Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Anti-Malarial Drugs > Flashcards

Anti-Malarial Drugs Flashcards

1
Q

What are the uses of anti-malarial drugs?

A

Anti-malarial drugs may be used for some or all of the following:
1. Treatment of malaria in individuals with suspected or confirmed infection
2. Prevention of infection in individuals visiting a malaria-endemic region who have no immunity (malaria chemoprophylaxis)
3. Routine intermittent treatment of certain groups in endemic regions (intermittent preventive therapy) e.g. in pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the advantages of combination therapy in malaria?

A

Advantages of combination therapy: (1) reduced risk of treatment failure (2) reduced risk of developing resistance (3) reduced adverse effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

List the classification of anti-malarial drugs based on life cycle stage affected

A
  1. Drugs acting on intrahepatic stages are subdivided into
    (1) Causal prophylactic drugs
    (2) Hypnozoitocidal
  2. Drugs acting on erythrocytic stages
  3. Gametocytocidal drugs
  4. Sporonticidal drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the MoA of causal prophylactic drugs which act on the intrahepatic stages

A

Inhibit liver stage from initiating erythrocytic stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the causal prophylactic drugs which act on intrahepatic stages

A

tetracyclines,
primaquine,
proguanil,
atovaquone-proguanil,
pyrimethamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the MoA of hypnozoitocidal drugs whic act on the intrahepatic stages?

A

Destroy exo-erythrocytic hypnozoites of P. vivax and P. ovale after treatment of acute erythrocytic phase to produce radical cure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

State which drug is used as a hypnozoitocidal drug acting on the intrahepatic stage of malaria

A

primaquine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

List the drugs which act on the erythrocytic stages of malaria

A

Clinical cure: Fast action on erythrocytic stages (artemisinin derivatives and quinolines)
Suppressive therapy: Slower suppressive action on erythrocytic stages (anti-folates, tetracyclines, clindamycin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the MoA of gametocytocidal drugs?

A

Destroy sexual forms of the parasite in erythrocytes preventing transmission to mosquito

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

List the gametocyocidal drugs

A

artemisinin derivatives,
primaquine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List the sporonticidal drugs

A

Destroy sporozoites and include :
primaquine,
pyrimethamine,
proguanil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the MoA of anti malarial drugs based on chemophrophylactic classification

A
  1. Causal prophylaxis – Inhibit liver stage from initiating erythrocytic stage
  2. Clinical or suppressive prophylaxis – Inhibit development of merozoites in erythrocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

List the anti-malarial drugs that cause causal phrophylaxis

A

atovaquone-proguanil,
primaquine,
chloroquine,
pyrimethamine,
proguanil,
doxycycline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

List the anti-malarial drugs that cause clinical/suppressive prophylaxis

A

atovaquone-proguanil,
mefloquine,
proguanil,
pyrimethamine,
primaquine,
dapsone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How are anti-malarial drugs classified according to MoA? List them and state the MoA

A
  1. Quinolines
  2. Artemisinins: 1. Binds haem iron and generate oxygen radicals which damage proteins in the parasite 2. Damages Ca2+ ATPase (calcium transporter)
  3. Anti-folates
  4. Atovaquone: Inhibits electron transport chain in the mitochondria
  5. Tetracyclines and clindamycin: Inhibit protein synthesis (ribosome inhibition)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

List the anti-malarial drugs that fall under anti-folate classification

A

pyrimethamine,
proguanil,
sulfonamides
dapsone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

List the quinoline derivatives (anti-malarial)

A

Include:
4-Methanolquinolines: quinine and quinidine
4-Aminoquinolines: chloroquine and amodiaquine
8-Aminoquinolines: primaquine and tafenoquine
Others: mefloquine, piperaquine, naphthoquine, lumefantrine and halofantrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the MoA of quinolines (anti-malarial)

A

Quinolines have activity against the erythrocytic stage of infection (primaquine also kills intrahepatic forms and gametocytes)
They act by accumulating in the parasite food vacuole and forming a complex with haem
They inhibit haem polymerase activity resulting in accumulation of cytotoxic free haem (haem polymerase polymerises haem to the non-toxic haemozoin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Differentiate between quinine and quinidine

A

Quinine is a derivative from the bark of the South American Cinchona tree and exists in oral and parenteral forms
Quinidine is a stereoisomer of quinine available in parenteral formulation and is very effective for treatment of severe malaria
Quinidine is a more active anti-malarial than quinine but more cardiotoxic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are the adverse effects of quinine and quinidine?

A

Cinchonism: Tinnitus, high tone hearing impairment, vertigo, nausea, vomiting, abdominal pain, dysphoria, headaches, dizziness and disturbed vision. These effects typically resolve with cessation of the medication
Other adverse effects: Hypersensitivity reactions, neurotoxicity, skeletal muscle paralysis and hypoglycaemia
Quinine is associated with black-water fever in patients sensitized to quinine (characterised by intravascular haemolysis, haemoglobinuria, disseminated intravascular coagulation and renal failure)
Quinine and quinidine have a narrow therapeutic window; overdosage may lead to cardiotoxicity, including arrhythmias and hypotension, respiratory depression, blindness or deafness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the clinical uses of quinine and quinidine?

A

Used in the treatment of severe, acute P.falciparum malaria
Quinine can be given oral, IM or by slow IV infusion. For severe disease, quinine is given IM or IV.
Quinidine is given by slow IV infusion
Quinine, in therapeutic doses, is safe in infants, children, pregnancy (all trimesters) and lactation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the contraindications of quinine and quinidine?

A

Hypersensitivity to quinine, quinidine or mefloquine
Prolonged QT interval
Myasthenia gravis
Optic neuritis
Glucose-6-phosphate dehydrogenase deficiency (intravascular haemolysis may occur)
History of black water fever
Haemolytic uremic syndrome
Thrombotic thrombocytopenia purpura and thrombocytopenia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the clinical use of mefloquine?

A

Used in the treatment of acute malarial infections and prophylaxis of chloroquine-resistant P. falciparum malaria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the adverse effects of mefloquine?

A

Nausea, vomiting, diarrhoea, abdominal pain, dizziness, neuropsychiatric manifestations (affective and anxiety disorders, hallucinations, sleep disturbances, nightmares, psychosis, toxic encephalopathy and convulsions) and bradycardia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the contraindications of mefloquine?

A

Seizure disorders, psychiatric disorders, children under 2 years, patients with cardiac conduction abnormalities, concurrent administration with drugs that alter cardiac conduction, pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is the clinical use of chloroquine?

A

Uses: Treatment of acute malaria for chloroquine-sensitive malaria strains (P. ovale, P. malariae, and some strains of P. vivax) and chemoprophylaxis for susceptible strains of plasmodium. Given orally. Parental chloroquine is very toxic and cause severe hypotension.

Widespread resistance in most malaria-endemic countries has led to decline in its use for the treatment of P. falciparum, although it remains effective for treatment of P. ovale, P. malariae, and, in most regions, P. vivax

27
Q

What are the adverse effects of chloroquine?

A

Include:
Headaches, dizziness, abdominal discomfort, vomiting, diarrhea and rashes , pruritus in some patients, neuromyopathy with long-term prophylaxis, retinopathy with prolonged high doses (as in treatment of rheumatoid arthritis) and idiosyncratic reactions, such as erythema multiforme and bone marrow toxicity, and haemolysis in patients with G-6-PD deficiency. Can provoke psoriasis. Cardiotoxic in high doses and when given parenterally.

28
Q

What is the clinical use of amodiaquine?

A

Amodiaquine is commonly used in malaria endemic countries to treat chloroquine-resistant infections and is available in co-formulation with artesunate. Given orally.

29
Q

What are the adverse effects of amodiaquine?

A

Adverse effects: GI effects, bradycardia, agranulocytosis and hepatotoxicity
Amodiaquine is not used for chemoprophylaxis (increased risk of agranulocytosis and hepatotoxicity with repeated doses)

30
Q

What is the MoA of primaquine?

A

Mechanism of action: Disrupts mitochondria (blocking oxidative metabolism) and binds to DNA interfering with DNA function

Active against blood schizonts (slow acting blood schizonticide), tissue schizonts, hypnozoites of P.ovale and P. vivax, sporozoites and gametocytes of P. falciparum

31
Q

What is the clinical use of primaquine?

A

It is largely used to effect radical cure of P.ovale and P. vivax (prevents relapse of P. ovale and P. vivax malaria by eliminating dormant hypnozoites). It is given in conjunction with chloroquine or artemisinin derivatives in the treatment of P. ovale and P. vivax
Also used as a gametocytocidal drug in P. falciparum infections to prevent transmission (in conjunction with another effective blood schizonticidal drug)
It is given orally

32
Q

What are the adverse effects of primaquine?

A

Adverse effects: Anorexia, nausea, vomiting, abdominal cramps, chest pain, weakness, anaemia, bone marrow suppression, intravascular haemolysis in people with G-6-PD deficiency

33
Q

What is the MoA of folates?

A

Inhibit enzymes involved in folate synthesis, a pathway in the biosynthesis of purines and pyrimidines, thereby halting the processes of DNA replication, cell division and reproduction

34
Q

List the anti-folate drugs

A

Type 1 anti-folate drugs: sulfonamides (sulfadoxine) and dapsone
Type 2 anti-folate drugs: pyrimethamine and proguanil

35
Q

Differentiate between type 1 and type 2 anti-folate drugs

A

Type 1 anti-folate drugs: inhibit dihydropteroate synthetase [thus inhibit synthesis of folic acid]
Type 2 anti-folate drugs: inhibit dihydrofolate reductase thereby blocking the conversion of dihydrofolate to tetrahydrofolate [thus inhibit utilization of folic acid]

36
Q

Briefly state the anti-malarial activity of anti-folates

A

Have activity on sporozoites (proguanil and pyrimethamine), hepatic schizonts (proguanil, pyrimethamine) and blood schizonts (all the anti-folates)

37
Q

Outline the indications of anti-folates in malaria

A
  1. Treatment of malaria (pyrimethamine-sulfonamide combination) [used in combination with artemisinins]
  2. Chemoprophylaxis (dapsone, proguanil, pyrimethamine-dapsone)
  3. Intermittent preventive therapy in pregnancy (sulfadoxine-pyrimethamine)

Sulfonamides are not recommended for chemoprophylaxis because of severe skin reactions experienced

38
Q

What are the adverse effects of anti-folates?

A

All: Gastrointestinal upset, headache and skin rashes
Pyrimethamine: Bone marrow suppression, megaloblastic anaemia with high doses
Sulfonamides: Severe cutaneous toxicity, including erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrosis. Sulfadoxine can precipitate hemolysis in patients with G-6-P-D deficiency.
Proguanil: Hair loss and mouth ulcers

39
Q

What are the contraindications of anti-folates?

A

Hypersensitivity to any sulfonamide, pyrimethamine, or any component of the formulation
Porphyria
Megaloblastic anemia
First trimester of pregnancy
Sulfonamides: G-6-P-D deficiency, children <2 months of age due to competition with bilirubin for protein binding sites (can result in kernicterus); pregnancy (at term)
Repeated prophylactic use of anti-folates is contraindicated in patients with renal failure, hepatic failure, or blood dyscrasias

40
Q

What is the MoA of atovaquone-proguanil?

A

Atovaquone inhibits electron transport in mitochondria resulting in the inhibition of key metabolic enzymes responsible for the synthesis of nucleic acids and ATP
Acts on hepatic schizonts and merozoites

41
Q

What is the clinical use of atovaquone-proguanil?

A

It is used for treatment and chemoprophylaxis of P. falciparum malaria (always in combination with proguanil for synergy and to prevent emergence of resistance). The combination retains excellent clinical efficacy for P. falciparum treatment and prevention throughout the world even in the presence of anti-folate resistance.
It is administered orally with meals (absorption is significantly increased with a high-fat meal)

42
Q

What are the adverse effects of atovaquone-proguanil?

A

Adverse effects include abdominal pain, vomiting, diarrhea, headache and pruritus and transient increases in transaminases

43
Q

What are the contraindications of atovaquone-proguanil?

A

Contraindications: Life-threatening allergic reaction to atovaquone or any component of the formulation

44
Q

Describe the MoA and clinical use of halofantrine

A

Halofantrine is chemically related to quinine and acts acting as a blood schizonticide effective against all plasmodium parasites
Use: Treatment of multi-drug resistant P. falciparum malaria
Oral absorption is increased by a fatty meal and it has very variable bioavailability

45
Q

What are the adverse effects of halofantrine?

A

Ventricular arrhythmias (prolongation of PR and QT interval) that have been associated with death. Cardiotoxicity has limited its use
Other adverse effects include nausea, abdominal pain, diarrhea, and pruritus

46
Q

What are the contraindications of halofantrine?

A

Heart disease, infants and young children (weight under 10 kg), pregnancy, lactation, and patients that have taken mefloquine previously

47
Q

Outline the action of lumefantrine

A

Is similar in structure to halofantrine, quinine and mefloquine, and has same mechanism of action
Is active against most chloroquine-resistant parasites although there is cross-resistance with halofantrine and mefloquine
Lumefantrine is a long-acting drug always given in combination with artemether in a widely used fixed-dose combination (Zambia has adopted this combination as first line antimalarial)

48
Q

What are the adverse effects of lumefantrine?

A

Lumefantrine is well tolerated, with rare mild adverse reactions such as diarrhea, nausea, abdominal pain and vomiting

49
Q

What is the MoA of artemisinins?

A

Artemisinins act by binding iron in haem, leading to the generation of free oxygen radicals that damage parasite proteins. Binds and inhibits Ca2+ ATPase (calcium transporter).
Artemisinins act rapidly, killing blood stages of all plasmodium species
Artemisinins have the fastest parasite clearance times of all anti-malarials currently used
Artemisinins act primarily on the trophozoite phase and are also active against gametocytes, the parasite form that is infectious to mosquitoes, and their use has been associated with reduced malaria transmission

50
Q

List and describe examples of artemisinin derivatives

A
  1. Artemisinin
  2. Dihydroartemisinin: Active metabolite to which artemisinin is reduced. It is the most effective artemisinin compound and the least stable.
  3. Artemether: A methyl ether derivative of dihydroartemisinin. Used in a fixed-dose combination with lumefantrine.
  4. Artesunate: A hemisuccinate derivative of the active artemisinin metabolite dihydroartemisin. Currently it is the most frequently used of all the artemesinin-type drugs. It is mostly used in combination therapy (with SP, mefloquine and amodiaquine). Given IV or IM for severe malaria.
  5. Arte-ether: An ethyl ether derivative of dihydroartemisinin
51
Q

Describe the clinical use of artemisinins

A

WHO recommends the use of artemisinins (in combination with other anti-malarials) as first line drugs for the treatment of P. falciparum malaria
Treatment of severe malaria: IV/IM artesunate (it is superior to quinine for treatment of severe malaria with respect to clearing parasitemia and reducing mortality)

52
Q

What are the adverse effects of artemisinins?

A

Artemisinins are generally well tolerated
Adverse effects that have been associated with artemisinins include headaches, nausea, vomiting, abnormal bleeding, dark urine, itching, drug fever, transient neurological abnormalities (nystagmus and disturbances in balance) and Type 1 hypersensitivity reactions

53
Q

What is the clinical indication of pyronaridine?

A

Used in combination with artesunate. Artesunate-pyronaridine has generally demonstrated excellent efficacy against falciparum and vivax malaria.
It is generally well tolerated

54
Q

What are the adverse effects of pyronaridine?

A

Adverse effects include eosinophilia and elevated aminotransferases

55
Q

Outline the therapeutic usage of tetracycline and clindamycin for malaria

A

Tetracycline and doxycycline are used in combination with quinine or artemisinin derivatives for the treatment of acute cases of P. falciparum infections. Doxycycline has a longer half life than tetracycline so is used more commonly
Clindamycin is used in conjunction with quinine for the treatment of acute cases of P. falciparum malaria
Tetracyclines and clindamycin have a very slow anti-malaria action and should not be used as monotherapy for treatment of malaria
Doxycycline is also used for P. falciparum malaria chemoprophylaxis in areas where chloroquine resistance exists

56
Q

What are the causes of malaria treatment failure?

A
  • Wrong diagnosis
  • Incorrect choice of drugs
  • Sub-optimal regimen (dose, schedule, duration)
  • Non-adherence
  • Sub-optimal absorption (nausea, diarrhea, vomiting, malabsorption)
  • Idiosyncratic pharmacokinetics (e.g. increased drug elimination)
  • Poor quality drugs
  • Interactions with other pharmaceuticals
  • Resistance of the pathogen to the drug
57
Q

Describe anti-malarial drug resistance

A

Anti-malarial drug resistance has been defined as: “the ability of a parasite to survive and/or multiply despite the administration and absorption of a drug given in doses equal to or higher than those usually recommended but within tolerance of the subject”
The drug in question must gain access to the parasite or the infected red blood cell for the duration of the time necessary for its normal action. Cases where anti-malarial prophylaxis has failed are excluded
Drug resistance is caused by spontaneous mutations that result in reduced sensitivity of the parasite to the anti-malarial drug

58
Q

What is the advantage of anti-malarial combination therapy?

A

Combination therapy is ‘the simultaneous use of two or more blood schizonticidal drugs with independent modes of action and different biochemical targets in the parasite’.
Combination therapy reduces the emergence of resistant strains and optimizes parasite clearance thus improving cure rates, with greater reduction in morbidity and mortality compared to monotherapy

59
Q

What are the classes of the combination drugs used in malaria?

A

The combinations of drugs currently prescribed can be divided into two categories:
1. Non-artemisinin based combinations
2. Artemisinin based combinations (ACTs)

60
Q

Which drugs fall under non-artemisinin combinations?

A
  1. Sulfadoxine-pyrimethamine (SP)
  2. Quinine plus tetracycline/doxycycline – retains a high cure rate in many areas
  3. Quinine plus clindamycin –Similar cure rate to quinine + tetracycline, therefore is an appropriate alternative regimen
61
Q

Describe the upside and downside of using sulfadoxine-pyrimethamine (SP) as a non-artemisinin combination

A

This fixed-dose combination has been used for many years, causes few adverse effects, is cheap and effective in a single dose, thus decreasing problems associated with adherence and compliance

In technical terms SP is not generally considered a true combination therapy since the components do not possess independent curative activity (they have the same biochemical target). SP should no longer be used alone for treatment of falciparum malaria.

62
Q

Why can’t artemisinins be used as single agents?

A

In general, artemisinins should not be used as a single agent, to prevent emergence of drug resistance and to avoid the need for prolonged therapy

63
Q

List the artemisinin-based combination therapies

A

ACTs combine the highly effective short-acting artemisinins with a longer-acting partner to protect against artemisinin resistance and to facilitate dosing convenience
Examples of ACTs:
(1) Artemether-lumefantrine
(2) Artesunate-amodiaquine
(3) Artesunate-mefloquine
(4) Artesunate-sulfadoxine-pyrimethamine
(5) Dihydroartemisinin-piperaquine
(6) Artemisinin-naphthoquine
(7) Artesunate-pyronaridine

Pharmacology (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions