoms of Tonsillopharyngitis?
Red & Nonspecific tonsils, Palatal Petichiae, Exudative Tonsils
Of those swabbed, how many children actually have streptococcal pharyngitis?
Children are only have strep w/ pharyngitis in 1 out of 4
What is the criteria for swabbing a pt with a sore throat?
Meeting the criteria swab: of no congestion, coughing or URI Sx, have sore throat, fever, and belly pain are the kids you are going to swab
What is Scarlet Fever desquamation?
Begins to peel in 10 days after the illness, Fine scales & large peels
How does Rheumatic Fever present on the Echocardiogram?
moderate aortic & mitral regurgitation
How does Rheumatic Fever present on the skin?
blanching faint erythematous rash over extremities, abdomen, more prominent with fever: macules with some confluence (they join together) & serpiginous borders (snake-like borders), no itch
How does impetigo present in scarlet fever?
Honey Yellow crusts GAS and/or Staph aureus, can be Bullous, Highly contagious, Benign, May lead to PSGN
Why is scarlet fever treated for 10-days?
Shorten the course, Prevent Rheumatic Fever, Prevent transmission
How is the diagnosis of Scarlet fever made?
Diagnosis usually clinical suspicion, May also be caused by Staphylococcus aureus
What are the pastia lines in Scarlet Fever?
Accentuation of rash at skin folds, Usually seen best at antecubital and bicipital line, Are petechial (they do not blanch)
What is the Eagle effect?
Due to the high number of strep bacteria that are replicating, its almost like the penicillin is paralyzed; Penicillin is sometimes not able to penetrate the cell wall; it is not a resistance to penicillin, but it is just an overwhelming amount of bacteria that is not enough to treat alone
What are the facial clinical signs of Scarlet fever?
Strawberry tongue (White or Red), Peri-oral and Peri-nasal sparing
What are the systemic clinical signs of Scarlet fever?
Exanthum produces erythrogenic toxin (what causes the rash); Skin: diffusely erythematous with tiny, pinhead-like papules: appearance of sunburn with goose bumps; Dark-skinned: may not appreciate erythema or pallor; only feel texture of rash; Without treatment, resolution in 1 week; Desquamation: occurs regardless of treatment
When does ARF appear?
ARF seems to follow 10 to 42 days after streptococcal sore throat
What is needed to make a diagnosis of RF based on the Jones criteria?
2 major or 1 major & 2 minor criteria plus evidence of preceding streptococcal infection indicate high probability of rheumatic fever
What are the additional Jones Criteria for Diagnosis of Rheumatic Fever?
evidence of preceding GAS infection and 1 of the following: (+) strep culture or rapid antigen, antibody rise (in blood work), scarlet fever (previous episode)
What are the minor Jones Criteria for Diagnosis of Rheumatic Fever?
Fever, Arthralgia, Previous RF, Elevated acute-phase reactants (ESR, CRP), Prolonged PR interval on EKG
What are the major Jones Criteria for Diagnosis of Rheumatic Fever?
Carditis, Polyarteritis (migratory), Erythema marginatum, Chorea, Subcutaneous nodules
What is the most common cause of acquired heart disease world wide?
RF
What is the familial predisposition w/ ARF?
a B cell marker (D8/17) has been identified in >90% of all patients with rheumatic fever tested in 5 different geographical and ethnic populations
How does Rheumatic Fever present on the EKG?
Prolonger QT interval
What is the pathogenesis of GASHS & Rheumatic Fever?
(1) Streptococcal toxin OR (2) Abnormal host immunologic response to GABHS…. Cross-reactive antigens in this autoimmune process
What is GASHS & Rheumatic Fever?
Immunologic reaction to a previous Group A strep infection which has resolved several weeks prior to onset of symptoms of RF
In pts with ARF without RHD on no prophylaxis, how many will develop RHD?
50% will develop RHD in the next 20 years, even if no apparent ARF recurrence
How long is Prophylaxis treatment for Rheumatic Fever without carditis?
5 years or until age 21 y, whichever is longest
What is the secondary prophylaxis of ARF?
Secondary prophylaxis: prevention of GAS in persons with prior acute rheumatic fever: pts who receive antibiotics continuously with prior RF do not have recurrences
What is the primary prophylaxis of ARF?
treatment of GAS tonsillitis/ pharyngitis with 10 course of appropriate antibiotic (attack rate approx. 3% in untreated or inadequately treated pts); Must be with bactericidal drug; Penicillin is drug of choice; Do NOT use Trimethoprim–Sulfa (only used for secondary prophylaxis), not a bactericidal drug; Erythromycin is recommended alternate (resistance is a real issue)
How is RF treated?
Treatment of GAS Disease: 10 days of oral agent or IM injection of 1,200,000 units benzathine penicillin G; Salicylates for arthritis and Sydenham chorea; Corticosteroids and/or salicylates for carditis; Other treatment ?: CHF, Sydenham chorea
In what order does RHD affect the heart valves?
Mitral > Aortic >> Tricuspid; May be pericarditis, pancarditis
In pts with ARF with RHD on prophylaxis, how many will heal or show improvement?
1/3 will heal completely or show improvement
What is used as evidence for strep infection based on culture and blood?
Positive throat culture, Elevated streptococcal antibodies: Anti- Streptolysin O, Anti- DNase B, Anti- Hyaluronidase
What is the presentation of Rheumatic arthritis?
Usually polyarticular; Usually migratory: hot swollen ankle one day --> ankle fine, elbow hot & swollen the next, VERY painful (even the bed sheets can cause pain), VERY responsive to ASA
What are the special diagnostic issues associated with ARF?
Sydenham’s Chorea; Indolent carditis: Aortic Regurgitation not due to bicuspid Aortic valve, syphilis; Recurrent ARF
How long is Prophylaxis treatment for Rheumatic Fever with carditis but no residual disease (i.e. valvar disease):
10 yr or well into adulthood,
whichever is longest
How long is Prophylaxis treatment for Rheumatic Fever with carditis and residual heart disease (valvar disease)?
At least 10 yr since last episode and at least until age 40 yr; sometimes lifelong prophylaxis
What drug of abuse has the highest tolerance?
Heroin – acute tolerance also occurs in cocaine (esp. when taking it IV), but not as much
What characterizes the psychological dependence of Amphetamines?
Similar to cocaine, may cause hallucinations
What are the uses of Amphetamines?
ADHD, obesity, nasal decongestant, narcolepsy
What is the mechanism of action of cocaine?
Inhibits DA reuptake – also causes increased activation of DA receptors, negative feedback inhibition, DA release from nerve endings, inhibition of NE/5-HT reuptake
What is the treatment for cocaine overdose after the acute effects are under control?
Antidepressants; Haloperidol: for psychosis; Alprazolam: for panic attacks
What is the acute treatment for cocaine overdose?
Beta blockers: for autonomic hyperactivity (β1 blockade with Atenolol, Metoprolol, Esmolol, Labetalol), controversial treatment since unopposed α effects may lead to an increased BP; Nitroglycerine: for angina; CCBs: for HTN (Verapamil, Diltiazem); Ice baths: for high fever; Acidify urine: to hasten excretion
What does cocaine overdose result in?
Excessive activation of sympathetic nervous system: tachycardia, HTN, MI, cerebrovascular hemorrhage, coronary vasospasms, cardiac dysrhythmias – can also see anxiety, paranoia, feeling of impending doom, restlessness – users exhibit unpredictable behavior and may become violent
What characterizes the pharmacology of cocaine?
In general, cocaine is very similar to Amphetamines; however, cocaine has a shorter half-life – cocaine can be injected (but rate of absorption is limited by vasoconstriction) or smoked (delivered directly into pulmonary circulation, left heart, brain)
What is meant by “the runs”?
Person takes cocaine, gets a craving, takes it again, gets another craving, etc.; continues in this cycle until a crash, followed by sleep; when person wakes up, will experience the blues (fatigue, depression, hyperphagia), and so will start taking cocaine again
What are the acute effects of cocaine?
Initial/temporary euphoria, craving starts within 30min of taking the drug; can see increased alertness, feeling of elation/well being, increased energy, feeling of competence, increased sexuality; user becomes more talkative, restless, irritable; consciousness is clear but delusions and hallucinations may occur; As sympathomimetic, cocaine increases HR/BP/skeletal muscle tension (though musculature of bronchi/intestine relax) – also causes a decrease in glucose metabolism
What are the negative effects of nicotine?
GI distress, hypothermia, emesis, HTN, seizures, respiratory distress
What are the “psycho” drugs?
Psychedelics/hallucinogens (e.g. LSD), Marihuana, dissociative anesthetics (e.g. PCP), anticholinergics (e.g. Atropine)
What is the mechanism of action of nicotine?
Stimulates nicotinic ACh receptors at low doses, and blocks them at high doses; Stimulates release of DA from VTA onto nucleus accumbens; Presynaptic receptors regulate release of NE/Epi/DA/ ACh/GABA
What are nicotine withdrawal symptoms?
Nervousness, anxiety, drowsiness, lightheadedness, insomnia, dizziness, tremor, sleep disturbances, decreased ability to concentrate, irritability, intense craving of tobacco – other physical symptoms incl. nausea, HA, constipation, increased appetite, weight gain
What characterizes detoxification treatment of nicotine?
Smoking therapy: substitution, tapering off; Nicotine gum, patches, nasal sprays
What are the chronic effects of nicotine/smoking?
Heart disease, lung disease, cancer, babies with small birth weight, asthma in children
What are the effects of acute intoxication with nicotine?
Respiratory arrest due to blockade of respiratory centers and NM junction controlling breathing
What characterizes the pharmacology of nicotine?
Half-life of 30min; Highly lipophilic: crosses BBB/placenta
What are the positive effects of nicotine?
Anxiolysis, cognitive enhancement, cerebro-vasodilation, neuroprotection, analgesia, antipsychotics (vigilance)
What are the acute effects of nicotine?
Decreased fibrinolytic activity; Increased FFA, NE/Epi release from adrenals, sympathetic and parasympathetic activity, ACTH release from pituitary; Depolarization of thermo- /mechano-/ nociceptors, carotid body, baroreceptors – depolarization of chemoreceptors in area postrema causes stimulation of emetic centers
What characterizes dependence on hallucinogens?
There is no physical dependence, but they have tremendous psychological dependence – use is occasional
What are the acute effects of PCP?
Low dose: dreamy/carefree state, mood elevation, heightened perception;
Moderate dose: dissociation, depersonalization, perceptual distortions, diminished pain sensitivity; High dose: all of the above and hallucinations
What characterizes PCP?
Dissociative anesthetic, most commonly used hallucinogenic agent; can be snorted, taken PO, smoked with tobacco, injected IV; usually gives bad trips: unpredictable, bizarre, violent
What characterizes the pharmacokinetic of Marihuana?
High lipid solubility, so if taken orally will have slow intestinal absorption, smoking causes 50% uptake
What is the active ingredient in Marihuana?
THC
What systems can be affected by hallucinogens?
5-HT, NE, ACh
What are the acute effects of hallucinogens?
At low doses: euphoria, changes in affect (anxiety, tension, labile mood), thought/feeling disorders (perceptual changes, depersonalization, illusions, visual hallucinations, time/visual distortions, synesthesias), nausea, mydriasis, increased HR/BP/temp/reflexes, tremors, panic, paranoia;
At high doses: dangerous behavior (may cause accidents) – for amphetamines: convulsions, coma
What are effects of acute toxicity/overdose with hallucinogens?
Tissue toxicity, neurotoxicity, psychic toxicity, acute transient psychosis, flash backs, behavioral toxicity, distorted behavior, aggression, violence
What are subjective reasons for taking hallucinogens?
Allows insight into oneself and new ways of looking at the world
What are the solvent/inhalant drugs of abuse?
Volatile solvents, aerosols, anesthetic agents, amyl/butyl/isobutyl nitrite
What is the mechanism of action of solvents/inhalants?
Stimulate GABA receptor
What are the acute toxicity/overdose effects of solvents/inhalants?
Photophobia, irritation of eyes, diplopia, rhinitis, sneezing, coughing, n/d, chest pain, muscle/joint pains – overdose can cause respiratory depression, usually die of asphyxia;
Halogenated hydrocarbons can cause cardiac arrest
What are the acute effects of solvent/inhalants?
Low doses: euphoria, dizziness, slurred speech, ataxia, impaired judgment, feelings of giddiness, drunkenness, perceptual distortions; High doses: generalized CNS depressant – amyl nitrite may be a sexual enhancer (penile vasodilation)
What characterizes the pharmacology of solvents/inhalants?
Rapid onset of action (except acetone); can see psychological and physical dependence, but no physiological dependence; alcohol potentiates effects, seem to disrupt membrane function
What are examples of the solvent/inhalant drugs of abuse?
Volatile solvents: “glue sniffing” (lighter fluids, cleaning solutions, etc.); Aerosols: fluorocarbons and other aerosol propellants, spray paint; Anesthetic agents: ethyl ether, chloroform, nitrous oxide, chloral hydrate (historic drug); Amyl/butyl/isobutyl nitrite: “poppers”, vasodilators to relieve angina (historic use)
What characterizes the anesthetics, volatile intoxicants?
Most likely to be abused by younger people; some solvents (e.g. toluene) may cause permanent neurological damage
What are the untoward effects of PCP?
Low dose: impaired judgment, mood swings, partial amnesia; Moderate dose: ataxia, confusion, preoccupation with abnormal body sensations, amnesia, nystagmus, mood swings, panic (!);
High dose: catatonia, “blank” stare, delirium, motor impairment, psychotic behavior, hypertensive crisis, meditation mortis, amnesia
What is the mechanism of action of PCP?
NMDA antagonist; may block DA reuptake
What characterizes the acute toxicity/overdose of PCP, and the treatment?
Intoxication may last 4-6hrs, usually not lethal; there is no treatment,
What characterizes lab findings with atopic asthma?
Positive skin tests, increased IgE (best correlation with asthma), blood eosinophilia
What are the criteria and treatment for intermittent asthma?
<2 attacks/wk, <2 nocturnal attacks/month, normal spirometry, FEV1>80%, SABA<2 days/wk; Treatment: SABA as needed
What findings are diagnostic of asthma?
Reversible airflow limitation on spirometry with SABA (12-15% and 200ccs); Diurnal variation of >20% by peak flow meter; Bronchoprovocation study (methacholine challenge);
ABG (with acute asthma)
What are the chances for remission of asthma?
Children: 50% by 2nd decade; Adults: 10%, complete remission unlikely (progressive disease is uncommon)
Besides smoking, what are other risk factors for asthma?
Children born to mothers <20; Premature girls (especially if they needed mechanical ventilation); Head circumference <37cm (may be related to maternal nutrition); Children born by C-section
In what age range is smoking a particularly important risk factor for asthma?
17-33; relapse in 30s is more common amongst smokers; environmental smoke leads to childhood asthma; maternal smoking is associated with asthma in the first year of life
What are cockroach allergens associated with?
Inner city; higher mortality
Which demographic is at higher risk for hospitalization/mortality due to asthma?
African-Americans
What is the prevalence of asthma regarding age and sex?
Up to puberty: male; 20-40 years: equal; After 40: female
What is the typical triad of symptoms associated with asthma?
Cough, dyspnea, wheezing
What form of COPD is usually seen in clinical practice?
A combination of chronic bronchitis and emphysema
What are the diagnostic classifications for COPD (COPD-GOLD)?
Stage 0(at risk): normal spirometry, chronic productive cough – above Stage 0 FEV1/FVC<70%;
Stage I(mild): FEV>80%
Stage II(moderate): FEV1=50-80%,
Stage III(severe): FEV1=30-50%
Stage IV(very severe): FEV1<30% (or <50% with chronic respiratory failure)
At what FEV1 is exertional dyspnea noted and when does it become disabling?
Exertional dyspnea: 50% FEV1; Disabling: 30% FEV1
Why does COPD remain asymptomatic for a long period of time?
FEV1 does not start its accelerated decline until age 35 (declines more rapid in smokers)
What is the risk of COPD in smokers?
1 pack/day: 15-20%; 2 packs/day: 25% (pipes/cigars have a lower risk associated with them)
What are two important mechanisms of COPD pathogenesis?
Imbalance of proteinases/anti-proteinases in the lungs (leading to centrilobular emphysema); Oxidative stress
Which classes of lymphocytes are involved in asthma vs. COPD?
Asthma: CD4+; COPD: CD8+
What are the criteria and treatment for mild persistent asthma?
>2 attacks/wk, 3-4 nocturnal attacks/month, FEV1>80%, SABA>2 days/wk but not daily
Treatment: low dose inhaled steroids (alt: leukotriene inhibitor, cromolyn sodium, theophylline)
What are the criteria and treatment for severe persistent asthma?
Continuous symptoms, limited physical activity, nocturnal attacks every night, FEV1<60%;
Treatment: medium-dose inhaled steroids and LABA (alt: theophylline, leukotriene modifiers, oral steroids, Omalizumab)
What are the criteria and treatment for moderate persistent asthma?
Daily symptoms, >1 nocturnal attack/week, daily use of SABA, FEV1=60-80%
Treatment: add LABA or increase inhaled steroids (alt: leukotriene modifier, theophylline, SABA)
What is the treatment for COPD?
All stages: avoid risk factors, influenza vaccination, each treatment stage builds on previous stage
Stage I: short-acting bronchodilator
Stage II: long-acting bronchodilator, pulmonary rehab
Stage III: inhaled steroids
Stage IV: oxygen for chronic respiratory failure, surgery
What are the characteristic inflammatory cells of COPD?
Neutrophils
Which treatment options help reduce mortality?
Smoking cessation, oxygen therapy
What is the definition of Addiction?
A primary, chronic medical disease, manifested by compulsive use of an addictive drug, with loss of control and irrepressible craving of the drug
What is Times until detection/death with Sufentanil abuse?
1-6 months
What is Times until detection/death with Fentanyl abuse?
6-12 months
What is Times until detection/death with sedative abuse?
1-2 years
What are the Methods anesthesiologists use to obtain drugs for abuse?
False recording on anesthesia record, Giving “breaks” and substituting syringes, Keeping wastage, Switching syringes during own cases, “Breakage” of ampules, Accessing ampules and resealing with other substances inside, Substituting inhalational agents and beta blockers during an opioid-based anesthetic
What drug of choice is most common in anesthesiologists and which ones are most common?
Opioids: Fentanyl and sufentanil most common, Meperidine and morphine next most common
What is the definition of Relapse?
Recurrence of psychoactive substance-dependent behavior in an individual who has previously achieved and maintained abstinence for a significant period of time beyond withdrawal
What is the definition of Recovery?
A lifelong process of overcoming both physical and psychological dependence on a psychoactive substance. Goal is a new lifestyle allowing for emotional and spiritual growth in sobriety
What is the definition of Abuse?
Use of a psychoactive substance in a manner detrimental to the individual or society but not meeting criteria for dependence
What factors for over-representation of anesthesiologists in addiction programs?
High addictive potential of fentanyl & sufentanil, More rapid identification of abusers , Access to drugs, Accustomed to giving large doses of mood-altering substances with immediate results, Lack of needle taboo, Control-oriented, Curiosity about what drugs feel like for the patient, Aerosol and contact exposure to drugs, Seekers of drug experiences select anesthesiology
What is the characteristic co-morbid psychiatric conditions of drug-addicted anesthesiologists?
57% personality disorder; 6% have primary psychiatric disorder
What is the % of drug-addicted anesthesiologists have family history of addictive disease?
33%
What is the % of polydrug users in drug-addicted anesthesiologists?
35-50%
What is the characteristic drug of abuse of drug-addicted anesthesiologists?
76-90% opioids
What is the characteristic sex of drug-addicted anesthesiologists?
67-88% male
What is the characteristic age of drug-addicted anesthesiologists?
50% less than 35 years
What risks are associated with drug abuse for anesthesiologists?
High rate of mortality docs with addictive disease, are 2.79 times more likely to die from drug overdose than internists, Relapse rate is approximately 19% per year for anesthesiologists with a history of opioid addiction who have returned to practice, Loss of license, family, self-esteem, ability to get health/disability insurance
What are contributing factors of addictive disease?
Genetic predisposition, A Family history of abuse or dysfunctional family interactions may contribute
Is addiction considered a disease?
Yes, Addiction is a disease and doctors are human beings
What % of drug-addicted anesthesiologists is associated w/ academic departments?
65%
What is the only pathognomic sign in drug-addicted anesthesiologists?
witnessed self-administration
What are some warning signs of addiction?
Someone close isolates him/herself, Less interest in family matters, Tendency to become angry, blame others, Less interest in a sexual relationship, An unusual interest in arriving early, taking another’s call, Excessive worry about professional excellence, Deterioration of appearance or body hygiene, Unexpected sweating, inappropriate dozing, Evasive or secretive
What are the Signs and symptoms of opioid withdrawal?
diaphoresis, tremors, mydriasis, rhinorrhea, myalgias , N&V
How can an opioid addicted anesthesiologist hide needle marks?
By wearing long-sleeved gowns
What does the pupils of an opioid addicted anesthesiologist look like?
Pin-point pupils
What are behavioral signs of opioid addiction in anesthesiologists?
Unusual changes in behavior (mood swings, periods of depression, anger and irritability alternating with euphoria), Sign-out of increasing quantities of narcotics (Inappropriately high doses for procedures being performed), Increasingly sloppy and unreadable charting, Desire to work alone, Refuse lunch relief or breaks, Frequently relieve others, Volunteer for extra cases or extra call
What parasites have been known to cause pneumonia?
Ascaris, Strongyloides
What other disease are caused by Streptococcus pneumonia?
Otitis media, sinusitis, meningitis
What factors increase the risk for pneumonia from Streptococcus pneumonia?
Elderly (<65), chronic heart/lung disease, smoking, immunocompromising conditions
What should be cultured when a patient shows up with pneumonia looking extremely sick?
Sputum and blood cultures (positive ~20% of the time, very diagnostic)
What does an elevated white count with a left shift usually indicate?
Bacterial infection
What non-infectious diseases have been known to mimic pneumonia?
CHF, atelectasis, PE, malignancy, vasculitis (Goodpasture’s), granulomatous disease (Wegener’s), hypersensitivity pneumonitis, drug reactions
Which organisms are most likely to cause a chronic pneumonia?
Anaerobic bacteria (originate in the mouth), Fungi, Nocardia, Mycobacteria (incl. M. tuberculosis)
What is the most common bacterial cause of pneumonia and what are some other causes?
Streptococcus pneumonia – also important are Staphylococcus aureus (severe pneumonia), Haemophilus influenza (normal flora, otitis media), mixed anaerobes (aspiration pneumonia), Gram– bacilli (nosocomial, E. coli/Enterobacter), Legionella (atypical pneumonia), Bacteria-like agents (Mycoplasma pneumoniae, Chlamydia), Mycobacterium tuberculosis (sub-acute/chronic presentation), and Rickettsia (Coxiella burnetii, Rickettsia rickettsiae)
What fungal agents have been known to cause pneumonia?
Aspergillus, Histoplasma capsulatum, Cryptococcus, Coccidioides, Pneumocystis jirovecii – all will cause a more sub-acute/chronic pneumonia; these are more common in immunocompromised patients (HIV/AIDS)
What viral agents have been known to cause pneumonia?
Respiratory syncytial virus, influenza, parainfluenza, adenovirus, hantavirus, herpesvirus, measles virus, SARS (coronavirus)
What is the drug of choice for M. pneumoniae?
Azithromycin – β-lactams are not useful for M. pneumoniae
What physical findings can be seen in a patient with pneumonia?
Fever, tachypnea, crackles, bronchial breath sounds, dullness to percussion
What is the treatment for nosocomial pneumonias?
IV antimicrobials directed at presumed etiologic agents – high morbidity/mortality seen
What are common organisms that cause nosocomial pneumonia?
Gram– bacilli (incl. enterics and Pseudomonas aeruginosa) or Staphylococcus aureus; also possible are oral anaerobes (much less important, unless aspiration pneumonia)
What is the usual treatment for Gram– rods?
Initially Gentamicin/Piperacillin; then switch when specific species/sensitivity is determined (e.g. if Enterobacter is found, can switch to trimethoprim/sulfamethoxazole, if sensitive)
What does an S3 gallop suggest?
Left ventricular failure
How does an M. pneumoniae infection usually present?
Very common cause of respiratory infections (esp. in children/young adults), often accompanied by hemolytic anemia (high reticulocyte count)
What is the treatment for pneumonia caused by Streptococcus pneumonia?
Start with Ceftriaxone or Vancomycin if patient is hospitalized; then switch to penicillin or azithromycin if isolate is sensitive
What type of pneumonia should be considered in a patient with a positive cold agglutinins test?
Mycoplasma pneumoniae
What are complications associated with Streptococcus pneumoniae?
Bacteremia, empyema, pneumatocele
What conditions predispose to aspiration pneumonia?
Decrease in mental status, inability to clear airway
What is the treatment for Legionnaire’s disease?
Azithromycin (and other macrolides)
What bacterial etiologic agents are the most common cause of pneumonia in a patient on high dose steroids?
Legionnaire’s disease (!), Mycobacteria, Nocardia
What are the most common bacterial etiologic agents of community-acquired pneumonia in smokers and patients with COPD?
Streptococcus pneumoniae (most commonly), Haemophilus influenza, Legionella species (!)
What is the major complication of influenza infection in adults?
Secondary bacterial pneumonia – bacteria come from normal flora and are most commonly Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus
What is the treatment for Staphylococcus aureus pneumonia?
Vancomycin; when sensitivities known (i.e. is it MRSA) ca n switch to IV Nafcillin/Oxacillin
What is the treatment for aspiration pneumonia (i.e. for oral anaerobes)?
Clindamycin
What pneumonia agents are suggested by animal exposures?
Anthrax (Bacillus anthracis, from cattle/animal hides), Plague (Yersinia pestis, from squirrels/ chipmunks/rabbits/rats), Tularemia (Francisella tularensis, from rabbits/foxes/squirrels), Q-fever (Coxiella burnetii, from goats/cattle/sheep), Psittacosis (Chlamydia psittaci, from exotic birds)
What is the predominant flora of the normal oropharynx?
Oral anaerobes: Peptococcus, Peptostreptococcus, Fusobacteria
What pneumonia agents are suggested by travel exposures?
SARS (travel to area of outbreaks), Coccidioidomycosis (S California/San Joaquin valley/SW US)
What test can be done to rapidly diagnose Legionnaire’s disease?
Legionella urinary antigen test
Which bacteria do not show up on Gram stain?
Legionella, Mycoplasma
What term is often used to describe Haemophilus influenzae?
Pleomorphic (Gram–)
What etiologic agent should always be considered in a patient with community-acquired pneumonia?
Streptococcus pneumoniae
What is a common presentation seen in a patient with disseminated histoplasmosis?
Verrucous, oral ulcer
What is a highly effective and rapid diagnostic test for histoplasmosis infection?
Exoantigen testing by RIA from urine (takes 24 hours to get results) – this test can also indicate whether a patient will progress to secondary histoplasmosis or recover from the primary infection
How is H. capsulatum diagnosed after being cultured?
By looking at its conidia: there are microconidia (infectious particles) and macroconidia (tuberculate)
What is meant by the biopsy for histoplasmosis being split?
Half of the biopsy is sent to pathology for H&E staining, and the other half is sent to the clinical lab to be cultured and stained with GMS
Why is the skin test for histoplasmosis not used much anymore?
Since it can raise the serological titer to H. capsulatum, it makes the differential diagnosis between primary and secondary histoplasmosis difficult, thus interfering with appropriate treatment
For what kinds of infections are skin tests useful?
TB, histoplasmosis, cocci
In what type of cell is the intracellular yeast form of H. capsulatum found?
Phagocytic cells – here they reproduce until the cell bursts (they appear to have a halo around them, but this is actually due to the staining technique)
What organism causes histoplasmosis and what are the different types of histoplasmoses?
Histoplasma capsulatum: pulmonary histoplasmosis (primary), disseminated histoplasmosis (secondary)
What is the difference between H. capsulatum and TB on x-ray?
Although they both present with granulomatous lesions in the lungs, the lesions seen with H. capsulatum are larger (coin lesions) than those seen with TB
What kind of microbe is H. capsulatum?
Dimorphic fungus
Where is the highest incidence of histoplasmosis found?
In the Ohio valley
What are alternative presentations associated with
histoplasmosis?
Addison’s disease, reactivation infection (analogous to TB), septic shock in AIDS patients, erythema nodosa (favorable prognosis), ocular histoplasmosis syndrome (blindness)
What is the treatment for progressive disseminated histoplasmosis?
L-AMB (1-2 weeks) --> Itraconazole (12 months)
How does the treatment differ between a solitary pulmonary histoplasmosis and chronic cavitary histoplasmosis (affecting entire lungs)?
There is no treatment recommended for the solitary form, but chronic cavitary histoplasmosis is treated as though it is secondary histoplasmosis
What are the physical signs/symptoms that a patient with histoplasmosis can present with?
Initially presents with general symptoms of infection (viral/bacterial/fungal); this can be followed by hilar lymphadenopathy and hepatosplenomegaly; in some cases the disease can cause pericarditis or Addison’s disease (due to destruction of adrenal gland functioning by affected phagocytic cells)
What people are least likely to go from a pulmonary histoplasmosis to a disseminated histoplasmosis?
White females (other races/males do not have the same level of resistance)
How does transmission of H. capsulatum occur?
Via birds (chicken coop/starling roost) and bats – due to inhalation of microconidia
What will happen to the diagnostic titer to serology by CF in a patient with histoplasmosis?
If the patient has primary histoplasmosis that is resolving, the titer will drop off as the infection is fought off; however, if the patient progresses to secondary histoplasmosis, the titer will remain elevated
What is the treatment for primary histoplasmosis?
Nothing; self-limited disease
What elements are important in the diagnosis of coccidioidomycosis?
Spherules and endospores; Erythema nodosa; CF (complement fixation) serology;
Coccidioidin DH (delayed hypersensitivity, skin test)
What is the distinguishing feature of paracoccidioidomycosis?
Disseminated cutaneous form spreads to the mucocutaneous tissues
What is the treatment for blastomycosis?
Itraconazole
What lab findings are associated with blastomycosis?
Thick-walled, extracellular yeast with broad-based budding
What can disseminated cutaneous blastomycosis resemble?
Squamous cell epithelioma
Which is the only communicable form of systemic, dimorphic mycoses?
Coccidioidomycosis
What is the treatment for coccidioidomycosis?
Primary: not treated; Disseminated: aggressive AMB or Itraconazole
How does the primary infection of Coccidioides immitis differ from that seen in histoplasmosis?
About 50% of primary infections is symptomatic (mild influenza-like fever, chest pain) – also on x-ray, a thin walled cavity is seen with C. immitis as opposed to a calcified lesion w/ Histoplasma
What are the infectious particles of C. immitis?
Arthrospores: separated cells of hyphae
How does the disseminated infection of Coccidioides immitis differ from that seen in histoplasmosis?
The patient complains of joint pain, which is not seen in histoplasmosis
What percentage of cryptococcal meningitis is opportunistic?
About half; 10% of AIDS patients will develop cryptococcal meningitis if not on prophylactic Fluconazole (only effective azole since it penetrates the CNS)
What is the epidemiology of PCP?
It is part of the non-pathogenic normal pulmonary flora of most mammals
What is the treatment for PCP?
TMP-SMX
How is PCP diagnosed?
Stain bronchoalveolar lavage specimen with either GMS or Calcofluor White
What are among the most common causes of death in HIV+ patients?
TB, CMV, PCP (Pneumocystis pneumonia – P. jiroveci)
What test will help measure the prognosis of cryptococcal meningitis?
LCAT
What elements are important in the diagnosis of cryptococcal meningitis?
Fever, HA, vomiting, stiff neck; budding yeast visible on India ink (narrow isthmus, large polysaccharide capsule); Reverse passive latex agglutination (RPLA), specifically the latex cryptococcal antigen test (LCAT) which measures glucuronoxylomannan (GXM);
Mucicarmine stain
What elements are important in the diagnosis of paracoccidioidomycosis?
Fever of unknown origin (FUO), travel to South America, “pilot wheel” budding yeasts, visceral affinity
How is cryptococcal meningitis acquired?
Respiratory exposure to avian feces
What is the treatment for paracoccidioidomycosis?
Itraconazole
In what percent of AIDS patients will P. jiroveci become a pathogen?
60-90% (mortality 20%)
How does transmission of TB occur?
Via respiratory mucus droplets in the air (inoculum size is high, repeated exposures are usually required – except in susceptible individuals)
What damage is seen in disseminated tuberculosis (miliary/extrapulmonary tuberculosis)?
Renal necrosis/scarring, damage to reproductive organs, degeneration of spine, meningitis
What are the signs/symptoms of an active TB infection?
Fever, weight loss, night sweats, cough, bloody sputum, fatigue decreased appetite, abnormal cxr
What describes the immune response regarding TB?
Starts out as a CD4+ T cell response --> they release cytokines (IFN-γ/TNF) which activate macrophages --> they in turn release cytokines (TNF/IL-1, 6, 8/GM-CSF) which cause inflammation and granuloma formation
What characterizes the tubercles seen in TB?
They are granulomas with a central core of M. tuberculosis surrounded by macrophages and T cells (bacilli cause caseous necrosis); the granulomas can calcify at which point they are known as a Ghon complex
What is meant by a secondary TB infection?
Reactivation of bacteria already present in the host (more commonly) or re-infection by M. tuberculosis (in endemic areas)
What is the pathogenesis of the primary course of TB?
Inhalation of bacteria --> bacteria are small and can access the alveoli where they invade alveolar macrophages and multiply (then they migrate to lymph nodes and initiate an immune response) --> in the lungs, lesions form and granulomas develop --> activated macrophages fight the infection --> bacteria stop growing and calcification of the lesion occurs
What characterizes Mycobacterium tuberculosis?
Longer, slender, straight or curved; Acid-fast (complex cell wall); Slow growers, obligate aerobes; Intracellular bacterium
What proteins are responsible for the phagosome-lysosome inhibition of M. tuberculosis?
ESAT-6 and CFP-10 (both found on the RD1 region of the chromosome)
What virulence factors are associated with Mycobacterium tuberculosis?
Complex cell wall (resists phagocytosis, impermeable); Intracellular (hidden from immune response); Siderophores (iron acquisition); Antibiotic resistance (via chromosomal mutations and genes); Inhibits phagosome-lysosome fusion
For which people is a 10mm induration with a PPD interpreted as positive for TB?
Persons with clinical conditions that place them at high risk, children <4yo, adolescents exposed to adults at high risk
What is meant by DOTS and what is its significance?
Direct observed treatment, short-course; has been important world-wide in the fight against drug resistant TB
What is the treatment for an active TB infection?
Rifampin, isoniazid, pyrazinamide, ethambutol; until drug sensitivity is known; treatment administered for 6-24 months due to drug resistance issues
What are the advantages of using QuantiFERON over TB skin testing?
Single patient visit, only responds to M. tuberculosis, no “booster phenomena”, eliminates subjectivity, safe, uses whole blood, results within 24 hours
How does QuantiFERON (TB Gold) work?
It is an in vitro assay that uses whole blood from the patient to measure a cell-mediated response to ESAT-6/CFP-10 antigens by looking for IFN-γ production (through ELISA)
What type of reaction is the response to a PPD?
Type IV, delayed-type hypersensitivity
For which people is a 15mm induration with a PPD interpreted as positive for TB?
People with no known risk factors for TB
How is the diagnosis of active TB made?
Tuberculin skin testing (PPD); Chest x-ray; Direct identification of acid-fast bacilli from sputum (or bronchoalveolar lavage); Cultivation of bacteria in the laboratory (Fluorometric detection, isolation of bacteria, drug susceptibility – total of 10-14 days)
For which people is a 5mm induration with a PPD interpreted as positive for TB?
HIV-positive patients, close contact to an infectious TB case, patients with positive chest radiographs, organ transplant recipients, immunosuppressed patients
How is the diagnosis of latent TB made?
Tuberculin skin testing (PPD) – measure induration, not erythema; a positive PPD does not necessarily mean current infection (it means current or prior infection)
What characterizes M. avium complex (MAC)?
Major cause of death in AIDS patients; found in soil/aqueous environments; can colonize GI and respiratory tract, then disseminate; very drug-resistant organisms (treat with multiple drugs)
What is the treatment for leprosy?
Tuberculoid form: dapsone, rifampin; Lepromatous form: dapsone, rifampin, clofazimine
What are the two major forms of leprosy?
Tuberculoid form: less severe, cell-mediated immune response (TH1);
Lepromatous form: severe form, poor cell-mediated immune response (TH2), damage to sensory nerves, loss of feeling leads to injury and secondary infections
What is the transmission/epidemiology associated with M. leprae?
Aerosol droplets; genetics, health, living conditions may determine susceptibility
What characterizes M. leprae?
Causative agent of leprosy (Hansen’s disease): progressive disease of the skin and nerves – intracellular bacterium that grows in macrophages and Schwann cells (long incubation period)
What characterizes Runyon group IV mycobacteria?
Rapidly growing mycobacteria, such as M. fortuitum; they are ubiquitous in the environment, and are opportunistic pathogens (skin lesions, abscesses) – can be a problem after plastic surgery
What characterizes M. kansasii and M. marinum, respectively?
M. kansasii: causes pulmonary infection, not communicable, treat with isoniazid/rifampin;
M. marinum: “swimming pool granuloma”/ulcers, no communicable, treat w/ rifampin/ethambutol
What prevention strategies associated with TB?
Sanitary conditions, improved standard of living; If a tuberculin-negative person converts to positive, they are given isoniazid prophylactically (also given to a person who has been in close contact with an active TB case)
What is the BCG vaccine and what are some issues associated with it?
Avirulent strain of M. bovis (lacks ESAT-6/CFP-10), safe/effective vaccine (protective against meningitis/disseminated TB in infants and young children); not used in the US since it will make the vaccinated person PPD positive
What do radiologists call a Ghon complex?
Ranke complex
What can be used as a living culture medium for M. leprae?
Armadillo (lower core temp.)
How is leprosy transmitted?
Aerosol transmission – low communicability
What can occur in a persistent cavity with a thick fibrous wall (even if no infection is present)?
Squamous metaplasia --> cancer
What should be done when a patient has an open TB cavity for more than 4-5 months?
Surgical removal
Where do pulmonary lesions of secondary TB usually occur?
Apical region of upper lobes (bacillus like high oxygen tension)
What is the most frequent form of extrapulmonary TB?
Cervical lymphadenitis - scrofula
How many organisms are required in a sputum sample in order to make a diagnosis of TB?
More than 10,000
Which TB drugs are active against extracellular (rapidly dividing) organisms?
INH, RIF, ETH (less), Streptomycin, Quinolones
What are the uses of RIF?
Bactericidal to actively dividing organisms (extracellular) and to slowly diving bacilli (intracellular); also somewhat effective against nearly dormant organisms – given PO, IV
What adverse effect can be seen with all anti-mycobacterial drugs?
Rash
What adverse effects are associated with INH?
Increased LFTs, hepatotoxic (can be fatal); Neurotoxic (reduced by giving pyridoxine!);
CNS toxicity (memory loss, psychosis, seizures)
What is the mechanism of action of INH?
Inhibits synthesis of mycolic acids (cell walls) – bactericidal
What are the indications for INH?
Treatment of active disease, and prophylactically – given PO, IM
Which TB drugs are active against intracellular (in macrophages) organisms?
INH, RIF, PZA, Quinolones
Why is combination therapy needed for TB?
Naturally occurring population of M. tuberculosis are often resistant to a single drug;
The organisms exist in different environments (intra- vs. extracellular, different pH levels);
Bacilli multiply at different rates (reason for prolonged therapy)
Which TB drugs are active against large populations of tubercle bacilli in cavities?
INH, RIF, ETH
What are the first line drugs for TB?
Isoniazid (INH), Rifampin (RIF), Pyrazinamide (PZA), Ethambutol (ETH), Streptomycin
What are the uses of Streptomycin?
Bactericidal to extracellular organisms only; (as an aminoglycoside it is effective against Gram– bacteria) – given IM only
What defines MDR-TB and XDR-TB?
MDR-TB: multi-drug resistant TB (resistant to both INH and RIF); XDR-TB: extensive drug resistant TB (resistant to INH, RIF, Quinolones, and Amikacin/Streptomycin)
What drugs are used as second-line treatment for active TB infections?
Quinolones, Amikacin/Capreomycin, Para-amino salicylic acid, Cycloserine, Ethionamide –
these are used for MDR-TB and XDR-TB
What is the 6-month treatment regimen for an active TB infection?
Daily INH, RIF, PZA, and ETH/Streptomycin (either one, until sensitivities come back);
Use direct observed therapy; After 8 weeks, continue with INH and RIF only, until regiment completed; Treat for a minimum of 6 months, or 3 months beyond sputum conversion
What adverse effects are associated with ETH?
Decreased visual acuity: optic neuritis, dose-related (send patient for eye exams);
↑ uric acid concentrations (need to reduce dose in renal insufficiency)
What are the uses of ETH?
Bacteriostatic against multiplying organisms (weak drug) – given PO
What adverse effects are associated with Streptomycin?
Vestibular/auditory toxicity; Nephrotoxicity – adjust dosage in renal insufficiency
What adverse effects are associated with RIF?
Since it undergoes hepatic metabolism, increased LFTs/hepatotoxicity, induces P450 enzymes (!);
Turns secretions red-orange (sweat, urine, ocular secretions)
What adverse effects are associated with PZA?
Hepatotoxicity; ↑ uric acid concentrations (less common)
What are the uses of PZA?
Bactericidal to actively dividing intracellular organisms only; Adding PZA to INH/RIF can shorten treatment course to 6 months in some cases – given PO
If a patient is not coughing, how can a sample from the lungs be obtained?
Induce cough or use bronchoscopy (or in children by sampling the stomach contents)
When should there be a high index of suspicion of TB?
In a patient with chronic pneumonia, patients at high risk, and recent exposure to TB
How does a TB infection in an HIV-positive patient differ from one in an HIV-negative patient?
The chest x-ray can look like anything; Extrapulmonary manifestations are more common
What is a possible reason why a patient with an active TB infection can have a negative PPD (i.e. anergy)?
If the immune system is so overwhelmed by the infection, it cannot muster up a response to the PPD
What is the treatment for a patient who recently converted their PPD from negative to positive but has no other signs/symptoms?
Isoniazid (9 months)
How does the treatment differ between pulmonary and disseminated tuberculosis?
The treatment for disseminated tuberculosis is longer (in the case, 12 months vs. 6 months)
If a patient is suspected to have TB, what should be done?
Put them in airborne isolation
What is the best way to prove that a patient has TB?
AFB stains and cultures (from sputum, urine, blood)
What characterizes the absorption of ethanol?
Absorbed from stomach, small intestine, and colon by passive diffusion; Peak plasma levels are delayed by food in the stomach; 60% of inspired ethanol vapor is absorbed through the lungs and can lead to intoxication; Percutaneous absorption also occurs (in infants); Women will have a higher peak concentration for the same dose of ethanol intake due to lower total body water and lower gastric alcohol dehydrogenase
What are the peripheral effects of ethanol?
Cardiovascular system: vasodilation of cutaneous vessels, depression of entire system at high doses; Liver/GI tract: induction of P450, fatty degeneration of liver (can lead to cirrhosis), erosive gastritis (high acid, normal pepsin), low doses stimulate appetite, high doses depress appetite (due to its high caloric content); Kidney: increases urine production due to fluid intake and decreased release of ADH
What are the CNS effects of ethanol?
Sedative-hypnotic; membrane-active CNS depressant similar to anesthetic agents; primarily affects the reticular activating system; may induce the release of endogenous opiates (basis for treatment with opiate antagonist Naltrexone)
What is the mechanism of action of ethanol?
Interaction with proteins structures affecting neuronal excitability: replaces water in protein cavities; Ion channels are affected: enhances activity of GABA at GABAA receptor, activity at nicotinic receptors (increased/decreased), NMDA receptors are inhibited, large conductance Ca2+-activated K+ channels are enhanced, N- and P/Q-type Ca2+ channels are inhibited
What describes ethanol excretion?
~100% of the dose is metabolized and enters the citric acid cycle; a very small amount is eliminated by the lungs and urine as ethanol
How is ethanol metabolized?
Mostly by alcohol dehydrogenase (to acetaldehyde --> acetic acid --> acetyl-CoA --> Krebs cycle);
Some by the P450 system (10% of administered dose, induces P450 system [2E1, also metabolizes Acetaminophen] )
What describes the distribution of ethanol in the body?
Volume of distribution is approximately equal to total body water (68% of total body weight in men, 55% in women); Regional differences in blood flow; Rapidly crosses BBB and placental barrier; Distribution is rapid with tissue levels approximating blood alcohol concentration
What are the alcohols?
Ethanol, Methanol, Ethylene Glycol
What are the therapeutic uses of ethanol?
Externally as rub; Injection into nerve plexuses (used in trigeminal neuralgia/inoperable cancer); Improve appetite in elderly; Beneficial effects on cardiovascular system (with moderate intake)
What characterizes ethanol?
Metabolized to yield energy (1gr yields 7Kcal of energy); high doses are required for effects
What describes the physical dependence of alcohol abuse?
A withdrawal syndrome upon abrupt discontinuation of intake, severity is proportional to level of intake; Two phases: initial symptoms appear within 12-72hrs, peal effects seen 24-48hrs after the start of symptoms, recovery within 5-7days (death can occur)
What effects are seen in a patient on Disulfiram who drinks ethanol?
HA, sweating, respiratory difficulties, n/v, chest pain, thirst, vertigo, orthostatic syncope –
these effects are due to the blocking of acetaldehyde dehydrogenase creating an elevation of blood acetaldehyde
What are treatment options for alcoholism?
Disulfiram: requires highly motivated patient, production of aldehyde syndrome, compliance is a major problem, requires close patient supervision; Naltrexone: blocks reward pathways (?); SSRIs: effective in some patients; 12-step approach: AA
What are CNS complications of chronic alcoholism?
Wernicke encephalopathy and Korsakoff’s psychosis – treat with massive doses of thiamine
What characterizes chronic alcoholism?
Physical dependence and withdrawal syndrome, liver cirrhosis (liver damage in 100%, cirrhosis in 20%), cardiovascular manifestations, nutritional problems, dehydration
What is the treatment of alcohol abuse withdrawal?
Slowly reduce ethanol dose; Switch to another CNS depressant (benzodiazepines are first choice)
What are the endocrine effects of ethanol?
Produces substantial effects on nearly every endocrine system; Chronic ethanol can produce gynecomastia and testicular atrophy; Interferes with the release of prolactin, GH, and ADH
What is the treatment of acute ethanol overdose?
Enhance elimination: gastric lavage, hemodialysis (in extreme cases); Supportive care: maintain respiration/perfusion, prevent aspiration of vomitus, maintain fluid balance, metabolic acidosis can be corrected with sodium bicarbonate, decrease intracranial pressure with mannitol
What signs/symptoms are associated with acute ethanol intoxication?
At blood level >0.25 g/dl: emesis, anesthesia, coma, hypotension (direct effect on peripheral vessels), decreased cardiac contractility (can have atrial/ventricular arrhythmias), respiratory depression (can be immediate cause of death)
What is the Mellanby effect?
The degree of intoxication is worse as your alcohol content goes up, then it is as it goes down
What characterizes Acamprosate?
Used for the treatment of alcohol dependence; Decreases glutamatergic transmission and modulates neuronal hyperexcitability during withdrawal – modestly effective; adverse effects incl. diarrhea (MC), suicidal ideation (rare), teratogenic (in animals), no potential for dependence/abuse
What can ingestion of ethylene glycol lead to?
Coma, death, acute renal failure; Ethylene glycol is also broken down by alcohol dehydrogenase, but at a lower rate than ethanol
What is the treatment of methanol poisoning?
Maintain airway, immediate infusion of sodium bicarbonate, administer large doses of ethanol soon after (if signs of toxicity are present, it’s too late), hemodialysis in severe cases, emesis can be attempted in a conscious patient if treatment is initiated shortly after ingestion
What characterizes methanol poisoning?
Initial symptoms: mild drunk; Methanol is metabolized like ethanol but its metabolites are more toxic --> retinal damage and metabolic acidosis; toxic symptoms appear within 3-36hrs, can see CNS toxicity (due to methanol) and other toxic effects (due to methanol metabolites); Immediate cause of death is respiratory arrest
What characterizes Fetal Alcohol syndrome?
Incidence: 4-7/1000 live births in US; Diagnosis is based upon three features: microcephaly, prenatal growth deficiency, short palpebral fissures – definitive risk above 3 oz/day
What are control strategies for antimicrobial resistance?
Educational/persuasive strategies: conferences, feedback, guidelines; Facilitative strategies: clinical specialists, computer help-screens; Power strategies: automatic stop orders, formularies, restriction of use by requiring approval
What can occur with overuse of third generation Cephalosporins?
Gram+ side: Enterococcus will not be covered (since it is naturally resistant) allowing it to overgrow --> subsequent treatment with Vancomycin can create VRE;
Gram– side: Klebsiella/E. coli with β-lactamases have resistance --> subsequent coverage with Carbapenems can lead to overgrowth of Acinetobacter, fungi, yeasts
What is the best way to control person-person spread of bacterial resistance genes?
Infection control policies (e.g. hand washing, isolation)
How can resistance genes be transferred from one bacterium to another?
Transfer of free DNA; Plasmid transfer; Transfer by viral delivery
What are the 4 basic mechanisms by which antimicrobial resistance occurs?
Stop entry of drugs (e.g. β-lactams/Pseudomonas); Efflux pumps (e.g. Tetracyclines, Quinolones); Destroy drugs (e.g. β-lactamases); Modify drug target (e.g. VRE)
How much of antibiotic use is inappropriate?
41%
What is the key distinction between antibiotics and antimicrobials?
Antibiotics: products of nature used for protection by certain microbial organisms (e.g. penicillin);
Antimicrobials: broader group that includes all medications against microbial organisms
What is the only way to truly eradicate resistant organisms?
Through the use of the immune system
What antibiotics should be used for the outpatient treatment of CA-MRSA?
Bactrim or Clindamycin (not Cephalexin)
What treatment shift has occurred regarding C. difficile colitis?
From Metronidazole to Vancomycin – C. difficile colitis has become much more virulent recently
What differential diagnosis should be thought of in a non-febrile patient with a high white count/left shift and diarrhea?
C. difficile colitis
How are total antimicrobial use and policies in a hospital reflected?
By the hospital C. difficile burden
How can a patient acquire C. difficile colitis?
Through the use of antibiotics, or by contact with affected patients
What organisms are often associated with a nosocomial or ventilator-associated pneumonia?
Gram– rods (e.g. Pseudomonas, Acinetobacter); some have no effective treatment options; resurgence in Polymyxin use seen (older drug, more toxic)
When a UTI is resistant to Bactrim and Ciprofloxacin, what other drug can be given?
Augmentin (Amoxicillin/Clavulanate)
What has resulted from antimicrobial pressure generated by the increased use of antimicrobials?
Common (primary) pathogens have become resistant (e.g. S. aureus, Pneumococcus); Opportunistic pathogens have been selected out (e.g. VRE, C. albicans, Acinetobacter)
How has initial antimicrobial treatment changed for acute pyogenic meningitis?
From Ceftriaxone only to Ceftriaxone + Vancomycin
What percent of S. pneumoniae is penicillin-resistant?
Up to 30%
What percent of people in the US has asthma in 2005?
7.7% (11.2% lifetime diagnosis) – black people have more ER visits and greater mortality associated with asthma (due to health care delivery disparities)
What is the importance of the late phase of an allergic reaction?
The involvement of cells like eosinophils and basophils cause airway inflammation and can cause chronic damage to the lungs
What happens in the late phase of an allergic reaction?
Chemotactic factors attract inflammatory cells to the site of allergen exposure;
(the early/immediate phase reactions are due to activation of mast cells)
What process is central to airway hyperresponsiveness and obstruction seen with asthma?
Inflammation
What is meant by the term atopy?
A genetically determined state of hypersensitivity to allergens (i.e. a tendency to develop IgE in response to environmental antigens)
Which cytokines control the balance between TH1 and TH2?
TH1 produces IFN-γ which downregulates TH2; TH2 produces IL-4 which downregulates TH1
What is the hygiene hypothesis of asthma?
Since children aren’t exposed to the same number of infections as they were in the past, there is a decrease in the TH1 response, which leads to an increase in TH2; this leads to excess IL-4 production which causes an increase in B cell switching to IgE, thus inducing allergy/asthma
What are markers of severe antimicrobial pressure?
Fungemia and VRE line sepsis
What are the different types of asthma?
Atopic (extrinsic), Non-atopic (intrinsic), Drug-induced, Occupational
What are the key features of asthma?
Chronic relapsing inflammatory disorder characterized by hyperreactive airways and episodic, reversible airway obstruction
What are the key indicators for considering a diagnosis of asthma?
Wheezing; h/o cough (at night), recurrent wheezing/difficulty breathing/chest tightness; Triggers; Symptoms worsen at night (awaken the patient)
What are creola bodies?
Compact clusters of desquamated columnar epithelial cells seen in asthmatic sputum
What type of cell is found in expectorated sputum of an asthmatic?
Eosinophils – eosinophil breakdown causes the release of eosinophil lysophospholipase (Galectin 10) which forms needle-like crystals known as Charcot-Leyden crystals
What is seen in a positive allergy skin prick test?
Wheal-and-flare reaction (IgE hypersensitivity, seen 15 min after prick)
What is a key feature of airway instability with asthma?
“Twitchy airways” – measured by methacholine challenge
What are additional studies for the diagnosis of asthma?
Assessment for IgE-sensitization to environmental allergens; Pulmonary function testing for bronchial hyperreactivity (methacholine testing, ambulatory expiratory peak flow monitoring); Assessment for airways inflammation (exhaled NO, sputum evaluation)
What physical exam features are indicative of asthma?
Coughing, wheezing; Prolonged forced expiration; Use of accessory muscles; Retractions; Hyperexpansion of the chest; Signs of other allergic diseases (atopic dermatitis, rhinitis)
Why do patients with asthma have difficulty breathing?
Their airways constrict, they have mucosal edema, and mucus plugging
What is the pathophysiology of aspirin-induced asthma?
Blocking the COX pathway shunts AA to the LPO pathway, thus producing leukotrienes – these patients often have nasal polyps and sinus disease along with asthma
What changes are seen in patients with chronic asthma?
An increase in goblet cells and hypertrophic bronchial glands, basement membrane thickening and sub-epithelial fibrosis, hypertrophy/hyperplasia of smooth muscle, as well as eosinophilic/lymphocytic inflammation
How is the treatment of asthma determined?
Severity is assessed (i.e. intermittent, mild, moderate, severe) and the appropriate Step is followed to try to normalize the patient’s life as much as possible – the amount of SABA used on a daily basis is indicative of the risk of hospitalization; proper control of asthma involves a written action plan made together with each patient
What medications are used as needed for the treatment of asthma?
Quick relief: short-acting β2-agonists (SABA); Severe exacerbations: systemic corticosteroids
What medications are used in the long-term treatment of asthma?
Corticosteroids (inhaled/systemic), Cromolyn/Nedocromil, Long-acting β2-agonists, Methylxanthines, Leukotriene modifiers
What is the goal of drug treatment for asthma?
Control inflammation
What additional information should be collected after the diagnosis of asthma has been made?
Identify precipitating factors (e.g. exposures); Identify comorbidities that may aggravate asthma (e.g. sinusitis, rhinitis, GERD); Classify asthma severity
What is an important differential diagnosis for asthma to remember in children?
Foreign body in trachea or bronchus
What are the biggest areas of use regarding antimicrobials?
50% animal husbandry (for growth); 50% human use
What can occur with overuse of third generation Cephalosporins?
Gram+ side: Enterococcus will not be covered (since it is naturally resistant) allowing it to overgrow --> subsequent treatment with Vancomycin can create VRE;
Gram– side: Klebsiella/E. coli with β-lactamases have resistance --> subsequent coverage with Carbapenems can lead to overgrowth of Acinetobacter, fungi, yeasts
Why do patients with asthma have difficulty breathing?
Their airways constrict, they have mucosal edema, and mucus plugging
What is the mechanism of action of the β-adrenoceptor agonists?
β2-adrenoceptor activation elevates cAMP, causing relaxation of airway smooth muscle; the increase in cAMP also inhibits release of inflammatory mediators, but to a lesser degree (in fact, the late phase process will still occur when β-adrenoceptor agonists are taken in the early phase)
What is the clinical use of the Theophylline?
Patients who are not responding to first-line therapy
What are the Methyl xanthines and what are possible explanations for their mechanism of action?
Theophylline, Aminophylline, (Caffeine); there are three explanations for the mechanism of action: cAMP phosphodiesterase inhibition (=smooth muscle relaxation), blockade of adenosine receptors (=bronchodilation), increased histone deacetylase activity (=decreased cytokine gene transcription, prevailing theory)
What adverse effects are associated with the β-adrenoceptor agonists?
Nonselective β-agonist effects: tachycardia, hypotension, palpitations;
Effects when taken PO: tremors
What are the classifications of the β2-selective agonists?
Short-acting β-agonists (SABA): onset of action is within seconds of being inhaled;
Long-acting β-agonists (LABA): not for acute bronchospasm, delayed onset, used for chronic prophylactic therapy – the β2-selective agonists can often be identified by the ending “–terol”
When is Epinephrine used clinically regarding asthma?
In the emergency management of asthma accompanied by anaphylaxis (since it causes less hypotension than β-agonists)
What are the clinical uses of β-adrenoceptor agonists?
Short-term relief/management of bronchospasm, Emergency room management of severe bronchospasm, Prophylaxis of bronchospasm (e.g. exercise-induced asthma)
What are the goals of asthma therapy?
Control symptoms and prevent exacerbations (status asthmaticus), normalize lung function and decrease airway hyperresponsiveness, normalize exercise intolerance, avoid nocturnal symptoms and sleep reduction, minimize drug side effects
What therapeutic agents are part of the bronchodilator class?
β-adrenoceptor agonists, Methyl xanthines, Anticholinergic drugs
What is an inhalation therapy disadvantage?
Airway obstruction (mucus plugging) limits delivery
What adverse effects are associated with Ipratropium?
Dry mouth, cough
What mechanisms of action and effects have been proposed for the anti-inflammatory drugs Cromolyn Sodium and Nedocromil?
May block chloride channels; Mast cell “stabilizer” (prevents mediator release); Prevents late-phase response and airway hyperreactivity; May interfere with C-fiber sensory nerve reflex; May exert an inhibitory transcriptional effect on leukotriene synthesis
What adverse effects are associated with Glucocorticoids?
Inhalation: few adverse effects, except occasional oral candidiasis; Systemic/high dose inhalation: osteoporosis, weight gain, HTN, DM, myopathy, psychiatric disturbances, skin fragility, cataracts
What is the difference in the clinical use of inhaled vs. oral/IV Glucocorticoids?
Inhaled: first-line prophylactic therapy in mild asthma – e.g. flunisolide, budesonide;
Oral/IV: oral in severe asthma, IV in status asthmaticus – e.g. hydrocortisone, prednisone
What are the single-dose and chronic-dose effects of Glucocorticoids?
Single-dose: attenuates late-phase response; Chronic-dose: inhibits immediate response, reduces bronchial hyperreactivity, and inhibits the inflammatory response
What is the mechanism of action of Glucocorticoids?
Prevents the synthesis of NF-κB-dependent cytokines by increasing histone deacetylase activity;
also may prevent “down-regulation” of β-receptors, thought to be decreased in asthmatic airways
What effect does the administration of anti-inflammatory drugs have on asthma?
It prevents chronic inflammatory processes from occurring, thus reducing the effects of the late phase response; it does not provide immediate relief of an acute attack, but can provide chronic relief of the early phase response; it does not cause bronchodilation – anti-inflammatory drugs are used in the management of status asthmaticus
What adverse effects are associated with the Methyl xanthines?
Plasma levels are unpredictable from dose and are affected by hepatic metabolism; they have a narrow margin of safety, and can cause nausea, HA, arrhythmias, seizures
How is Ipratropium administered?
Via inhalation, thus reducing systemic absorption and CNS effects; given in combination with a β2-adrenoceptor agonist (since Ipratropium has a slower onset; however, it has a longer duration)
What anticholinergic drug can be used for the treatment of asthma and what are its effects?
Ipratropium: blocks muscarinic receptors, non-selective (M3: blocks bronchoconstriction,
M1: blocks mucus secretion) – has little effects on the late-phase response
How does Zileuton prevent the synthesis of leukotrienes?
It is a 5’-lipoxygenase inhibitor – it also blocks the synthesis of LTB4 which has anti-inflammatory properties
With a patient in Step 5 or 6, what can be given if they have allergies to standard treatment?
Omalizumab
Why will a patient in Step 5 or 6 probably not go down to Step 4?
Because lung remodeling has done permanent damage
In the Step Up therapy approach to asthma, what is the final drug added (i.e. in Step 6)?
Oral glucocorticoids
When is Omalizumab used?
As an alternative therapy for mild/severe asthma not controlled by inhaled steroids and LABA
What is the mechanism of action of Omalizumab?
It is an anti-IgE antibody, which means it binds to IgE and prevents it from attaching to mast cells, thus inhibiting the release of inflammatory mediators
What is the major concern with the leukotriene receptor antagonists as well as with the leukotriene synthesis inhibitor?
When patients with Churg-Straus syndrome are tapered off these medications, symptoms of the syndrome which were previously suppressed may surface leading to necrotizing vasculitis, skin rash, pulmonary inflammation, eosinophilia, and heart failure
What are the clinical uses of Cromolyn Sodium and Nedocromil?
Alternative therapy for prophylaxis of mild/moderate asthma (e.g. with exercise-induced asthma); Can be given to children to avoid the adverse effects of steroid therapy (although they are less effective than steroids) – always given via inhalation
When are the leukotriene receptor antagonists used?
When patients cannot tolerate inhaled steroids – however, they are less efficacious
What are the leukotriene receptor antagonists and what is their mechanism of action?
Zafirlukast, Montelukast, (Pranlukast); MOA: as leukotriene receptor antagonists (block CysLT1 receptor) they prevent the effects of LTC4, LTD4, and LTE4
What is the therapy for emergency management of asthmatic exacerbations (status asthmaticus)?
Inhaled SABA (or terbutaline/epinephrine if mucus plugging is a problem); Conventional IV steroids; also, consider theophylline (IV as aminophylline) and ipratropium
What drugs are used in the treatment of COPD?
Ipratropium/tiotropium, β2-agonists (SABA/LABA) – used in combination therapy; Theophylline (may improve exercise performance); Glucocorticoids (less effective); Oxygen (causes free radical formation); Mucolytics (acetylcysteine)
What are contraindications/cautions in the asthmatic patient?
Aspirin: blocking of COX will
shunt AA metabolism to leukotriene synthesis;
Non-selective β-adrenoceptor blockers: may provoke bronchoconstriction
What are the clinical manifestations associated with typical pneumonia?
Sudden onset of fever, chills, cough, purulent sputum, pleuritic chest pain, findings of pulmonary consolidation
What is the treatment for community-acquired pneumonia?
Azithromycin/Clarithromycin/Doxycycline
What are the clinical criteria for ventilator-associated pneumonia (VAP)?
Mechanical ventilation >48-72 hours; Fever; Leukocytosis/Leukopenia; Purulent sputum; Growth of a pathogen; Infiltrates for >24 hours
What characterizes hospital-acquired pneumonia?
Occurs >48 hours after admission – Early onset (<5days): Strep pneumo, H. flu, Oxacillin-sensitive Staph aureus; Late onset (>5days): Gram– bacilli, Oxacillin-resistant Staph aureus
What clinical signs associated with pneumonia are indications for hospitalization?
Confusion; Respiratory rate >30; BP <90/60; Age >65
Which pneumonia-associated bacteria can be detected by urinary tests?
Pneumococcal antigen, Legionella antigen
What are the clinical manifestations associated with atypical pneumonia?
Gradual onset of cough accompanied by extrapulmonary symptoms (e.g. HA, myalgia, fatigue, sore throat, GI symptoms, skin manifestations, renal/hepatic abnormalities)
What is the term used when the “syndrome” of pneumonia is not caused by an infectious agent?
Pneumonitis
What associations can be made between organisms causing pneumonia and risk factors?
Most frequent CAP agent: pneumococcal pneumonia; College student/wheezing: Chlamydia pneum.; COPD: H. flu; Stoke/poor teeth: anaerobes; Infants <6mo: respiratory syncytial virus;
HIV: Pneumocystic jerovecii; Cystic Fibrosis: Pseudomonas cepacia; Ventilator associated pneumonia: Staph aureus; Neutropenia: Aspergillus; Military: Mycoplasma pneumoniae
What are the four most important mechanisms of transmission associated with pneumonia?
Aspiration, Inhalation (most important), Hematogenous dissemination, Direct inoculation
What happens during the compressive and expulsive phases of cough?
Compressive: glottis closure, expiratory muscle contraction; Expulsive: glottis opens, lungs clear
How is the diagnosis of GERD made?
Response to therapy, ambulatory esophageal pH monitoring
What diseases are associated with night sweats?
TB, lymphoma, GERD
What are the most common causes of post-nasal drip (PND)?
Sinusitis > perennial non-allergic rhinitis > allergic rhinitis > drugs/environmental irritants
What are the most common reasons for chronic cough?
PND > asthma > GERD >chronic bronchitis > bronchiectasis
What diagnostic tools are used for the differential diagnosis of cough?
CXR, sinus/allergy evaluation, spirometry, upper GI evaluation, sputum culture, EKG, bronchoscopy
How can GERD cause cough?
By stimulating the terminal esophagus thus initiating the cough reflex
What drugs can be used for the initial empiric treatment of early onset VAP?
If no suspicion of MDR organisms: Ceftriaxone and a macrolide
What is the anatomy of cough?
Mechanical/chemical stimulation --> vagus n. --> tractus solitarius --> medulla oblongata (“cough center”) --> cough
What are the different types of cough?
Acute (<3weeks): common cold, pneumonia, pertussis, PE, CHF; Chronic (>3-8weeks): non-infectious (postnasal drip, bronchial asthma, GERD, drugs, interstitial lung disease), infectious (post-infectious cough, pneumonia, chronic bronchitis, bronchiectasis, Tb, tropical problems), tumors
What characterizes eosinophilic bronchitis?
Chronic cough, negative work-up (incl. spirometry and MCT), sputum eosinophilia >3%, response to inhaled corticosteroids
What are non-pulmonary causes of dyspnea?
Heart disease (LV failure, valvular disease, etc.), anemia, high altitude, obesity, febrile state, metabolic acidosis, sepsis, hepatic failure, intra-abdominal pathology, de-conditioning, anxiety
What characterizes paroxysmal nocturnal dyspnea?
Occurs 2-4 hours after lying down, usually cardiac in origin (heart failure)
What is platypnea?
Dyspnea when erect, relieved by recumbence (can be seen with liver disease)
What is a sign of hyperventilation/decreased CO2?
Tingling, numbness
What are chronic causes of dyspnea?
COPD, asthma, interstitial lung disease, occupational exposures
What are acute causes of dyspnea?
Trauma, smoke inhalation, bronchospasm, infection, PE, airway obstruction, heart failure
What are common pulmonary causes of dyspnea?
PE, pulmonary hypertension, chest wall dysfunction (e.g. trauma), diaphragm dysfunction (e.g. ascites), neuromuscular disorders (e.g. myasthenia), inhalation of toxic/irritant chemicals, cancer
What is dyspnea?
The patient’s perception of shortness of breath (sense of labored, uncomfortable, difficult breathing for an inappropriate setting); also defined as the failure of the respiratory system to provide adequate gas exchange to meet the body’s demand
What airway problems can be responsible for dyspnea?
Upper airway: airway obstruction, increased resistance; Lower airway: foreign body, tumor of trachea/bronchi; Parenchymal problem
What CNS problems can be responsible for dyspnea?
Increased breathing: acidosis, toxins, hypoxemia, hypercarbia, CVA, drugs (e.g. aspirin);
Decreased breathing: sleep apnea, tumor, drugs (e.g. narcotics, sedatives)
What are predisposing factors to dyspnea?
Diabetes, renal/liver failure, CNS problems, bleeding, anxiety
How is diagnosis of pneumothorax made?
Hyperresonance to percussion, decreased/absent breath sounds, x-ray confirmation
Which form of oxygen therapy can give a maximum oxygen concentration of 100%?
CPAP facemask
What may stridor indicate?
Upper airway obstruction
How is subcutaneous air distinguished from subcutaneous fluid?
Air will create crackles, whereas fluid will create a fluid wave
What does a tracheal shift indicate?
To same side: atelectasis; To opposite side: pneumothorax, hemothorax, pleural effusion
What is the scale used to grade dyspnea?
Modified Borg scale or American Thoracic Society SOB scale
What characterizes orthopnea?
Dyspnea precipitated by lying down; patients will use pillows to prop themselves up, usually a sign of CHF
What species of Acinetobacter is often responsible for infection?
A. baumannii (preferentially colonized aquatic environments)
What characterizes the clinical picture of a Pseudomonas infection?
2nd most common cause of nosocomial pneumonia (greatest mortality/morbidity, most common cause of ICU pneumonia); Symptoms: chills, fever, productive cough, dyspnea, blue-tinted skin;
Most common pathogen isolated from patients hospitalized >1wk; causes 10% of nosocomial infections
What is the treatment for Acinetobacter infections?
Generally self-limited; however, treatment for severe infections is difficult since Acinetobacter is inherently multi-drug resistant (due to resistant gene island) – remove infected lines/drains/shunts
Where is Acinetobacter normally found?
Skin, oropharynx, respiratory secretions, urine
How is the diagnosis of Acinetobacter made?
Isolation of the organism from blood/lymph nodes is diagnostic; When isolated from any surface area, it is not diagnostic since it can grow there normally
How is Acinetobacter transmitted?
Colonizes irrigating/IV solutions; colonizes patients in ICU; associated with wound infections
What describes the disease associated with Acinetobacter?
Opportunistic pathogen, infections are rare, associated with immunocompromised patients;
low virulence, disease manifestation depends on site of infection (e.g. pneumonia, bacteremia)
What are examples of ways a host can become compromised and allow opportunistic infections to grow?
Damage to epithelium, introduction of bacteria to sites where they are not normal flora (catheters, prosthesis, biofilms), antibiotic use, immunosuppression by drugs, impairment of host defenses by infection
What characterizes
Acinetobacter?
Gram– coccobacillus, strict aerobe, non-motile, found in soil/surface water/sewage/foods
When a patient presents with a bacterial infection and has recently been overseas in the military service, what organism should be part of the differential?
Acinetobacter
How is the diagnosis of Pseudomonas aeruginosa presence made?
Nature of disease, isolation of bacteria; Forms smooth, fluorescent green colonies at 42° (differentiates P. aeruginosa from other Pseudomonas); Characteristic sweet (grape-like) odor
What is exotoxin A?
AB-toxin that transfers ADP-ribose to EF-2, inactivating protein synthesis (like diphtheria toxin); however, exotoxin A binds to α2-macroglobulin (found mainly in animals), thus making it less toxic to humans (as opposed to the DT receptor of diphtheria toxin, which is much more prevalent in humans)
What characterizes the genome of P. aeruginosa?
It reflects adaptability (contains many regulatory genes) and innate antibiotic resistance (contains many genes involved in transport catabolism, efflux pumps); P. aeruginosa found in biofilm with CF patients has lost a significant portion of its genome (as opposed to the free-living organisms)
What P. aeruginosa virulence factors are responsible for acute and chronic infection?
Acute: LPS, pilin/non-pilin adhesins/flagella, innate antibiotic resistance, exotoxin A, proteases, leukocidin, pyocyanin, hemolysins, T3S effectors, quorum sensing (bacterial communication);
Chronic: type IV pili, biofilm formation, quorum sensing, alginate (mucopolysaccharide coat)
What extracellular products are made by P. aeruginosa?
Exotoxin A (AB-toxin), proteases (elastase, alkaline protease), hemolysins, pyocyanin (metal chelators, for competition against other bacteria), Type III secretion system (T3S effectors)
What virulence factors are associated with P. aeruginosa?
Flagellum, LPS, alginate (type IV pili for establishment of biofilms), non-pilus adhesions, polar pili (twitching motility)
What people are affected by Pseudomonas aeruginosa?
Hospitalized patients, immunocompromised patients, patients with CF
What types of infections can be caused by Pseudomonas aeruginosa?
Lung; Heart/blood; Bone/joint; CNS; Eye/ear (contact lens infection, “swimmer’s ear”);
Urinary tract (catheters); Skin/soft tissue (green nail syndrome, hot tub dermatitis);
Burn infections
How is Pseudomonas aeruginosa transmitted?
It is a ubiquitous, highly adaptable organism, can survive in aquatic environments
What characterizes Pseudomonas aeruginosa?
Gram– rods, motile aerobe (can grow anaerobically using nitrate), catalase/oxidase positive,
non-fermentor, nutritional diversity, important in toxic waste degradation
What causes CF and how is the disease characterized?
Mutation in CFTR gene – lethal autosomal recessive disease (mainly in Caucasians); characterized by pulmonary obstruction, pancreatic exocrine deficiency, high Na/Cl in sweat, male infertility
What cells are particularly affected by P. aeruginosa?
Tumor cells
What is the treatment used for P. aeruginosa infection?
Fluoroquinolones, Amoxicillin, Aminoglycosides (– for severe infections, use 2);
Recently, Macrolides have come into use (e.g. Azithromycin, mechanism unknown)
What happens when P. aeruginosa enters the lungs of a patient with CF?
Binds asialo GM1 glycolipid (increased in CF), activates/internalized by CFTR expression cells (decreased in CF), the organisms then increase alginate expression, alter LPS expression, decrease expression of proteases/toxins, and alter their genome
What bacterial infections are common in patients with CF?
First: Staph aureus; Second: H. flu; Third: P. aeruginosa; Fourth: Burkholderia cepacia;
Finally: Stenotrophomonas maltophilia, Ralstonia pickettii, Burkholderia gladioli
What is the most frequent mutation that leads to CF?
ΔF508: not a severe mutation, but altered protein is recognized as non-functional , not modified in the ER, and subsequently degraded
What is the main cause of morbidity in CF lung infections?
P. aeruginosa infection
546. What effectors are secreted by the type III secretion mechanism of P. aeruginosa?
ExoS: GAD/ADP-ribosyltransferase (targets Ras/Rho, inactivates cell function);
ExoT: GAD/ADP-ribosyltransferase (targets Crk/Rho, inactivates cell function);
ExoU: PLA2 (cytotoxic); ExoY: adenylate cyclase (increases cAMP)
What is the most important P. aeruginosa virulence factor regarding CF patients?
Alginate (polysaccharide polymer): provides bacterial protection against phagocytosis and opsonization; can also be induced in nature to provide protection against dehydration
What is the function of quorum sensing by P. aeruginosa?
As bacterial density increases, the concentration of quorum sensing molecules (homoserine lactones) increases; this signal indicates that nutrients will soon become depleted, and the molecules alter transcription to induce more virulence factors (incl. LasA, LasB, alkaline protease, ETA, pyocyanin)
What is meant by Coley’s toxins?
S. pyogenes/Serratia marcescens (killed): used in the treatment of sarcomas/lymphomas due to their predilection for tumor cells (not effective against carcinomas/melanomas)
Why is the Pseudomonas T3S mechanism more effective in cancer cells?
Cancer cells (like healing epithelium) are moving cells; the leading edge of these cells contains pores that facilitate entry of the T3S translocon; this makes the T3S mechanism a candidate for the delivery of anti-tumor drugs
How are anaerobic bacteria effective in cancer treatment?
They work in solid tumor that include large hypoxic, poorly vascularized regions – e.g. Clostridium novyi: COBALT treatment, CDEPT (Clostridium, Cytosine Deaminase, 5-FU)
What is Bacillus Calmette-Guerin (BCG, attenuated M. bovis) used to treat?
Superficial bladder cancer (applied directly to tumor site, induces complex immune response)
What are the requirements for live bacterial anti-tumor agents?
Selective toxicity to tumor cells, infect/multiply within tumor, function at low numbers,
sensitive to antibiotics
By what mechanism do Coley’s toxins cause tumor destruction?
There is an induction of the immune response due to the presence of the pathogen leading to a cytokine cascade and diverse cellular/humoral immune responses (they shift the immune response balance to defensive mode)
Why are children and immunosuppressed patients given INH irrespective of PPD status?
Because they may not react to the protein derivative
What should the air pressure be in the OR?
Positive pressure in order to maintain clear air and prevent outside air from entering
What can shaving of skin pre-operatively increase the risk of?
MRSA infection
How is Varicella transmitted?
Airborne route and direct contact
What is the incubation period of Varicella?
10-21 days; with ZIG: up to 28 days
What is the purpose of ZIG?
Zoster immune globulin: given to immunocompromised patients and in pregnancy in order to prolong the incubation period of Varicella; also given to newborns whose mother developed chicken pox 5 days before-2 days after delivery, and in premature infants
What is a large problem with Varicella transmission?
The patient is infectious a couple of days before the characteristic rash develops; possible transmission continuous until all of the lesions have crusted
Who should receive INH prophylaxis for suspected TB?
Recent converters and <35yo with positive PPD; also >35yo with underlying disease that predisposes to TB reactivation
What is meant by the “ring approach” to PPD testing?
In the case of widespread exposure over a short period of time, the people in closest contact to the exposure will be tested first; if they are positive, then the next closest group of people will be tested, and so on
What should be done with people who have been exposed to a patient with TB?
PPD skin testing immediately, and if negative again at 3 months (if positive, give INH)
How do healthcare-acquired blood stream infections most often come about?
Catheters (e.g. central venous catheters) – most common organism is S. aureus
What is included in the Institute for Healthcare Improvement (IHI) central line “bundle”?
Hand hygiene, maximal barrier precautions, chlorhexidine skin antisepsis, optimal catheter site selection, daily review of line necessity
What is the difference between sterilization and disinfection?
Sterilization: complete elimination/destruction of all forms of microbial life (incl. spores);
Disinfection: elimination of many/all pathogenic microorganisms on inanimate objects with the exception of bacterial endospores
Why has C. difficile become a problem?
It makes heat-resistant spores, and has become more resistant to quinolones
Which organism has become much more virulent in recent years?
C. difficile
What is the leading cause of death with HAI?
Ventilator-associated pneumonia – most common organisms are Gram– rods
What is the most common HAI and how does it come about?
UTI from Foley catheter – most common organisms are Gram– rods
What should the air pressure be in the OR?
Positive pressure in order to maintain clear air and prevent outside air from entering
What percent of hospitalized patients will get a healthcare associated infection (HAI) and what are the most common sites of infection?
5%; most commonly in urinary tract, blood stream, lower respiratory tract, surgical sites
What type of study should be done with an infection control investigation?
Case-control
What is included in the IHI VAP “bundle”?
Elevate head of bed (30-45°), daily “sedation vacation”/daily assessment of readiness to extubate,
PUD prophylaxis, DVT prophylaxis – caused 45% decrease in VAP incidence
What is included in the IHI surgical site infection “bundle”?
Antimicrobial prophylaxis (1 hr before surgery), avoid shaving of surgical site, maintain perioperative serum glucose (for major cardiac surgical patients), immediate post-operative normothermia (colorectal surgical patients)
Which pathway is most important in the treatment of negative symptoms with schizophrenia?
Serotonin pathway
Why is Clozapine a difficult medication to use?
It requires close blood monitoring – also, a life-threatening agranulocytosis can develop (as well as myocarditis, cardiomyopathy, DVT, pulmonary embolism)
Which atypical antipsychotic is safer to use in the elderly and why?
Quetiapine, because of its low EPS effects
What side effect is specific for Ziprasidone?
Prolongs the QT interval
What characteristics are associated with low potency (e.g. Chlorpromazine) typical antipsychotics?
Fewer EPS (extrapyramidal signs), more sedation, and more anticholinergic effects – whereas high potency drugs (e.g. Haloperidol) will have more EPS, and less sedation/anticholinergic effects
What is a key difference between the typical and atypical antipsychotics?
Although they have the same effectiveness, the atypical antipsychotics have fewer side effects (they are also more expensive)
Which atypical antipsychotics have a greater chance of causing a metabolic syndrome?
Clozapine and Olanzapine (inferred from their effects on weight gain) – the lowest weight gain is associated with Aripiprazole and Ziprasidone
Which dopaminergic pathway is involved in the positive symptoms of schizophrenia?
Mesolimbic pathway: connects the ventral tegmental area of midbrain to the nucleus accumbens in the limbic system
Which dopaminergic pathway is involved in the motor side effects (EPS) of schizophrenia?
Nigrostriatal pathway: connects the substantia nigra to the striatum – treatment for schizophrenia (i.e. drugs that decrease dopamine) can result in Parkinson-like signs/symptoms
Which dopaminergic pathway is involved in the negative symptoms of schizophrenia?
Mesocortical pathway: connects the ventral tegmental area of the midbrain to the frontal lobes
During what time period can a diagnosis of adjustment disorder with depressed mood be made?
Between 3 and 6 months
What are characteristics of Venlafaxine?
SSRI/SNRI, associated with a Serotonin withdrawal syndrome
What are characteristics of Sertraline?
Very little CYP interaction, is used for many diagnoses
What are characteristics of Mirtazapine?
Sedating at low doses, energizing at higher doses – very little CYP interaction
What are characteristics of Fluoxetine?
Long half-life, high incidence of sexual dysfunction
Which antidepressant acts on both the NE and DA systems and can be used to quit smoking?
Buproprion – has low sexual side effects, but has a black box warning for eating disorders and seizure disorders, since it lowers the seizure threshold
What diagnosis should be made in a patient who presents with a 7 month history of tearfulness, feelings of hopefulness, poor sleep, and weight loss?
Major depressive disorder
What is a positive aspect of Clozapine use?
It is very effective at reducing the suicide rate (benefits outweigh risks in a treatment-resistant schizophrenic)
During what time period can a diagnosis of bereavement be made?
<2 months
How long do symptoms have to be present to make a diagnosis of dysthymic disorder?
More than 2 years
What can cause neuroleptic malignant syndrome?
The use of antipsychotic drugs – FEVER: fever, encephalopathy (confusion), vital signs unstable (hypotension, tachycardia), elevated creatinine kinase, rigidity (muscle tension);
Treatment: stop the antipsychotic, hydration, can use DA agonist (Bromocriptine)
What is special about Lorazepam?
It is not extensively metabolized by the liver – so it can be used in people whose liver function is questionable (e.g. an alcoholic); Lorazepam is often used for detox or to protect someone from going into withdrawal seizures
What are examples of low inhibitors of P450 enzymes?
Venlafaxine, Sertraline, Citalopram, Escitalopram, Mirtazapine
What are examples of high inhibitors of P450 enzymes?
Fluoxetine, Paroxetine, TCAs, Fluvoxamine (high anticholinergic effects, used for severe OCD)
What are the effects of taking Clarithromycin (Macrolide antibiotic)?
Inhibition of CYP3A4 – this can increase blood levels of Alprazolam causing excess sedation
What are the hallmark signs/symptoms of Serotonin withdrawal?
Dizziness, flu-like symptoms, achiness, insomnia, GI distress, unusual sensations, recurrence of mood/anxiety disorder
What are the hallmark signs/symptoms of Serotonin syndrome?
Lethargy, confusion, diaphoresis, flushing, tremors, myoclonic jerks
What risk factors are associated with fungal infections?
Neutropenia, prolonged antibiotic use, lines, organ transplant/HIV/chronic granulomatous disease, significant environmental exposure (e.g. construction workers, spelunkers)
How does invasive Aspergillosis present?
Necrotizing pneumonia with cavitation
Besides invasive Aspergillosis, what other forms of disease can Aspergillus cause?
Allergic Bronchopulmonary Aspergillosis (ABPA): hypersensitivity reaction, treated with steroids, not anti-fungals; Mycetoma: fungal ball within old cavitary lesion
What differentiates Aspergillosis from a fungal infection caused by Rhizopus?
Aspergillus branches at narrow angles and has septae whereas Rhizopus is non-septate and branches at 90° angles
What treatment would be appropriate in a patient on long-term steroid who present with Cryptococcal meningitis?
AMB with 5-FC, followed by Fluconazole
What treatment would be appropriate in an HIV+ patient with oral Candidiasis?
Fluconazole
Which forms of Candida are resistant to Fluconazole?
C. glabrata, C. krusei
What characterizes the superficial fungal infections?
Known as dermatophytes or tineas/ring worms (e.g. tinea pedis, tinea capitis, tinea unguium = onychomycosis); spread by direct contact; treated with topical medications
With what route of infection is Sporotrichosis associated with?
Trauma (gardener who receives injury from thorn rosebush)
What are the most important deep/systemic fungal infections?
Yeasts: Candida, Cryptococcus
Moulds: Aspergillus, Zygomycosis; Dimorphic fungi: Histoplasmosis, Blastomycosis, Coccidioidomycosis, Sporotrichosis (not endemic)
Which two fungal infections can affect the brain?
Cryptococcus, Coccidioides
How does the dose intensity and total dose differ between fungal infections when treated with Amphotericin B?
Zygomycoses > Aspergillus > Cryptococcus > C. albicans
What is the most broad-spectrum anti-fungal agent?
Amphotericin B – especially for the Zygomycoses after surgical debridement since no other anti-fungal agent is effective
What type of fungal infection is Caspofungin (an Echinocandin) used for?
Non-albicans Candida infections – Caspofungin is not effective against Cryptococcus
What type of fungal infection is Voriconazole used for?
Invasive Aspergillosis
What type of fungal infection is Itraconazole used for?
Dimorphic fungal infections
What characterizes Sporotrichosis?
Caused by Sporothrix schenckii; Worldwide distribution; Presents with peripheral lymphocutaneous lesions that move up the arm; Spreads through lymphatics (sporotrichotic spread); can go deeper and cause an osteoarticular disease
What treatment would be appropriate in a diabetic patient with Zygomycosis?
Aggressive surgical debridement – also supportive anti-fungals
What are predisposing factors to Zygomycosis?
Diabetic ketoacidosis, Iron overload (with multiple transfusions), Deferoxamine use,
Bone marrow transplant patients – all are angioinvasive
What three species are associated with Zygomycosis?
Rhizopus, Rhizomucor, Mucor
What does Guaifenesin cause?
Stimulates secretion of ions/water, Initiates cough
What serious adverse effects are associated with n-Acetylcysteine?
Bronchospasms occur when administered by inhalation (co-administer with SABA);
The drug has a “rotten egg” smell from the sulfide group in its structure, and it has emetogenic effects (n/v) through its actions on the chemoreceptor trigger zone (even when given IV);
Also, drug-induced fever and an anaphylactoid reaction can occur
What adverse effects are associated with Bromhexine?
Inhalation of Bromhexine causes cough/bronchospasm (can give SABA prophylactically);
also dizziness, sweating, skin rash; since it causes disruption of the mucosal barrier, GI disorders can become problematic (caution in PUD)
What are the uses of Bromhexine?
Used in the ICU for respiratory disorders; Through its depolymerization action, it thins mucus thus enhancing penetration of antibiotics into bronchial secretions; It can also be used for dry eye (Sjögren syndrome) associated with abnormal mucus production
What are the primary mucolytics and what are their mechanisms of action?
Bromhexine: hydrolytically depolymerizes mucoproteins (lowering viscosity) and functions as an expectorant (stimulates ion secretion and sputum volume); Acetylcysteine: severs disulfide bonds in mucoproteins to lower viscosity; Dornase Alfa: cleaves DNA tangles which are components of tenacious mucous in CF patients
What adverse effects are associated with Guaifenesin?
Excessive use may cause nephrolithiasis since a Guaifenesin metabolite is a major component of stones; rarely reported are GI disturbances, dizziness, HA, rash – when cough is associated with excessive mucus production (e.g. chronic bronchitis, smoking, emphysema) the patient should be supervised (since mucus clearance can become problematic)
What is Guaifenesin indicated for?
Dry, non-productive cough; but also effective in productive cough – it is often combined with cough suppressants (e.g. dextromethorphan), although this use is debatable since cough helps clear loosened secretions (however, distress of chronic cough may need to be relieved)
What are the classes of drugs that improve mucus clearance?
Expectorants (cause hydration of mucus), Mucolytic drugs (chemically alter mucus), Indirectly acting drugs (reduce mucus production/improve mechanisms of clearance)
What are the expectorants used for mucus clearance?
Hydration, Guaifenesin/Guaiacolsulfonate, Potassium Iodide (not used much due to concern for thyroid dysfunction and lack of efficacy)
What is an effective way to hydrate mucus without the use of drugs?
Use water: drinking, humidification, nebulization (hypertonic saline, also stimulates cough)
What is Dornase Alfa?
A recombinant human DNase (used for the cleavage of DNA tangles in CF)
What adverse effects are associated with pulmonary surfactants?
It can clog the airway as it is administered causing hypoxia; Lowering of surface tension can cause a rapid increase in oxygenation leading to hyperoxia/hypocarbia (can reduce blood flow to brain)
How are pulmonary surfactants administered?
Intratracheally along with cetyl alcohol/tyloxapol to improve spread/adsorption
What are the pulmonary surfactants used to improve mucociliary clearance?
Colfosceril palmitate: synthetic compound (expensive); Beractant: derived from bovine surfactant, so there may be a hypersensitivity reaction (contraindication)
What is unique about Ipratropium when given as an inhalant?
Since it is a quaternary amine, it does not get out of the lungs; it also does not cross the BBB
What are drugs that improve mucociliary clearance indirectly?
Bronchodilators, Anti-inflammatory drugs, Antibiotics, Pulmonary surfactants
What adverse effects are associated with Dornase Alfa?
Contraindicated in patients with hamster protein sensitivity (absolute contraindication);
also conjunctivitis, pharyngitis, fever, dyspnea
When is n-Acetylcysteine used?
With acetaminophen toxicity! (protects liver from reactive metabolite of acetaminophen)
How is the diagnosis of CF made?
Gold standard is sweat test: Westcor Macroduct or Gibson Cook Methods; also useful is DNA mutation testing, nasal potential (NP), newborn screening (immunoreactive trypsinogen – IRT)
What other microbe are associated with CF patients?
Stenotrophomonas maltophilia, Alcaligenes xylosoxidans, Burkholderia cepacia;
rarely: Klebsiella, Serratia, atypical Mycobacterium
What makes a Pseudomonas infection permanent?
Biofilm formation due to an overproduction of alginate
Where does Pseudomonas come from?
Water sources (e.g. showers, toilets, resp. equipment, pools)
What does the presence of P. aeruginosa mean in a CF patient?
It is an independent predictor of clinical deterioration – found in 85% of CF patients by age 16
What characterizes the treatment of Pseudomonas?
The organism is often resistant Ampicillin/Penicillins/Cephalosporins
What microbes are commonly found in young infants and children?
Staph aureus, nontypeable H. flu, Pseudomonas – obtain culture by deep throat swab or bronchoscopy
What characterizes the genetics of CF?
Autosomal recessive: long arm of chromosome 7; Mutation is a 3 AA deletion/change in the coding domain for the CF Transmembrane conductance Regulator protein (CFTR) which leads to a defective chloride channel
What is the pathogenesis of CF?
Defective chloride channel causes apical membranes to be impermeable to Cl, Na and water --> creates dehydrated secretions which leads to abnormal clearance --> this causes air flow obstruction, duct obstruction, destruction of exocrine pancreas, sticky GI luminal contents, and obstructive problems (e.g. GU, liver, gallbladder)
What is the most common mutation seen in CF patients?
ΔF508 (causes a block in CFTR processing)
What characterizes Stenotrophomonas maltophilia and Alcaligenes xylosoxidans?
Emerging pathogens in CF, can be very resistant
What characterizes Burkholderia cepacia?
Known CF person-person spread; 13 known genomovars (III is most virulent); can cause cepacia syndrome: rapid deterioration upon acquisition of B. cepacia; Multi-drug resistant
What is the differential diagnosis for a child with rash and pneumonia?
Rubeola (measles), Rubella, VZV, toxic shock (Staph aureus, Group A Strep), tick-borne illness
What is the number one cause of bronchiolitis and pneumonia in children?
RSV
How is the diagnosis of RSV infection made?
Nasopharyngeal swab: rapid enzyme immunoassay (EIA); followed by PCR testing – viral isolation in culture is possible (3-5 days)
What is the differential diagnosis for apnea and respiratory distress in a 3 week old infant?
Sepsis/meningitis/bacterial pneumonia; Pertussis; Viral etiology: respiratory syncytial virus (RSV), influenza, human metapneumovirus (MPV), adenovirus, parainfluenza virus
What is the incubation period for chickenpox?
10-21 days; highly contagious, spread through respiratory route and vesicular fluid
What is the treatment for chickenpox?
Supportive, IV Acyclovir
How is the diagnosis of chickenpox made?
Mostly a clinical diagnosis; can use Tzanck smear, culture (viral), or serology – can use PCR to differentiate between virus strains
What type of disease in indicated by a rash that has the appearance of a dew drop on a rose petal?
Chickenpox
What is particularly worrisome regarding a chickenpox infection and why?
A fever that resolves and subsequently reappears, since it can be indicative of a secondary bacterial infections (most commonly Group A Strep)
What differentiates a chickenpox rash from a smallpox rash?
In smallpox the vesicles will all be at the same stage of development, whereas with chickenpox they are all at different stages
What immunoprophylaxis is available for RSV?
RSV-IGIV, Palivizumab (high titers of RSV neutralizing antibody)
What frequently follows measles in the developing world?
Malnutrition, diarrhea, FTT; Secondary bacterial pneumonia with Staph aureus
What is the treatment for measles?
Vitamin A supplementation; Supportive care: IV fluids, analgesia, oxygen
What characterizes the transmission of measles?
Incubation period: 8-12 days (usual interval exposure to rash is 14 days); Contagious 1-2 days before onset of symptoms (3-4 days before onset of rash); Transmission by direct spread of infectious droplets, may be airborne
What is the differential diagnosis for exanthemas (skin eruptions)?
Enterovirus, EBV, fifth disease (parvovirus), varicella, rubella, rubeola, rheumatic fever/group A strep, toxic shock syndrome (Staph aureus), Staph scalded skin syndrome, drug reaction, Kawasaki’s disease
What are the characteristic signs of measles?
The three C’s: cough, coryza, conjunctivitis; also photophobia, fever, (morbilliform) rash, Koplik’s spots, otitis media, hoarse voice with frequent cough
What is a good measure of RSV control?
Isolation of hospitalized patients since nosocomial spread is common
What characterizes the transmission of RSV?
Incubation: 2-8 days; Viral shedding 3-8 days (can last 3-4 weeks); Transmission occurs via contaminated secretions, fomites, surfaces (lives on hands >30min, surfaces for hours)
What are the risk factors for RSV?
<6 wks of age, prematurity, congenital anomalies, neurologic disease, chronic lung disease, congenital heart disease
What is the treatment for RSV?
Supportive care: fluids, oxygen, intubation; maybe a β-agonist
What complications are associated with measles?
Otitis media, pneumonia, obstructive laryngotracheitis, acute encephalopathy, thrombocytopenia, death in immunocompromised/HIV/malnourished; also subacute sclerosing panencephalitis (SSPE): degenerative CNS disease that occurs 10.8 years later
How does the resistance of VRE come about?
It has altered the D-Ala D-Ala terminus to D-Ala D-Lac – encoded on the VanA/B/C genes
When will a D-test be performed regarding Staph aureus?
If initial testing shows resistance to Erythromycin but susceptibility to Clindamycin
What does MLS phenotype stand for?
Macrolide lincosamide streptogramin phenotype: found in bacteria that are resistant to those classes of drugs by undergoing target alteration (e.g. through addition of a methyl group)
What are the mechanisms of resistance against protein synthesis inhibitors?
Lack of drug binding with target alterations: erm gene (Erythromycin resistance), MLS phenotype;
Efflux pumps: mef gene (pumps out Macrolides)
What is the problem with protein synthesis inhibitors?
They have to cross the bacterial cell wall
Which antimicrobial agents have activity against VRE?
Synercid, Linezolid, Daptomycin, Tigecycline (also, Chloramphenicol)
What is the danger of using Chloramphenicol?
Aplastic anemia
What do new antimicrobial drugs have in common?
They all have Gram+ activity
Which Enterococcus is usually VRE?
E. faecium
What are the most common nosocomial blood culture isolates?
Coagulase-negative staph (i.e. Staph epidermidis) > S. aureus > Enterococcus > Candida > E. coli
How have Penicillin-resistant pneumococci come about?
Certain strains have developed altered PBPs
What adverse effects are associated with Synercid?
Infusion related side-effects: Arthralgias > Myalgias > Nausea > Pain > Asthenia > Rash
What are the indications for Synercid?
VRE (more frequent dosing), complicated skin infections caused by Gram+ organisms
What is the mechanism of action of Synercid?
Dalfopristin binds to 50S to prevent chain elongation, and it produces a conformational change in 50S; this conformational change increases the affinity for Quinupristin which also binds 50S and prevents polypeptide chain formation (thus there is a synergistic effect) – alone they are bacteriostatic, but together they are bactericidal
What drug interactions are associated with Synercid?
CYP3A4 interaction
What organisms are affected by Synercid?
Gram+ bacteria: Staphylococcus, Streptococci, Enterococcus faecium, VRE; but NOT E. faecalis
What is Synercid composed of?
Streptogramins: Quinupristin/Dalfopristin
What do the results of a D-test indicate, regarding Erythromycin-resistant, Clindamycin-susceptible Staph aureus?
If a D-shaped clearance is formed around the Clindamycin disc, it means that the strain of bacteria has a MLS-type resistance (induced by the presence of Erythromycin), and will thus be resistant to Clindamycin (i.e. there is an inducible resistance); if the clearance around Clindamycin is circular, it means that the Erythromycin resistance is due to an efflux pump and will not affect Clindamycin (since it is structurally different from the Macrolides)
How have certain strains of Staph aureus acquired Vancomycin resistance (VRSA)?
By acquiring the Van A gene (seen in VRE)
By what mechanism do MRSA and MRSE acquire their resistance?
They produce a different PBP (i.e. PBP 2a) for which the β-lactams have no affinity –
it is encoded for by the mecA gene
What characterizes the pharmacokinetics of Linezolid?
It has 100% bioavailability PO, and can be given IV
How does Tigecycline differ from Tetracyclines?
It has an added methyl group that makes it effective in many Tetracycline-resistant strands – it also has a vey broad-spectrum activity: Gram+/Gram–/atypicals/anaerobes
What adverse effects are associated with Daptomycin?
Mild/moderate muscle pain/weakness (monitor CPK levels) seen after about 1 week of treatment
What are the uses of Daptomycin?
Complicated skin infections caused by Gram+ bacteria: Staph (incl. MRSA, endocarditis), Strep, Enterococcus (VSE only) – NOT indicated for pneumonia since lung surfactant renders it inactive
Which drug is part of the Lipopeptide class and what is its mechanism of action?
Daptomycin: irreversibly binds to the bacterial cell membrane forming a pore through which a K+ efflux can take place; this K+ efflux destroys the ion-concentration gradient causing cell death
Besides MAOI effects, what other adverse effects are associated with Linezolid?
Blood dyscrasias: mainly thrombocytopenia – seen in patients who have been on the drug for more than 2 weeks
What are the major adverse effects of Linezolid associated with?
Its weak, reversible MAOI effects: use caution with other MAOIs and drugs that increase serotonin levels (e.g. SSRIs, Meperidine) since they can lead to a serotonin syndrome
What organisms are affected by Linezolid?
Gram+ bacteria: Staph, Strep, Enterococcus, Mainly used for pneumonias and skin infections caused by VRE/MRSA; No Gram– activity; Typically bacteriostatic
How has Linezolid resistance come about?
Lack of drug binding by target alteration
What is the mechanism of action of Linezolid?
It blocks the formation of the 70S initiation complex (as opposed to most other antibiotics blocking protein synthesis after the 70S initiation complex has already formed)
What are the uses of Tigecycline?
Empiric coverage for skin and intra-abdominal infections; NOT used for bacteremia/pseudomonas
What are the most common drugs used to treat CA-MRSA?
Bactrim (co-trimoxazole) or Clindamycin
What virulence factor is found with CA-MRSA, but not so much with HA-MRSA?
Panton-Valentine leukocidin (PVL) toxin
How does community-acquired MRSA differ from the hospital-acquired form?
Its mecA gene is found on a type IV Staphylococcal chromosomal cassette (SCC) which is smaller than the type II SCC found in the hospital-acquired form; this means that it is less capable of storing other resistance genes along with mecA, thus making it more sensitive to non-β-lactams
What describes the life cycle of coronavirus?
Virus binds host cell receptor --> vesicle pinches off and moves into the cell --> pH of endosome is pumped down which allows the virus to undergo a conformational change --> virus fuses with membrane of limiting vesicle --> RNA is released into cell --> RNA is translated so that the RNA-dependent RNA-polymerase is produced --> –RNA is produced and subsequently many copies of +RNA --> viral proteins are formed and enter vesicles along with viral genome to produce mature virions --> vesicle moves out of the cell to release virions
What are prevention and control mechanisms?
Quarantine, supportive care, interferon, drugs/vaccines in development
How is SARS virus detected?
ELISA; RT-PCR
How does transmission of SARS occur?
Close person-person contact (directly or via surfaces); Transmitted by large respiratory droplets
What is the reservoir for SARS?
Bats; jumped from bats to civets and humans
What coronavirus protein is used as a drug target?
Main proteinase (Mpro): it processes the newly made SARS proteins through proteolysis; the protein is required for virus assembly
What is unique about the replication strategy of coronavirus?
It generates transcripts via nested sequences (i.e. the genes overlap)
What characterizes SARS?
Coronavirus (ss +RNA with pleomorphic membrane, enveloped) that causes common cold, atypical pneumonia; virus particles contain “club-shaped” peplomers that give it the appearance of a corona
What characterizes the structure of coronaviruses?
Spike glycoprotein (S): receptor binding, cell fusion, major antigen; Membrane glycoprotein (M): transmembrane, budding and envelope formation; Hemagglutinin-esterase (HE): present in a few types; Nucleocapsid protein (N): basic phosphoprotein associated with RNA genome
What is the case definition for a suspect case of SARS?
Person with onset of fever and lower respiratory tract symptoms within 10 days of either travel to an area with documented transmission of SARS or close contact with a person believed to have SARS
What is the case definition for a probable case of SARS?
A suspect case who also had CXR findings of pneumonia, ARDS, or unexplained illness resulting in death, with autopsy findings of ARDS without identifiable cause
What is the management of SARS?
Supportive care, treat empirically for other possible pneumonias; Strict isolation (airborne, contact, goggles) – also, good hand hygiene
How is the diagnosis of SARS made?
Acute/convalescent serum Ab titers, PCR, viral cultures; exclude other causes of atypical pneumonia
What features are nearly always present with SARS and which are uncommon with SARS?
Present: fever, non-productive cough; Uncommon: coryza, sore throat – also, with SARS GI symptoms are common
What was found on CXR with SARS and what is the case fatality rate?
CXR: non-specific, bilateral patchy focal infiltrates/consolidation; Fatality rate: 3-12% overall (higher in elderly and with comorbid conditions) – labs often show low platelets/WBC
What clinical features describe the respiratory phase of SARS?
Onset within 2-4 days of fever; Dry, non-productive cough; may progress to SOB/hypoxemia
What are the clinical features of SARS?
Incubation period of 2-10 days; Early influenza-like symptoms (fever, myalgia, HA, but absent rash/neurological findings); diarrhea in 25%; 10-20% may require intubation
What is the pathology associated with orbital inflammatory pseudotumor?
Chronic inflammation: lymphocytes, plasma cells, eosinophils; also fibrosis
What is a hordeolum (stye) most often caused by?
Staphylococcal infection of eyelash follicle (external) or Meibomian glands (internal)
What is a chalazion?
Lipogranulomatous reaction to lipid material released from blocked salivary glands
What are the Meibomian and Zeis glands associated with?
Meibomian: inner tarsal plate; Zeis: eyelashes
What is the key feature in the H&E of a meningioma?
Whorls
How is adenoid cystic carcinoma distinguished from lymphoma?
Adenoid cystic carcinoma has circular carcinomatous spaces (glandular appearance) on H&E
What are examples of orbital neoplasms?
Vascular tumors (children: capillary hemangioma, lymphangioma; adults: cavernous hemangioma), lymphoma, lacrimal gland (salivary gland tumors), optic nerve (glioma, meningioma), sinonasal tumors, metastasis
Which three bones form the “lamina papyraceus”?
Ethmoid, lacrimal, nasal bones
What are causes of orbital inflammation?
Spread of sinus infection to the orbit (mucormycosis), orbital involvement in systemic disease (Wegener’s granulomatosis), idiopathic orbital inflammation (orbital inflammatory pseudotumor), sclerosing dacryoadenitis (lacrimal gland), orbital myositis (extraocular muscles), posterior scleritis (Tenon’s capsule – fascial layer around the eye)
What is meant by proptosis?
Exophthalmos: forward displacement of the eye
What infection should be considered in a patient with conjunctivitis?
Trachoma: caused by Chlamydia trachomatis, may produce significant conjunctival scarring, cytoplasmic inclusion seen in conjunctival smears (elementary bodies!)
What are precursors to conjunctival melanomas?
Conjunctival nevi, primary acquired melanosis
What are examples of conjunctival neoplasms?
Squamous papilloma, conjunctival intraepithelial neoplasia (CIN, precursor to squamous cell carcinoma), squamous cell carcinoma, mucoepidermoid carcinoma (lacrimal gland tumor)
What is meant by pinguecula?
Yellowish submucosal elevation due to solar elastosis
What is meant by pterygium?
Submucosal growth of fibrovascular connective tissue that migrates onto the cornea
What do degenerative disorders of the conjunctiva result from?
Actinic damage (sun rays) to sun-exposed regions of the conjunctiva
What are examples of causes associated with conjunctival scarring?
Exposure to caustic alkalis (resembling a burn), ocular cicatricial pemphigoid (autoimmune blistering), iatrogenic (drugs/surgery)
What are examples of eyelid neoplasms?
Basal cell carcinoma (most common), sebaceous carcinoma (more serious, almost exclusively found on the eyelid), Kaposi sarcoma (AIDS)
What characterizes conjunctivitis?
Usually bacterial/viral; Self-limited disease, but can cause itching and redness
What characterizes sebaceous carcinomas?
Most common on the eyelid (!); focal lesion mimics chalazion or diffuse thickening of the eyelid; usually spreads by direct extension to adjacent structures, but can metabolize; vacuolization of the cytoplasm seen (!); Pagetoid spread: cells puncture epidermis and spread out in diffuse fashion
What is the definition of keratitis?
Inflammation of the cornea
What characterizes Fuchs endothelial dystrophy?
Patient presents with blurring and vision loss in late middle age; It is a major indication for corneal transplantation; Primary loss of endothelial cells; Characterized by Guttata: drop-like deposits of abnormal basement membrane material; also seen are stromal edema and bullous keratopathy
What characterizes corneal dystrophies?
They are bilateral and hereditary; Classified topographically (i.e. epithelial, Bowman membrane, stromal, endothelial
What characterizes keratoconus?
Common disorder characterized by progressive, bilateral ectasia of the cornea after puberty; may require corneal transplant; cornea is cone-shaped, Fleisher ring may be seen (iron deposition at the base of the cone), thinning of cornea with breaks in Bowman layer
What are examples of degenerative disease of the cornea?
Calcific band keratopathy: deposition of calcium in Bowman layer, may complicate chronic uveitis in patients with juvenile RA; Actinic keratopathy: also known as climatic/oil droplet keratopathy, due to chronic exposure to UV light, characterized by solar elastosis in superficial layers of corneal stroma
What type of pathology is seen in Herpes simplex keratitis?
Stromal/interstitial keratitis with granulomatous inflammation centered on Descemet membrane
What type of infection used to affect soft contact lens wearers, but less so now?
Acanthamoeba keratitis
What do conjunctival melanomas spread to?
Parotid/submandibular nodes – 25% mortality rate
What are the layers of the cornea from outside to inside?
Epithelium, Bowman membrane, Stroma (largest layer), Descemet membrane (PAS positive), Endothelium (derived from neural crest)
What are conditions associated with blue sclerae?
Repeated episodes of inflammation (scleritis, can occur in RA), high intraocular pressure (staphyloma), osteogenesis imperfecta, nevus of underlying uvea (congenital melanosis of oculi, nevus of Ota)
What differentiates primary and secondary open-angle glaucoma?
Primary: few structural changes, seen with mutations in the GLC1A/TIGR gene (chromosome 1);
Secondary: due to cell debris in trabecular meshwork (RBCs, lens material, iris pigment granules)
What pathological features are associated with ocular inflammation?
Hypopyon: inflammatory cells in anterior chamber; Keratic precipitates: inflammatory cells adherent to corneal endothelium; Anterior synechiae: adhesions between iris and trabecular meshwork or cornea; Posterior synechiae: adhesions between iris and anterior surface of lens
What are the causes of endophthalmitis?
Exogenous: penetrating trauma, ocular surgery; Endogenous: hematogenous spread to eye
What is endophthalmitis?
Inflammation of one or more coats of the eye (retina, choroid, sclera) and adjacent cavities (vitreous humor) – panophthalmitis means all three layers are involved
What are glaukomflecken?
Minute subcapsular opacities seen with primary closed-angle glaucoma
What differentiates primary and secondary closed-angle glaucoma?
Primary: hyperopic patients, ↑ pressure damages lens epithelium --> minute subcapsular opacities;
Secondary: due to pathologic membranes forming over surface of iris, or neovascular glaucoma
What can stromal dystrophies be caused by?
Defects in the gene encoding β-keratoepithelin – typically present in young adulthood
What are the types of cataracts?
Cortical (soft): caused by proliferation/migration/metaplasia of anterior epithelial cells, can see Morgagnian globules; Nuclear (hard): opacification of lens nucleus with accumulation of urochrome pigment
What is the definition of a cataract?
Opacification of the lens; may be congenital or acquired; seen in galactosemia, DM, Wilson’s, atopic dermatitis, corticosteroid use, radiation, trauma, intraocular disorders; most are age-related!
What are the two types of stromal dystrophies?
Lattice dystrophy: deposits of amyloid; Granular dystrophy: deposits of granular, trichrome-positive material
What is the morphology of a uveal melanoma?
Contain spindle cells: fusiform in shape, grow in a syncytium with indistinct cell borders, consist of spindle A cells (inconspicuous nucleoli) and spindle B cells (prominent nucleoli); also contain epitheloid cells (large, poorly cohesive, pleomorphic, with distinct borders and abundant cytoplasm) whose presence correlate with a worsening prognosis
What are examples of retinal vascular diseases?
Retinopathy of prematurity (occurs in low-birth weight infants treated with oxygen); Sickle retinopathy (neovascularization, “sea-fans”); Retinal vasculitis; Radiation retinopathy; Retinal artery and vein occlusion (occlusion of central retinal artery: “cherry-red spot”, also seen in storage diseases)
What are causes of diabetic retinopathy in the proliferative phase?
Neovascularization due to increased levels of VEGF, neovascular membrane, retinal detachment, neovascular glaucoma
What are causes of diabetic retinopathy in the preproliferative phase?
Thickened basement membranes of retinal vessels, microaneurysms/microhemorrhages, macular edema (major cause of visual loss), hemorrhagic exudates in outer plexiform layer
What retinal vascular diseases are seen with hypertension?
Retinal arteriolosclerosis; Focal choroidal infarcts (Elschnig’s spots); Exudate in the outer plexiform layer (hard exudates); Infarcts of the nerve fiber layer (cotton-wool spots/cytoid bodies)
What are the two types of retinal detachment?
Rhegmatogenous: caused by a tear in the retina; Non-rhegmatogenous: no retinal break, but secondary to retinal vascular disease with exudation of fluid into the subretinal space
What characterizes the retina and its response to injury?
Consists of 10 layers; Derived from an outpouching of the brain; Responds to injury with gliosis; Its vitreous layer is avascular
What can posterior synechiae lead to?
Anterior subcapsular cataracts
What is the most common primary intraocular neoplasm?
Uveal melanoma: thought to arise from pre-existing nevi; More common in white patients and those with blue irises; May cause retinal detachment or glaucoma; Metastasize via hematogenous routs (usually to liver); Treated with enucleation or radiation; Mortality approaches 50%
What are causes of uveitis?
Infections: CMV, toxoplasmosis; Sarcoidosis; Sympathetic ophthalmia (bilateral autoimmune granulomatous uveitis secondary to penetrating injury of the eye); also can be a component of systemic disease (e.g. arthritis, IBD)
What are causes of retinal degeneration?
Drug-induced: chloroquine; Cancer/melanoma-associated: autoimmune
What are causes of papilledema?
Acute glaucoma, central retinal vein occlusion, hypertensive retinopathy; however, more commonly the cause is increased intracranial pressure (don’t do lumbar puncture!)
What is anterior ischemic optic neuropathy and what the different types?
Sudden or rapidly progressive monocular visual acuity loss, similar to stroke – Arteritic: due to inflammation of vessel supplying optic nerve; Nonarteritic: due to thromboembolic events
What is the morphology of retinoblastoma?
Small, round cells with hyperchromatic nuclei; necrosis, mitosis, dystrophic calcification;
Flexner-Wintersteiner rosette! (early retinal differentiation); Fleurettes (aggregates of neoplastic photoreceptors)
What is meant by a trilateral retinoblastoma?
Involvement of both eyes and the pineal gland
What is the most common primary intraocular tumor of childhood?
Retinoblastoma: familial/sporadic forms, loss of RB tumor suppressor gene on chromosome 13, presents clinically with leukocoria, can spread to brain and bone marrow
What are causes of retinitis?
Candida: disseminates to retina hematogenously, especially in the setting of drug abuse;
Toxoplasma/CMV: seen in association with uveitis in AIDS
What is the most common cause of irreversible visual morbidity in the US?
Age-related macular degeneration: due to a disturbance in the retinal pigment epithelium (RPE), Bruch’s membrane (basement membrane of RPE), or innermost layer of the choroidal vasculature
What characterizes retinitis pigmentosa?
Inherited disorder due to mutations in genes that regulate the functions of either the photoreceptor cells or RPE – symptoms due to loss of rods/cones (incl. night blindness, constricted visual fields)
What are the two types of age-relayed macular degeneration?
Atrophic (dry): focal/diffuse deposits of basement membrane products in Bruch’s membrane (drusen) with atrophy of RPE; Exudative (wet): choroidal neovascularization, vessels originate in choriocapillaris and penetrate through Bruch’s membrane
What can mutations in the optineurin gene lead to?
Normal-tension glaucoma: normal intraocular pressure but similar visual field changes
What characterizes phthisis bulbi?
End-stage eye; Can be caused by trauma, intraocular inflammation, chronic retinal detachment; Associated with hypotony (low intraocular pressure); Globe is small and internally disorganized; Can see osseous metaplasia in the eye
What does optic neuritis frequently refer to?
Loss of vision secondary to demyelination of the optic nerve – associated with MS
What are causes of optic neuropathies?
Leber hereditary optic neuropathy (mitochondrial disorder); tobacco-alcohol amblyopia; methanol
What is the agent that causes trachoma?
Chlamydia trachomatis
What is the WHO grading system for trachoma?
TF: trachomatous follicle; TI: trachomatous inflammation; TS: trachomatous scarring; TT: trachomatous trichiasis; CO: corneal opacity
What is the pathway to blindness regarding trachoma?
It affects the upper tarsal and superior bulbar conjunctivae bilaterally; there is a papillary reaction and a follicular reaction; the biggest problem is repeated infection (chronicity) leading to tarsal scarring and tarsal shortening; this leads to entropion (infolding of the eyelid), which causes trichiasis (irritation caused by eyelashes on cornea), followed by corneal abrasion and secondary bacterial infection, eventually resulting in corneal scarring
What is the epidemiology of trachoma?
Poor hygiene, frequent transmission of infection within family, “cluster disease”; found especially in areas of poverty which are hot, dry, dusty
Which groups are most affected by trachoma?
Children, female>male, sight is lost in middle age
What is the definition of trachoma?
Specific, chronic keratoconjunctivitis which infects bulbar and tarsal conjunctiva and cornea
What characterizes C. trachomatis?
Obligate intracellular pathogen
What is the most common cause of blindness in the world?
Cataracts
What causes of blindness are common in Africa?
Cataracts, open-angle glaucoma, trachoma, xerophthalmia, onchocerciasis
What is the most common cause of preventable blindness in the world?
Trachoma
What are characteristic findings in trachoma?
Pannus: blood vessels at the limbus in active trachoma; Arlt’s line: scarring of the upper tarsal conjunctiva
What is the algorithm for the elimination of trachoma?
Surgery for trichiasis, Antibiotics, Face washing, Environmental change
What is the surgical management for trachoma?
Entropion surgery; epilation not recommended
What is the treatment for trachoma?
Topical tetracycline, tid for 6 weeks; Oral azithromycin, once or twice per year (given to children)
What is the vision chart for preschool-aged children called?
Lea symbol chart
How can a strabismus be brought out if not immediately apparent?
Cover testing
What can be a cause of pseudoesotropia?
Prominent epicanthal folds
What is the Hirschberg test?
Corneal light reflex test; used to estimate the amount of deviation present in an eye (e.g. esotropia, exotropia, hypertropia)
What is the treatment for amblyopia?
Occlusion of the good eye in order to restore vision development of the bad eye
What is anisometropia?
A difference in the refractive power of the two eyes
What is amblyopia?
Poor vision development in the brain because of an abnormality in one eye or greater in one eye
What are the 5 basic elements of the pediatric eye examination?
External exam, visual acuity, eye alignment, eye movement, red reflex testing
How can a child’s fixation preference be determined?
When the bad eye is covered up the child doesn’t care, but when the good eye (the one with the fixation preference) is covered the child will push away the object covering it up
What are the visual development milestones?
Birth: blink to bright light; 1 month: fixates on faces; 2-3 months: follows objects of interest; 4 months: intermittent eye crossing stops; 5-6 months: visually directed grasps; 9-10 months: attentive to distant objects; 1-2 years: points to pictures in book; 2-3 years: identifies shapes;
3+ years: adult-like visual acuity and color vision
What can prisms be used for regarding strabismus?
Assessing the angle of drift in the bad eye
What cause minute changes in the red reflex (e.g. crescent-shaped light area in one eye)?
Nearsightedness, farsightedness
What can cause a red reflex to be absent?
Cataract
What is the exam finding called where on eye appears lighter than the other during red reflex testing?
Leukocoria (may indicate retinoblastoma)
What is the Bruckner test?
Red Reflex test
What is the treatment for strabismus?
Glasses, surgery, patching for amblyopia
How do the anticholinergic agents used for pupil dilation differ?
In their duration of action (4 hrs – 2 wks)
What are the effects of changing a patient from a non-selective beta blocker to a β1-selective beta blocker?
Although adverse effects are less prominent, the decrease in intraocular pressure is also lowered
What are the desired and adverse effects of topical beta blockers?
Decrease aqueous production (cornerstone of glaucoma treatment);
Adverse effects: bronchoconstriction, cardiac inhibition, depression, visual hallucinations
What are the effects of the various glaucoma medications?
Slow down production of aqueous humor; Enhance filtration of aqueous humor back into circulation
What will fluorescein staining look like in a patient with an ocular Herpes simplex infection?
Branching, dendrite pattern on cornea due to ulceration
What is the most common corneal staining agent?
Fluorescein – fluoresces when exposed to protein and excited by cobalt blue light (elicits epithelial defects/abrasions)
What topical anesthetics are used to relieve eye pain?
“-caine” medications; act almost instantly with a 15-20 min. duration; however, these medications are toxic to the cornea: pH, delays epithelial growth, slows blinking (natural defenses)
What are the three categories of diagnostic tools used in ophthalmology?
Pupil dilation, corneal staining, topical anesthetics
What is the typical sympathomimetic used for pupil dilation?
Phenylephrine
What is the purpose of drugs used in pupil dilation?
Block sphincter muscle (anticholinergic), stimulate dilator muscle (sympathetic) – cycloplegia may result from anticholinergic use (i.e. accommodation of the lens is temporarily lost)
What are the adverse effects associated with topical cholinergic agents?
Pupil constriction, HA; also, drug must be applied 4qd
How do osmotic agents lower intraocular pressure?
They raise the osmolarity of the blood flow around the eye, causing vitreous humor to move into the blood circulation (thus dehydrating it)
What are adverse effects associated with prostaglandin analogs?
Redness of eye, lengthening of eye lashes – not used in pregnancy due to the fear that it might be abortive (although no evidence exists for this effect)
What are the effects of prostaglandin analogs on aqueous humor?
Enhances uveoscleral outflow at low doses (30% pressure reduction, qd dosing most effective) – at high doses the opposite effect is seen
When would oral CAI be used?
When surgery is not an option and the patient needs to be on chronic CAI medication; however, the side effects profile will make this a difficult form of treatment
What are adverse effects associated with carbonic anhydrase inhibitors (CAI)?
Nausea, tingling lips/fingers, anemia, kidney stones – side effects are only seen with systemic use
Where in the body is carbonic anhydrase found in significant quantities?
Ciliary body (helps in production of aqueous humor), meninges, kidneys
How do α-selective adrenergic agonists lower intraocular pressure?
They decrease the production of aqueous humor
What are the effects of cholinergic agents on the intraocular pressure?
They constrict the pupil which puts tension on the iris, thus promoting outflow of aqueous humor; it also increases accommodation (since it stimulates the ciliary muscle causing nearsightedness)
What side effects are associated with α-selective adrenergic agonists (e.g. Alphagan)?
Delayed hypersensitivity reactions (follicular conjunctivitis with cobblestone bumps), dry mouth, somnolence (soon after application)
How does ocular treatment with antibiotics differ from systemic treatment?
Higher doses of antibiotics can be used due to decreased adverse effects (e.g. with Aminoglycosides, high doses can be used so that the drug becomes effective in both Gram+ and Gram– bacteria)
How should eye drops be administered?
Pull down lower eyelid and make a cul-de-sac between the eyelid and the eyeball; patient should be looking up so that they won’t blink as a reaction to seeing the dropper approach them
What ocular lubricants are commonly used?
Artificial tears, viscous artificial tears, ointments/gels – the thicker the medication, the fewer applications are necessary (however, too much application can make it hard to see through)
What ocular allergy medications are used?
Decongestants for red eye (chronic use can lead to rebound), H1-antihistamines,
Mast cell stabilizers (must use chronically), NSAIDs
How are antivirals used for eye infections?
Treatment is only given for Herpes simplex infections
When are Quinolones used regarding ocular treatment?
Post-surgery and corneal ulcers – they are very expensive
What combination treatment will fight H. flu conjunctivitis?
Polymyxin with Trimethoprim
What adverse effects are associated with osmotic agents?
When given systemically, it pulls fluid out of all third spaces, and thus can precipitate congestive heart failure; Also, the osmotic agent Glycerin cannot be used in diabetics since it is quickly metabolized to sugar
What adverse effects are associated with topical steroid use?
Cataract formation, elevation of intraocular pressure (can occur after 2 wks of use), worsening of ocular Herpes simplex infection
How do steroids affect the eye?
They reduce inflammation
Where is ocular fluid made?
Ciliary bodies
What is the purpose of gonioscopy?
Examination of the drainage angle (through the use of a special contact lens)
What is often found in peripheral visual field testing in a patient with glaucoma?
Peripheral vision loss emanating from the optic nerve in an acuate manner, preferentially affecting the nasal area
What is examined regarding the diagnosis of glaucoma?
Eye pressure, optic nerve, visual field; also, laser analysis of optic nerve, contact lens examination of internal drainage system, corneal thickness (via ultrasound)
Besides looking at the color of the optic disc, what else should be looked at?
The pattern of the blood vessels in the optic disc
What Cup:Disc ratio could be considered abnormal?
C:D ratio > 0.4
What is the difference between open-angle and closed-angle glaucoma?
Open-angle: aqueous humor has access to trabecular network; Closed-angle: aqueous humor does not have access to trabecular drainage network
What are the risk factors for glaucoma?
Age>40, elevated eye pressure, black race, myopia, family history (esp. siblings), thin corneas (!)
What does glaucoma cause?
Slow, progressive irreversible damage to the optic nerve (usually from high eye pressure), resulting in gradual loss of peripheral vision first; loss of vision goes unnoticed until severe
What is glaucoma?
Chronic, progressive optic neuropathy with typical visual field changes (often associated with elevated intraocular pressure)
What symptoms are associated with closed-angle glaucoma?
Severe pain (mostly over their eyebrow, patient may complain of headache); severe redness; foggy vision, colored halos around light; repeated nausea, vomiting
What type of glaucoma is seen in diabetics?
Neovascular glaucoma
What is the most common eye surgery performed for glaucoma?
Trabeculectomy (creation of a fistula between the anterior chamber of the eye and the subconjunctival space – can also use drainage tubes)
What is the purpose of laser trabeculoplasty?
Improves drainage of fluid out of the eye by unclogging outflow tracts; works best with pigment or “lens flakiness” glaucoma
What are the chances of getting a closed-angle glaucoma in the other eye after the first attack?
50% - treated prophylactically with laser iridotomy
What people are at risk for closed-angle glaucoma?
Elderly, Eskimos/Native Americans/Asians, females>males, farsighted eyes (!), family history
What is the treatment of choice for closed-angle glaucoma?
Laser iridotomy
What is the most common type of glaucoma in the US?
Primary open-angle glaucoma
What type of glaucoma is an emergency?
Closed-angle glaucoma (also known as narrow-angle or angle-closure glaucoma)
What type of glaucoma can be affected by cold medicines (i.e. adrenergic agonists)?
Closed-angle glaucoma
What is the problem with pseudoexfoliation glaucoma (“lens flakiness”)?
The basement membranes of the eye become flaky and clog the trabecular drainage network
Can glaucoma be cured?
No, it can only be controlled
What are the most common types of glaucoma in the US?
Primary open-angle glaucoma (80%), angle-closure glaucoma (5%), secondary glaucoma (3%), congenital glaucoma (<1%), glaucoma suspects (do not manifest all glaucoma criteria, 11%)
What eye symptoms are associated with Graves’ disease?
Prominent eyes, chemosis (swelling of conjunctiva), lid swelling, diplopia, foreign body sensation, photophobia, pain, decreased vision
What treatment option is available for patients with proliferative retinopathy?
Panretinal photocoagulation: laser beam in peripheral visual field causes local coagulation and thus a decrease in VEGF formation --> this reduces neovascularization which will reduce destruction of the macula
What can occur when background diabetic retinopathy is not treated?
It can progress to proliferative retinopathy: ischemic retinal tissue due to capillary dropout leads to neovascularization and subsequent vitreous hemorrhage/traction retinal detachment
What is the most common cause of vision loss in diabetics?
Macular edema
What is the most common eye problem in diabetics?
Background diabetic retinopathy: capillary basement membrane dysfunction, loss of pericytes, leads to exudation of fluid into retina and microaneurysms
How does eye examination differ between Type I and Type II diabetics?
Type I diabetics should be seen within 5 years of diagnosis, whereas Type II diabetics should be examined at time of diagnosis
How are thyroid levels related to thyroid eye disease?
Although hyperthyroidism is common, some patients are euthyroid and eye problems are the presenting symptoms; also, some patients are hypothyroid but are taking replacement therapy
What are ocular manifestations of systemic disease?
Thyroid ophthalmopathy, diabetic retinopathy, hypertensive retinopathy, retinal artery and vein occlusions
What can happen to the ocular muscles with Graves’ disease?
They can thicken
What is the ocular first sign that a patient with thyroid dysfunction (Graves’ disease) present with?
Redness of conjunctiva
What eye symptoms are associated with Graves’ disease?
Prominent eyes, chemosis (swelling of conjunctiva), lid swelling, diplopia, foreign body sensation, photophobia, pain, decreased vision
What treatment option is available for patients with proliferative retinopathy?
Panretinal photocoagulation: laser beam in peripheral visual field causes local coagulation and thus a decrease in VEGF formation --> this reduces neovascularization which will reduce destruction of the macula
What can occur when background diabetic retinopathy is not treated?
It can progress to proliferative retinopathy: ischemic retinal tissue due to capillary dropout leads to neovascularization and subsequent vitreous hemorrhage/traction retinal detachment
What is the most common cause of vision loss in diabetics?
Macular edema
What is the most common eye problem in diabetics?
Background diabetic retinopathy: capillary basement membrane dysfunction, loss of pericytes, leads to exudation of fluid into retina and microaneurysms
How does eye examination differ between Type I and Type II diabetics?
Type I diabetics should be seen within 5 years of diagnosis, whereas Type II diabetics should be examined at time of diagnosis
How are thyroid levels related to thyroid eye disease?
Although hyperthyroidism is common, some patients are euthyroid and eye problems are the presenting symptoms; also, some patients are hypothyroid but are taking replacement therapy
What are ocular manifestations of systemic disease?
Thyroid ophthalmopathy, diabetic retinopathy, hypertensive retinopathy, retinal artery and vein occlusions
What can happen to the ocular muscles with Graves’ disease?
They can thicken
What is the ocular first sign that a patient with thyroid dysfunction (Graves’ disease) present with?
Redness of conjunctiva
What is meant by an acephalic migraine?
Migraine visual symptoms without the headache
What characterizes bacterial conjunctivitis?
Bilateral mucopurulent discharge; treatment with topical or systemic antibiotics, warm compresses
What are non-traumatic causes of red eye?
Conjunctivitis, iritis, corneal inflammation/infection, acute angle-closure glaucoma
What is the treatment for corneal abrasions?
Antibiotics for Gram– organisms; Do no patch; Follow up with ophthalmology within 24 hours; additional treatment includes topical cycloplegic and topical antibiotic
What treatment is needed for an ocular chemical burn?
Immediate irrigation is essential and malpractice if not performed; initial management in the clinic is topical anesthetic, removal of foreign bodies, and copious irrigation
What is a chalazion/hordeolum?
Obstructed meibomian/Zeis gland: presents as eyelid lump, swelling, pain, tenderness, erythema; it is a visible, palpable mass/nodule within the eyelid – usually spontaneously resolves with warm compresses (if persistent, can treat by draining or injecting with steroids)
What are the signs of an ophthalmoplegic migraine?
Extraocular muscle paralysis, ipsilateral, often seen in childhood
What factors affect retinal arterioles?
Severity and duration of HTN
What visual complaints are associated with migraines?
Bilateral flashing lights (in the same spot of the eye), blurred vision, visual field defects
What symptoms accompanying headache can be indicative of eye disease?
With temporal arteritis: scalp tenderness, weight loss, pain w/ mastication, malaise, >55yo, fever;
With meningitis/increased intracranial pressure: altered mental status, neck stiffness, blurred vision, and other neurological signs
What is the treatment for orbital cellulitis?
Immediate treatment, nasopharynx/blood cultures, IV antibiotics, possible surgery; always rule out opportunistic infections like mucormycosis in immunocompromised patients
What is the treatment for AMD?
Prevention: healthy diet, avoid smoking, multivitamin, avoid sun damage, routine screening
What are risk factors for AMD?
Systemic: age, HTN, smoking (causes dry --> wet), family history; Ocular: soft drusen (deposits under retina), macular pigment changes, choroidal neovascularization (CNV) in fellow eye
What are the two types of Age-related Macular Degeneration (AMD)?
Dry: non-exudative, slowly progressive disease; Wet: exudative, due to chorial neovascularization, causes subretinal scarring (less common but more rapid/devastating; however, treatment exists)
What is a Hutchinson sign?
Involvement of the tip of the nose from Herpes zoster; indicates that the nasociliary nerve, and thus the eye may be involved
What signs are associated with Herpes Zoster Ophthalmicus?
Prodromal fever, scalp tenderness
What is the management for a hyphema (blood in anterior chamber)?
Assume ruptured globe; Shield eye; Manage nausea, pain with IV meds; Refer to ophthalmology
What characterizes viral conjunctivitis?
Bilateral watery/mucoid discharge, lymphoid follicles (bumps) on conjunctiva, preauricular lymphadenopathy
What characterizes orbital cellulitis?
Pain, decreased vision, impaired ocular motility/diplopia (!), afferent pupillary defect, proptosis, optic nerve swelling
What characterizes preseptal cellulitis?
Eye pain, lid erythema, conjunctival injection/chemosis, no diplopia (!) – treatment: warm compresses, systemic antibiotics, x-ray/CT if history of trauma/sinus infections
What can be caused by beta-carotene found in multivitamins for age-related vision changes (AREDs)?
Lung cancer in smokers – they should take the ARED with Lutein instead
What is the current treatment for AMD?
Anti-VEGF agents – stops vision loss in 95% of patients and restores vision in 33%
What is the benefit of taking AREDs?
May prevent development of severe macular degeneration in the other eye