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biopharm > module 5 > Flashcards

module 5 Flashcards

1
Q

what are most infectious diseases caused by in North America

A

viruses (more than 95% of all resp. disease)
all class 4 pathogens are viruses

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2
Q

describe class 1 pathogens

A
  • no risk or limited risk - P1 LAB
  • work on open lab bench
  • example: e. coli
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3
Q

describe class 2 pathogens

A
  • moderate risk - P2 LAB
  • limited access to lab, lab coat required
  • laminar hoods used (unidirectional air flow)
  • example: herpes
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4
Q

describe class 3 pathogens

A
  • restricted access, special training required - P3 LAB
  • surgical gowns. gloves, respirators
  • all air and liquids coming in or out are treated or filtered
  • everything coming out is autoclaved and incinerated
  • example: HIV, Y. Pestis
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5
Q

describe class 4 pathogens

A
  • lethal, highly infectious and untreatable - P4 LAB
  • lab accessed by airlock, special training
  • space suit, shower
  • low pressure in lab, airlocks
  • all liquids and gasses filtered going in or out
  • example: Ebola, smallpox, Marburg
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6
Q

describe the general structure of viruses

A
  • protein capsid surrounds genetic information
  • some capsids can also carry viral proteins and enzyme
  • some viruses are enveloped which means capsids surrounded by a membrane containing viral proteins
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7
Q

what are 2 elements common to all viruses

A
  • duplication of genetic info
  • production of viral protein
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8
Q

what are oncogenes

A
  • cancer causing mutated gene
  • structurally related to host proteins
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9
Q

how do viral proteins work

A
  • viral protein bind to post protein and alter it’s protein function
  • control cellular regulatory systems
  • utilize host proteins and machinery (ribosome + nucleic acid polymerase)
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10
Q

what do ribosomes do

A

protein formation

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11
Q

what do nucleic acid polymerase do

A

nucleic acid formation

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12
Q

what are 3 antiviral drugs that exist today

A
  • hepatitis C (cure)
  • herpes (treat)
  • HIV (manage)
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13
Q

what is the all time greatest achievement in medicine

A
  • immunization (biologics)
  • small pox: eliminated
  • polio (almost eliminated)
  • measles
  • mumps
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14
Q

where are most viral enzymes involved

A

nucleic acid replication

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15
Q

list steps of the viral life cycle

A
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16
Q

What are major problems with antiviral drugs

A
  • selectivity
  • diagnosis
  • resistance
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17
Q

what are the difficulties in developing antiviral drugs

A
  • each virus is unique
  • most viral proteins act by binding to host proteins
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18
Q

drug target for adsorption and penetration (step 1)

A
  • UNLIKELY DRUG TARGET
  • limited success in HIV
  • maraviroc as a small molecule which prevents unwinding of viral cell
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19
Q

drug target for release of viral nucleic acid (step 2)

A
  • UNLIKELY DRUG TARGET
  • 2 successful drugs
  • influenza and block ion channel
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20
Q

drug target for synthesis of regulatory proteins (step 3)

A
  • UNLIKELY
  • NO DRUGS EXIST FOR THIS PHASE
21
Q

drug target for synthesis of nucleic acid (step 4)

A
  • MOST DRUG TARGET
  • require unique viral enzyme (RNA polymerase)
22
Q

drug target for synthesis of structural proteins (step 5)

A
  • UNLIKELY
  • protease drugs for HIV and Hepatitis C
23
Q

drug target for assembly (step 6)

A
  • UNLIKELY TARGET
24
Q

drug target for release (step 7)

A
  • UNLIKELY TARGET
  • few drugs (HIV and Influenza)
25
Q

what makes some viral cycle steps bad targets

A
  • protein protein interactions
  • proteins bind tightly and use large contact surfaces
  • difficult to target as drugs are small molecules
26
Q

describe the requirements of viral enzyme targets

A
  • structurally unrelated to host enzyme to provide selectivity
27
Q

describe herpes

A
  • virus causes chronic recurrent infections
  • able to escape immense system (latency in neurons
  • 2 types: HSV1 and HSV2
28
Q

Describe HSV 1

A
  • cold sores and blisters on mouth, nose, sometimes eye
  • 80% of pop infected
  • only 10-20% experience breakouts
  • escapes immune system through latency
  • trigger by stress and sunlight
  • travels down axion to skin cells
29
Q

Describe HSV1 outbreaks

A
  • lytic infection: only in epithelial cells does not damage neurons
  • viral activity short (less than 24 hours)
  • viral damage is minimal
  • most damage is caused by immune system (over stimulated and destroys most tissue)
  • drug needs to be administered quick
30
Q

Describe HSV 2

A
  • sores and blisters on anus and genitals
  • injects 15-20% of population
  • infection much more painful than HSV1
  • one outbreak per year
  • MOST COMMON STD
31
Q

Describe HSV2 outbreaks

A
  • short viral activity + minimal dmaage
  • most damage done by immune system
  • drug needs to be administered quick
32
Q

describe herpes virus structure

A
  • genetic info is DS DNA
  • very complex (more than 70 genes compared to usually less than 1)
  • has its own polymerase which is drug target
33
Q

what are the 3 components of nucleic acid

A
  • nucleosides (with phosphate: nucleotides)
  • sugar (2 deoxyribose DNA, ribose RNA)
  • base (nitrogen containing aromatic hetereocycle)
34
Q

what are the 4 nucleic acid bases

A

PURINE
adenosine and guanosine

PYRAMIDINE
- cytidine and thymidine (uracil in RNA)

35
Q

How are bases recognized

A
  • shape and h bonding pattern
36
Q

what are the advantages of nucleic acid forming double strands

A
  • stabilizes molecule + long term info storage
  • second strand provides an easy way to replicate or read info
  • error checking
37
Q

what is the function of polymerases

A
  • copy nucleic acids
  • use one strand as template to make other strand
  • nucleotides added one at a time, matching each base against compliment on other strand (AT, GC)
  • 3’ OH USED AS NUCLEOPHILE
38
Q

What is the method used to design drugs to target polymerase

A
  • rational drug design
  • use knowledge of enzyme mechanism and substrates
39
Q

what can poor selectivity lead to

A
  • toxicity, interference with normal cells can lead to problems as they store genes and synthesize protein
40
Q

what is the selectivity problem with nucleic acids

A
  • must block viral enzyme without blocking host enzyme
41
Q

what are 2 strategies of targeting polymerase

A
  • non natural base
  • chain termination
42
Q

describe non natural base

A
  • replace base with non natural
  • resulting nucleic acid not readable by host enzymes (spelling mistake)
  • substrate structure disrupted, polymerase cannot function
43
Q

what are the requirements for a non natural base

A
  • drug is a substrate for kinase
  • drug is a substrate for VIRAL polymerase (into viral nucleic acid and creates unreadable strand)
  • DO NOT WANT DRUG TO BE SUSBSTRATE FOR HOST POLYMERASE
44
Q

EXAMPLE OF NON NATURAL BASE

A
  • idoxuridine
  • substrate for both viral and host polymerase so highly toxic due to non selectivity
  • topical use only (eye infection of herpes)
45
Q

describe chain termination

A
  • add something non nucleophilic
  • non nucleophilic OH isotere, nucleic acid replication stops
  • can be combined with non natural base
46
Q

what are the requirements for chain termination

A
  • drug is phosphorylated via kinase, viral or host
  • drug is a substrate for VIRAL protein
  • gets incorporated into viral nucleic acid, stops replication to form short piece of nucleic acid, viral proteins do not get made
  • DRUG SHOULD NOT BE SUBSTRATE FOR HOST POLYMERASE
47
Q

Explain chain terminator toxicity

A
  • drugs have structures similar to normal substrate
  • drugs incorporated into host nucleic acid by host polymerase
  • improve selectivity by changing the sugar
48
Q

describe acyclovir

A
  • very high selectivity for virally infected cells
  • selectivity due to bioavailability
  • low incidence of side effects
  • low severity of side effects
  • is a prodrug, only phosphorylated in viral kinase
  • selectivity caused by THYMIDINE KINASE
  • FOUND BY GERTRUDE IN 1974
49
Q

describe how acyclovir is a clean drug

A
  • circulates randomly in body
  • accumulates only in virally infected cells
  • drug concentration in normal cells too low to cause problems (diffuse in and out)

biopharm (8 decks)

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