CD Flashcards

Question

MACROLIDES (unwanted effects)

Answer 1

* GI effects (erythromycin > others) * cardiac toxicity → causing arrythmias, QT prolongation * hepatotoxicity

Answer 2

* respiratory infections (Pertussis, Legionella) * chlamydia * myoplasma infections * skin infections

Answer 3

e.g. **amoxicillin, flucoxacillin** * bacterioCIDAL (G-) * frequently administered with a beta lactamase inhibitor * oral use (amoxicillin absorption greater than ampicillin) * [therapeutic] in joint, pleural (lung), pericardial (around the heart), fluid & bile * rapid renal elination → high drug conc. in urine * short t1/2 (30-60mins)

Answer 4

* normally well tolerated, high therapeutic index (TI) * hypersensitivity (1-10% chance) * hapten carrier conjugates promote immune response * anaphylaxis, itching, rash * GI → change in gut flora * diarrhoea, c. difficile colitis

Answer 5

* upper respiratory tract infections (URTIs) * urinary tract infections (UTIs) * salmonella infections

Answer 6

Penicillins

Answer 7

cefalexin (1st gen) cefaclor (2nd gen) ceftriaxone (3rd gen) cefepime (4th gen) ceftaroline (5th gen) * as generation increases → increased activity for G-, increased BBB penetration, longer t1/2 (cetriazone > 8h)

Answer 8

* bacterioCIDAL (G-) * more resistant to beta lactamase than penicillins * similar MOA to penicillins * oral absorption (except ceftriaxone = i.v. or i.m.) * renal excretion, dose adjust in renal insufficiency (ceftriaxone doesn't need as much) * conc. high in synovial, pericardial fluid * ceftriaxone has sufficient CNS pentration for meningitis Tx

Answer 9

* hypersensitivity: similar to penicillins * anaphylaxis, bronchospasm, urticaridal (immediate) * maculopapular (delayed) * *cross-reactivity with penicillins* * hepatotoxicity (low compared to aminoglycosides) * antibiotic-associated colitis (with broad spectrum agents)

Answer 10

* skin, soft tissue infections (1st gen) * pneumonia, resistant/pregnancy UTIs (2nd gen) * gonorrhoea, meningitis, CAP (3rd gen) * hospital acquired (nosocomial) infections (4th gen)

Answer 11

e.g. **imipenem, meropenem, ertapenem** * bacterioCIDAL?? * similar mechanism to penicillins * very resistant to beta lactamase & have the **broadest antimicrobial spectrum** than other beta lactams or antibiotics * poor oral bioavailability → therefore usually given parentally (i.v. or i.m.) * renal excretion, short t1/2 (except ertapenam, once daily dosing) * imipenem: rapid hydrolysis, partial inactivation (kidney) given with cilastatin (dihydropeptidase inhibitor)

Answer 12

* similar to other beta lactams * nausea & vomitting * neurotoxicity, seizures (high dose, renal failure, CNS injury/disease)

Answer 13

* severe hospital acquired infections! (MRSA) * septicaema * hospital-acquired pneuomonia * intra-abdominal infections * complicated UTIs

Answer 14

e.g. **aztreonam** * bacterioCIDAL?? (only G-) limited spectrum * interacts with PBPs & causes formation of long filamentous bacteria * resistant to many beta lactamases * antimicrobial activity more like aminoglycosides

Answer 15

* generally well tolerated * similar to other beta lactans * little cross-reactivity with penicillins/cephalosporins (except ceftazidine, structurally similar)

Answer 16

* only useful for G- infections! * pseudomonas aeruginosa * haemophilis influenza * neisseria meningitidis

Answer 17

e.g. **vancomycin, teicoplanin, daptomycin** * bacterioCIDAL (active against G+ infections (MRSA)) * prevent addition of murein monomers to peptide chain * poor oral absorption → i.v., t1/2 = 8h (teicoplanin = i.m.) * excreted orally * dose adjustment in renal impairment! → drug conc. plasma monitoring for vancomycin to minimise toxicity

Answer 18

* nephtrotoxicity (worse + aminoglycoside) * hypersensitivity, rashes, SJS/TEN 'red man syndrome' (rapid i.v. injection >500mg/h → histamine release) (with vancomycin)

Answer 19

* **serious G+ infection** * MRSA * Bacterial endocarditis * C. difficle colitis (oral admin

Answer 20

* commensalism → microbes **do not** cause disease, e.g. normal microflora * colonisation → may not cause disease * disease → damage resulting from infection with a harmful microbe (pathogen)

Answer 21

* low virulence * normal microflora * mostly protective → beneficial role * can/may cause disease if colonise a sterile area (e.g. via a wound) in a susceptible host

Answer 22

* disease causing microbes * multiple virulence factors → toxins, adhesion molecules, immune response modifiers * virulence factors allow them to cause disease in many hosts

Answer 23

* age (neonates & eldery) * pregnancy * nutrition (malnutrition & alcoholism) * illness (e.g. diabetes, cancer, liver disease) * immunosuppressive drugs * chemotherapy * atmospheric pollution * surgery/trauma * physical defects * stress * immune diseases (acquired or genetic) * gender/genetic predisposition

Answer 24

1. the pathogen (virulence factors) 2. the host (susceptibility)

Answer 25

* signs → **measurable** (observation, lab tests), objective, physical changes * symptoms → felt & reported by the individual, **subjective**, cannot be measured

Answer 26

* a response to LPS (endotoxin) aka an 'endogenous pyrogen' * LPS stimulates the pyrogenic response (fever response) * early warning for immune system

Answer 27

* designed to enhance immune function * accelerates immune response → increased phagocytosis, T-helper cell adherance * prolongs/reduces growth of invading microoganism * reduced TNF⍺ & IFNɣ

Answer 28

* increased metabolic demand & oxygen consumption * source of patients discomfort? * children's seizures? (controversial)

Answer 29

* assessment criteria for fever in under 5's * green (low risk), amber (intermediate risk), red (high risk)

Answer 30

specific therapy to kill microbes/inhibit their growth

Answer 31

substance (biological or chemical) that inhibits the growth of bacteria (bacteriostatic) or kills them (bacteriocidal)

Answer 32

subset of antibacterials produced by microorganisms

Answer 33

* are **prokaryotes** * NO nucleus, double stranded DNA genome in cytoplasm * NO cellular organelles (i.e. mitochondria, ER) * **cell wall** * +/- capsules, spore forming * **unicellular** * extra-chromosomal DNA (plasmids) * reproduce by binary fission, logarithmic growth

Answer 34

* folate pathway * bacterial cell wall * outer membrane * protein synthesis * replication

Answer 35

* folate pathway → used in making DNA & proteins * humans get folic acid from our diet BUT bacteria make their own dihydrofolate (DHF) → selective target for sulfonamides * **trimethoprim** = a dihydrofolate reductase (DHFR) inhibitor → higher affinity for the bacterial enzyme

Answer 36

* human cells don't have a wall, just a membrane → therefore can target bacterial cell wall * major component = peptidoglycan * synthesis of peptidoglycan is a major drug target (β-lactams, glycopeptides) * bacterial cell wall = a 3D meshwork of peptide crosslinked sugar molecules

Answer 37

* G + cell walls have a thick peptidoglycan cross linking layer * G- cell walls more complex * G- cell walls have an outer membrane → is a barrier to some antimicrobals

Answer 38

* process the same in pro & eukaryotes BUT ribosomal subunits are different * eukaryokes → 40s & 60s * prokaryokes → 30s & 50s

Answer 39

* differences in some enzymes * DNA gyrase (quinolones) * RNA polymerase (rifapicin)

Answer 40

* are **eukaryotes** (& so are humans) * bigger than bacteria * have nucleus & cellular organelles * **unicellular** * **miotic division** → division time 20hr * **cell wall** * NO extra-chromosomal DNA

Answer 41

* cell membrane contains **ergosterol** rather than cholesterol * can inhibit sterol synthesis (azoles & allylamines) * or selectively bind to ergosterol & influence cell membrane permeability (polyene anti-fungals e.g. amphotericin B)

Answer 42

* fungi cell wall is a complex network of proteins & carbohydrates → **glucan & chitan provide strength** * can have glucan synthesis inhibitors (echinocandins) * or chitin synthase inhibitors (nikkomycin & polyoxins)

Answer 43

* Penicillins * Cephalosporins * Monobactems * Carbapenems

Answer 44

* useful, most frequently prescribed * all have a common β lactam ring * are all exclusviely bacteriocidal * either inhibit peptidoglycan synthesis OR target other penicillin-binding proteins

Answer 45

* PBPs → penicillin-binding proteins * all bacteria have several * e.g. maintance of shape, etc.

Answer 46

**1. resistance** **2. enzymatic degradation** G+ produce & secrete large amounts of β lactamases, G- produce smaller amounts in periplasmic space **3. biofilm formation** e.g. catheters, prosthetic joints & heart values produce more polysaccharide, slower growing → less sensitive **4. density & age of infection** number or resistant bacteria antibiotics most active in logarithmic growth phase

Answer 47

* breaks down the β lactam ring of β lactam antibiotics

Answer 48

* molecules that can inactivate β lactamases * e.g. **clavulanic acid**, **tazobactam** * **prevents the destruction of β lactam antibiotics** * mostly active against plasma-encoded β lactamases * inactive against type I chromosomal β lactamases induced in G- bacteria * **improve the spectrum of penicillins**

Answer 49

* G+ cocci * grape like **clusters** * produce microcapsules → help invade the immune system * produce numerous toxins → causes increased or decreased virulence * faculatatively resistant → can cope with low oxygen, thus can penetrate into deep tissue * **multi-drug resistant**

Answer 50

* G+ cocci * **chain** forming *produce microcapsules → help invade the immune system * produce numerous toxins → causes increased or decreased virulence * faculatatively resistant → can cope with low oxygen, thus can penetrate into deep tissue * **penicillin sensitive**

Answer 51

* cogulase = enzyme that breaks down components in blood * cogulase positive → more virulent (better human pathogens)

Answer 52

* distingushed by the golden colour of colonies, has coagulase enzyme * wide range of infections (range from benign to life-threatening)

Answer 53

* skin and soft tissue infections (SSTI) * joints, bone (osteoarticular) * blood, lung, heart * GI, urinary, reproductive tract, mastitis...

Answer 54

* carried by 30-50% of people * carriage increases risk of infection! * carriage is increased in populations with high rates of smoking * infections also via exposure to a carrier (community or hospital) or an environmental source * drug resistance → β-lactamase inactivates pencillin; mecA gene encodes low-affinity penicillin-binding protein, VanA modifies the target

Answer 55

* damage to an epithelial barrier → colonisation of bacteria in tissue or boood * phagocytosis of bacteria by macrophages * activated macrophages attract neutrophils which secrete mediators (ROS, MPO, NETS) * bacteria fight back → destroy NETS, produce toxins & superantigens * abscesses form to contain bacteria, do not always work → spread to blood ...

Answer 56

* host factors * bacterial factors * social/environmental factors * healthcare inequities * medical procedures, devices (sutures, catheters, valves, joints) → biofilm formation leading cause of bacteremia (blood bourne infections)

Answer 57

* classified based on ability to rupture red blood cells (hemolysis) & traditionally of cell wall polysaccharides (lancefield group) * streptococcus pyogenes causes most serious infections * now being replaced by sequencing the emm gene, encodes the highly polymorphic M surface protein

Answer 58

lancefield group A, β hemolysis

Answer 59

* have many virulence factors including capsules, toxins & superantigens

Answer 60

multiple virulence factors inpact on pathogenesis * direct tissue damage * induction of coagulopathy → helps bacteria to cause infection * inactivation of cytokines & immune cells extensive tissue damage, bacteremia, organ damage

Answer 61

* GAS **colonizes epithelial surfaces** * most disease is from superficial infections but can be serious * **invasive disease follows a breach of epithelia ** → variety of disease with high morbidity & mortality

Answer 62

* rates higher with social deprivation * pateinst die within 7 days of infection * most common invasive dieseases = SSTI & bacteremia * may be complicated by development of STSS (streptococcal toxic shock syndrome)

Answer 63

* opportunistic skin pathogens → S. aureus & S. pyogenes * risk groups for invasive disease → skin lesions, very young, eldery, immune compromised * morbidity → organ failure & amptutation * rate in NZ kids higher than similar countries * higher incidence in boys * highest in pre-school aged children

Answer 64

* bacterial infection of the skin & sub cutaneous tissue (fascia, muscles, tendons) * commonly caused S, pyogenes, S. aureus organism must gain entry through a wound (cut, abrasion, burn, sting, bite, surgery) commonly occurs in the extremities

Answer 65

* presentation → ill defined lesions, red, painful, swollen, may/may not have systemic symptoms (fever, chills, regional lymphadenopathy) * diagnosis → biopsy, culture only used in situations where complications may occur

Answer 66

* **uncomplicated cellulitis** → (small area of involvement, no risk factors, no systemic symptoms, minimal pain) = **oral antibiotics** * **complicated cellulitis** → (systemic symptoms & risk factors) = **hospitalisation, i.v. antibiotics, surgical drainage/debridement**

Answer 67

* caused by release of Staph & Strep toxic "superantigens" * widespread immune system activation → cytokine storm → multi organ failure & high mortality

Answer 68

* early symptoms → redness, swelling & pain at wound site (starts off like a normal skin infection!) * late symptoms → plumet in BP, issues with organs, etc..

Answer 69

* treatment is aggressive * supportive care * antibiotics * wound care (drainage &/or debridement) * IVIG?

Answer 70

* tissue infection in which extensive necrosis accompanies the cellulitis * massive destruction of soft tissue, damage to blood vessels, muscle liquefaction * potentially fatal * also known as streptococcal gangrene * cause by S. pyrogenes & S. aureus * organism must gain entry through a wound * risk factors → age, vascular disease, diabetes, immune suppression

Answer 71

* early symptoms → slight tramua → local discomfort in area of tramua, general malaise, headache, fever, joint & muscle pain * advanced symptoms → pain gets worse, seem out of proportion to the small wound visible, blisters, skin & tissue looks dead * critcal symptoms → disease progresses, less local pain, more systemic symptoms from bacterial toxins, coma & death

Answer 72

* seek treatment early! * hospitalisation, i.v. antibiotics, supportive therapy, surgical drainage & debridement * amputation * costemic surgery → skin grafts

Answer 73

* development has been difficult! * pfizer vaccine got antibody production but NO protection from infection * NO VACCINE → because the infection is so variable

Answer 74

* working on a vaccine since the 1940's... * whole cell vaccines → too many side effects & no protetction * still NO vaccine

Answer 75

* aka mycoses * are widespread * associated with skin & mucous membranes * in temperature climates (like NZ) fungal infections are usually associated with the skin * minor in healthy individuals * only when in immunocompromised patients or when they gain access to the systemic circulation, they can become lifethreatening

Answer 76

* yeast → unicellular, simple, single cellular organisms * mould → a growth phase of the yeast * aspergillus fumigatis (opportunistic pathogens) * candida albicans (opportunistic pathogens) * cryptococcus neoformans (opportunistic pathogens) * coccocidoides immitis (systemic)

Answer 77

* examples → **fluconazole, itraconazole, miconazole, voriconazole, posaconazole**

Answer 78

* inhibit microsmola CYP (14-⍺-sterol demthylase) → **impairs ergosterol synthesis** * some increase permeability of plasma membrane (conc. dependent, topical use) * **fungiSTATIC** (broad spectrum)

Answer 79

* orally or i.v. (miconazole generally topical/oral gel) * itraconazole absorption variable, extensive hepactic metabolism * short t1/2 (6-8h) → miconazole, voriconazole * long t1/2 (30-40h) → fluconazole, itraconazole, posaconazole

Answer 80

generally mild * nausea * headache * abdominal pain * rare → allergic skin reactions (SJS = stevens-johnson syndrome) * AVOID DURING PREGNANCY

Answer 81

* candidiasis → miconazole, only topical use * cryptococcal meningitis (AIDS) * invasive aspergillosis → voriconazole * prophylaxis against candidiasis, aspergillosis in patients with neutropenia or GVHD (graft vs host disease)

Answer 82

* azoles interact with hepatic CYPs as substrates AND inhibitors * azoles can increase [drug] in plasma of some co-administered drugs * other co-administered drugs can decrease [drug] in plasma of azoles

Answer 83

* OTC **topical **treatment * superficial fungal infections → thrush (candidiasis), tinea, funal keratitis, nappy rash * interferes with aa transport into fungus! * small amount absorbed is metabolised by livre & excreted in bile * **may still be used to treat yeast infections in pregnant women!** * may cause stinging, redness, itching

Answer 84

polyenes are naturally occuring antifungals produced particular strains of bacteria

Answer 85

* is the 'gold standard' polyene antibiotic (streptomyces) * **binds to ergosterol in fungal membrane** * relative specificity * forms pores/channels → increases permeability, leakage

Answer 86

* GI absorption of all amophotericin B formulations is none exsistant * used topically & systemically → slow i.v. infusion (lipid formulations) * highly protein bound * excreted very slowly by kidneys

Answer 87

* most common, most severe = renal toxicity (80% of patients) * hypokalemia (20%) * acute response to i.v. → fevers, chills, worst with collodial dispersion, least with liposomal * irritant, thrombophlebitis

Answer 88

* candida oesophagitis (HIV/AIDS) * mucormycosis (weakened immune system, e.g. organ transplant) * meningitis * cryptococcus

Answer 89

* useful for topical use, superficial infections * tetraene macrolide (streptomyces noursei) * structurally similar to amphotericin → same MoA

Answer 90

* not absorbed from the GI tract, skin, or vagina * good for 'topical' use

Answer 91

* none of note! * allergic reactions very uncommon

Answer 92

* only for candidiasis (thrush) * supplied in preparations for cutaneous, vaginal, or oral administration

Answer 93

* examples → **caspofungin, micafungin, anidulafungin**

Answer 94

* inhibit synthesis 1,3-β-glucans → **decrease structural integrity** → death * fungiCIDAL

Answer 95

* no oral bioavailability (size), given i.v. * extensive protein binding (>97%) * don't penetrate into CSF * no renal clearance * (little effect on [drug] in plasma in renal impairment)

Answer 96

* remarkably well tolerated * phlebitis (inflammation of veins) at injection site (caspofungin) * histamine-like effects (rapid infusion)

Answer 97

deeply invasive candidiasis salvage therapy for invasive aspergillosis

Answer 98

particularly for immunocompromised patients 1. **caspofungin & micafungin are mild inhibitors of CYP3A4** (increase [drug] in plasma of immunosuppresant tracolimus, an anti rejection drug used in organ transplant patients) 2. **drugs that are inducers of CYP3A4** (rifampicin, an antibiotic for TB, decreases [drug] in plasma of caspofungin)

Answer 99

* unapproved medicine * inhibited DNA synthesis in fungal cells (converts to 5-FU) * limited spectrum * combined with amphotericin &/or azoles * resistance common

Answer 100

* given by i.v. or orally * t1/2 approx. 3-5h * 90% excreted unchanged by kidney * **dosage should be reduced in renal impairment**

Answer 101

infrequent * GI disturbances * anaemia * neutropenia * alopecia more significant in patients with AIDS?

Answer 102

* with Ampho B for → serious fungal infections * cryptococcal meningitis in patients with AIDS * canididiasis * alone or w/ other antifungals for →chromomycosis (skin infection foun in subtropical & tropical areas)

Answer 103

* selective **inhibitor of** squalene epoxidase (**ergosterol synthesis**) * highly lipophillic & keratinophilic → will preferentially accumulate in skin, nails, & hair * fungiCIDAL

Answer 104

* topical or oral * well absorbed (decreased bioavailability due to first pass metabolism) * metabolised in liver, excreted in urine

Answer 105

well tolerated * low incidence of GI distress, headache or rash * not recommended in hepatic failure → check LFTs * SYSTEMIC THERAPY AVOIDED DURING PREGNANCY rifampin (antibiotic) decreases [terbinafine] cimetidine (acid reducer) increases [terbinafine]

Answer 106

* nail onychomycosis (oral) * tinea (cream or spray)

Answer 107

antimicrobials are different to other medicines as they don't just affect the patient receiving treatment! they also affect the patient's immediate community & the global community * they have a societal impact!!

Answer 108

* **cure** a diagnosed infection (individual) * reduce morbidity & mortality (individual) * prevent spread of disease (societal)

Answer 109

1. obtain a thorough history of the patient's **symptoms (patient report)** & presentation 2. are there tests **(signs, clinical finding)** which may indicate an infective process? both signs and symptoms are helpful - but not specific to infection!!

Answer 110

a positive culture

Answer 111

* empiric therapy is medical **treatment** or **therapy** based on experience &, more specifically, therapy begun on the **basis of a clinical "educated guess"** in the absence of complete or perfect imformation" * it covers a variety of organisms that are possible suspected causes of infection (hedging bets)

Answer 112

1. consider patient symptoms 2. consider signs/tests 3. consider risk factors for infections 4. suspected source 5. antimicrobial treatment needed? 6. culture/swab/viral PCR 7. begin empiric antimicrobial therapy

Answer 113

bug, drug and patient

Answer 114

* likely organism & location * severuty of infection → systemic? localised?

Answer 115

* spectrum of activity (broad vs narrow) * PK/PD: distribution, half life * toxicity & ADR profile (risk/benefit) * local sensitivities * formulations available * funding considerations

Answer 116

MOST IMPORTANT CONSIDERATION!! * allergy status * age → neonates, eldery * renal & hepatic function * co-morbidities (including immunosuppression) * prenancy/breastfeeding * history of MDR infection * drug interactions * clinical setting: inpatient/outpatient * site of infection: e.g. CNS infection vs eye infection

Answer 117

narrowing the antimicrobial spectrum (target)

Answer 118

aim of de-escalation is to **reduce the risk of antimicrobial resistance** (AMR) & **improves efficacy** by selecting therapy that targets specific infective organisms

Answer 119

* once cultures & sensitivities are back * patient is clincially improving (if not → aim for broader coverage)

Answer 120

* serum levels (peaks & troughs) - conc. dependant * serum levels (AUC) - time dependent

Answer 121

* most common infections have a standard treatment regimen → refer to local guidelines * guidelines typically provide a range → this requires the use of clinical judgement (severirty of infection, location of infection, & drug tolerability)

Answer 122

* was it truely an infection? * was the empiric therapy appropriate (i.e. appropriate spectrum for supected organism?, dose & frequency?) * recurrent infection? * was the patient compliant? * antimicrobial resistance? → review cultures

Answer 123

* review antimicrobial choice, sensitivity * review antimicrobial dose, route & interactions * review antimicrobial duration * consult AMS team * if non-compliance is apparent, consider why? - e.g. dose frequency, pill burden, special instructions, intolerance

Answer 124

* they are GUIDES * they ASSIST in provision of patient care * CLINICAL JUDEMENT & PATIENT CENTRED CARE MUST STILL BE APPLIED * **there is no "one size fits all"**

Answer 125

a "meeting"

Answer 126

* a **formal welcome** * has to be on a marae - or a maori immensed place

Answer 127

a **formal welcome of the marae**

Answer 128

1. mihimihi 2. whakawhanaungatanga 3. kaupapa 4. whakamutunga

Answer 129

* first element of of the hui process * **intial greeting & engagement** * pharmacists clearly introduce themselves & describe their role & the specific purpose of engagement. They should also confirm that patient identfies as Maori

Answer 130

* second element of hui process * **making a connection** i.e. connecting at a personal level * requires pharmacist to draw on their understanding of te ao Maori & relevant patient & whanau maori beliefs, values, experiences *

Answer 131

* 3rd element of the hui process * **attending to the main purpose of the encounter** * in pharmacy: the point at which the focus moves to history taking or whatever the clincal task at hand is (e.g. counselling)

Answer 132

* finial element of the hui process * **concluding the encounter** * ensure you have understood what the patient has said, ensure patient understands what you have said, ensure patient is clear about the next steps

Answer 133

* mainly becuase of the spread of bacterial resistance * bacteria can be innately resistant to an antimicrobial or resistance can develop (be accquired) due to a genetic mutation

Answer 134

due to unique properties of bacterial replication * reproduce quickly →vertical transmission of mutations that provide a survival advangtage e.g. AMR &... * extra-chromosomal DNA (plasmids) facilitates spread of AMR horizontally, within & between bacterial species (conjugation, transformation, transduction) * many types of resistance can & will develop

Answer 135

* 1959 → found that AMR was being readily transferred from 1 bacteria to another → through plasmids! * found that genes conferring resistance could be carried on plasmids → a single plasmid may contain more than 1 resistance gene * can transfer across species

Answer 136

innate/instrinic resistance is due to → an inherant feature of the bacteria e.g... * drug target is not present * bacteria may have efflux pumps which removes the drug * drug can't cross the outer membrane (OM) of G- bacteria

Answer 137

**decrease entry (influx)** accquired mutations that: * reduce the no. of pores * change the type of pore * impair pore function **increased exit (efflux)** * genes for efflux pumps can be encoded on plasmis & cause accquired AMR as bacteria gain new efflux pumps * mutations can also increase expression of pumps

Answer 138

another way the bacteria can become resistant is if the target is mutated is someway so that the antimicrobial agent can no longer have it's effect - e.g. * **replace the target** → via gene transfer with a new target that has low affinity for the drug * **modification of the target** → via mutation of the binding site while retaining function * **protection of the target** → dislodge drug or compete with drug for target * **overproduce the target** → via mutation to retain function

Answer 139

can develop resistance if the bacteria develop some sort of mutation that will alter the drug acquires an enzyme that: **inactivates/breaks down the drug** * many enzymes indentified, chromosome & plasmid encoded, transfer quickly * e.g. β-lactamases, carbapenemases **changes/modifies the drug** * modifies the drug through the addition of acyl, phosphate, nucleotidyl & ribitoyl groups * can no longer interact with target * large antibiotics (aminoglycosides) more susceptible

Answer 140

* misuse/overuse of antibiotics * OTC supply of antibiotics * incorrect prescribing (viral infections) * empirical use of antibiotics * prophylactic use * increased use of broad specturm antibiotics * use of antibiotics in animal feeds * not taking the entire course of antibiotics???

Answer 141

* common misconception → has no impact on resistance!! * may impact on disease control * **dose & complicance more important as regards to resistance** * i.e. resistance develops when you have subtherapeutic levels of antibiotic

Answer 142

**YES** → but not such a big problem as with bacteria * as bacterial replication rate is much faster * bacteria can transfer resistance on plasmids * bacterial replication is more mutation-prone

Answer 143

same types of mechanisms as in bacteria * drug target alteration * drug target overexpression * efflux pump overexpression

Answer 144

* systemic infections with azole resistant candida are becoming increasingly common * now also developing resistance to polyenes & flucytosine * less resistance to amphotericin B! * OPTIONS → more drug/better delivery, combination therapy, new drugs, new therapies

Answer 145

* disabilities (mental & physical health) * disabilities exacerbated by lack of money (e.g. foot problems, inability to afford special shoes) * care of childern & others * work → long hours, physcial exhaustion

Answer 146

* insufficient income & rising prices * food as the last item of expenditure * shared kitchen in boarding house etc. * lack of storage & preparation space

Answer 147

multiple sources of stress * poverty * poor physical health * waiting for healthcare * access to healthcare * house insecurity * mental health problems * past trauma * worrying about the future for youself, childern & grand children

Answer 148

* busy, stressful lives * knowledge of how health system works * frustration & distrust in the health system * difficulties with arranging & attending appoinments

Answer 149

* may be unable to afford appointments & medicines * may be in debt to medical practise, pharmacy * shame/stigma

Answer 150

* respectful * positive * encouraging * supportive

Answer 151

receive it understanding it is intended to help you on your learning journey * listen * be open * understand the message * reflect * decide

Answer 152

* right 5 → right to effective communication * right 6 → right to be fully informed * right 7 → right to make an informed choice & give informed consent

Answer 153

1. find out what people know → determines baseline understanding 2. build health literacy skills & knowledge → links new info to what the person already knows 3. check you were clear (&, if not, go back to step 2) → use the teach-back method

Answer 154

* what are the** symptoms**? * what are the **characteristics** of the symptoms? * what is the **history** of the symptoms? * when was the **onset**? * what factors **aggravate** the symptoms? * what factors **remit** the symptoms?

Answer 155

* **m**edicines * **a**llergies & adverse effects * medical **c**onditions * **s**ocial history (if relevant)

Answer 156

* Pharmacokinetics = the change in conc. ovr time in the plasma after administration of the drug → **'what the body does to the drug'** * Pharmacodynamics = usually the effect of the drug conc. on the body → **'what the drug does to the body'**

Answer 157

* the lowest conc. of antibiotic required to kill a particular bacterium

Answer 158

* lowest conc. of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation

Answer 159

* an aminoglycoside → used for serious infections due to aerobic G- baccilli * generally the starting dose is 5-7 mg/kg IBW (ideal body weight) given once daily

Answer 160

* Administration - Usually give by IV infusion over 30 mins * Data fits a one-compartment model * Renally cleared (NOT metabolised) - base dose on ideal body weight (IBW) * CL = 4L/h = 80% of GFR * V = 18L = Extracellular fluid volume (EFV) * t1/2 = 3.1h, **almost completely eliminated between doses!** * F = 0 so there is no oral formulation

Answer 161

PD effect on microorganisms: * conc.-dependent bactericidal effect → optimise the Cmax (peak) for max. bactericidal effect * post-antibiotic effect (PAE) → effect on the bug continues when drug is not there! * adaptive resistance

Answer 162

* uptake to the kidneys & cochlear → prolonged high concentrations lead to toxicity

Answer 163

* **concentration-dependent** killing! * bigger Cmax = bigger bacterial kill * extent & rate of bacterial kill is related to Cmax!

Answer 164

* antimicrobials are usually regarded as bactericidal if the MBC is no more than 4 times the MIC

Answer 165

* nephrotoxicity (4-40%) → kidney damage in the tubules, usually reversible * ototoxicity (1-20%) → sensory & vestibular (cochlear) damage, usually NOT reversible * due to the uptake into the kidneys & cochlear * toxicity is rare if doses are adjusted appropriately!

Answer 166

major * **duration of treatment** * **dose** minor * liver disease * prior aminoglycoside exposure * female * other nephrotoxic drugs

Answer 167

* **to reach the highest Cmax:MIC ratio within an acceptable exposure level** * Cmax less than 10mg/L (at least 4-5x the MIC) * Cmin more than 0.5mg/L * AUC of 70 to 100mg/L.h * **the aim is to ensure that high peak levels are acheived (conc.-dependant kill) but that drug is cleared before the next dose**

Answer 168

* a penicillin - used for minor & serious infections due to aerobic G+ baccilli * used for Staph. spp, Strep. spp * has better activity against beta-lactamase producing bacteria * often given in community setting (PO) for uncomplicated, but also given in hospital (PO or IV) for complicated infections

Answer 169

PO, or IV push over 3-5mins or IM

Answer 170

* fe = 0.7 * CL (total) = 8.2 L/h * CL (renal) = 5.4 L/h * V = 10 L * t1/2 = 50 min * F = 0.3 (affected by food) * only 30% of an oral dose is absorbed, rest is degraded in gut or unabsorbed. If taken with food the F is reduced by 20%

Answer 171

* even though it has a short half-life, **the conc. is above the MIC for the whole dosing interval** * the conc.s are very high (80-100 mg/L) on average, & the Cmax greatly exceeds the MIC of the organism

Answer 172

**kill kinetics of flucloxacillin (& all beta-lactams) dependent on time above MIC - needs to be 40% or more** * time-dependent bactericidal effect (time above MIC) * no post-antibiotic effect * minimal toxicity - some bleeding at high doses * doses generally provide a much higher conc. than the MIC in order to account for the short half-life

Answer 173

* choosing a dosing regimen where the **conc. is above the MIC for the longest period of time** * current thinking is that a successful dosing regimen where the plasma conc. is above the MIC **for at least 40% of the dose interval** * so can give as a constant infusion

Answer 174

* beta-lactams * macrolides * tetracyclines **conc.s above MIC for as much as possible of the dose interval**

Answer 175

* aminoglycosides * fluroquinolones **highest Cmax to MIC ratio as possible**

Answer 176

* vancomycin **optimise ratio of AUC to MIC**

Answer 177

antimicrobial resistance occurs when microorganisms such as bacteria, viruses, fungi & parasites change in ways that render the medications used to cure the infections they cause ineffective - WHO

Answer 178

* **public health crisis** * morbidity/mortality * spread of disease * cost: individual, healthcare system & societal

Answer 179

* reduced efficacy when using 2nd line antimicrobials * higher toxicity & rates of adverse effects from the use of 2nd line agents * patient cost/inconvenience with hospital visits for antimicrobial therapy (affecting rural/low socioeconomic groups disproportionately) * longer hospital stays * poorer outcomes from surgery (e.g. joint replacement), cancer care & other interventions * increased mortality * elevated healthcare costs

Answer 180

1. **improve awareness & understanding of antimicrobial resistance** (through effective communication, education & training) 2. **strengthen the knowledge & evidence base** (through surveillance & research) 3. **reduce the incidence of infection** (through effective sanitation, hygiene & infection prevention measures) 4. **optimise the use of antimicrobial medicines **in human & animal health 5. **develop an economic case for sustainable investment** (that takes account of the needs of all countries, & increase investment in new medicines, diagnosis tools, vaccines & other interventions)

Answer 181

1. awareness & understanding 2. surveillance & research 3. **infection prevention & control** 4. **antimicrobial stewardship**

Answer 182

"to optimise the use of antimicrobial agents in the prevention & treatment of infections, & minimise the potential harms that may result from their use including AMR, adverse drug reactions & excessive healthcare surveillance of the quantity & quality of antimicrobial use, education & training, & implementation of quality improvement initiatives" * AMS directly addresses objective 4 of the NZ AMR action plan, & WHO action plan

Answer 183

usually fall into two categories: 1.** broad**, higher level activities→ how can we impact the use of antimicrobial agents to a specific population? 2. **specific**, ground level activities → looking at individual patient context

Answer 184

1. **guideline & clinical pathway** development & review * develop local empiric antibiotic guidlines * base on evidenced based medicine & local antibiotic sensitivies * promotes appropriate use * antibiograms 2. **antimicrobial restrictions** * certain medicines require specialist approval before use 3. **auditing** * surveillence of restrictions * what is being used & why? * used to measure effectiveness of interventions

Answer 185

utilised in practise to: * inform empiric guideline creation * rationalise antibiotic use through targeted therapy (de-escaltion) * improve treatment outcomes * slow down antimicrobial resistance

Answer 186

**IV to PO (oral) switch** * using PO where appropriate, reduces needs for IV line (risks associated) **dose optimisation** * therapeutic drug monitoring (TDM) * avoid sub-therapeutic treatment (right dose, route, duration) **eliminate duplicates** * rationalise combination therapy to avoid overlappomh spectrum **de-escaltion** * cultures * empiric therapy → targeted therapy **duration (hospital charts)** * indicates duration or review date * automatic-stop orders (e.g. perioperative) **interactions** * review for interactions that may increase or decrease the dose requirement **allergy warnings** * very important with b-lactam agents **document indication on chart or script** * poromotes thoughtful prescribing, facilitates clear assessment of suitability of treatment & compliance with best practise

Answer 187

* lay language * written info to describe the WHY & HOW * personalise the message

Answer 188

* water or alcoholic lotion containing a dissolved powder

Answer 189

* usually considered thicker than a solution & more likely to contain oil as well as water or alcohol. A shake lotion separates into parts with time so needs to be shaken to suspension before use * thinner than cream, therefore easy to spread over large area

Answer 190

* thicker than a lotion, maintaining its shape, e.g. a 50/50 emulsion of water & oil. Requires preservative to extend shelf life. Often moisturising

Answer 191

* semi-solid, water-free or nearly water-free (80% oil) * greasy, sticky, emollient, protective, occusive. * no need for preservative, so contact allergy is rare * not that nice to use, as very oily, but good for night time use

Answer 192

* aqueous or alcoholic monophasic semisolid emulsion, often based on cellulose & liquefies upon contact with skin. Often includes preservatives & fragrances * often good for treating hairy areas

Answer 193

* a concentrated supsension of oil water & powder * good for treating particular areas

Answer 194

* wet, oozy skin conditions → creams, lotions, pastes →not as occlusive * dry, scaly conditions → oinments, oils →more occlusive, hydrating * inflamed skin → wet compress, soaks, then creams or ointments * crack & sores → bland, basic formulations → avoid alcohol or acidic

Answer 195

* thick skin (palms soles) → ointment or cream * skin folds → cream or lotion → not as occlusive * hairy areas → lotion, solution, gel, foam → not as messy * mucosal surfaces → non irritating, avoid alcohols & acidic preparations * large areas → lotions can be easier to apply

Answer 196

* histamine = mediator of immediate allergic (urticaria) & imflammatory conditions * also has a role in gastric acid secretion & functions as a neurotransmitter & neuromodulator * most histamine is stored in granules within mast cells or basophils → complexed with a protein (macroheparin) * stimuli trigger its release → then histamine exerts its effects

Answer 197

* is **released by exocytosis** during inflammatory or allergic reactions * causes local increase in permeability of capillaries & venules → redness, itching, swelling

Answer 198

* are all **G-protein coupled receptors** BUT act through different secondary messengers when activated * H1 & H3 elevate cyclic AMP * H3 & H4 stimulate phospholipase C * a rise in cytosolic Ca2+ initiates hisatmine release

Answer 199

* first gen. → more sedating, pharmacist only * second gen. → reduced distribution to the CNS - less sedating

Answer 200

* reversible binding to the H1 receptor to prevent release of histamine * 1st gen H1 antagonists enter CNS readily, have anticholinergic side effects since they interact with muscarinic cholinergic receptors * the active metabolites of hydroxyzine, terfenadine, & loratine are available as drugs (cetirzine, fexofenadine, & desloratadine)

Answer 201

* superficial inflammation of the skin * not causes by infectious agents! * are an immune dysfunction to innocuous foreign/external substances (allergens) or self-proteins (autoimmunity)

Answer 202

* immediate responses from granulocytes → mast cells, eosinophils, neutrophils, basophils * delayed/accquired response → helper T cells (Th cells), many diff. types with diff. roles

Answer 203

* subsets have a physiological role & a pathological role * good & bad! * provide protection to pathogens & destroy transformed cells, BUT can also cause tissue destruction, remodelling, DNA mutation & cancer

Answer 204

* very **common** skin disease, inflammation of sebaceous gland * common at puberty, also present in adults

Answer 205

closed comedone = white head open comedone = black head

Answer 206

* androgens → plays a crucial role in pathogenesis, does NOT develop in their absense * androgens stimulate the growth of sebaceous glands & stimulate sebum production

Answer 207

* anabolic steroids further increase sebum production, estrogens decrease sebum production by decreasing androgen production

Answer 208

* spontaneous changes in keratinocytes → increased turnover * altered pattern of kertinisation * keratinous material becomes denser, altered lipid metabolism

Answer 209

* Stap. epidermis → top of the follicle * Propionibacteria: P. acne, P. granulosome, P. parvum → lower, initiate inflammation through interaction with keratinocytes

Answer 210

* **genetics** * no link between 'cleanliness' & acne! * diet, stress, smoking → ***may*** impact

Answer 211

* usually heal spontaneously, main treatment aim is to reduce scarring & prevent new lesions * CAM use is widespread → no good evidence to support use but gives a feeling of control & being more natural. Can have adverse effects

Answer 212

* **atopic dermatitis** (atopic/allergic eczema) → allergic immune response * **contact dermatitis** (contact eczema) → can occur both allergic/atopic individuals & non-atopic individuals, some evidence for increased rate of ACD in atopic indiviudals * irritant contact dermatitis (ICD) * allergic contact dermatitis (ACD) * protein contact dermatitis (PCD)

Answer 213

* commonly diagnosed in childhood * geographic variations in prevalence * complex disease → genes & environment * strongest risk factor = family history

Answer 214

**acute** * allergens enter via damaged skin & stimulate release of inflammatory mediators from granulocytes **chronic** * driven by cytokines released by T cells * keratinocyte (KC) dysfunction * skin becomes thick

Answer 215

* all studies reported some symptom reduction * impact depends on when used (in pregnancy, early or late) * depends on strains of Bifidobacterium & Lactobacillus used * minor adverse effects in healthy individuals

Answer 216

* physical (UV, heat, cold, damp) or chemical (detergents, solvents, bleaches) agents causing direct irritation/injury * can be acute (mins to hours) or chronic/cumulative, mild or severe, recurrent

Answer 217

* immune response to small organic & inorganic allergens that can penetrate skin e.g. nickel * sensitizing phase (asymptomatic) of weeks to months then an inflammatory phase * T cell response

Answer 218

* immune response to large protein allergens * can NOT penetrate intact skin * sensitizing phase (asymptomatic) of weeks to months then an inflammatory phase * IgE & cellular response → similar to allergic dermatitis

Answer 219

* varied clinical presentation → erythema, scales, crusts, erosion * ICD usually dryer than ACD

Answer 220

* ICD (irritant contact dermatitis) caused by irratants (ammonia in urine, proteolytic enzymes in faeces), friction, damp * redness, swelling, initially scaly, progresses to erosions, can be acute or chronic * complication is yeast infection (pustules) or bacterial (crusty) secondary infection * treatment if its uncomplicated → regular nappy changes, careful cleaning, barrier creams * treatment if its complicated → treat infections

Answer 221

* common * itchy weheals (hives), localised oedema of the upper dermais, or can occur in deeper dermal layers (angioedema) * can be acute or chronic → self resolving

Answer 222

* pathophysiology → mediated by mast cell degranulation * causes → idiopathic/'one-off', physical triggers - pressure (scratching), heat, cold, chemical contact, allergies * treatment → avoid triggers, pharmacotherapies

Answer 223

* chronic **T cell mediated** inflammatory disease that can develop into psoriatic arthritis (within 10 years) * onset in yoing adults * lesions variable, sharp boarders, erythema, scale, pustules * 1 in 4 patients experience psychosocial distress * common co-morbidities → psoriatic arthiritis (11-30%), CVD

Answer 224

* higher prevelance in: adults, higher income contries * genetic pre-disposition * enviromental risk factors: medications, infection/GI dysbiosis?, trauma, smoking, alcohol

Answer 225

initiation: * damaged KC release 'dangre' molecules that activate DC, go to lymph node & activate T cells * trigger??, antigen - self?? inflammation: * Th cells release cytokines → activate KC, neutrophils, mast cells, macrophages * dermal hyperplasia, impaired KC differentiation → plaque formation

Answer 226

* pharmacotherapy * NO cure, just manage disease * initial treatments centered on lytic & anti-miotic drugs. Now targte very specific molecules of the immune system * probiotics, faceal microbiotic transplant?

Answer 227

* job is to produce hormones & steriods * consists of the medulla & the cortex * medulla (core) → nerve endings → makes neurotransmitters * cortex (surrounding layer) → gland tissue

Answer 228

* mineral corticoids * glucocorticoids * androgens * catecholamines * peptides

Answer 229

* cortisol is the predominant corticosteriod secreted from the adrenal cortex * secreted according to a **diurnal pattern** (highest after wakening) under the influence of ACTH from the pituitary gland under the influence of CRH from the hypothalamus ACTH = adrenocorticotrophin CRH = corticotrophin releasing hormone

Answer 230

* secreted from → Zona fasciculate of the adrenal cortex * Cortisol half life = 70-90 mins * Mainly effect the metabolism of glucose via carbohydrate, protein and lipid metabolism * Control the carbohydrates, fats and other proteins within the system * Help with healing wounds of minimising pain in injury

Answer 231

* secreted from → Zona glomerulosa of the adrenal * half life = 20mins * main action on minerals like Na, K and H ions * Control of electrolytes and water balance of the body

Answer 232

is a corticosteriod naturally produced by the body

Answer 233

1. diurnal variation 2. stress (physical & psychological) 3. negative feedback (helps to regulate the amount released)

Answer 234

anti-inflammatory & immunosuppresant drugs routes of administration: * oral → prednisone, budesonide * iv → methylprednisolone, hydrocortisone * enema → hydrocortisone * rectal foams → hydrocortisone * topical → hydrocortisone & betamethasone

Answer 235

* Activated GR complex up regulates the expression of anti-inflammatory proteins * Activated GR complex decreases the expression of pro-inflammatory proteins

Answer 236

* not stored - rate of synthesis = rate of release * synthesized rhythmically and controlled by irregular pulses of ACTH * influenced by light and major pulses occur in the morning and after meals * Glucocorticoids act via their receptors (GR) in the nucleus * GRs are widely distributed and located in almost all cells in the body

Answer 237

* most physiological effects of glucocorticoids & mineralocorticoids hormones are **mediated through binding to intracellular** that operate as ligand-activated transcription factors to regulate gene expression * mineralocorticoid & glucocorticoid receptors are closely related & share similarities in their ligand & DNA binding domains

Answer 238

are classified into: * **type 1** → specific for minieralocorticoids, but have high affinity for glucocorticoids * **type 2** → are specific for glucocorticoids & are expressed in virually ALL cells

Answer 239

**adrenal axis suppression** * risk of death with abrupt cessation of dosing * requirement for dose-tapering effects on carbs, protein and fat metabolism **effects on carb, protein & fat metabolism** * promotes gluconeogenesis * can precipitate hyperglycemia * skeletal msucle wasting * hypertension (mineralocorticoid effects) * redistribution of body fat ('moon face', 'buffalo humps') * elevation of mood * skin thinning * acne * bruising

Answer 240

* are use for the treatment of inflammatory coniditions of the skin (other than those from infection!) → e.g. eczema, contact dermatitis, insect stings, & eczema of scabies * corticosteriods **suppress the immune system** * are **not curative** & on disocontinuation a rebound exacerbation of condition may occur * generally used to **relieve symptoms & suppress signs** of disorder (when other measures like emollients are ineffective) * can get different potencies! (mildly potent, potent, very potent)

Answer 241

* powder * paste * cream * lotion * oinment * drops * foam

Answer 242

* forearm absorbs 1% * armpit absorbs 4% * face absorbs 7% * **eyelids & genitals absorb 30% (max)** * palms absorb 0.1% * **sole absorbs 0.05% (min)** the less absorption, the more potent of a steroid you can use (generally) * minimal systemic absorption (i.e. into the body) → however after a few weeks treatment, tempory HPA axis suppression does occur, resolves upon cessation

Answer 243

**uncommon or rare if used appropriately** * skin thinning * stretch marks * easy bruising * enlarged blood vessels * susceptibility to skin infections * localised increase in hair thickness & length * allergy

Answer 244

* Apply to affected areas only * do not apply more frequently than twice daily * use the least potent formulation which is fully effective * use appropriate formulation for the area * use appropriate quantity * use for the shortest time possible

Answer 245

* aka 'Tinea pedis' a fungal infection * superfical mycosis → doesn't go deep, doesn't cause systemic infection * very common infection * prevalence rates 15-20% * common in tennage & adult males * rar in children under 12

Answer 246

* causitive agents → Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum * spores found in shoes, carpet, bath mats, showers (can survive for months) * is **not highly infectious**, but loves warm, moist enviro's (inside sweaty shoes & shoes) * chronic recurrent disease * predisposing factors → immune deficiency, poor circulation, sweaty feet

Answer 247

* **variable presentation** * interdigitating, scaling, splitting * onychomycosis * 'moccasin' type → dry, scaly, red, itchy (heels, toes, side of feet) * blistering * complications → secondary bacterial infections in broke skin (needs to be treated) * treatment → OTC preparations

Answer 248

* different causative agents → often zoonotic (from pets) * T. rubrum, Microsporum canis, T. verrucosum * can be acute or chronic * inflammed red patches, white healing midle, itchy, inflamed, pustular * commonly confused with non-fungal conditions such as impetigo, psoriasis, discoid eczema, allergic dermatitis * quick test to distinguish fungal & non-fungal conditions is to use a Wood's light

Answer 249

* **scalp infection** → inflammation, hair loss * common in school age children * in NZ commonly from infected cats → M. canis * transmissable via spores on hairbrushes, clothing

Answer 250

* OTC ointments & shampoos (also for contacts who may be asymptomatic)

Answer 251

* warts (verruca vulgaris) are **cutaneous tumors** (benign) → **caused by** human pailliomarviruses (**HPV**) * very common, caused by a large no. of HPV, many different types of lessions * human to human transmission, long incubation time, also get auto-inoculation * differential diagnosis → if it looks like a wart it probably is, only refer eldery or immunocompromised patients with atypical warts

Answer 252

* no therapy as will generally disappear by themsleves (but this may take years) * cosmetic removal or warts → laser, chemical, surgical removal * cytostatic agents, keratolytic agents * stimulate the immune system to kill warts → imiquimod cream

Answer 253

* causative agent → Herpes simplex virus Type 1 (**HSV 1**) * viruses are endemic, virus remains latent in nerve infections * 1º infection usually occurs in childhood, **7 day incubation**, widespread sores (red bump, blister, crust, drops off 7-10 days) usually no scarring! * recurrence → fewer or no sores, sores maybe preceded by burning or itching * triggers for recurrance → sunlight, fever, menstruation, immune suppression * **treatment → acyclovir**

Answer 254

* **caused by varicella-zoster virus (VZV)** * human reservoir * moderate to highly contagious, generally a self limiting infection * **transmitted by airborne route** → vesicles shed from skin * endemic in temperate countries * primary infection → varicella (chickenpox) * **reactivation → herpes zoster (shingles)**

Answer 255

* 14-16 day incubation * prodromal phase (fever, malaise, fatique) then the rash * raised red bumps, scalp face & trunk (3-5 days, few to many) * itchy, fluid filled blisters → rupture, then scab over (24-48 hours - no longer infectious!)

Answer 256

* most common → secondary bacterial infection of rash with a Staph. or Strep. * hospitalisations → overall rate 8.3/100,000 * inequalities in hospitilisation * rate increasing? → support for inclusion of a vaccine on the nation immunisation schedule (NIS)

Answer 257

* mild disease → supportive therapy only * prevention → live attenuated vaccine, Oka strain VV (Varilix) added to NZ schedule in July 2017

Answer 258

**superficial:** * follicle infections * impetigo * leprosy **invasive:** * cellulitis * closteridial infections

Answer 259

* folliculitis (single infection), boils (multiple) → furuncles or carbuncles * hair follicile is infected generally by a bacteria (Staph. a.) but may be a fungal or viral infection * occurs commonly in → groin, armpits, scalp (moist, warm environment) * often occurs as a complication to acne or after waxing/shaving

Answer 260

* **Folliculitis** → localised small inflamed pustules, itchy or painful * **bolis (furunculosis)** → more severe, deeper infection of one or more follicles, often has a central yellow 'plug', bigger lesions, commonly in areas of friction, usually will drain themselves, systemic symptoms * **Carbuncle** → conglomeration of several furuncles → massive amounts of necrosis and bacteria (pus), systemic symptoms, will need to be drained

Answer 261

treatment: * depends on severity & if it needs drainage * antibiotics → topical, local or i.v. complications: * rare, assocaited with severe infection → endocarditis, sinus thrombosis

Answer 262

* Superficial infection of the epidermis caused by staphylococcus aureus or streptococci pyogenes * In NZ and Australia commonly known as 'school sores' * Highly infectious * risk factors → broken skin (viral infections, trauma, scratching) * No systemic symptoms, resolves without scarring

Answer 263

**nonbullous** (impetigo contagiosa): * immine response to bacteria → vesicle to erosion to honey-coloured crust * highly contagious often around nose & mouth **bullous**: * due to toxin, fluid filled blisters, when burst get crust * less contagious * can occur in armpits, neck folds, etc. (moist areas)

Answer 264

autoinnoculation from nose, person to person, towels, face clothes

Answer 265

* **"clean, cut, cover"** * topical or systemic antibiotics * child can return to school 24 hours after starting treatment * complications → systemic spread → glomerulonephritis (4%) or scarlet fever (rare)

Answer 266

* gram positive, anaerobic, rod shaped, spore forming & toxin producing * environmental infection of deep tissue through an open wound, no person-person transmission * minor cause of serious skin infections in NZ, vaccine for C. tetani * examples → C. tetani, C. perfringens

Answer 267

* 14-28 day infection * early symptoms → tissue infection, weakness, stiffness, cramps. late - spasms, seizures * 1% mortality for localised tissue infection, >60% for infection in neonates * After infection exotoxin is secreted binds to presynaptic nerve endings and prevents release of GABA and glycine - no inhibition - spasms and seizures * **vaccine widely used** * neonatal infection in low income country

Answer 268

* risk factors → vascular disease, diabetes, trauma, surgery * **necrotising disease** similar to streptococcal NF but progresses faster, * **major toxin is alpha-toxin** * early → pale skin - fluid filled blisters - discharge - gas production * Late → severe pain, tachycardia, fever - progresses to hypotension and organ failure * iv antibiotics and debridement, hyperbaric oxygen therapy

Answer 269

* chronic, slow progressing, minimally contagious infection * caused by Mycobacterium leprae * curable * involves skin, mucosal membranes & nerve endings in skin * can infect any age group! * social implications → historically patients sent to leprosy colonines * transmission → person to person, respiratory?, insects? * 1991 WHO developed a program to eliminate leprosy

Answer 270

* most people will not be infected (<5%), rates increase with deprivation * long incubation time → average of 5 years * 2 main types of leprosy → tuberculoid & lepromatous (with 3 intermediate borderline classifications)

Answer 271

* **non-infectious** * paucibacillary * small defined dry, scaly lesions, slow growing, hair loss * systemic nerve damage * trauma to extremities common!

Answer 272

* progressive * contagious infection * multibacillary * involement of the face, earlobes & nose * chronic nasal discharge * systemic nerve damage → slow to develop

Answer 273

* are a number of antimicrobials available → e.f. dapsone, rifampicin, clofamizine * to combact resistance multi-drug therapy is used, generally for 12 months * plus surgical reconstruction * prevention → tuberculosis vaccine, bacillus calmette-guerin (BCG) has some efficacy

Answer 274

* **topical** → is for the localised treatment of a dermatological condition e.g. Zinc & castor oil oinment, topical corticosteriods * **transdermal** → refers to producst that use the skin surfaces as a portal for systemic delivery of bioactives e.g. voltaren emugel

Answer 275

* the stratum corneum (top layer of the skin)

Answer 276

* rate-limiting process → diffusion * disease condition to treat → tinea, corns & calluses

Answer 277

* rate-limiting step → diffusion * disease condition to treat → psoriasis, eczema

Answer 278

* rate-limiting step → blood supply & diffusion * disease condition to treat → psoriasis, eczema, urticaria

Answer 279

* rate-limiting step → metabolism & excretion * disease condition to treat → hypertension, angina, nausea

Answer 280

**atopic skin:** * not tightly packed → breakdown of skin layer * The breakdown of the skin barrier means that irritants, allergens and pathogens can penetrate the skin causing inflammation and itching * water is lost from the skin * comeocytes shrink and gaps form between them Atopic presenting skin symptoms →dry skin, inflammation and itching **normal skin:** * tightly packed * penetration of irritants, allergens & pathogens is blocked by the natural skin barrier * water is attracted into & retained within the comeocytes causing them to swell & sit together nicely

Answer 281

**mainstay → hydration!** * moisturiser's * soap substitute **medicated products** * keratolytics (scaly) * topical corticosteroids (inflammation) * antipruritic (itch) **products (topical) types** * oils * lotions * creams * oinments **pain relief (if required)**

Answer 282

reduce the lose of water (bond with water to withdraw moisture from deeper layers of the skin or from the atmosphere to the skin) e.g. glycerine, hyaluronic acid, urea

Answer 283

* soften/smooth skin ('fill' voids between rough/peeling skin cells) * e.g. oils, shea/cocoa butter

Answer 284

* form a barrier on the stratum corneum * e.g. vaseline (petroleum), mineral oil, lanolin, silicone * stops air escaping skin

Answer 285

* typcally contain absorption bases (contain w/o emulsifying agent) * can absorb large amounts of water (approx. 50% their volume) & thereby produce w/o emulsions

Answer 286

* synthetic analogues of cortisol (HC) * Anti-proliferative/anti-inflammatory actions → atopic condition e.g. eczema and psoriasis * Ideal topical CCs permeate SC into the dermis (not into systemic circulation) → governed by lipophilicity * Modification of ring structure ± side chains → potency and modulation of ADRs (side effects)

Answer 287

**changing structure slightly will change action!** * HC backbone modified to change potency → OH group at C11 required for glucocorticoid activity * double bond: C1-2 to → anti-inflammatory activity (e.g. HC → prednisolone) * halogenation: (6⍺ or 9⍺ position, fluorination → increase potency/receptor affinity) * esterification or addition of acetonide → increase lipophilicity → increase skin absorption

Answer 288

efficacy ('potency') = potency (CCs chemisty) + vehicle (formulation) * i.e. efficacy = pharmacological potency + ability to be absorbed & reach target cells can have: * very potent or superpotent * potent (100-150 times as potent as hydrocortisone) * moderate (2-25 times as potent as hydrocortisone) * mild

Answer 289

* need to get into the viable layers of the skin → e.g. the viable epidermis & dermis * glucocorticoid receptor (keratinocytes & fibroblasts)

Answer 290

* skin properties dertermines bioavailablity * occulusive dressings → increase permeability < 10-fold, however decrease in use due to availability of super potent CCs * eyelids & genitals absorb the most → as skin is thinnest there

Answer 291

vehicle (formulations) **play a key role in the appearance, feel & successful application** of topical CCs * physical form * solubility * rate of drug release * degree of hydration * chemical/physical stability * physical and chemical interactions with the skin and active molecule * location and extent of disease * emollient properties

Answer 292

at any given strength of a corticosteroid → ointments > cream formulations > lotions * i.e. **ointments are always the MOST POTENT** * occlusive vehicles → trap transepidermal moistures → increase skin water content * hydration of the SC → swells the membrane → increase drug permeability

Answer 293

* reversible decreases the barrier resistance of the SC without damaging any viable cells → increases drug absorption * e.g. interact with head group or insert between bilayer → affect lipid packing disorder

Answer 294

(numbering = relative potency) 1. Diprosone OV ointment → e.g. propylene glycol 2. > Diprosone OV cream → e.g. propylene glycol 3. > Diprosone ointment → e.g. soft white paraffin; liquid paraffin 4. > Diprosone cream → e.g. cholrocrestol

Answer 295

* lubricant, decreases transepidermal H2O loss, occlusive → increase absorption * good for dry scaly lesions or non-hairy skin * BUT low patient acceptance

Answer 296

* cosmetically appealing (can be washed off) * good for larger areas

Answer 297

* hairy areas/large areas have to be treated * cooling & drying effect (useful for treating moist lesions &/or pruritus)

Answer 298

* spread readily & are easier to apply * complex delivery systems - so expensive!

Answer 299

**problems:** * regulatory requirements increase * patents expire relatively soon after market introduction * treatment times tend to decrease * new drugs often reserved for special patients or situations **solutions:** * tax incentitives, patent extensions, academia-industry collaborations * 2012 → FDA offered a series of marketing incentives for new antibiotics

Answer 300

* quantity over quality? * limited number of new agents * pipeline mainly consists of derivatives of known drugs * many prone (to some degree) of existing cross-reactive resistance * incomplete coverage * not keeping up with resistance

Answer 301

* new anti-bacterial agent → 2015 * isolated from a soil organism (using new culturing technique) → binds to peptidogylcan precursor in gram +ve organisms, active against MRSA * Low (no) resistance? (as it binds to lipids!) * years away from clinic... issues → difficult to synthesize, low oral bioavailability

Answer 302

**immunotherapy:** * cytokines * TLR agonists * antibodies * vaccines **anti-microbial therapies:** * peptides * bacteriophages * predatory bacteria

Answer 303

***Prevent infection *** * boost immunity or provide immunity (passive immunisation) in vulnerable populations * active immunisation ***Treat infection *** * act on the immune system to boost existing immune responses * act on the pathogen directly ***treat inflammation*** (pathology mediated by immune system) * act on the immune system to modulate inflammation

Answer 304

* used to prevent disease in individuals & decrease spread through a community (herd immunity) * active immunization = vaccines on NZ immunisation schedule * passive immunisation = antibody given not not able/no time for active immunisation

Answer 305

used to treat individuals already sick, still experimental → HIV, hepatitis

Answer 306

* use of antibodies was **one of the first anti-microbial therapies** * use before the discovery of antibiotics to treat disease such as diptheria, tatanus * excellent therapy * **reduce/remove/reverse toxicity **from exotoxins, immune mediators * kill → pathogens & pathogen infected cells * modulate cell activity

Answer 307

* therapeutically → used to treat infectious disease → e.g. tatanus, diphtheria, rabies, anti-venom, new uses - hepatitis, RSV, meningitis, C. difficile * prophylatically → given to vulnerable populations (e.g. healthcare workers, leukemics, pregnant women), also known as passive immunisation

Answer 308

* both polyclonal & monoclonal antibodies manufactured for use in prevention & early treatment of COVID * bind to virus & prevent infection of new cells * combinations of monoclonal antibiotics used to prevent selection of resistant virus

Answer 309

* short term effect? (months) * anaphylaxis * unwanted activities * cost???? * but their use is increasing...

Answer 310

* soluble messengers of the immune system * proteins → need to be given by injection * most act as short range (cell -cell) * act at low concentration (10^-10 M) * short half life * multiple, overlapping activities * produced by many cells or few cells * potential therapeutic use in infections, cancer, autoimmunity

Answer 311

of the 130 known cytokines 18 are approved for human therapy as recombinant preparations * Actimmune → trialed fro use in treating Mycobacterial infections in combination with Leukine * Pegasys → pegylated to increase half life, for viral hepatitis * neupogen & proleukin → in use or trialed for HIV

Answer 312

* main limitation → toxicity - encapsulation? * lack of specificity * effect on pathogens → some cytokines can also act as growth factors for pathogens * short half life → pegylation * bioavailability * cost

Answer 313

* Pattern recognition receptors (PRR) on cells of innate immune system recognise conserved 'patterns' from microbes e.g. Toll-like and NOD - like receptors (TLRs and NLRs) * agonists can be used to stimulate innate immune response * antagonists can suppress pathological inflammation

Answer 314

* **advantages **→ target the host not the pathogen → no selective pressure/resistance * **disadvantages** → overactivation of innate immunity → pathologic inflammation, autoimmunity

Answer 315

* can be isolated from both eukaryotes and prokaryotes * new, natural 'antibiotics' from bacteria, sea sponges, trees, plants, animals, milk * small - 10-15 amino acids (aa) usually cationic * issues with bioavailability and stability resistance will develop * activity against bacteria, viruses and fungi * also have effects on the immune system * activity related to aa composition and properties (such as positive net charges, flexibility, size, hydrophobicity

Answer 316

* viruses of bacteria * specific host ranges * can kill bacteria very quickly → new phage produced within 30 minutes * first discovered in 1886 * hot topic until the discovery of antibiotics * resurgence in research with the development of antibiotic resistance

Answer 317

* advantages → very specific, easy to grow & isolate, little toxicity (?), self-replicating & self-limiting, good biodistribution * disadvantages → bacteria develop resistance (therefore mixtures of phages are used), immune response to phages

Answer 318

* interesting alternative... * use with antimicrobials (are innately resistance to b-lactams and antifolates) and bacteriophages * Bdellovibrio and like organisms (BALOs) show particular promise * BALOs are motile bacteria that predate gram - bacteria for energy and nutrients * potentially useful for biofilms e.g. catheters, periodontal disease and other situations where antibacterials can't gain access to infection - ocular infections, burns, infections in cystic fibrosis patients... * more research needed...

Answer 319

* **erythromycin**