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Yr3 CSP > Anti-Viral Therapy, September 8th > Flashcards

Anti-Viral Therapy, September 8th Flashcards

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1
Q

Generally, how do Anti-virals work?

A

Some work by blocking the Ligand-Receptor binding

Done by either binding to the Ligand or the Receptor

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2
Q

Where can drugs interfere with the Viral Lifecycle

A
  1. Membrane Fusion
  2. DNA/RNA Replication
  3. Integrating DNA into Genome
  4. Translating Viral RNA to Proteins (Not always)
  5. Assembly/Maturation of Virions
  6. Escape from Host Cell
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3
Q

What diseases is Aciclovir effective against?

A

Herpes Simplex 1/2

Herpes Zoster

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4
Q

What is the composition of Aciclovir?

A 
Guanosine Analogue (Acyclo-Guanosine)
Partial Nucleoside Analogue
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5
Q

What is the MOA of Aciclovir?

A
  1. Converted by Viral Thymidine Kinase to Monophosphate Acyclo-GMP
  2. Converted to Triphosphate using a Cellular Enzyme
  3. Inhibits action of Viral DNAP by terminating chains
  4. High Therapeutic Ratio (Viral TK is 3000x more effective at converting A-G to Monophosphate, and Viral DNAP is better at incorporating Triphosphate into Growing DNA chain than Cellular DNAP)
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6
Q

How is Aciclovir/Valaciclovir administered?

A

Topically (To Cold Sores/Eyes)
Orally
IV

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7
Q

What are the main side effects of Aciclovir/Valaciclovir?

A

Psychiatric (Cotard’s Syndrome)

Toxicity in overdose (Lethargy, Confusion, Myoclonus)

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8
Q

How does Valaciclovir compare to Acyclovir?

A

Valaciclovir is Acyclovir that is ESTER-LINKED to Valine

Thus, Greater Oral Bioavailability

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9
Q

Why do viruses grow resistant to Aciclovir/Valaciclovir

A

Mutation of Viral Thymidine Kinase/DNAP

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10
Q

What is Idoxuridine?

A

NucleoSide Analogue

Modified form of Deoxyuridine containing Iodine

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11
Q

When is Idoxuridine used?

A

Topically for Herpes Keratitis

Too toxic for Systemic Use

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12
Q

What can Ganciclovir and Valganciclovir kill?

A

CMV

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13
Q

What is Ganciclovir made up of?

A

Synthetic Analogue of Deoxyguanine

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14
Q

What is the MOA of Ganciclovir?

A
  1. Phosphorylated to Monophosphate by CMV Thymidine Kinase
  2. Then made into Triphosphate by Cellular Kinases
  3. Inhibits Viral DNAP more than Cell DNAP
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15
Q

What is Valganciclovir compared to Ganciclovir?

A

Valganciclovir is a VALINE Ester with Greater Oral Bioavailability

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16
Q

What are the main side effects of Val/Ganciclovir

A

BM Suppression

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17
Q

What is Foscarnet?

A

Pyrophosphate Analogue

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18
Q

What is the MOA of Foscarnet?

A

Blocks Viral DNAP

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19
Q

What is Foscarnet used for?

A

Herpes Simplex Virus 1/2
Herpes Zoster
CMV (Especially Retinitis as an Intravitreous Injection, it can also be as an IV injection)

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20
Q

What are the main side effects of Foscarnet?

A
  1. Nephrotoxicity
  2. Electrolyte Disturbances (CaMg)
  3. Genital Ulceration
  4. CNS issues (Parasthesia, Irritability, Hallucinations)
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21
Q

What is Cidofovir used against?

A

DNA Viruses

  1. Herpes
  2. Papilloma
  3. Adenoviruses
  4. Poxviruses
  5. MOSTLY CMV
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22
Q

What is the MOA of Cidofovir?

A

Blocks Viral DNAP

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23
Q

What are the Adverse effects of Cidofovir?

A
  1. GI
  2. Haematological
  3. Iritis
  4. Headache
  5. Weakness
  6. Hair Loss
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24
Q

What is the MOA of Trifluridine?

A

Nucleoside Analogue from modified Deoxyuridine

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25
What does Trifluridine kill?
Herpes Simplex | Zoster Keratitis
26
What are the adverse effects of Trifluridine?
Burning | Stinging Oedema
27
What is the MOA of Vidarabine?
Adenosine Analogue with Different sugar needing Triple Phosphorylation
28
What is Vidarabine used for?
Herpes Simplex | Herpes Zoster
29
What are the adverse effects of Vidarabine?
GI Leukopenia Thrombocytopenia
30
What drugs are generally effective against Retroviruses?
Reverse Transcriptase Inhibitors
31
What are the different types/analogues of RTI
Nucleoside and Nucleotide Analogues
32
What is the function of the NRTI analogues?
They inhibit Reverse Transcriptase by incorporating themselves into the growing DNA chain This stops a linkage to the subsequent base
33
What are NucleoSide analogues?
They are molecules with a Ribose sugar and Base Requires Three Phosphorylations to incorporate it
34
What are examples of NucleoSide analogues?
Lamivudine (Hep B) Abacovir and Emtricitabine (first line) Zidovudine (second line)
35
What are the side effects of Lamivudine?
``` Nausea Fatigue Headaches Diarrhoea Cough Pro-inflammatory response Autoimmunity ```
36
What are examples of NucleoTide analogues?
Tenofovir (HepB) and Adefovir
37
What are the side effects of Tenofovir?
Renal Insufficiency | Fanconi syndrome
38
What is Fanconi Syndrome?
Condition where normally absorbed products are excreted in urine
39
What is the MOA of NNRTIs?
They bind to RT away from the active site Hampering its effect via distortion
40
What are the first-line choices of NNRTIs?
Efavirenz and Rilpivirine
41
What are the other less favourable NNRTIs?
Etravirine (Can cause CNS toxicity) and Doravirine Nevirapine has more serious effects
42
What is the MOA of PIs?
Bind to Viral Proteases responsible for the viral precursor proteins that usually make up Virions
43
What are the main PIs?
Darunavir and Ritonavir
44
What suffix underlies all Integrase Inhibitor drugs?
-tegraVir
45
What suffix underlies most NNRTI drugs?
-INE or -VIRINE except Efavirenz
46
What suffix underlies most HCV PI drugs?
-preVir
47
What suffix underlies most NS5A inhibitor drugs?
-asVir
48
What suffix underlies most NS5B drugs?
-buVir
49
What suffix underlies most NRTI drugs?
-INE except Abacavir
50
What two drugs make up Truvada?
Tenofovir and Emtricitabine
51
What is the MOA of Integrase Inhibitors?
Inhibits Integrase which usually mediates integration of the HIV DNA (made by Reverse transcription) into the host genome
52
What are some examples of Integrase Inhibitors?
Raltegravir Dolutegravir Bictegravir
53
What is the MOA of Fusion Inhibitors?
Blocking GP41 on the surface of HIV Virions GP41 usually mediates fusion between HIV envelope and Cell membrane?
54
What is an example of Fusion Inhibitors
Enfuvirtide
55
What is the MOA of Entry Inhibitors?
Blocking CCR5 on the Cell surface | Together with CD4 can enable GP120 to bind to HIV and allow Cellular entry
56
What is an example of Entry Inhibitors?
Maraviroc
57
What is the usual combination of Anti-retroviral therapies?
Two NRTI + something else 1. Tenofovir + Emtricitabine 2. Abacovir + Lamivudine Either of these PLUS a Third * *3. Integrase Inhibitor (Raltegravir) 4. Protease Inhibitor (Darunavir) 5. NNRTI (Doravirine, Rilpivirine
58
For Anti-retroviral therapy, what do you use if you cannot use Tenofovir or Abacovir?
Usually a combination of: 1. Integrase + Protease 2. Integrase + Lamivudine 3. Boosted Protease + Lamivudine
59
When is PrEP given?
To people with sexual practices that could expose them to HIV Truvada into a single daily pill
60
What do you do during a Post-exposure to body fluids/needlestick injury?
Wash with antiseptic/fluid on part | Truvada combo + Dolutegravir/Raltegravir for TWENTY EIGHT DAYS
61
What is Ribavirin?
Guanosine Analogue
62
What can Ribavirin do?
Inhibits Viral RNA-dependent RNAP | Incorporates to new RNA chain and terminates it
63
What is Ribavirin effective against?
``` Hepatitic C Viral Haemorrhagic Fever RSV Flu (Sometimes) Herpes (Mystery but true) ```
64
What are the adverse effects of Ribavirin?
Haemolytic Anaemia BM Suppression Psychiatric effects (Depression) Cough
65
What are the main classes of drugs to treat Influenza?
1. Neuraminidase Inhibitors 2. M2 Inhibitors 3. Ribavirin
66
What does Neuraminidase do and how do Neuraminidase Inhibitors stop this?
1. Viral Neuominidase cleaves Sialic Acid from Glycoprotein 2. This will release Virions from the host 3. Virions will stop aggregating 4. Reduction of inactivation of Virions by Host mucus - NI will stop all of this lol
67
What are examples of Neuraminidase Inhibitors?
OseltAMIVIR | ZanAMIVIR
68
What is the suffix that underlies Neuraminidase inhibitors
-AMIVIR
69
What is the MOA of M2 Inhibitors?
Inhibits M2 protein of the Virus from decreasing H+ influx | This will STOP uncoating/recoating
70
What are the main drugs of the M2 Inhibitor class?
Amantidine | Rimantidine (Less neuro side effects)
71
What is the suffix that underlies M2 inhibitors?
-TIDINE
72
What drugs do we usually use to treat Hepatitis C?
``` Ribavirin Pegylated IFN (Though usually B) ```
73
What is Pegylated IFN?
Alpha or Beta Cytokines enhancing immune response Pegylated so they are linked to Polyethylene-Glycol to prolong Half Life Given by Injection
74
What are the side effects of Pegylated IFN?
Malaise | Fever
75
What are the new Treatments for Hepatitis C?
``` Direct Acting Agents (DAAs) ------------------------------- Protease Inhibitors NS (Non-structural) inhibitors - NS5A, NS5B ```
76
Give examples for Protease Inhibitors against Hepatitis C
Glecaprevir Grazoprevir Tenofovir (Not active against Hep C Protease but boosts the drugs via blocking metabolism)
77
What is the function of Protease inhibitors?
Inhibition of Viral NS3/4A serine protease
78
What is the function of NS5A inhibitors?
Inhibits NS5A which is a viral protein promoting Assembly
79
Give examples of NS5A inhibitor drugs
Daclatasvir Elbeasvir Ledipasvir
80
What is the function of NS5B inhibitors?
Inhibits NS5B which is a viral RNA-dependent RNA polymerase
81
Give examples of NS5B inhibitors
Sofosbuvir (NucleoT/Side analogue) | Dasabuvir (Non-NucleoT/Side analogue)
82
Can Hepatitis C be cured?
Yes | It is an RNA virus so it cannot integrate itself into the genome
83
What is SVR?
Relating to Hep C, Cure | After Antiretroviral therapy, it is defined as the presence of no HCV RNA in the blood after 6 months
84
When do we typically give Ribavirin for Hep C cases?
When first line fails
85
How many different genotypes of Hep C are there?
6 (1 and 3 are the most common)
86
What is the main disadvantage of DAA
Expensive and takes a 12 week course
87
When considering elimination therapy for Hep C, what must you consider?
1. Liver damage? (Cirrhosis/Fibrosis/Carcinoma) 2. Transplant or Consideration? 3. Manifestations OUTSIDE Liver (Cryoglobulinemia, Glomulonephritis) 4. Positive for HepB/HIV 5. Alcohol/Recreational Drugs 6. Which Genotype 7. Previous failed treatment with other drugs?
88
What types of drug types are commonly used to treat against Hep B?
RTIs (Lamivudine and Tenofovir) | Interferon (Peg IFN)
89
What is Hepatitis B?
Hepadnavirus: DNA virus using RT to integrate its genome into host cell cycles
90
What is the big issue regarding Hep B for relapsing?
Patients with both Hep B and C whilst being treated for C may cause relapsing of Hep B
91
How is RSV usually treated?
Palivizumab: mAb against RSV Fusion glycoprotein Ribavirine via inhalation
92
How is Ebola usually treated?
mAb blocking the docking
93
How is Coronavirus generally treated?
Remdesavir: Inhibitor of RNA-dependent RNAP

Yr3 CSP (4 decks)

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