exam 3 lecture 2

Question 1

Antimicrobial Drugs

Answer 1

Chemicals used to treat microbial infections
Before antimicrobials, large number of people died from common illnesses
Now many illnesses easily treated with antimicrobials
However, many antimicrobial drugs are becoming less useful

Question 2

Chemotherapeutic agent

Answer 2

a chemical of natural or synthetic origin used for its specific action against disease, usually against infection

Question 3

Antimicrobial drug

Answer 3

agents used against small, unicellular organisms aka antibiotics – used to kill living organisms

Question 4

Different types of antimicrobial drugs:

Answer 4

Antibacterial drugs
Antiviral drugs
Antifungal drugs
Antiprotozoan drugs
Anthelminthic drugs

Question 5

Bacterial Structure and Function

Answer 5

ranging in size from 0.2 to 10.0 μm in diameter
Structure:
Rigid cell wall
Lack of a true nuclear membrane
Contain basic subcellular organelles needed to synthesize proteins and maintain cellular metabolism
Depend on nourishing medium to provide substrates to maintain function

Question 6

The Ideal Drug*

Answer 6

• Selective toxicity: against target pathogen but not against host
• LD50 (high) vs. MIC and/or MBC (low)
• Bactericidal vs. bacteriostatic
• Favorable pharmacokinetics: reach target site in body with effective concentration
• Spectrum of activity: broad vs. narrow
• Lack of “side effects”
• Therapeutic index: effective to toxic dose ratio
• Little resistance development

Question 7

Selective Toxicity

Answer 7

Cause greater harm to microorganisms than to host
Chemotherapeutic index= lowest dose toxic to patient divided by dose typically used for therapy
= Toxic dose / therapeutic dose

Question 8

Antimicrobial Action:
Bacteriostatic
Bactericidal

Answer 8

Bacteriostatic: inhibit growth of microorganisms

Bactericidal: kill microorganisms

Question 9

Antimicrobial Drugs:Spectrum of Activity

Answer 9

Antimicrobial medications vary with respect to the range of microorganisms they kill or inhibit
Some kill only limited range : Narrow-spectrum antimicrobial
While others kill wide range of microorganisms: Broad-spectrum antimicrobial

Question 10

Antimicrobial Drugs:Effects of Combining Drugs:
Synergistic
Antagonistic

Answer 10

Combinations are sometimes used to fight infections
Synergistic: action of one drug enhances the activity of another
Antagonistic: activity of one drug interferes with the action of another

Question 11

Antimicrobial Drugs:Adverse Effects

Answer 11

Allergic Reactions: some people develop hypersensitivities to antimicrobials
Toxic Effects: some antimicrobials toxic at high concentrations or cause adverse effects
Suppression of normal flora: when normal flora killed, other pathogens may be able to grow to high numbers

Question 12

Antimicrobial Drugs:Resistance to Antimicrobials

Answer 12

Some microorganisms inherently resistant to effects of a particular drug
Other previously sensitive microorganisms can develop resistance through spontaneous mutations or acquisition of new genes

Question 13

Mechanisms of action of Antibacterial Drugs

Answer 13

Inhibit cell wall synthesis
Inhibit protein synthesis
Inhibit nucleic acid synthesis
Injury to plasma membrane
Inhibit synthesis of essential metabolites

Question 14

Types of antibiotics

Inhibiting Cell Wall Synthesis

Answer 14

Inhibit cell wall synthesis
b-Lactam Drugs
penicillins, cephalosporins, monobactams
2. 	Non-b-Lactam Drugs
	imipenem/cilostatin (Primaxin), vancomycin (Vancocin IV)

Question 15

Types of antibiotics

Inhibit protein synthesis

Answer 15

Inhibit protein synthesis
Aminoglycosides
Tetracyclines
Macrolides

Question 16

Types of antibiotics :

Inhibit nucleic acid synthesis

Answer 16

Fluoroquinolones

Rifamycins

Question 17

Types of antibiotics

Injury to plasma membrane

Answer 17

Injury to plasma membrane

Polymyxin B

Question 18

Types of antibiotics

Inhibit synthesis of essential metabolites

Answer 18

Sulfonamides

Question 19

Penicillins

Answer 19

*Natural Penicillins
PCN G (IV/IM)
PCN V (oral)
Used for common oral infections
*Anti-Staphylococcal Penicillins
Methicillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin
Methicillin is rarely used due to toxicity
Dicloxacillin – highest serum levels orally
Nafcillin – preferred parenteral drug

Question 20

Aminopenicillins

Answer 20

Ampicillin (IV)
Ampicillin/sulbactam (Unasyn; IV)
Amoxicillin (Oral)
Amoxicillin/clavulanate (Augmentin)
Sulbactam and clavulanic acid increase activity against β-lactamase producing organisms
Extended antimicrobial spectrum - Gram negatives
Used as first line therapy for acute otitis media and sinusitis

Question 21

Antipseudomonal Penicillins

Answer 21

Ticarcillin, Piperacillin
Piperacillin/tazobactam (Zosyn, IV)
Ticarcillin/clavulanate (Timentin, IV)
Lower activity against gram positives
Often used with aminoglycosides when treating pseudomonal infections

Question 22

Adverse Reactions to Penicillin

Answer 22

5% of patients will develop a hypersensitivity reaction (penicilloic acid)
Rashes – most common reaction. 50% do not have a recurrent rash
Ampicillin – rash in 50-100% of patients with mononucleosis
Anaphylaxis – 1/10,000 patients
Hives, angioedema, rhinitis, asthma, and anaphylaxis
10% mortality rate
Anaphylaxis possible after negative skin testing
Desensitization is an option if penicillin must be given
Avoid all other beta-lactams???

Question 23

Cephalosporins

Answer 23

Generally more resistant to β-lactamase
Four Generations
Spectrum: gram negative > gram positive
Adverse reactions
5-10% cross-sensitivity with pen allergic pts
1-2% hypersensitivity reactions in non-allergic patients
Broader spectrum leads to opportunistic infections (candidiasis, C. difficile colitis)

Question 24

Carbapenems

Answer 24

Imipenem-cilostatin (Primaxin, IV)
Cilostatin – dehydropeptidase inhibitor that inhibits degradation into a nephrotoxic metabolite
Broadest spectrum β-lactam
Toxicities
PCN allergy cross reactivity
Seizures noted in imipenem studies

Question 25

Vancomycin

Answer 25

Tricyclic glucopeptide – Streptomyces orientalis Active against gram-positive bacteria Synergy with aminoglycosides Resistance: changes in permeability and decreased binding affinity Adverse effects Fever, chills, phlebitis, and red man syndrome Slow injection and prophylactic antihistamines Ototoxic Renal excretion (90-100% glomerular filtration) Normal half-life 6-10 hours Half-life is over 200 hours in pts with ESRD

Question 26

Antibacterial medications that inhibit protein synthesis

Answer 26

Target ribosomes of bacteria Aminoglycosides: bind to 30S subunit causing it to distort and malfunction; blocks initiation of translation Tetracyclines: bind to 30S subunit blocking attachment of tRNA Macrolides: bind 50S subunit and prevents continuation of protein synthesis

Question 27

Aminoglycosides

Answer 27

Neomycin, Gentamicin, Tobramycin, Amikacin Synergism with cell wall inhibitors is seen because they increase permeability of the cell Antibacterial spectrum: gram negatives Adverse effects Ototoxic – associated with high peak levels and prolonged therapy. Pts on loop diuretics, vancomycin and cisplatin are at higher risk Nephrotoxic

Question 28

Tetracyclines

Answer 28

Doxycycline (Doxyl, Vibramycin; IV/PO) Minocycline (Minocin; Oral) Tetracycline (Achromcyn V; IV/PO) Active against a variety of bacteria including many gram-positive and gram-negatives Adverse effects N/V/D Hypersensitivity reactions (such as rashes) Photosensitivity Impairs the growth and development of calcified tissues such as bone and teeth, esp. in children

Question 29

Macrolides

Answer 29

``` Erythromycin (IV) Clarithromycin (Biaxin, IV; Oral) Azithromycin (Zithromax, Z-Pak; Oral) Adverse effects 10-15% of pts do not finish the prescribed course of erythromycin because of GI distress Jaundice Ototoxic (high doses) ```

Question 30

Clindamycin

Answer 30

Clindamycin (Cleocin, IV/Oral) Used for deep neck space infections, chronic tonsillo-pharyngitis, and surgical prophylaxis in contaminated wounds Pseudomembraneous colitis – clindamycin > cephalosporins (Ceftin) > aminopenicillins Abdominal pain, fever, leukocytosis, bloody stool Diarrhea commonly develops on days 4-9 of treatment Typically resolves 14 days after stopping the antibiotic Treat with Flagyl (PO or IV) Life threatening cases can be treated with oral Vancomycin

Question 31

Antibacterial medications that inhibit nucleic acid synthesis

Answer 31

``` *Target enzymes required for nucleic acid synthesis Fluoroquinolones Rifamycins Rifampin Metronidazole ```

Question 32

Fluoroquinolones (type of antibacterial med that inhibits nucleic acid synthesis)

Answer 32

Ciprofloxacin (Cipro; IV/PO/Topical) Levofloxacin (Levaquin, IV/PO) Wide distribution – CSF, saliva, bone, cartilage Adverse effects H/A, dizziness, nausea, lightheadedness Limit use in pregnancy, nursing mothers, and children

Question 33

Metronidazole

Answer 33

Type of nucleic acid synthesis inhibition drug: Flagyl (IV/PO) Forms cytotoxic compounds by accepting electrons on its nitro group Distribution: nearly all tissues, including CFS, saliva, bone, abscesses Antibacterial spectrum: anaerobes and parasites Used for C. difficile and other anaerobic infections Toxicity: disulfram reaction

Question 34

Antibacterial drugs that inhibit synthesis of essential metabolites

Answer 34

``` Competitive inhibition by substance that resembles normal substrate of enzyme Sulfonamides aka Sulfa drugs Sulfadiazine (Silvadene) Sulfamethoxazole (Gantanol) Sulfisoxazole (Gantrisin) ** Adverse effects: Gastrointestinal distress Photosensitivity Allergic reactions Blood dyscrasias ```

Question 35

How do bacteria become resistant?

Answer 35

Spontaneous Mutation: happen as cells replicate | Gene Transfer: Usually spread through conjugative transfer of R plasmid

Question 36

Slowing the emergence and spread of antimicrobial resistance

Answer 36

Responsibilities of Physicians: must work to identify microbe and prescribe suitable antimicrobials, must educate patients Responsibilities of Patients: need to carefully follow instructions Educate Public: must understand appropriateness and limitations of antibiotics ; antibiotics not effective against viruses Global Impacts: organism that is resistant can quickly travel to another country - in some countries antibiotics available on non-prescription basis - antibiotics fed to animals can select for drug- resistant organisms

Question 37

Superinfections

Answer 37

Receiving therapeutic doses of antibiotics results in alterations in the normal flora of the GI, upper respiratory and genitourinary tracts ! individual may be prone to superinfection Removal of the inhibitory influence of the normal flora, which produce antibacterial substances and compete for nutrients A superinfection is the appearance of a new infection during pharmacotherapy of the primary infection Relatively common and potentially dangerous because the new infection may be a drug-resistant strain of the primary infection

Question 38

Special Considerations in Rehabilitation

Answer 38

-PTs are often involved with administering topical antibacterial agents like sulfadiazine for burns -Bone infections (osteomyelitis), infections from trauma and wounds, infections following joint replacement and other types of surgery all require antibacterial therapy -UTIs are common inpatient and outpatient -Help recognize the onset of adverse effects like skin rashes, itching, and respiratory difficulty -*Common S/Es such as GI problems (N/V/D) – not serious but bothersome Tetracyclines, sulfonamides, and fluoroquinolones cause increased photosensitivity => problem if ultraviolet treatments are administered Must maintain appropriate sterile technique when dealing with open wounds, adequate sterilization of pools to prevent spread of infection, hand washing is a must!

Question 39

Antiviral Drugs

Answer 39

Very few antiviral drugs approved for use in US Effective against a very limited group of diseases Targets for antiviral drugs are various points of viral reproduction

Question 40

Antiviral Drugs Treatment

Answer 40

Nucleoside and Nucleotide analogs Acyclovir- used to treat genital herpes Cidofovir- used for treatment of cytomegaloviral infections of the eye Lamivudine- used to treat Hepatitus B

Question 41

Antiretrovirals

Answer 41

``` Drugs used to treat HIV Six major classes Nucleoside and nucleotide reverse transcriptase inhibitors Non-nucleoside reverse transcriptase inhibitors Protease inhibitors Fusion inhibitors Integrase inhibitors Entry inhibitors ```

Question 42

Goals of Antiretroviral Therapy

Answer 42

``` Control of viral replication Prevention or delay of progressive immunodeficiency Delayed progression to AIDS Prolonged Survival Decreased selection of resistant virus ```

Question 43

Modes of Action for Antiretrovirals

Answer 43

**Antiretroviral drugs (ARVs) act on HIV by interfering with its reproductive cycle *The main stages of the cycle where these drugs act to inhibit replication of the virus are: NRTIs and NNRTIs prevent formation of proviral DNA Mechanism: inhibit reverse transcriptase enzyme PIs inhibit maturation of virion Mechanism: interrupt the protein processing and virus assembly Fusion Inhibitors Mechanism: disrupt the HIV-1 molecular machinery at the final stage of fusion with the target cell, preventing uninfected cells from becoming infected Integrase Inhibitors Mechanism: block integrase, the enzyme HIV uses to integrate genetic material of the virus into its target host cell Entry Inhibitors Mechanism: block binding of viral envelope, gp120, to CCR5 to prevent the membrane fusion events necessary for viral entry

Question 44

Antiretrovirals Types

Answer 44

``` Non-nucleoside reverse transcriptase inhibitors -Nevirapine (Viramune) -Delavridine (Rescriptor) -Efavirenz (Sustiva) Fusion inhibitors -Enfuvirtide (Fuzeon) Entry inhibitors -Maraviroc (Selzentry) ```

Question 45

Nucleoside and nucleotide reverse transcriptase inhibitors | ADVERSE EFFECTS

Answer 45

``` Class adverse effects: Lactic acidosis with hepatic steatosis -Rare complication of NRTI therapy Signs/Symptoms: Abdominal distention, abdominal pain, nausea, vomiting, diarrhea, weight loss, difficulty breathing, generalized weakness, myalgias Risk Factors: Stavudine and didanosine use during pregnancy Female gender Obesity Prolonged use of NRTIs ```

Question 46

Protease Inhibitor Adverse Effects and General Statements

Answer 46

Hepatic metabolism-no renal dosage adjustments Resistance usually requires multiple mutations Many drug interactions Food restrictions Take all with food EXCEPT: Indinavir: take on empty stomach when not combined with ritonavir Fosamprenavir: can take with or without food Lopinavir/ritonavir tablets: take with or without food Class adverse effects Hyperglycemia, lipodystrophy, hyperlipidemia (less with atazanavir), increased transaminases

Question 47

Why Does Antiviral Treatment Fail?

Answer 47

Intolerance Infection with a resistant virus Malabsorption NON-ADHERENCE TOPS THE LIST Rates of adherence have a direct correlation with success of HAART Near perfect viral suppression in DOT trials

Question 48

Ways to promote long term antiviral adherence

Answer 48

HAART has increased long-term survival of patients with HIV Before HAART, median survival: 8 to 10 years After HAART, median survival: may be 36 years Drug “holidays” or treatment interruptions result in rapid viral rebound within 2 to 3 weeks of treatment discontinuation Simplification of dosing regimens to twice or once daily may improve long-term adherence Initiate therapy at the optimal time Patient factors, viral load, CD4 Simplify regimens Provide support Social, medical, psychiatric, rehabilitation

Question 49

Considerations in Rehabilitation for Antiviral Drugs

Answer 49

Keep on top of advances in treating and preventing viral infections There is a considerable neuromuscular involvement in patients with AIDS – peripheral neuropathies, myopathies, and various CNS manifestations (dementia) secondary to opportunistic infections Peripheral neuropathies are a common S/E of certain anti-HIV meds (didanosine, zalcitabine) and myopathies (zidovudine) Pts with AIDS often have painful symptoms including joint pain, back pain, and pain related to neuropathies and myopathies (a degenerative neuromuscular)

Question 50

Antifungal drugs

Answer 50

FUNGI more of an annoyance - only affects outside of body -systemic infections more serious More difficult to find point of selective toxicity in eukaryotes than in prokaryotes Targets of antifungal drugs: Agents affecting fungal sterols Agents affecting fungal cell walls Agents inhibiting nucleic acids

Question 51

Anti Fungal targets : **ATHLETES FOOT**

Answer 51

Many antifungals target the sterols in the plasma membrane Polyenes- used in systemic fungal infections, very toxic to kidneys Amphotericin B ***Azoles- used for athlete’s foot and vaginal yeast infections *Clotrimazole (Lotrimin, Mycelex Troches) *Fluconazole (Diflucan) *Ketoconazole (Nizoral) *Miconazole (Monistat) Nystatin – wide spectrum of activity against fungi used primarily to treat GI infections or topically for skin and mucous membranes

Question 52

Agents affecting fungal cell walls

Answer 52

``` Primary target of selective toxicity is β-glucan Caspofungin- first new class of antifungals in 40 years ```

Question 53

Protozoal Infections

Answer 53

Protozoa – single-celled organisms that represent the lowest division of the animal kingdom Common disease caused by protozoal infection (plasmodia) is malaria***

Question 54

Malaria

Answer 54

Cause: the bite of an infected adult female anopheline mosquito Also transmitted by infected individuals via blood transfusion, congenitally, or infected needles by drug abusers

Question 55

AntiMalaria Drugs

Answer 55

Kill parasitic organisms Chloroquine and hydroxychloroquine also have antiinflammatory effects Indications Kills Plasmodium organisms, the parasites that cause malaria The drugs have varying effectiveness on the different malaria organisms Some drugs are used for prophylaxis against malaria 2 weeks prior and 8 weeks after return Chloroquine is also used for rheumatoid arthritis and systemic lupus erythematosus ** ADVERSE EFFECTS: nausea, vomiting, diarrhea, anorexia, and abdominal pain

Question 56

Protozoal Infetions Transmissions

Answer 56

``` Transmission Person to person Ingestion of contaminated water or food Direct contact with the parasite Insect bite (mosquito) ``` ** ANTI PROTOZOAL DRUG TO REMEMBER: metronidazole (Flagyl) – anti-bacterial / anaerobes

Question 57

Antifungal Significance in Rehabilitation

Answer 57

Sports PT – topical antifungal agents used for treatment of cutaneous ringworm infections (tinea pedis, tinea cruris, etc.) Discuss prevention techniques with athletes PTs working with AIDS patients encounter patients taking systemic antifungal and antiprotozoal agents PTs working or traveling to countries where parasitic infections remain a problem will encounter pts taking these meds and might need to take some of these meds themselves for prophylaxis

Question 58

What Is Cancer?

Answer 58

Cells constantly replicating in a normal cycle to remain in homeostasis Important steps in cell cycle: replication, death Cells control malfunction, cells grow faster than normal, tumors may form Benign tumors: noncancerous (moles, warts, lesions) Malignant tumors—cancers: produce cells that can move and colonize new sites Four main types of cancer based on location For four possible outcomes

Question 59

Outcomes and Causes of Cancer

Answer 59

``` Outcome of cancer treatments: Determined by early diagnosis Type of treatment Genetics Attitude of patient Three causes other than genetics: Environmental contaminants (carcinogens) Viruses Radiation Example: cigarette smoking ```

Question 60

Side Effects of Chemotherapy

Answer 60

Cancer: Caused by malfunction of our own cells Hard to differentiate between defective and normal cells Fighting off cancer cells—good cells are killed also to ensure full remission Side effects: hair loss, emesis, weight and energy loss, pain

Question 61

Biological Response Modifiers for Cancer

Answer 61

``` Chemotherapeutic agents destroy cancer cells and immune system cells Patients anemic, develop leukopenia Two agents used to boost immune cells: Erythropoietin Filgrastim Both agents used to stimulate bone marrow production of blood cells Erythropoietin stimulates RBC production Filgrastim stimulates WBC production ```

Question 62

Considerations in CANCER Rehabilitation

Answer 62

Side Effects!!! GI, blood disorders, fatigue Neurotoxic effects (ataxia, convulsions) and peripheral neuropathies with alkaloids Pain attenuating techniques – TENS Provide vital support role for cancer patients => improved QOL Encouragement is key! Be sensitive to patient’s needs on daily basis Reassure patients that S/Es are transient