Basics Of Chemotherapy- Anti Malaria’s And HIV Treatment

Question 1

What are considered to be parasites when it come to chemotherapy

Answer 1

Bacteria, Protozoa, viruses, helminths, fungi and cancer cells

Question 2

What is the principle mechanism of action when it comes to chemotherapy

Answer 2

We try to identify a qualitative or quantitative difference in the bio chemical machinery between the host and parasite, which when exploited by a selective drug results in a cytotoxic effect to the parasite but not the host

Question 3

What e variations are there on the theme of chemotherapy

Answer 3

A) That the target is completely absent on the host leading to no cytotoxic effect
B) The target is present on the house but there is a significant difference in the structure between the host and parasite target. To the extent that a selective drug for the parasitic target can be selectively modulated
C) The target of our drug is found in both the parasite and the host however the host contains an escape mechanism a.k.a. an alternative pathway which protects against the target being modulated in the host the compensatory mechanism is absent in the parasite

Question 4

What is the therapeutic index

Answer 4

It evaluates safety it measures the degree to which we can find differences between the parasites by chemical machinery and that of the hosts can have a major effect on our drug

Question 5

What is the therapeutic index in humans

Answer 5

Therapeutic index = TD 50/ ED50

Question 6

What is the therapeutic index in animals

Answer 6

Therapeutic index = LD 50/ ED 50

Question 7

What does ED 50 mean/ represent 

Answer 7

ED 50 represents the median effective dose a.k.a. is the dose that produces the therapeutic affect in 50% of the population

Question 8

What does TD 50 represent

Answer 8

TD 50 is the median toxic dose a.k.a. is the dose that produces the toxic affect in 50% of the population

Question 9

What does LD 50 represent

Answer 9

LD50 is the medium lethal dose is those that produces the lethal effect and 50% of the population

Question 10

What does it mean when we have a high therapeutic index

Answer 10

A high therapeutic index indicates a safe drug a.k.a. the therapeutic window in which we can see a beneficial effects of a drug without any toxic effect is a large

Question 11

Name two problems of chemotherapy

Answer 11

A) whilst bacteria and protozoa have many differences viruses have fewer differences but in cancers they are essentially derived by the host cell ( we look for quantitative differences- uncontrollable proliferation)
B) development of resistance ( adaptation/mutation)

Question 12

What does the first class of target in chemotherapy represent

Answer 12

Class one represents bio chemical reactions which are involved in energy production they are usually not targeted by therapeutic agents and they are fundamental for self biology glycolysis is an example 

Question 13

What does the second class at target in chemotherapy represent

Answer 13

The second class of targets are bio chemical reactions which are involved in the small molecule synthesis. A number of therapeutic drugs against malaria etc. target these mechanisms biosynthesis of amino acids is an example

Question 14

What does class three of the targets of chemotherapy represent

Answer 14

Class three represents bio chemical reactions which involve macromolecule production a.k.a. polymers for example the bio synthesis of DNA. These bio chemical reactions are a good source of targets for the generation for chemotherapeutic agents

Question 15

What are the three lifecycles of malaria

Answer 15

A) exo-erythrocyticcycle. (prior to infection ot liver cells. )
B) erythrocytic cycle (infection of erythrocytes ) -involves schizont and the rupture of them causing re infection of erythrocytes
C) sporogonic cycle (mosquito stages)

Question 16

What is the main cellular consequences of malaria due to

Answer 16

Lysis of erythrocytes

Question 17

What is uncomplicated malaria

Answer 17

A patient who represents with symptoms of malaria and a positive parasitological test but with no features of severe malaria

Question 18

What is severe malaria

Answer 18

Severe malaria occurs when infections are complicated by serious organ failures or abnormalities in the patient’s blood or metalbolism

Question 19

What are malaria relapses

Answer 19

Malaria relapses are associated with those species of malaria which at the lifecycle stage within the liver the parasite is dormant until reactivated which causes reinfection of erythrocyte leading to symptoms

Question 20

What does drug treatment response depends on

Answer 20

Malarial species and strains, drug metabolism, side effects, hosts immunity

Question 21

What are the purposes of drug treatment for malaria

Answer 21

To protect and prevent infection, cure established infection, prevent malaria transmission

Question 22

What is one major mechanism of action that anti-malarial drugs take

Answer 22

They interfere with the folate pathway

Question 23

What drugs can be used to interfere with the folate past week and what do they do

Answer 23

Note that the malaria parasite synthesises folate whereas the host does not synthesize it this accounts for a qualitative difference in bio chemical pathways between the host and the pathogen

Usually Sulphonamides and sulphones target dihydropteroate synthetase ( rely on the fact that malaria synthesises folate and the host doesn’t)

Proguanil and pyrimethamine targets dihydrofolate reductase in the parasite (rely on the different sensitivity of malaria and host dihydrofolate reductases to antagonists)

Question 24

What is another major pathway that anti malarial drugs interfere with

Answer 24

The heme catabolism
Choloroquine and Quine target another qualitative difference between malaria and host, that of heme catabolism.
In malaria the enzyme harm polymerase breaks down free haem to hemozoin
Whereas in the host heme oxygenase is used. ( into iron, co, bilirubin)

Question 25

What is Artemisinin

Answer 25

It is a drug that has a little resistance is isolated from sweet wormwood and is used in combination therapy mode of action is complex and relies on artemisinin activation/ metabolism- it’s activated in digestive vacuole of the malaria parasite by the mechanism in hemoglobin breakdown

Question 26

What diseases give a natural resistance to malaria

Answer 26

A) sickle cell anemia
B) thalassemia
C) glucose 6 phosphate dehydrogenase deficiency
These have been shown to have a certain amount of protection for individuals with the disease against malaria this is due to the dysfunctional erythrocyte function this occurs in the erythrocytes in individuals with these diseases, Aretha site has a little appetizing environment for the malarial pathogen

Question 27

What are the main events that occur in HIV infection

Answer 27

A) Fusion of HIV to the wholesale surface this happens by the GP 120 proteins on the HIV molecule finding to the city for receptors on the host molecule this fusion is also aided by a Co Receptor on the lymphocyte.
B) HIV RNA, reverse transcriptase, integrase and other viral proteins enter into the host cell
C) viral DNA is formed by reverse transcription
D). Viral DNA is transported across the nucleus and integrates into the host DNA
The integrated DNA then becomes reactivated and new viral RNA is used as genomic RNA and makes viral proteins
E) The gnu viral proteins and viral RNA accumulates at the cell surface and a gnu immature HIV molecule forms, the virus is released
Viral protease cleaves new poly proteins to create mature infectious virus.

Question 28

What is a nucleoside

Answer 28

It is the base and a sugar

Question 29

What is a nucleotide

Answer 29

It is a bass a sugar and a phosphate

Question 30

What are the purine bases

Answer 30

Adenine and guanine 

Question 31

What are the pyramidine bases

Answer 31

Uracil, thymine, cytosine

Question 32

What are the two types of reverse transcriptase inhibitors

Answer 32

Nucleotide reverse transcriptase inhibitors and non-nuclear side reverse transcriptase inhibitors
Both of these drugs inhibit the conversion of HIVRNA to HIV DNA by the enzyme reverse transcriptase this enzyme is encoded for by the viral genome human cells do not convert RNA to DNA and therefore this enzyme is not present therefore this enzyme represents a qualitative difference between host cells and virally infected lymphocytes

Question 33

What are the main features of nucleoside reverse transcriptase inhibitors

Answer 33

They are analogues of naturally occurring nucleosides the major difference is the modification of the ribose ring plus the removal of a hydroxyl molecule this result in the inability to add new triphosphate nucleotides to the structure

Question 34

What is the mechanism of action of nucleoside reverse transcriptase inhibitors in HIV

Answer 34

The nucleoside transcriptase inhibitor can act as a substrate to reverse transcriptase I said can insert the triphosphate AZT into the elongating viral DNA chain causing termination and preventing viral replication
AZT is converted to the triphosphate nucleotide form once inside the cell- carried out by kinases

Question 35

What about the structure of non-nucleoside reverse transcriptase inhibitors

Answer 35

Their structure varies

Question 36

What is the mechanism of action of a non-nucleoside reverse transcriptase inhibitors in HIV

Answer 36

They act on the P51 subunit of reverse transcriptase, and can be considered as three fingered. Between the thumb and the first finger we find the catalytic site and also a binding region for the inhibitor.between the second finger and the thumb we find RNASE site which breaks down RNA. HIV RNA enters the molecule and the complementary DNA molecule is synthesised and as it exists the molecule the RNA itself is broken down by the RNASE, essentially RNA enters the enzyme while the DNA exists. The Inhibitors bind to their binding site and inhibit this reaction

Question 37

A problem with NNRTI

Answer 37

Is that because their binding site is not within the catalytic site a number of mutations can occur in the enzyme that can lead to the resistance of these drugs and this can happen relatively rapidly.

Question 38

How do integrase inhibitors work

Answer 38

Integrase represents a qualitative difference Between host and parasite - raltegravier

Question 39

HIV protease inhibitors what do they do

Answer 39

Prevents the cleavage of these structural proteins and thus their assembly thus resulting in the inability for a HIV viral protein to mature - indinavir