Sesh4 - Drug Action : Targeting Photogenic Organism

Question 1

What are the main antibiotic bacterial targets ?

Answer 1

• Bacterial cell wall
• Bacterial cell membrane
• DNA and RNA synthesis
• protein synthesis and folate synthesis

Question 2

Antibiotics that target cell wall synthesis are called ?

Answer 2

Beta-lactam antibiotics.

They contain a beta lactam ring. Its a 4 membered cyclic amide found in every single beta-lactam antibiotic.

Question 3

how does beta lactams target the cell wall?

Answer 3

During cell wall synthesis in the bacteria, transpeptidase enzymes which are also known as penicillin binding protein (PBP) catalyse the cross links between these adjacent peptide chains, which causes the removal of a D-alanine from these peptides. These cross links make the cell wall particularly strong.

Beta lactams Mimick the shape of the of the D-ALA D-ALA peptide on the terminal residue. The beta lactam antibiotic binds to the penicillin binding protein, inhibiting the enzyme and preventing cell wall synthesis.

Question 4

how has some bacteria developed resistance to beta lactam antibiotics?

Answer 4

Some bacteria have developed resistance to beta lactams by synthesising an enzyme called beta lactamases that degrade the beta lactam ring, rendering it inactive.

Answer 5

flucloxacillin is an isoxazolyl-penicillin which is designed with a bulky side chain attached to its chemical structure.

it acts as a steric, which is a spatial shield that blocks the enzyme (beta-lactamases) access to the beta lactam ring.

This is often used against bacteria that are naturally resistance against beta-lactams (via beta lactamases)

Question 6

MOA of flucloxacillin?

Answer 6

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, flucloxacillin inhibits the third and last stage of bacterial cell wall synthesis.

Cell lysis is then mediated by bacterial cell wall

It is possible that flucloxacillin interferes with an autolysin inhibitor.

Question 7

what are cell wall antibiotics?

Answer 7

Penicillins and cephalosporins are the major antibiotics that inhibit bacterial cell wall synthesis. They are called beta-lactams

Question 8

gram negative and positive facts

Answer 8

Gram-negative bacteria is an effective barrier, regulating the passage of large molecules such as antibiotics into the cell.

In contrast, the thick, porous peptidoglycan layer in the cell wall of Gram-positive bacteria gives greater access to antibiotics, allowing them to more easily penetrate the cell and/or interact with the peptidoglycan itself.

Narrow-spectrum antibiotics are effective against either Gram-positive or Gram-negative bacteria, whereas broad-spectrum antibiotics are effective against both types.

Question 9

what is vancomycin?

Answer 9

Vancomycin is used to treat colitis (inflammation of the intestine caused by certain bacteria)

Vancomycin is in a class of medications called glycopeptide antibiotics. It works by killling bacteria in the intestines.

Question 10

MOA of vancomycin?

Answer 10

Inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminal of the growing peptide chain during cell wall synthesis, resulting in inhibition of the transpeptidase, which prevents further elongation and cross-linking of the peptidoglycan matrix

Question 11

MOA of vancomycin simple:

Answer 11

It inhibits bacterial cell wall synthesis, which stops the bacteria growing and dividing properly. The cell walls are made of strings of sugars, crosslinked by short peptide chains. By binding to D -alanyl- D -alanine groups on the end of the peptide chains, it stops the crosslinks forming.

Question 12

who should not take vancomycin?

Answer 12

low levels of a type of white blood cell called neutrophils.
hearing loss.
kidney disease with likely reduction in kidney function.

Question 13

beta lactam antibiotics?

Answer 13

• penicillin derivatives (penams)
• cephalosporins and cephamycins
• monobactams
• carbapenems and carbacephems.

Question 14

what are polymyxins?

Answer 14

Polymyxins are antibiotics. Polymyxins B and E are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane.

Question 15

polymyxin is? and its structure

Answer 15

Polymyxin is a lipopeptide isolated from bacillus polymyxa, which is a bacteria.
It consists of a heptapeptide ring, exocylic chain and fatty acid tail.

Question 16

simple definition of MOA for polymyxin?

Answer 16

Polymyxins bind to and disrupt the negatively charged lipopolysaccharide (LPS) of the outer membrane of Gram-negative bacteria, allowing the passage of the polymyxin (and of other drugs) into the periplasmic space.

Question 17

Detailed explanation of MOA for polymyxin?

Answer 17

Lipopolysaccharides (LPS) is a major component of the cell membrane in gram negative bacteria.

The heptapeptide ring of the polymyxin binds to the LPS , and it destabilises calcium and magnesium bridges Which normally stabalise the LPS.

The peptide ring has a higher affinity for the LPS.

The calcium and magnesium ions are displaced and further the outer membrane is disrupted.

The fatty acids side chain also interacts with the LPS. Contributing to the insertion of the polymyxin into the membrane. This membrane has gaps and holes in it. This leads to permeability changes within the membrane allowing the passage of molecules within the bacteria out, and outside of the bacteria in as well.

Polymyxin will have a promoter effect on itself by causing some gaps in the membrane, its going to allow more polymyxin to enter which also affects the inner membrane. Promoting the intake of polymxin. The disruption in the membrane causes the bacteria to die.

Question 18

polymyxin:
most common types?
administration?
side effects?

Answer 18

The most common are polymyxin B and E (a.k.a colistin)

Polymyxin are not readily absorbed by mouth and these need to be given by injection.

Side effects: neurotoxicity and nephrotoxicity with these being the most serious side effects and are dose related. The more you give to the patient the more side effects you’re going to see.

because these side effects are quite severe we limit its use to those serious infections e.g. aerobic gram negative bacteria that are quite resistant so there are limited treatment option

Question 19

Define bacteriostatic and bactericidal?

Answer 19

Bacteriostatic” means that the agent prevents the growth of bacteria (i.e., it keeps them in the stationary phase of growth), and “bactericidal” means that it kills bacteria.

Question 20

are polymyxins limited to gram positive or gram negative bacteria?

Answer 20

Polymyxins have bactericidal action against Gram-negative bacteria, including Pseudomonas species, but are inactive against Gram-positive bacteria.

Question 21

why are polymyxins less effective for gram positive bacteria?

Answer 21

Gram-positive bacteria lack an LPS-containing outer membrane, it is generally acknowledged that polymyxins are less active against Gram-positive bacteria.

find more infoo!!

Question 22

what do tetracyclines target?

Answer 22

Tetracyclines, target protein synthesis.

Protein synthesis happens within the ribosomal unit of the bacteria.

Tetracycline bind to the 30s ribosomal subunit. By binding to this subunit they prevent the binding of tRNA preventing protein synthesis.

Question 23

Tetracycline use should be avoided in pregnant, lactating women and in children, why is this?

Answer 23

Tetracycline can pass into breast milk and may affect bone and tooth development in a nursing infant. Do not breast-feed while you are taking tetracycline

Question 24

Tetracycline is considered a broad spectrum antibiotic. What does this mean?

Answer 24

A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative,

Question 25

what is trimethoprim?

Answer 25

Trimethoprim is an antibiotic that is used to treat bladder or kidney infections, or ear infections caused by certain bacteria.

Question 26

what does trimethoprim do?

Answer 26

TMP is a synthetic antibiotic that binds with the enzyme dihydrofolate reductase (DHFR) inhibiting the folic acid synthesis pathway

Question 27

why is folate needed?

Answer 27

Folate is required for DNA synthesis

Question 28

folate synthesis pathway?

Answer 28

Para-aminobenzoic acid Is converted to tetrahydrofolate by bacterial enzymes dihydropterolate synthetase and dihydrofolate reductase.

Trimethoprim is a structural analog of dihydrofolatic acid thus binds to dihydrofolate reductase.
Completely inhibits tetrahydrofolate synthesis

Question 29

What do you think would happen to drugs that are normally metabolised by CYP2C8 (such as warfarin) if given alongside Trimethoprim?

Answer 29

Trimethoprim selectively inhibits CYP2C8

If trimethoprim given alongside a drug that is metabolised by CYP2C8 e.g. warfarin, the drug wont be metabolised as predicated increasing its availability in the body and thus it potency.

You may need more frequent monitoring of your prothrombin time or INR by your doctor to safely use both medications.

In this example Trimethoprim increases the anticoagulant effect of warfarin.

Question 30

what are Sulphonamides ?

Answer 30

Group of medicines used to treat bacterial infections.

Question 31

Mode of action of sulphonamides?

Answer 31

The sulfonamides inhibit the bacterial enzyme dihydropteroate synthetase (DPS) in the folic acid pathway, thereby blocking bacterial nucleic acid synthesis.

Sulfonamides substitute for PABA, preventing its conversion to dihydrofolic acid. Alone, this action is considered bacteriostatic.

Sulfonamides competitively inhibit the incorporation of PABA into folic acid, thereby preventing the synthesis of folic acid.

Trimethoprim binds reversibly to and inhibits dihyrofolate reductase, an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, decreasing folic acid synthesis

Question 32

what do fluoroquinolones target?

Answer 32

DNA/RNA synthesis

Question 33

How does fluoroquinolones work by inhibitting DNA/RNA synthesis? (mode of action)

Answer 33

During protein synthesis and DNA replication: double-stranded DNA is unwound to allow for complementary base pairing and synthesis of mRNA to proceed.

This is done by the enzyme DNA gyrase which is consists of subunit gyrA and gyrB.

gyrA function is the breakage, passage and rejoining of double-stranded DNA

Fluroquinolones bind to gyrA inhibiting DNA replication and protein synthesis

Question 34

Rifampicin is a known inducer of cytochrome P450 enzymes. What affect does this have? And What impact could this have on the patient?

Answer 34

An inducing agent can increase the rate of another drug’s metabolism by as much as two- to threefold that develops over a period of a week.

Rifampicin is a known inducer of cytochrome P450 enzymes-
 It increases the metabolism of drugs
 What impact could this have on the patient? It Decreasing their concentrations making them less effective or ineffective

Question 35

mode of action of rifampicin?

Answer 35

Rifampin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

Rifampicin affects RNA synthesis

Question 36

what is antibiotic propholaxysis?

Answer 36

Antibiotic prophylaxis is defined as the administration of antibiotics before contamination by surgical incision has occurred and is given with the intention of preventing infection.

Question 37

what is mupirocin?

Answer 37

Mupirocin is an antibiotic that prevents bacteria from growing on your skin.

It is used in particular to treat infections caused by bacteria called meticillin-resistant Staphylococcus aureus (MRSA).

Question 38

check the table on word for bacterial drug overview

Answer 38

x

Question 39

Antifungal antibiotics that target various aspects of the fungal cell include?

Answer 39

Azole antifungal drugs and allylamine targets cell membrane synthesis
Antimetabolite antifungal drugs target antimetabolite DNA/RNA synthesis
Echinocandins targets fungal cell wall
Griseofulvin targets microtubule function
Polyene antifungal drugs targets direct cell membrane interaction.

Question 40

what is Amphotericin B?

Answer 40

Amphotericin B is an antifungal medication used for serious fungal infections

Question 41

Type of sterol in fungi and mammalian cells?

Answer 41

In fungi, the sterol is primarily ergosterol whereas in mammalian cells its cholesterol.

Question 42

what does Amphotericin B target and what is it made up of ?

Answer 42

Amphotericin B Targets the ergosterol in the fungi Amphotericin B is made up of a Polyene domain, a Polyol domain and Sterol A ring binding domain

Question 43

Amphotericin B targeting cell membrane?

Answer 43

Sterol A ring domain that binds to ergosterol in the fungal membranes. It has a greater affinity for ergosterol , but can still interact with cholesterol.
When it binds to the ergosterol it results in the insertion of the Amphotericin B into the cell membrane, leading to loss of membrane integrity and leakage of intracellular cations resulting in gaps in the membrane to get this kind of circular death ring that develops within the membrane and the loss of cations from the cell.

Question 44

MOA of Amphotericin B

Answer 44

The drug acts by binding to sterols (ergosterol) in the cell membrane of susceptible fungi.

This creates a transmembrane channel, and the resultant change in membrane permeability allowing leakage of intracellular components.

Ergosterol, the principal sterol in the fungal cytoplasmic membrane, is the target site of action of amphotericin B and the azoles.

Amphotericin B, a polyene, binds irreversibly to ergosterol, resulting in disruption of membrane integrity and ultimately cell death.

Question 45

In the membrane off kidney cells, these are very rich in cholesterol. So what effect did you think the Polyene have on the host kidneys?

Answer 45

The membranes of Kidney cells are rich in sterols e.g. cholesterol
 Interact with the cholesterol in the kidney causing cellular damage via similar mode of action
 Kidney damage = could lead to nephrotoxicity

Question 46

An example of an Polyene antifungal drugs ?

Answer 46

Amphotericin B that targets direct cell membrane interaction

Question 47

Azole antifungal drug?

Answer 47

Targets cell membrane synthesis

MOA
Inhibits the fungal enzyme 14-alpha lanosterol demethylase: a key enzyme in ergosterol biosynthesis

Depletion of ergosterol in the fungal cell membrane and accumulation of toxic intermediate sterols

Key info:
Azoles are antagonistic to the antifungal Amphotericin B as azoles deplete ergosterol which is the target of Amphotericin B

Question 48

Flucytosine aka 5-FC is a synthetic antifungal?

Answer 48

Targets: Antimetabolite-dna/rna synthesis

MOA=
5-FC form has no intrinsic antifungal activity. When taken into the fungal cell its converted to active form 5-FU

5-FU is incorporated into RNA where it causes miscoding and halts protein synthesis

5-FU is also phosphorylated which inhibits DNA synthesis

key info:
•Fungi can alter uptake pathway and become resistant to Flucytosine

• Often combined with Amphotericin B to overcome this.
• AmB creates pores in membrane facilitating Flucytosine transport into the fungal cell to be converted to the active form 5-FU

Question 49

Echinocandins (antifungal drugs)

Answer 49

targets fungal cell wall

MOA=
Inhibit Beta-glucan synthase enzyme preventing Beta-glucan production (responsible for fungal cell wall strength and shape)

• Weakens the cell wall structure
• Leading to cell wall lysis

Key info=
•Distributes well into the tissues, including lung, liver, and spleen
•Minimal penetration into central nervous system (CNS) tissues, including the eye, due to their high protein binding and large molecular weight.

Question 50

Griseofulvin (antifungal drug)

Answer 50

Targets microtubule function

MOA= Binds to and disrupts both the α and β tubulin subunits preventing spindle formation and miosis in fungi

key info=
•Fungalstatic: Inhibits growth while not necessarily killing the organism

Question 51

what does fungalstatic mean

Answer 51

inhibit growth of fungi

Question 52

basic characteristics of viruses?

Answer 52

They have a nucleic acid molecule, DNA or RNA, single strain or double strain.

They also have a protein coat or capside. And some viruses will have a lipid envelope. When that happens, the lipid envelop contains some protein spikes that are important to attach to host cells.

One very important characteristic of viruses is that they multiply only within the host living cells using the host’s molecular machinery; and this is important in terms of designing drugs.

Question 53

Stages involved in infection of host cells and viral replication

Answer 53

The first step is the attachment to host cells.

The second one is penetration that can be done by endocytosis or membrane fusion.

The next step is uncoating, which allows the release of the viral genome.

The replication stage comes next and involves synthesis of viral RNA and protein production. A key step at this point of the cycle is the replication of the viral genome. Normally viruses will carry their RNA polymerase, or DNA polymerase, or, in the case of retroviruses, the reverse transcriptase that they need to replicate their genome.

Once all the components are there, the assembly step takes place in which all the parts are assembled together to form the new viral particles.

And, finally, there is the release of the new viral particles from the host cell.

Question 54

Types of infections?

Answer 54

lytic infections: infected host cell will release a large number of infective particles of new viruses.

Persistent infection: This is still an active infection, the viruses are still replicating, but normally the infected cells release a lower number of new viral particles.

Latent infection: For example, in HIV when the virus gets integrated in the human genome. Some of these infected people will be asymptomatic, but they are still carriers; they still carry the virus genomic information

Question 55

what are the challenges faced by antiviral drugs

Answer 55

• Antiviral drug specificity: Viral genomes encode very few proteins. It is difficult to find viral molecules to target because much of the viral life cycle uses host cell components.
• Broad-spectrum activity: there are not many drugs that can be used in multiple viral infectious diseases. And even some drugs are effective against some viral subtypes but not others.
• Drug resistance: viral genomes are highly variable, and emerging drug resistance mutations are a major problem.
• Viral reservoirs: DNA viruses and retroviruses can integrate their genomes into human genomes, and current antiviral drugs cannot eradicate this.
• Fast emerging viral infectious diseases: it is challenging to develop antiviral drugs and vaccines rapidly enough.
• Co-infections: There is a need for antiviral treatments against viral co-infections, for example, HIV and Hepatitis B virus co-infections.
• Drug delivery: economic and logistic challenges for the delivery of some new therapies, especially in resource-limited settings.

Question 56

Viral entry inhibitors:

Answer 56

Enfuvirtide (for HIV)
Palivizumab (for respiratory syncytial virus)
variZIG (for varicella zoster virus)
Docosanol (for herpes simplex virus)

Question 57

what are entry inhibitors/fusion inhibitors?

Answer 57

Entry inhibitors, also known as fusion inhibitors, are a class of antiviral drugs that prevent a virus from entering a cell, for example, by blocking a receptor. Entry inhibitors are used to treat conditions such as HIV and hepatitis D.

Question 58

In the case of HIV what two drugs block entry?

Answer 58

Enfuvirtide blocks the fusion of HIV-1 gp41 protein interaction with the extracellular membrane of the host cell.

Maraviroc inhibits the human CCR5 receptor, HIV binds to CCR5 through its viral gp120 protein. Maraviroc blocks gp120-CCR5 interaction to inhibit HIV entry

Question 59

what are the two antiviral drugs that are based on human immunoglobulins blocking RSV entry.

Answer 59

Palivizumab targets the viral fusion protein.

RSV-IGIV are neutralizing antibodies to RSV that target surface glycoproteins F and G.

Question 60

what is the Entry Inhibitor for Herpes Simplex Virus. ?

Answer 60

Docosanol.

It is used to treat cold sores caused by HSV.

It is thought to disrupt the interaction between the viral envelope proteins and the epithelial cell membrane receptors. It prevents viral entry and viral replication

Question 61

what is hydroxychloroquine and its MOA?

Answer 61

It is an antiretroviral drug.

It changes the pH of the endosomes; this interferes with viral entry but also late stages of replication.

Raised pH in endosomes, prevent virus particles from utilizing their activity for fusion and entry into the cell

Question 62

what does viral uncoating mean?

Answer 62

Uncoating is the process of capsid disintegration, which leads to the release of the genomic material. This step is performed by viral or host enzymes, or by capsid dissociation alone.

Question 63

what is amantadine?

Answer 63

Amantadine is an inhibitor of influenza A virus.

Its mechanism of action involves inhibition of the transmembrane domain of the viral M2 protein, thus preventing viral uncoating during early stages of replication.

Question 64

Importance of viral M2 protein?

Answer 64

After the virus enters the infected cell by endocytosis, the M2 proton channel opens in response to the low pH of the endosome.

This allows proton flux into the virus, which triggers the dissociation of the viral RNA and the fusion of the viral and endosomal membranes.

viral RNA is released in to the cytoplasm for replication by the host cell.

Successful uncoating of Influenza Virus requires the action of the M2 ion channel.

Viral Uncoating Inhibitors interfere with the M2 ion channel and in doing so inhibit viral uncoating and thus infection of host cells.

Question 65

Name the viral genome replicating inhibitors?

Answer 65

NRTIs
NNRTis
Integrase inhibitors
Acyclic nucleoside phosphonate analogues.

Question 66

what are Reverse-transcriptase inhibitors?

Answer 66

Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.

Question 67

difference between NRTIs and NNRTIs?

Answer 67

NRTIs work as nucleotide chain terminators; that bind to the growing viral DNA chain and cause termination.

In contrast, NNRTIs target the allosteric site of HIV-1 reverse transcriptase. HIV has two species, HIV-1 and HIV-2, but NNRTIs cannot target HIV-2 reverse transcriptase due to structural properties.

NNRTIs do not need any metabolic processing. In contrast, NRTIs are given as pro-drugs.

Question 68

Types of reverse transcriptase inhibitors: NRTIs

Answer 68

Zidovudine
Didanosine
Stavudine
Lamivudine
Abacavir
Emtricitabine

Question 69

Types of reverse transcriptase inhibitors: NNRTIs

Answer 69

Nevirapine
Efavirenz
Etravirine
rilpivirine

(target HIV-1)

Question 70

what are integrase inhibitors?

Answer 70

Integrase inhibitors (INIs) are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus.

Question 71

examples of inhibitors of HIV integrase?

Answer 71

inhibits HIV integrase to prevent the viral genome being incorporated into the human genome.

Raltegravir
Elvitegravir
dolutegravir

Question 72

Viral DNA replication inhibitors?

Answer 72

5 substituted 2 deoxyuridines
Pyrophosphate analogues
Acyclic guanosine analogues
Acyclic nucleoside phosphonate analogues

Question 73

what is Idoxuridine

Answer 73

First antiviral drug.

It is phosphorylated by cellular kinases to reach its active form.

It is a modified form of deoxyuridine.

Able to replace thymidine in the enzymatic step of viral DNA replication. The iodine atom added to the uracil component blocks base pairing causing DNA chain termination.

Question 74

MOA of Idoxuridine ?

Answer 74

Idoxuridine acts as an antiviral agent by inhibiting viral replication by substituting itself for thymidine in viral DNA. This in turn inhibits thymidylate phosphorylase and viral DNA polymerases from properly functioning. The effect of Idoxuridine results in the inability of the virus to reproduce or to infect/destroy tissue.

Question 75

what are Acyclic guanosine analogues?

Answer 75

Acyclic guanosine analogues, including acyclovir (ACV), famciclovir (FCV), ganciclovir (GCV), penciclovir (PCV), and valaciclovir (VACV), are antiviral drugs used for treatment of herpes simplex viruses, varicella-zoster viruses, and cytomegalovirus (CMV)

they are pro-drugs; they need to be metabolized to become active

Question 76

what are acyclic nucleoside phosphonate?

Answer 76

acyclic nucleoside phosphonate analogues are another group of antivirals.

They cause irreversible DNA chain termination. because they have a phosphonate linkage instead of the normal phosphate linkage. The hydrolase enzyme esterase cannot cleave this phosphonate group.

Question 77

what is Fomivirsen?

Answer 77

Fomivirsen:

An antisense antiviral drug used in cytomegalovirus retinitis in immunocompromised patients, it is administered via intraocular injection
It binds to the viral RNA, preventing it to be translated to protein

Question 78

what are Viral proteases ?

Answer 78

Viral proteases are responsible for cleaving the precursor proteins into functional and structural proteins that are needed for the virus life cycle.

Question 79

what are protease inhibitors?

Answer 79

Protease inhibitors are one type of antiretroviral drug used to treat HIV. The goal of these drugs is to reduce the amount of HIV virus in the body (called the viral load) to levels that are undetectable. This slows the progression of HIV and helps treat symptoms.

Question 80

protease inhibitors?

Answer 80

Protease inhibitors, which figure among the key drugs used to treat HIV, work by binding to proteolytic enzymes (proteases). That blocks their ability to function. Protease inhibitors don’t cure HIV. But by blocking proteases, they can stop HIV from reproducing itself.

Question 81

An example of a virus that can be treated by protease inhibitors?

Answer 81

Hepatitis C virus can also be treated with protease inhibitors. In this case the targets that are being inhibited are HCV NS3/4A proteases.The NS3-4A is a serine protease. It is a non-covalent, heterodimer complex formed by:
• NS3, the catalytic subunit
• and the NS4A cofactor, which is the activation subunit.
The NS3-4A serine protease is responsible for the proteolytic cleavage of the viral polyprotein precursor.

Question 82

what is Viral neuraminidase?

Answer 82

Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell.

Question 83

What Drugs target viral neuraminidase to inhibit influenza virus A and B release from host cells.

Answer 83

Zanamivir
Oseltamivir
Laninamivir octonoate
peramivir

Question 83

What Drugs target viral neuraminidase to inhibit influenza virus A and B release from host cells.

Answer 83

Zanamivir
Oseltamivir
Laninamivir octonoate
peramivir

Question 84

MOA of zanamivir?

Answer 84

The proposed mechanism of action of zanamivir is via inhibition of influenza virus neuraminidase with the possibility of alteration of virus particle aggregation and release. By binding and inhibiting the neuraminidase protein, the drug renders the influenza virus unable to escape its host cell and infect others.

Question 85

interferon treatment:

Answer 85

interferon treatments is that the administration is difficult, they are expensive, and usually have multiple side effects.

Pegylated interferon alfa variants 2a and 2b cause:

1) Stimulation of leukocytes; this is CD8 cells and natural killer T cells.
2) Stimulation of the expression of innate antiviral genes and proteins to block viral replication.

Question 86

In the case of Human Papilloma Virus, what are warts treated with?

Answer 86

In the case of Human Papilloma Virus, the warts are treated with antimitotic or immune-modulating drugs.

Podofilox is an antimitotic that inhibits cell division.
Imiquimod and Sinecatechins target the host immune system.

Question 87

What is Protozoa , Helminths and arthropods ?

Answer 87

Protozoa - unicellular eukaryotes
Helminths - parasitic worms
Arthropods - mites , fleas and lice

Question 88

What causes malaria ?

Answer 88

Plasmodium falciparum

Question 89

What makes an ideal anti parasite drug ?

Answer 89

Selective toxicity to parasites 
Target many species and life stages 
Cost effective 
Easy to administer 
Unlikely to develop resistance

Question 90

What to consider with anti-parasite drugs ?

Answer 90

Parasites are eukaryotes and share much of their metabolic machinery with humans

Most anti-bacterial do not work on parasites

Therapeutic window might be very narrow

Question 91

Anti parasite drug strategy and what to target :

Anti-protozoal agents and anti-helminthic agents

Answer 91

Anti-protozoal agents - targeted at rapid proliferating , young and growing cells.
Target:
Nucleus acid synthesis /damage
Protein synthesis
Specific metabolic pathways (folate metabolism)
Detoxification mechanisms

Anti-helminthic agents: targeted to non-proliferating adult organisms

Target:
Neuromuscular coordination (needed for feeding movements )
Carbohydrate metabolism
Micro tubular integrity (needed for egg laying and hatching, larval development, glucose transport and enzyme activity and secretion)

Question 92

Diff types of quinolines ?

Answer 92

Quinine 
Chloroquine 
Amodiaquine
Mefloquine 
Primaquine

Question 93

Diff types of anti folate ?

Answer 93

Sulfonamides
Pyrimethamine
Proguanil
Chlorproguanil

Question 94

Diff types of artemisinin compounds ?

Answer 94

Artesunate
Artemether
Dihydroartemisinin

Question 95

What does malaria chemotherapy include?

Answer 95

Quinolines
Anti-folates
Artemisinin

Question 96

Antimalarial drugs - MOA

Answer 96

To begin with -

The parasite worms are within the RBC, will take haemoglobin from the RBC and will take the digestive part of the parasite . The haemoglobin is digested here , this supports growth and maturation of the parasite .

When hb digested it released heme that’s toxic , the way the parasite deals with the toxicity is it creates the heme group to hemozoin crystals .

So quinolines act through disruption of haemoglobin digestion - blocks parasite detoxification of heme

Artemisin- interacts with heme - iron . It generates free radicals that alkylate and oxidise proteins and lipids within infected red blood cells

Question 97

What do anti-folates do?

Answer 97

Antagonise the actions of folic acid
Inhibit dihydrofolate reductase DHFR, whcih catalysed the reduction of dihydrofolate to tetrahydrofolate

Inhibition if dihydropteroate synthase , interfering with folate synthesis . DHPS present in plasmodium

Question 98

X

Answer 98

Pyrimethamine and trimethoprim are the most widely used dihydrofolate reductase inhibitors.

Question 99

MOA for Pyrimethamine?

Answer 99

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are essential for DNA synthesis and cell multiplication.

Question 100

What is trimethorpim?

Answer 100

Trimethoprim is an antifolate antibiotic often used in combination with sulfamethoxazole to treat a number of infections,

Trimethoprim is a reversible inhibitor of dihydrofolate reductase, one of the principal enzymes catalyzing the formation of tetrahydrofolic acid (THF) from dihydrofolic acid (DHF)

Question 101

Pharmacologic target of anti folate drugs used for toxoplasma gondii (Pyrimethamine and sulfonamides)

Answer 101

Pyrimethamine (TARGET- protozoal dihydrofolate reductase DHFR)

sulfonamides (TARGET- protozoal dihydropteroroaye synthase- DHPS)

Question 102

What is metronidazole and tinidazole used for ?

Answer 102

Amoebiasis
Giardiasis
Trichomoniasis

Question 103

Info on metronidazole ?

Answer 103

Metronidazole is a nitroimidazole used to treat trichomoniasis

Penetrates protozoal and bacterial cell walls but can’t enter mammalian cells

Must be activated once entered the cell

The activating enzymes : nitro reductase is only found in anaerobic organism

The reduced metronidazole inhibits DNA replication by causing breaks and inhibiting repair of the DNA

Question 104

Albendazole , mebendazole

Answer 104

Treats helminth infections
(Soil transmitted Helminthases include ascaris, whipworms and hookworms)

These drugs target micro tubular integrity .
They bind to beta Tubulin and inhibit tubulin polymerisation which districts motility and replication

Loss of cytoplasmic microtubules in intestinal cells leads to impaired uptake of glucose by the larval and adult parasites

Question 105

Schistosomiasis

Answer 105

It is the second only to malaria as the most devastating parasitic disease
More than 200 million people are infected worldwide

Question 106

What drug is used to treat schistosomiasis ?

Answer 106

Praziquantel.
It causes severe spasms and paralysis of the worms muscles

Paralysis is accompanied and caused by rapid calcium influx inside the schistosome

Question 107

What is Onchocerciasis

Answer 107

Onchocerciasis, or river blindness, is a neglected tropical disease (NTD) caused by the parasitic worm Onchocerca volvulus

Question 108

Treatment choice for Onchocerciasis?

Answer 108

Ivermectin .

It imbolises the parasite by tonic paralysis of musculature by activating glutamate - gated chloride ion channels

Question 109

MOA of ivermectin ?

Answer 109

Ivermectin binds with high affinity to glutamate gated chloride ion channels in invertebrate muscle and nerve cells of the microfilaria

Binding causes increase in permeability of cell membrane to chloride ions and results in hyperpolarisation of the cell leading to paralysis and death of parasite .

Question 110

Check tb lecture

Answer 110

X