Antimicrobial Drugs Flashcards
What is an Infection?
When an organism enters another and causes disease.This is usually achieved through replication of the invading organism
Numerous agents can cause infection: (5)
Bacteria Fungus Virus Protozoans Helminths
Describe bacteria
Prokaryotic, single-celled microscopic organisms
• Shapes: spherical, rod, spiral, coma, filamentous, star-shaped, rectangular, hyphae
• No nucleus, contains cell wall (stains gram positive or negative)
Infections: bacterial meningitis of the CNS, staphylococcus aureus, chlamydia, sinusitis, upper respiratory tract infections, gastritis, some food poisonings
Describe Fungi
(larger and more complex than bacteria)
• Mould (can produce persistent spores) and yeast (unicellular)
• Saprophytic (feeds on dead organic matter)
• Parasitic (feeds on living organisms)
• Fungal pathogens exist insoil, decaying plants or the general environment. It includes normal flora (skin, mouth, GIT, vagina)
Mild and superficial vs. life threatening and systemic
Describe Protozoa
One-celled animals; classified based on their mechanism of movement:
• Sarcodina - the amoeba (e.g. Entamoeba)
• Mastigophora - the flagellates (e.g. Giardia, Leishmania)
• Ciliophora - the ciliates (e.g. balantidium)
• Sporozoa - organisms whose adult stage is not motile (e.g. plasmodium, cryptosporidium)
*Infections range from asymptomatic to life-threatening
Describe Viruses
Intracellular parasites which gain entry into human hosts by binding to receptors on cell membranes - thus, specific receptors are needed. Once inside host cells, they utilise host cellular metabolic activities for survival and replication –> release more virus from the infected cell into the blood and surrounding tissues –> spread to other cells and process repeats (the body produces antibodies to the virus and then develops immunity)
How an infection effects its host is dependent on a number of factors such as how they became —— in the first instance
How an infection effects its host is dependent on a number of factors such as how they became exposed in the first instance
Transmission
Infections is transferred to the host
Mechanism of Transmission (9)
- Skin-to-skin, lesion secretion or mucosal surface (herpes, syphilis)
- Placenta (HIV, Rubella)
- Transplants/ transfusion (Hepatitis B/C, HIV)
- Faecal - Oral (Enterovirus)
- Water (Hepatitis A)
- Air-borne (chickenpox)
- Objects (Scarlet fever, toys in a nursery)
- Vectors (Malaria)
- Sneezes, coughs (droplets) (Influenza)
Host Defence Mechanisms
• Physical Barriers:
○ Intact skins and mucous membranes prevent infections from entering
○ Expels the infective process through mechanical movement including coughing, swallowing, peristalsis
• Anti-infective secretions and Immune inflammatory processes (prevent or minimise infection spreading to the rest of the body)
○ Phagocytic cells
○ Immune Processes
○ Inflammatory processes
Impairments to the host defence mechanism can lead to the host susceptible to infections. These include: (4)
- Damage to the physical barrier (breaks in the skin and mucous membrane)
- Trauma
- Inflammation
- Open lesions
- These breaks may be intentional (insertion of prosthetic devices, tubes, catheters)
Impairments in the host defences may also be related to (7)
- Malnutrition
- Poor personal hygiene
- Physicality problems (e.g. suppression of immune system through medications)
- Other treatment or pathophysiology (e.g. those effecting blood supply, neutropenia and other blood disorders)
- Diabetes mellitus
- Other chronic diseases
- Advanced age
What is infection diagnosis ?
Using diagnostic tests and identifying signs and symptoms through a physical assessment to determine which body systems are affected (microscopy, culture, immunologic tests, nucleic acid based identification, non-nucleic acid based identification)
What is susceptibility testing?
Determines an infective processes vulnerability to antimicrobial drugs - done by exposing the organism to specific concentrations of antimicrobial drugs (can be done for bacteria, fungi, viruses). *Result of one drug may predict similar results of another drug
What are antimicrobial medications used to treat? When are they necessary?
Antimicrobial medications are used to treat or prevent infections caused by pathogens. They are necessary when host defence mechanisms are inadequate to combat infection.
Antibacterial agents can be a ——/—— (synthesised in the lab) or ——– (hybrid)
Antibacterial agents can be a synthetic agent/ chemotherapeutic (synthesised in the lab) or semi-synthetic (hybrid)
What does a high therapeutic index mean?
Interferes with vital functions of bacteria with minimal effects on host cells
Bactericidal
Kills bacteria
Bacteriostatic
stops bacteria from reproducing
There are several classes of antibacterial compounds that are typically classified based on their —— ——-
There are several classes of antibacterial compounds that are typically classified based on their bacterial target
Once an infection is suspected/ confirmed, a —— ——can be used to identify the infecting pathogen (bacteria)
Once an infection is suspected/ confirmed, a gram stain can be used to identify the infecting pathogen
For some pathogens, it may be possible to make a diagnosis based on —— ——-, clinical signs, and ——– examination
For some pathogens, it may be possible to make a diagnosis based on past history, clinical signs, and physical examination
——— treatment may be commenced prior to confirmation to prevent ——- in treatment which may cause harm to the patient. These clinical decisions are typically based on established guidelines
Empirical treatment may be commenced prior to confirmation to prevent delay in treatment which may cause harm to the patient. These clinical decisions are typically based on established guidelines
If the pathogen is unknown, a ———- drug (single/combo) may be appropriate. Once a known pathogen is known and confirmed, a ———– drug may be appropriate
If the pathogen is unknown, a broad-spectrum drug (single/combo) may be appropriate. Once a known pathogen is known and confirmed, a narrow spectrum drug may be appropriate
Patient factors are important when selecting therapy: (4)
- Patient history or drug allergies
- Ability to excrete and metabolise the medication (renal and hepatic function)
- Contraindications for children, pregnancy, lactation
- Drug-drug interactions
ARM emerge (grow and multiply) —— or —— antimicrobial therapy when susceptible organisms (including normal flora) are ——–
ARM emerge (grow and multiply) during or after antimicrobial therapy when susceptible organisms (including normal flora) are suppressed
ARM leads to prolonged ——- or hospitalised medications and increased mortality –> often more —— and ——– medications are required
ARM leads to prolonged illness or hospitalised medications and increased mortality –> often more toxic and expensive medications are required
ARM occurs due to —– (using medication when not needed), —— (not taking the full course), —– (not an appropriate drug) or —— of antimicrobial treatment
ARM occurs due to overuse (using medication when not needed), interruption (not taking the full course), inappropriate (not an appropriate drug) or misuse of antimicrobial treatment
A broad spectrum antibiotic can suppress —– flora leading to ARM to become the dominant strain causing what’s known as a ———-
A broad spectrum antibiotic can suppress normal flora leading to ARM to become the dominant strain causing what’s known as a superinfection
Microbes develop resistance through a number of mechanisms (by producing enzymes that inactivate medications): (4)
- Modifying antibiotic target sites
- Production of alternate enzyme to bypass antibiotic activity
- Changing cell wall permeability
- Acquiring/ increasing ability to pump medications out of the cell
Antibiotics are considered the —– line of defence as most common infections resolve through bodily mechanisms
Antibiotics are considered the last line of defence as most common infections resolve through bodily mechanisms
ARM can be prevented by (3)
- Completing the course of the antibiotics
- Not using other’s medications
- Not using leftover medication
Bacterial infection medications can be administered —— (skin and mucous membranes) or ——–(intravenous (IV) and oral)
Bacterial infection medications can be administered topically (skin and mucous membranes) or systemically (intravenous (IV) and oral)
The major classes of antibacterial drugs include: (4)
- Inhibitors of bacterial cell wall synthesis
- Inhibitors of bacterial protein synthesis
- Inhibitors of bacterial DNA replication
- Inhibitors of bacterial metabolic pathways
Inhibitors of bacterial cell wall synthesis (4)
- Beta-lactam antibacterial
- Cephalosporin
- Carbapenems
- Glycopeptides
Beta-lactam antibacterial
• Derived their name from the beta-lactam ring (chemical structure) which is essential for antibacterial activity –> enzymes can disrupt the ring and inactivate their mechanism
• Inhibits synthesis of bacterial cell wall binding proteins producing a defective cell wall, destroying the microorganism
• Initially given parenterally due to destruction by gastric acid
• Extensive use has produced drug-resistant strains of Staphylococci
• Safe and widely used
*Include penicillins (amoxicillin, amoxicillin with clavulanic acid, ampicillin, benzathine benzylpenicillin, benzylpenicillin, dicloxacillin, flucloxacillin, phenoxymethylpenicillin) - used for gram positive > gram negative
- Contraindications for patients with hypersensitivity/ allergic reaction to penicillin and potential cross-allergenicity with cephalosporin and carbapenems - similar spectrum of action
- Adverse effect profile: diarrhoea, nausea, pain and inflammation at injection site, superinfection with prolonged treatment, allergy
Cephalosporins
• Broad spectrum antibiotics, derived from a fungus, to fight against gram-positive and negative bacteria (more active against gram-negative bacteria in comparison to penicillin)
• Damages the bacterial cell wall by binding to penicillin-binding proteins leading to cell lysis and death (bactericidal)
• Clinical use include surgical prophylaxis, treatment of infections (respiratory tract, urinary tract, skin, soft tissues, bones, joints, CNS and septicemia)
• Common adverse effects are diarrhoea, nausea, vomiting, rash and headache.
• Contraindications for use include previous anaphylactic reaction to penicillin or a cephalosporin allergy.
*Include cefalexin, cefalotin, cefazolin, cefepime, cefotaxime, cefoxitin, ceftaroline, ceftazidime, ceftriaxone and cefuroxime
Carbapenems
• Broad-spectrum, bactericidal beta-lactam antimicrobials
• Inhibit synthesis of bacterial cell walls by binding with penicillin-binding proteins
• Common adverse effects includes nausea, vomiting, diarrhoea and headache
*Include ertapenem, imipenem and meropenem
Aminoglycosides
• Widely used to treat serious gram-negative infections - bactericidal agents with similar pharmacologic, antimicrobial and toxicologic characteristics to penicillin
• Work by penetrating the cell walls of bacteria and preventing bacterial synthesis
• Usually given parentally as they are poorly absorbed from the GIT
• Common adverse effects include nephrotoxicity, ototoxicity, anaphylaxis, bronchospasm, oliguria and peripheral neuropathy
*Include amikacin, gentamicin, streptomycin and tobramycin
Macrolides
• Immunomodulatory and anti-inflammatory effects
• Similar spectrum of antimicrobial activity to benzylpenicillin
• Useful alternative for patients with a history of penicillin and cephalosporin allergy
• Depending on the concentration and bacterial species, they can either be bactericidal or bacteriostatic
• Common adverse effects include nausea, vomiting, diarrhoea, abdominal pain and cramps as well as candida infections
*Includes azithromycin, clarithromycin, erythromycin and roxithromycin
Inhibitors of bacterial DNA replication
Quinolones/ Fluoroquinolones
Quinolones/ Fluoroquinolones
• Synthetic bactericidal which are active against gram-negative and gram-positive organisms and are well absorbed orally
• Interferes with bacterial DNA enzyme synthesis
• Used for infections of the respiratory and genitourinary tract, GI tract, bone, joints, skin and soft tissues
• Common adverse effects include rash, itch, nausea, vomiting, diarrhoea, abdominal pain and dyspepsia
*Includes ciprofloxacin, moxifloxacin, norfloxacin and ofloxacin
Inhibitors of Bacterial Metabolic Pathways
Sulphonamides
Sulphonamides
• Bacteriostatic against a wide range of gram-positive and gram-negative microbes, however, they are now decreasing in efficacy due to AMR
• Should only be used after susceptibility is proven by culture and sensitivity testing
• Adverse effects such as burning, itch, rash and transient leucopoenia
*Include sulfadiazine, sulfisoxazole, trimethoprim–sulfamethoxazole, mafenide and silver sulfadiazine
The development of effective antifungal treatments is difficult as fungal cells are —— to human cells. Thus, drugs toxic to —— would also be toxic to —— cells
The development of effective antifungal treatments is difficult as fungal cells are similar to human cells. Thus, drugs toxic to fungi would also be toxic to healthy cells
Most antifungal drugs target the fungal —– ———- and disrupt the ——- and —— of fungal cell components. This can produce potentially serious toxicities and drug interactions.
Most antifungal drugs target the fungal cell membrane and disrupt the structure and function of fungal cell components. This can produce potentially serious toxicities and drug interactions.
Azoles
• Impairing the synthesis of ergosterol in fungal cell membranes causing cell breakdown, cell leakage and thus cell death
• Common adverse effects include rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea and elevated liver enzymes
*Include fluconazole, isavuconazole, itraconazole, ketoconazole, miconazole, posaconazole and voriconazole
Echinocandins
• Destroy fungi by inhibiting 1,3-beta-D-glucan synthase which inhibits synthesis of 1,3-beta-D-glucan in the fungal cell wall and alters cell membrane permeability
• Common adverse effects include nausea, vomiting, diarrhoea, rash and hypokalaemia
*Include anidulafungin, caspofungin and micafungin
Amphotericin B
Common antifungal
• Binds irreversibly to ergosterol in fungal cell membranes causing cell death by altering their permeability and allowing leakage of intracellular components
Common adverse effects include infusion reactions, thrombophlebitis, anaemia, nephrotoxicity, hypoxia, hyperglycaemia, tachycardia and hyponatraemia
Antiprotozoal medications are a class of medication used to treat infections caused by protozoa by either ——- or ——— their growth and ability to reproduce
Antiprotozoal medications are a class of medication used to treat infections caused by protozoa by either destroying or inhibiting their growth and ability to reproduce
There are 2 main types of antiprotozoal medications:
antimalarial and other antiprotozoal medications (They kill or inhibit the growth of protozoa by affecting different stages of the parasitic lifecycle)
Metronidazole and tinidazole work by interfering with —– ——- of protozoa and are commonly used in treating non-protozoal infections
Metronidazole and tinidazole work by interfering with DNA synthesis of protozoa and are commonly used in treating non-protozoal infections
——- are used to prevent viral infections
Alternatively, ——– can be used to inhibit viral reproduction (but cannot eliminate the virus from host tissue) - typically ——, relatively —— and have limited —–
Vaccines are used to prevent viral infections
Alternatively, medications can be used to inhibit viral reproduction (but cannot eliminate the virus from host tissue) - typically expensive, relatively toxic and have limited efficacy
Viral Vaccines: produce —— immunity before —— and can control —— of viral disease within a community
Viral Vaccines: produce active immunity before exposure and can control epidemics of viral disease within a community
Neuraminidase inhibitors
(oseltamivir, peramivir and zanamivir) are specifically used in thetreatmentandpreventionof influenza A and B, to reduce virus replication. Adverse effects include bronchospasm, dyspnea and allergy
Herpes Virus: main goals of therapy include decreasing duration of ——, reducing —– and pain
Herpes Virus: main goals of therapy include decreasing duration of lesions, reducing itching and pain
Treatment Guanine Analogues
○ Treatment of a herpes simplex infection or cytomegalovirus include aciclovir, famciclovir, ganciclovir, valaciclovir and valganciclovir
○ Inhibits viral DNA polymerase and DNA synthesis
Adverse effects include nausea, vomiting, diarrhea, hallucinations, headache and encephalopathy
Human immunodeficiency Virus (HIV):
• Transmitted by (5)
• Decreases the number of —– lymphocytes which impairs the immune system leading to infections and some cancers
There is no cure: treatmentrationale ???
Human immunodeficiency Virus (HIV):
• Transmitted by unsafe sexual practices, injections, medical procedures, blood transfusion and childbirth
• Decreases the number of CD4 T lymphocytes which impairs the immune system leading to infections and some cancers
There is no cure: treatmentrationaleincludesrestoration and preservation of immune function
Antiretrovirals (4)
class of medication used to treat HIV
• Stop virus replication in the body, thus preventing further damage
Usually requires a combination of drugs
- Nucleoside reverse transcriptase inhibitors (NTRI)
- Non-nucleoside reverse transcriptase inhibitors
- HIV-protease inhibitors
- Integrase Inhibitors
Nucleoside reverse transcriptase inhibitors (NTRI)
· Treatment of HIV infection or transmission by inhibiting viral reverse transcriptase and viral DNA
· Adverse effects include headache, nausea, vomiting, anorexia, myalgia and asymptomatic hyperlactataemia
*Includes Abacavir, emtricitabine, lamivudine and zidovudine
Non-nucleoside reverse transcriptase inhibitors
· Rilpivirine inhibits HIV‑1 reverse transcriptase and thus reducing viral DNA synthesis
· Common side effects include rash, malaise, nausea, vomiting, elevated liver enzymes, headache and fever
*Includes efavirenz, etravirine and nevirapineor
HIV-protease inhibitors
· Inhibits HIV‑1 and HIV‑2 proteases thus preventing virus replication
· Common side effects include headache, diarrhoea, nausea, vomiting, abdominal pain, elevated liver enzymes, weight gain, hyperglycaemia, new-onset or worsening diabetes, hypertriglyceridaemia and hypercholesterolaemia.
*Includes atazanavir, darunavir, fosamprenavir, ritonavir, saquinavir and tipranavir
Integrase Inhibitors
· Inhibit HIV integrase and thus stop the insertion of viral DNA into the host DNA
· Common side effects include headache, fatigue, nasopharyngitis, increased liver enzymes, increased creatine kinase, rash and nausea
*Includes bictegravir, dolutegravir, elvitegravir and raltegravir
Viral Hepatitis Infections:
Inflammation of the liver caused by infection by one of several viruses (hepatitis A-E). Only B, C, and D can also cause chronic hepatitis
Hepatitis B
Most prevalent and leading cause of liver cancer. Transmission includes unsafe sexual practices, injections, medical procedures, blood transfusion and childbirth. Medications include adefovir, entecavir and lamivudine block viral DNA synthesis. These drugs can cause diarrhoea, abdominal pain, rash, malaise, fatigue, fever, raised liver enzymes, anaemia and neutropenia
Hepatitis A
Transmission via contaminated (faecal matter) food and water or person to person via faecal- oral transmission. There are no specific treatments
Hepatitis C
Transmission usually through unsafe injections, medical procedures and blood transfusions. Treatments include daclatasvir, ribavirin and sofosbuvir that work by blocking viral DNA synthesis. These drugs can cause headache, fatigue, nausea, diarrhea, unconjugated and hyperbilirubinaemia
Hepatitis D
Satellite virus which can only infect people who have hepatitis B. Drug therapy goals can only be to treat symptoms
Hepatitis E
Transmission is through contaminated (faecal matter) food and water or person to person via faecal-oral transmission. Goals of drug therapy can only be to treat symptoms
Inhibitors of Bacterial protein synthesis
- Aminoglycosides
2. Macrolides
