Antimicrobials. UWORLD
Other pharmacodynamic concepts
(Choice D) (Choice E)
Time dependent killing aka little doses over long periods (multiple-daily dosing)
(eg, beta-lactams - [penicillins, (cell wall cross linking) - cephalosporins], clindamycin) 50S
PROTEIN SYNTHESIS inhibitors BacterioSTATIC (stop growth but don't kill) The only bactericidal ones are: - aminoglycosides (30s) - linezolid (50S)
30S subunit: AT 30 Aminoglycoside (mycins). 30- GNATS-mycin - Gentamycin, Neomycin, Tobramycin, Streptomycin, Amikacin Glycylcycline - Tigecycline Tetracyclines (-cycline) ( tetracycline, Doxycycline, Minocycline) 50S Subunit: CELL at 50 - Chlormaphenicol - Clindamycin - Erythromycin (macrolide example) - Linezolid Macrolides: (Omycin) 50- ACE-OMYCIN - Azithromycin, Clarithromycin, Erythromycin Streptogramins: - Quinupristin - Dalfopristin
SE of NRTIs
Bone marrow suppression (give epo & gran colony stimulating factor) peripheral neuropathy lactic acidosis
how do NRTIs work? Zidovudine
By inhibiting phosphodiesterase bond formation HIV enzyme reverse transcriptase grows DNA by adding nucleotides to the terminal 3′-hydroxyl group using a 3′-5′ phosphodiester bond. Nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine block this step in viral replication. This class of medications is composed of nucleoside/nucleotide analogues that do not have a 3′-hydroxyl group. When reverse transcriptase incorporates an NRTI into a growing DNA strand, it results in chain termination because no 3′-hydroxyl group is available to add additional base pairs.
DOC for ESBL (beta lactamases)
Carbapenems (eg, imipenem) are the treatment of choice for ESBL-producing organisms
ATTACK DNA
DNA gyrase: Fluoroquinolones: - floxacin - ciprofloxacin - levofloxacin etc RNA polymerase (mRNA synthesis) - Rifampin DNA integrity (via free radicals) - Metronidazole
beta-lactamases are spread through PLASMIDS!!
ESBL enzymes can inactivate: - extended-spectrum penicillins - cephalosporins (including third- and fourth-generation cephalosporins) - monobactams (aztreonam). Genes encoding these enzymes are often located on plasmids and therefore can be transferred. Carbapenems (eg, imipenem) are the treatment of choice for ESBL-producing organisms
Pt is tx with medication for tuberculosis presents with blurry vision, central scotomas What med caused visual changes?
ETHAMBUTOL (aka EYE-thambutol) The most notable side effect of ethambutol is optic neuropathy, which clinically manifests as decreased visual acuity, central scotoma, or color blindness. It may be reversible with discontinuation of the drug.
Attachment CCR5 antagonist MARAVIROC prevents gp120 from interacting with CCR5
For HIV to infect a cell, the envelope glycoprotein gp120 must bind to both a CD4 molecule and a chemokine receptor (eg, CXCR4 or CCR5). CCR5 antagonists, such as maraviroc, exert their antiviral activity against HIV by blocking attachment and entry of CCR5-tropic viruses into CD4+ T cells and macrophages.
Tx for CMV se?
GANGICLOVIR SE: neutropenia, anemia, and thrombocytopenia. First-line therapy for CMV colitis and retinitis is ganciclovir. This medication inhibits viral synthesis by blocking CMV DNA polymerase. However, ganciclovir also blocks host DNA polymerase to a lesser degree, which can lead to hematologic side effects such as neutropenia, anemia, and thrombocytopenia.
CELL MEMBRANE integrity
Gram + - Daptomycin Gram - - Polymyxin
Isoniazid most important side effect
HEPATOTOXICITY also NEUROTOXICITY which can be prevented with pyridioxine
pt infected by MRSA with mecA gene
Methicillin-resistant strains are able to grow in the presence of oxacillin due to the acquisition of a mobile genetic element that contains the mecA gene, which encodes for penicillin-binding protein (PBP) 2a. Unlike other PBPs, PBP 2a has a low affinity for beta-lactams and continues to cross-link peptidoglycan in the presence of oxacillin, methicillin, cephalosporins (eg, cefazolin), and other beta-lactam medications. Therefore, treatment of methicillin-resistant S aureus (MRSA) generally requires the use of a non-beta-lactam drug. Common medications for MRSA include: - trimethoprim-sulfamethoxazole (inhibits 2 steps in folate synthesis), - clindamycin (inhibits bacterial protein synthesis by binding to the 50s ribosomal subunit), - doxycycline (inhibits protein synthesis by binding to the 30s ribosomal subunit), or vancomycin (inhibits integration of peptidoglycan subunits)
Linear vs Sigmoid dose-response relationship
Most drugs exhibit a sigmoid-shaped dose response curve that shows no effect until a threshold concentration is exceeded. After this occurs, the effects increase with increasing drug concentration until a saturation threshold (ie, maximum effect) is reached. In contrast to this sigmoidal response, the risk of cancer following exposure to ionizing radiation shows a linear dose-response relationship (ie, risk increases proportionately with increased exposure).
Gonorrhea/urethritis with discharge in a male
Must tx for BOTH gonorrhea and chlamydia so: IM ceftriaxone + p.o. azithromycin/doxycycline Urethritis in a young man is most likely to be due to Neisseria gonorrhoeae or Chlamydia trachomatis, both of which cause dysuria and mucopurulent urethral discharge . The standard treatment for suspected gonococcal urethritis presumes infection by both organisms. Therefore, ceftriaxone is given for N gonorrhoeae, and doxycycline or azithromycin is given for C trachomatis.
Isoniazid specific target
ONLY affects mycobacteriam. specifically inhibits the synthesis of mycolic acids, Without mycolic acids, the mycobacteria lose their acid-fastness and become unable to synthesize new cell walls or multiply.
Protease inhibitor: - NAVIR (atazanavir, darunavir etc)
Prevents viral protease from cleaving the HIV polypeptide precursor into individual proteins by viral and cellular protease enzymes.
HIV
The HIV genome encodes several enzymes and structural proteins in polycistronic mRNAs that are then translated into polyproteins and cleaved by proteases into the individual proteins that compose the virus. The env gene encodes the polyprotein gp160, which is extensively glycosylated in the endoplasmic reticulum and Golgi body and subsequently cleaved into the mature envelope proteins gp120 and gp41. These envelope proteins remain associated by noncovalent attachments and form the glycoprotein spikes that pepper the surface of the HIV virus. gp120 forms the outside surface of the glycoprotein spike and mediates viral attachment to the host cell by binding with the CD4 receptor and a chemokine coreceptor (CXCR4, CCR5) (Choice A). Binding of gp120 to these host receptors induces a conformational change in the structure of the glycoprotein spike that exposes the underlying transmembrane glycoprotein gp41. gp41 mediates fusion of the viral cell membrane with the host cell membrane, thereby allowing the viral core to enter the cell. Drugs that selectively bind gp41 (eg, enfuvirtide) are known as fusion inhibitors because they prevent gp41 from undergoing the conformational changes necessary for viral fusion, which prevents the HIV genome from entering uninfected cells.
Stem describing bacterial cell wall lysis/ damage "spherical configuration when placed in an isotonic solution and disintegrate rapidly when placed in a hypotonic solution."
The bacterial cell wall protects the organism from osmotic stress. Antibiotics that target the CELL WALL result in bacterial lysis in hypotonic solutions. Fosfomycin, vancomycin, penicillins, and cephalosporins all disrupt bacterial cell wall synthesis.
Therapeutic index
The therapeutic index (ie, [toxic dose]/[effective dose]) is a measurement of the relative safety of a drug; it is an intrinsic property upon which drug dosing regimens are devised. A relatively high therapeutic index is usually necessary to prevent toxicity with extended-interval dosing because the administered drug amounts lead to higher serum levels than seen with more frequent dosing regimens.
Threshold dose
The threshold dose is the lowest dose at which drug effects are first seen.
30S subunit buy AT 30 30 GNATS-mycin
30S subunit Aminoglycoside (mycins) - Gentamycin - Neomycin - Tobramycin - Streptomycin - Amikacin Glycylcycline - Tigecycline Tetracyclines (-cycline) - tetracycline - Doxycycline - Minocycline
50S subunit CCEL at 50 50- ACE-OMYCIN
- Chlormaphenicol - Clindamycin - Linezolid Macrolides: (mycin) - Azithromycin - Clarithromycin - Erythromycin Streptogramins: - Quinupristin - Dalfopristin
Other parasitic tx
- Diethylcarbamazine is indicated for the treatment of Loa loa (loiasis) and Wuchereria bancrofti (lymphatic filariasis) infections. - Ivermectin is used to treat infections caused by Strongyloides stercoralis (strongyloidiasis) and Onchocerca volvulus (onchocerciasis). - Nifurtimox is used to treat diseases caused by trypanosomes, including Trypanosoma cruzi (Chagas disease). - PRAZIQUANTEL: Infections caused by Schistosoma (schistosomiasis), Clonorchis sinensis (clonorchiasis), and Paragonimus westermani (paragonimiasis) are treated with praziquantel.
Avoid ANTACIDS when taking which antibiotics? also: - iron - calcium - magnesium - aluminum
- Tetracyclines - fluoroquinolones (ciprFLOxacin) - levothyroxine this can lead to CHELATION and impaired absorption and a significant decrease in drug bioavailability.
Antifungal that inhibits p450 inhibitors: - antifungals - antibiotics - grapefruit juice
-AZOLES!! ketoconazole, fluconazole, itraconazole, voriconazole UWE: Azoles are antifungal medications that inhibit the demethylation of lanosterol into ergosterol in fungal cells. They exert their antifungal effects by suppressing synthesis of ergosterol, an essential component of the fungal cell membrane. However, azoles also inhibit the activity of the human P450 cytochrome oxidase system. Causes drug toxicity/overdose of drugs normally metabolized by liver P450 enzymes. For this reason, medications such as warfarin, cyclosporine, tacrolimus, and oral hypoglycemics should be avoided (or have their use carefully monitored) in patients who are receiving azole therapy. Cytochrome oxidase inducers (eg, rifampin, phenytoin, carbamazepine, phenobarbital) increase azole metabolism, thereby lowering azole concentration in serum.
UNDERSTANIDNG HIV
1. HIV viron attaches, penetrates, uncoats itself & releases contents into host cells. med: - Maraviroc (attachment - CCR5 antagonist) - Enfuviritide (penetration - p41 protein) REVERSE TRANSCRIPTASE 2. After an HIV virion enters a host cell, viral RNA is transcribed into DS-DNA by reverse transcriptase. - NRTIs: (abavavir, didanosine, zidovudine, lamivudine, tenoforvir etc) - NNRTIs: (DEN: delaviridine, efavirenz, nevirapine, ) aka. HIV enters the target. Then it releases its viral RNA and uses reverse transcriptase to change it into DS-DNA INTEGRASE 2. The viral DNA then enters the nucleus and, through the actions of integrase, permanently inserts into the host cell's chromosomes to become a provirus. 3. RNA polymerase II then transcribes viral mRNA from the proviral DNA. - TEGRAVIRs (doluTEGRAvir, elviTEGRAVir, RalTEGRAvir) 4. Once synthesized, HIV mRNA exits through the nuclear pores into the cytoplasm, where it uses the host cell's ribosomes to translate the enzymes, glycoproteins, structural proteins, and regulatory proteins needed to promote viral replication and transmission. Protease inhibitors (NAVIRS) 5. The full-length mRNA also serves as the viral genome that is packaged into newly synthesized virions.
Pt presents with pinworm perianal itching in child, eggs seen on inspection
ALBENDAZOLE. (Bendazoles) Mebendazole
ANTIFUNGALS
ANTIFUNGALS
ANTIVIRALS
ANTIVIRALS
Antiviral contraindicated in patient who has HLA B*5701 mutation
Abacavir hypersensitivity reaction is strongly associated with the HLA-B*57:01 allele. (an NRTI)
Abacavir contraindication explained
Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) Allergic responses can occur with many HIV/AIDS medications. Abacavir hypersensitivity reaction (AHR) is an allergic reaction that is strongly associated with the HLA-B*57:01 allele. results in a delayed hypersensitivity reaction (type IV). Manifestations are mediated by a cytotoxic T-cell response and typically include fever, malaise, gastrointestinal symptoms, and a delayed rash. genetic testing is usually done prior to administering the medication.
Acyclovir must be PHOSPHORYLATED to work
Acyclovir has significant antiviral activity (cytopathic effect) against - herpes simplex virus type 1 (HSV 1), HSV 2, - varicella zoster virus (VZV) but has weak activity against Epstein-Barr virus (EBV) and cytomegalovirus (CMV). acyclovir is a guanosine analog. Once acyclovir enters the HSV-infected host cell, it is phosphorylated to acyclovir monophosphate, principally via a virally-encoded thymidine kinase (TK). This is the rate-limiting step in acyclovir activation. Acyclovir monophosphate is then phosphorylated by cellularenzymes into the active triphosphate form, which impairs viral DNA polymerase-mediated replication of HSV. EBV and CMV do not produce the same TK as HSV and VZV. As a result, EBV- or CMV-infected cells cannot easily convert acyclovir into its pharmacologically active form.
SE of AMPHOTERICIN B
Amphotericin B: NEPHROTOXICITY leading to HYPERKALEMIA!! (damage to renal tubules) - infusion related rxns: fever, chills, rigors - nephrotoxicity - electrolyte imbalance: hypokalemia, hypomagnesia Anemia!!! (due to dec EPO caused by renal damage thrombophlebitis: inflammation of injection site
Anti-parasite
Anti-parasite
Pt is treated for CMV with a medication described as "intravenous agent that does not require intracellular activation and is known to bind in vitro with viral-encoded enzymes such as DNA polymerase, RNA polymerase, and reverse transcriptase."
FORSCARNET: (used to tx ganciclovir resistant CMV) This patient with HIV likely has cytomegalovirus (CMV) colitis (intranuclear and intracytoplasmic inclusions), which, in some patients (eg, with ganciclovir resistance or refractory thrombocytopenia), is treated with foscarnet. Foscarnet is a pyrophosphate analog that does not require intracellular activation. It directly inhibits both DNA polymerase in herpesvirus and reverse transcriptase in HIV. Foscarnet must be administered intravenously. In addition to treating ganciclovir-resistant CMV infections, foscarnet is useful in patients who have acyclovir-resistant herpesvirus infections. Ganciclovir, a guanine nucleoside analogue structurally similar to acyclovir, is often used for CMV infections. However, it requires intracellular conversion by a virally encoded kinase and then by cellular kinases.
Common side effects of antibiotics
HYPERKALEMIA: TMT/SMX Trimethoprim: Hyperkalemia, granulytopenia, leukopenia, - rash, n&v, folate def : megaloblastic anemia, ESOPHAGITIS: tetracylines & clindamycin - tetracyclines also GI distress, teeth discoloration, inhibition of bone growth, photosensitivity Tetracyclines (eg, doxycycline, minocycline) and clindamycin are associated with esophagitis due to their low pH and irritant effects on the distal esophagus. OTOTOXICITY/TINNUTIS : AMINOGLYCOSIDES - also Nephrotoxicity, teratogenicity, neuromuscular blockade Aminoglycosides (eg, gentamycin, tobramycin) have broad-spectrum activity against aerobic gram-negative organisms and are most often used in severe gram-negative infections (eg, intraabdominal infections, osteomyelitis). These medications are associated with ototoxicity and may lead to tinnitus and hearing loss. PULMONARY FIBROSIS: NITROFURANTOIN (Choice D) Nitrofurantoin has activity against many gram-positive and gram-negative urinary tract pathogens and is used for both acute treatment of urinary tract infections and long-term prophylaxis in patients with recurrent cystitis. It is associated with pneumonitis and pulmonary fibrosis. TENDON RUPUTURE: Fluoroquinolones Fluoroquinolones (eg, levofloxacin, ciprofloxacin) have activity against aerobic gram-negative rods and many respiratory pathogens. They are commonly used to treat pneumonia, pseudomonal infections, and urinary tract infections. These medications are associated with tendinopathy, including tendon rupture.
SE of protease inhibitors -NAVIRS
Hyperglycemia Lipodystrophy (buffalo hump) Nephropathy, hematuria (INDINAVIR) Ritonavir (-) cytoP450 The following important adverse effects can be seen with PIs: - Lipodystrophy leads to increased fat deposition on the back and abdomen and decreased adipose tissue on the face, extremities, and buttocks. This gives patients a "buffalo hump" appearance with central obesity and peripheral wasting. - Hyperglycemia results from increased insulin resistance and may lead to diabetes. - Inhibition of cytochrome P450 may cause interactions with other drugs. Rifampin increases/ induces P450 activity and will therefore decrease PI serum levels; as a result, rifampin can be replaced with rifabutin in the treatment of tuberculosis in patients on PIs.
Pt is tx with Acyclovir & develops renal damage how could it be prevented?
IV HYDRATION! Intravenous acyclovir can cause crystalline nephropathy if adequate hydration is not also provided. Acyclovir is excreted principally in the urine via glomerular filtration and tubular secretion. When the acyclovir concentration in the collecting duct exceeds its solubility, crystallization, crystalluria, and renal tubular damage can occur. In most cases, this toxic complication is transient and can be prevented (as well as treated) with adequate hydration and a reduction in the rate of drug infusion.
Aminoglycoside (AT 30S) 30-GNATS-mycin gentamicin, neomycin, amikicin, tobramycin, streptomycin 30 Min(mean) GNATS caNNOT kill anaerobes
MOA: inactivates 30S AE: NNOT: nephrotoxicity, neuromuscular blockade, ototoxicity, teratogenicity uses: severe gram neg reactions. CANNOT kill anaerobes. neomycin: prophylaxis for bowel surgery Resistance: bac inactivation by acetylation, phosphorylation etc e.g. Pseudomonas
Antiviral used for tx of influenza MOA
Oseltamivir is a neuraminidase inhibitor useful in the treatment of both influenza A and B virus infections. MOA: Prevents release of progeny viruses Must be started within 48 hrs UWE: Neuraminidase is required for the release of virus from infected cells and for the spread of virus within the respiratory tract. Neuraminidase inhibitors cause the newly synthesized virions to adhere to the host cell surface and form viral aggregates, thereby reducing the spread of virus to other host cells. Oseltamivir (Tamiflu) can shorten the course and complications of influenza A and B infections if taken within 48 hours of the onset of symptoms. In addition, oseltamivir works to slow viral penetration of the mucous secretions that protect the respiratory epithelium. Oseltamivir can therefore be used to treat or prevent influenza.
CMV & GANGICLOVIR UWE
Patients who undergo organ transplantation and are on immunosuppressive therapy are at risk for cytomegalovirus(CMV) reactivation with end-organ disease (eg, colitis, retinitis, pneumonitis). This patient has classic manifestations of CMV colitis including fever, fatigue, abdominal pain, and diarrhea. Because serum testing for CMV DNA may be negative, patients with suspected CMV colitis usually undergo colonoscopy with biopsy. Typical findings include colonic mucosal erythema/ulcerations. Biopsy generally reveals large cells with intranuclear eosinophilic inclusions and intracytoplasmic basophilic inclusions ("owls-eye" appearance). First-line therapy for CMV colitis is intravenous ganciclovir.
Cell WALL synthesis
Peptidoglycan synthesis: glycopeptides - Vancomycin - Bacitracin PEPTIDOGLYCAN CROSSLINKING : huge target!!!!! Penicillinase-sensisitive penicillins (PAPA is sensitive) - Pen G, Pen V - Ampicillin - Amoxicillin Penicillinase- resistant penicillins (DON is resistant) - Dicloxacillin - Oxacillin - Nafcillin Antipsuedomonal penicillins -Ticarcillin - Piperacillin Cephalosporins (1-4) 1: cefazolin 2. Cefoxitin 3: ceftriaxone 4: Cefepime 5: Ceftaroline Carbanepems - Imipenem - Meropenem - Ertapenem - Doripenem Monobactams - Aztreonam
Pt presents with Pseudomonas question describes the kind of resistance: antibiotic-modifying enzymes "an enzyme that is located on the cytoplasmic surface of the cell membrane and that catalyzes the transfer of acetyl groups to exogenous substances" then asks what medication would the pseudomonas be resistant to? Ans: GENTAMYCIN (aminoglycoside)
Pseudomonas aeruginosa is a gram-negative, opportunistic pathogen with multiple mechanisms of antibiotic resistance, including: - beta-lactamases, - efflux pumps, - and antibiotic-modifying enzymes. Antibiotic-modifying enzymes add chemical groups (eg, acetyl, adenyl, phosphate) to a target drug and are the most common mechanisms of aminoglycoside (eg, gentamicin) resistance. Altered aminoglycosides have a reduced ability to bind to the 16S ribosomal RNA within the 30S ribosomal subunit, leading to increased minimum inhibitory concentrations and reduced bactericidal effects. term-10 Most antibiotic-modifying enzymes arise via transfer of plasmids or transposons rather than chromosomal mutations.
Pulmonary TB tx
Pulmonary TB is treated with a 4-drug regimen, sometimes referred to as RIPE: (R)ifampin MOA: Inhibition of bacterial DNA-dependent RNA polymerase SE: GI side effects, rash, red-orange body fluids, cytopenias (I)soniazid MOA: inhibition of mycolic acid synthesis SE: Neurotoxicity (give vitamin B6/pyridoxine), hepatotoxicity (P)yrazinamide MOA: Unclear SE: Hepatotoxicity, hyperuricemia (E)thambutol MOA: Inhibition of arabinosyl transferase SE: Optic neuropathy
Vancomycin resistance: (cell wall peptidoglycan synthesis)
Resistance stems primarily from substitution of the terminal D-alanine with D-lactate, which prevents vancomycin binding. Vancomycin binds to the terminal D-alanine-D-alanine in bacterial pentapeptide peptidoglycan subunits, which prevents transpeptidase from binding to the pentapeptide, thereby inhibiting cell wall cross-linking.
NNRTI not nucleosides do not need to be phosphorylated
Retroviral reverse transcriptase inhibitors prevent the synthesis of viral DNA from the RNA template. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) do not require activation via intracellular phosphorylation. The more common NNRTIs include nevirapine and efavirenz. They are best used in conjunction with other antiretroviral agents for the treatment of HIV infection. Adverse effects are common with NNRTIs. Abrupt-onset flulike symptoms, abdominal pain, jaundice, or fever may indicate potentially life-threatening hepatic failure (most likely to occur within the first 6 weeks of NNRTI therapy). Life-threatening skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis) have also been observed.
Shistosomas
Schistosomaspecies Location Symptoms S haematobium North Africa, Sub-Saharan Africa, Middle East Urinary schistosomiasis Terminal hematuria, dysuria & frequent urination Hydronephrosis, pyelonephritis & squamous cell carcinoma of the bladder S mansoni Sub-Saharan Africa, Middle East, South America, Caribbean S japonicum Asia, particularly China, Philippines, Japan BOTH ARE: Intestinal schistosomiasis Diarrhea & abdominal pain Intestinal ulceration → iron deficiency anemia Hepatic schistosomiasis Hepatomegaly, splenomegaly Periportal fibrosis & subsequent portal hypertension
NRTIs must be phosphorylated to be active
Tenofovir (only nucleotide), emtricitabine, abacavir, lamivudine, zidovudine, didanosine, stavudine MOA: competitive inhibitor of HIV reverse transcriptase (terminate DNA chain bc lack a 3' OH) Toxicity: bone marrow suppression (alleviated by GCSF and EPO, peripheral neuropathy, lactic acidosis, anemia (ZDV), pancreatitis (didanosine) *if patient has concurrent Hep B infection, use tenofovir
diff tx for UTI/STI
Simple UTI: TMP-SMX or nitrofurantoin Chlamydia: Azithromycin and doxycycline Vaginal candida: flucanazole Trichomonas: Metronidazole Gonorrhea: IM Ceftriaxone
Pt presents with cystitis/UTI symptoms what med?
TMP-SMX Most cases of acute simple cystitis are caused by the enteric bacteria Escherichia coli. However, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus saprophyticus are also frequently isolated. Patients with no risk factors for resistant bacteria (eg, recent inpatient hospitalization or antibiotic use) are generally treated empirically with 3-6 days of nitrofurantoin or trimethoprim-sulfamethoxazole (TMP-SMX) due to their excellent efficacy and low risk of side effects.
malaria why is primaquine added to chloroquine??
To prevent disease relapse P vivax and P ovale are unique in that they also establish a latent hepatic infection (exo-erythrocytic cycle) in the form of hypnozoites, responsible for relapses. Chloroquine has no activity against the latent hepatic infections established by P vivax and P ovale. Primaquine must be added to the regimen to completely eradicate the hypnozoites.
Tx for schistosomas Diagnostic confirmation requires the identification of round/oval eggs with a characteristic terminal (S. haematobium) or lateral spine (S. mansoni) on stool/urinary testing or tissue biopsy. labs: eosinophils & lymphocytes
Treatment with praziquantel, which alters parasite digestion and calcium transport, is generally curative. Tx also with ALBENDAZOLE Schistosomiasis is a blood fluke infection that occurs when humans bathe or swim in freshwater that contains contaminated snails. Adult worms mature in the liver, lodge in the mesenteric venules or vesicular venous plexus, and secrete eggs into feces or urine. Eggs can trigger granulomatous inflammation, leading to symptoms in the gastrointestinal, urinary, or periportal tract. Diagnosis is typically made when round or oval eggs with a terminal or lateral spine are identified in urine, feces, or biopsy.
TMP/SMX
Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination of 2 bacteriostatic antibiotics that act synergistically to inhibit bacterial tetrahydrofolate formation, (THF) resulting in bactericidal activity. It has a broad spectrum of activity against many aerobic gram-positive and gram-negative bacteria and is commonly used for urinary tract infections, Pneumocystis jiroveci pneumonia, and Nocardia infections. - UTI!! - Shigella - Salmonella - PJP - Toxoplasmosis - Nocardia HYPERKALEMIA trimethoprim blocks the epithelial sodium channel in the distal tubule and collecting duct. This reduces transepithelial voltage and impairs sodium-potassium exchange, leading to reduced potassium excretion and hyperkalemia. This effect is often magnified in the elderly population, those with renal failure, or those given other potassium-sparing diuretics (eg, spironolactone, amiloride), ACE inhibitors (eg, lisinopril), or angiotensin receptor blockers (eg, losartan).
Pt presents with Tinea pedis fungal infectionpruritic, erythematous rash between the toes that frequently extends along the sole KOH: branching hyphae tx?
Tx of Tinea pedis: TOPICAL ANTIFUNGALS (clotrimazole)
antibiotics with concentration dependent killing aka one heavy dose, once a day
aminoglycosides (-mycin) (GNATS) - 30s - gentamicin, neomycin, amakicin, streptomycin etc) fluoroquinolones (floxacin) - DNA gyrase - ciprofloxacin - levofloxacin
What NRTI antiviral can be given to PREGNANT women for HIV prophylaxis?
Zidovudine (nucleoside NRTI)
clinical disinfectants
alcohol: - disrupts cell membranes - denatures proteins chlohexidine - cell membrane - disrupts coagulation of cytoplasm WORKS ON SPORES hydrogen peroxide: - free radicals iodine: - halogenation of proteins & nucleic acids
Nephrotoxic effects of amphotericin B are due to?
binding to the cell membrane cholesterol of nephrons Amphotericin B binds the ergosterol of fungal cell membranes to exert its antifungal effects. However, it also binds cholesterol to some degree, causing toxicity to human tissues. The most important adverse effects of amphotericin B are nephrotoxicity, hypokalemia, and hypomagnesemia.
Fusion inhibitors enFUviritide
binds to gp41, HIV's transmembrane envelope protein These drugs prevent gp41 from undergoing the conformational changes necessary for viral membrane fusion with the host cell membrane.
Attack FOLIC ACID synthesis & reduction via silencing via dna methylation
inhibition pf PABA -> DHF: enzyme inhibited: dihydropteroate synthetase Sulfonamides: (-xasole) - Sulfamethoxazole - Sulfisoxasole - Sulfadiazine Inhibition of DHF -> THF enzyme inhibited: dihydrofolate reductase - Trimethoprim - methotrexate - pyrimethamine Trimethoprim, methotrexate, and pyrimethamine inhibit dihydrofolate reductase. Trimethoprim restricts bacterial growth through this process, and works particularly well in conjunction with sulfonamide, which inhibits an earlier step in the bacterial folic acid pathway.
how does Acyclovir stop viral replication?
inhibits DNA polymerase by incorporation into newly replicating viral DNA NRTI!!! In infected host cells, acyclovir (a nucleoside analog) is converted into acyclovir monophosphate principally via virus-encoded thymidine kinase. Cellular enzymes then convert the monophosphate into acyclovir triphosphate, which competes with deoxyguanosine triphosphate for viral DNA polymerase. When acyclovir triphosphate becomes incorporated into the replicating viral DNA chain, viral DNA synthesis is terminated. This patient's new genital rash and positive Tzanck smear are consistent with a primary genital herpes simplex virus (HSV) infection, likely due to HSV-2. Antiviral drugs for the treatment of primary genital herpes include acyclovir, valacyclovir (acyclovir prodrug with better oral bioavailability), and famciclovir. Acyclovir treatment during a primary episode can reduce duration of viral shedding, time to lesional healing, constitutional symptoms, and local pain. Chronic daily suppressive therapy (lower dose) can be used in patients who have recurrent episodes. Acyclovir does not significantly impact uninfected cells in vitro as uptake into these cells is poor, phosphorylation in the absence of viral thymidine kinase is minimal, and cellular α-DNA polymerase has significantly less affinity for acyclovir triphosphate than does viral DNA polymerase.
Pharmacodynamics
pharmacodynamics
pt is infected with BACTERIODES species which has a beta-lactamase what should be used to tx?
piperacillin with beta-lactates inhibitor such as tazobactam β-lactamase inhibitors such as tazobactam, clavulanic acid, and sulbactam prevent these enzymes from functioning. The combination of piperacillin (extended-spectrum penicillin) and tazobactam is effective against a large number of gram-positive, gram-negative, and anaerobic bacteria. Other antimicrobials with anaerobic activity include metronidazole, carbapenems, and clindamycin (in most cases).
Ganciclovir requires
requires intracellular conversion by a virally encoded kinase and then by cellular kinases.
pt on isoniazid presents with fever, anorexia, nausea
signs of HEPATOTOXICITY (Frank hepatitis presents as fever, anorexia, nausea)
Integrase inhibitors MOA -TEGRAVir RalTEGRA-vir BicTEGRA-vir etc
they inhibit HIV genome integration into the host cell chromosome, preventing synthesis of viral mRNA. You need to integrate the viral DNA into the host cell in order to induce viral gene expression and prevent degradation of the viral genome.
pt is administered piperacillin (beta lactam) with tazobactam why?
to decrease bacterial inactivation of the piperacillin Resistance is often due to beta-lactamase, a bacterial enzyme that hydrolyzes and inactivates the beta-lactam ring. The coadministration of a beta-lactamase inhibitor such as tazobactam prevents beta-lactamase producing organisms from inactivating penicillins, which extends their spectrum of activity (broadens the range of microbes that can be treated). Some penicillin-derivative antibiotics (eg, late-generation cephalosporins, carbapenems) have beta-lactam rings with additional chemical components, which make them partially or completely resistant to beta-lactamases.
uses of other antibiotics
vancomycin: - MRSA - C-diff Ciprofloxacin (fluoroquinolone) - gram negative rods & bacilli - legionella - pseudomonas ceftriaxone - H. influenza - klebsiella - neisseria - serratia Azithromycin (macrolide) - 50S - chlamydia - mycoplasma - h. influenza - moraxella catarrhlis - Mycobacterium avium (MAC) Acylovir: - HSV 1, 2, - Varicella Foscarnet - CMV (gancyclovir resistant cmv) - acyclovir resistant HSV TMT-SMX: - PJP