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Anti-Malarial Drugs Flashcards

1
Q

Malaria is a/an (acute or chronic?) infectious disease caused by 4 species of the protozoa genus _____.

A

Acute

plasmodia

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2
Q

P.________ is the most dangerous species.

Others are _______,______,_______

A

falciparum

P. malariae, P.ovale, P.vivax

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3
Q

One ______ of the world population is at risk of malaria more than 300 million cases each year. (WHO 1998).
•

A

fifth

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4
Q

Malaria kills more than a million people annually

T/F

A

T

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5
Q

Majority of mortality due to malaria are children under _____ who die cause they do not receive treatment quickly enough. (Alnwick 2000).

A

five

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6
Q

Nigeria is a malaria-endemic area

T/F

A

T

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7
Q

_______ is the principal cause of childhood mortality.

A

malaria

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8
Q

At least 20% of all childhood deaths are due directly to malaria

T/F

A

F(10)

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9
Q

_____-_____ children die from malaria each day! (FMOH)

A

300 – 500

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10
Q

________ countries accounted for 95% of malaria cases globally.

A

Twenty-nine

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11
Q

Nigeria (_____%), and _____ other countries accounted for about 51% of all cases globally. Similar stats for death
■

A

27

4

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12
Q

SUMMARY OF LIFE CYCLE of MALARIA

• Infected mosquito inject _________
• this migrate to _____ where they form ______
• these are ________ and invade _________

•________ of these cells releases ______, which (can or can’t?) infect other red cells.
• (Male or Female?) mosquito picks up _________ from infected individual

A

sporozoites

liver; merozoites

released; red blood cells

Rupture; merozoites; can

Female; gametocytes

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13
Q

Signs and symptoms of UNCOMPLICATED MALARIA

______
_______

____________ pains
_________

Malaise

_______
___________
Nightmares

A

Fever
Headache

Joint and body
Weakness

Vomiting
Diarrhea

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14
Q

Severe malaria

The presence of one or more of the following clinical or laboratory features
classifies the patient as suffering from severe malaria:

Clinical features: (WHO)
– impaired _______ or ___________
– ___________, i.e. generalized ______ so that the patient is unable walk
or sit up without assistance

– failure to ______
– multiple _______ – more than ___ episodes in ______

– deep breathing, respiratory distress (_______ breathing)

A

consciousness or unrousable coma

prostration; weakness

feed; convulsions

two; 24 h

acidotic

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15
Q

The presence of one or more of the following clinical or laboratory features
classifies the patient as suffering from severe malaria:
Clinical features: (WHO)

-__________ collapse or ______

– clinical _______ plus evidence of other vital organ dysfunction
– __________uria
– abnormal spontaneous _______
– _________ oedema (radiological)

A

circulatory; shock

jaundice

haemoglobin

bleeding

pulmonary

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16
Q

circulatory collapse or shock, in severe malaria may be characterized by systolic blood pressure < ____ mm Hg in adults
and < _____ mm Hg in children

A

70

50

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17
Q

SEVERE MALARIA
Laboratory findings:

– _____glycaemia
– (metabolic or respiratory ?) (acidosis or alkalosis?)
– severe ______cytic anaemia (Hb < 5 g/dl, packed cell volume < 15%)

A

hypo

metabolic; acidosis

normo

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18
Q

SEVERE MALARIA
Laboratory findings:

– __________uria
– hyper ___________
– hyper_________
–______ impairment (serum creatinine > 265 μmol/l).

A

haemoglobin

parasitaemia

lactataemia

renal

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19
Q

Malaria in Pregnancy

Despite _________________________, women living in endemic areas suddenly become _____________ when they become pregnant.

A

being clinically immune from P. falciparum malaria

susceptible to the disease

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20
Q

Malaria during pregnancy is characterised by very ___________ of the placenta.

A

heavy parasitization

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21
Q

Protection against P. falciparum malaria acquired prior to the first pregnancy works against the parasites

T/F

A

F

Protection against P. falciparum malaria acquired prior to the first pregnancy for some reason does not work against the parasites causing pregnancy-associated malaria.

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22
Q

Malaria in Pregnancy

The severity and prevalence of parasitaemia both rapidly decline with ______________

A

increasing parity

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23
Q

The Available Antimalarial Medicines

List them allllll

A

NAPS BAA (sleep and mosquitoes bite you)

The Naphthoquinolines
The Antibiotics
The Peroxides
Sulphones

The Biguanides
The Arylaminoalcohol
4-Aminoquinolines
8-Aminoquinolines

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24
Q

The Arylaminoalcohols

Divided into 2

________ methanols

___________ methanols

A

Quinoline

Phenanthrene

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25
Q

The Arylaminoalcohols

Quinoline methanols (______,______,______)

Phenanthrene methanols ( ________,_______)

A

Quinine, Quinidine, Mefloquine

Halophanthrene, Lumefantrine

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26
Q

The Arylaminoalcohols: Mefloquine

Aka: _______________

Mode of Action
Activity on the ____________.

Alters the binding affinity of the parasite through the _____-binding _______

A

4-quinoline methanol

mid- to late trophozoite

ATP; cassette transporter.

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27
Q

The Arylaminoalcohols: Mefloquine

Mode of Action

Is a ———- ________cide active against _____,_______,________

A

Blood schizonticide

P.falciparum, P.malariae, P.vivax

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28
Q

The Arylaminoalcohols: Mefloquine

Adverse Effects
Dizziness, nausea, vomiting, diarrhoea and abdominal pain.

Major adverse effects include ________ reactions and _______ abnormalities. However, these effects seem to be dose- related and possibly associated with prophylactic use. Concurrent use with quinine can potentiate the dose-related adverse reactions to mefloquine.

A

neuropsychiatric; cardiovascular

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29
Q

Quinoline methanols :Quinine, Quinidine

Efficacy
Is a ______ ————cide effective against P.__________

A

Blood schizonti

Falciparum

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30
Q

Quinoline methanols : Quinine, Quinidine

Mode of Action
Acts like CQ

_______________ stage of the parasite.

A

Mid to late trophozoite

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31
Q

Quinoline methanols : Quinine, Quinidine

Adverse Effects
_______,________, sometimes ______ or dizziness.

Quinine can cause severe _____tension if _____________.

May cause enhanced ______ toxicity when administered to individuals who have taken ________.
Hypoglycaemia

A

Tinnitus, muffled hearing; vertigo

hypo; injected too rapidly

cardiac; mefloquine

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32
Q

Quinidine is cardiotoxic

T/F

A

T

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33
Q

4-Aminoquinolines

________ ,________ ,_________, _________, Mepacrine (______), Pyronaridine (benzonaphthyridine)

A

Chloroquine

Amodiaquine

Piperaquine; Naphthoquinoline

acridine

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34
Q

4-Aminoquinolines

Mode of Action

Activity on _____________ stage

Prevents ____________ by ________ or _____

A

mid- to late trophozoite

detoxification of haem by polymerization to haemozoin or malaria pigment.

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35
Q

4-Aminoquinolines

Efficacy
•Marked and rapid _______cidal activity against all infections of ________________ in areas

•_______cidal against P.vivax, P.malariae and P.ovale

•Has both _________ and _________ effect.

A

schizonti

P.falciparum, P.malariae, P.ovale and P.vivax

Gametocyto; an antipyretic and anti inflammatory

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36
Q

4-Aminoquinolines

Chloroquine Adverse Effects

Nausea, vomiting, headache, GIT symptoms

_______ disturbance and ——— (commoner in ___-skinned people).

(Irreversible or reversible?) _____ impairment.

_________ has rarely, if ever, resulted from doses recommended for malaria prophylaxis. Attacks of porphyria and psoriasis may be precipitated in susceptible individuals.

A

visual; pruritus; dark

Irreversible; visual

Retinopathy

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37
Q

4-Aminoquinolines

Amodiaquine Adverse Effects

Repeated and prolonged use of AQ has been associated with __________ and __________.

However, adverse reactions to standard doses of AQ used in the treatment of malaria are generally similar to those of _________.

A

leucopaenia and agranulocytosis

chloroquine

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38
Q

Itching is more common with which

AQ or CQ

A

Itching is less common with AQ.

Itching is more common with CQ

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39
Q

8-Aminoquinolines

Examples

______,_________

A

Primaquine, Pamaquine

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40
Q

8-Aminoquinolines

Mode of Action
The mechanism of action is ____________.

A

unknown

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41
Q

8-Aminoquinolines

Efficacy

Effective against _______ forms of ___ types of malaria parasite.

For radical cure of _____________

Gametocytocidal against _______

significant blood stage activity against P. ________ (and some against asexual stages of P. ________).

A

intrahepatic

All types

P. V and P. O,
Falciparum

vivax; falciparum

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42
Q

8-Aminoquinolines

Efficacy

For radical cure of _____________

Gametocytocidal against _______

significant blood stage activity against P. ________ (and some against asexual stages of P. ________).

A

P. V and P. O

Falciparum

vivax; falciparum

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43
Q

8-Aminoquinolines

Adverse Effect
________ in individuals with _________

A

Haemolysis

G6PD Deficiency

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44
Q

Sulfones
Examples

•Sulphonamides (_____,________,_________),

•_________

A

sulphadoxine, sulphalene, co- trimoxazole

Dapsone

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45
Q

Sulfones

Mode of Action
Works synergistically with ________ against the parasite specific enzymes, _____ and _____.

Activity on ________ to _________ stage.

Inhibits ___________, which is essential for _______ synthesis

A

pyrimethamine

DHPS

DHFR

mature trophozoite to early schizont

parasite synthesis of folate; pyrimidine

46
Q

Sulfones

Adverse Effects

Serious adverse reactions to sulfa drugs include severe _______ reactions, such as _________ and __________.

A

cutaneous

Stevens Johnson syndrome and TEN

47
Q

DHPS acts as __________

A

PABA analogues

48
Q

Severe cutaneous reactions to sulfones are Commoner amongst the ______ and _______ taking the drug for ———-.

A

Europeans and North Americans

prophylaxis

49
Q

TEN appears to be more common in ____________ patients.

Dapsone causes varying degree of ———— and _________

A

HIV infected

haemolysis

Methemoglobinemia

50
Q

The Biguanides

Examples

_______,__________,______,_____ and , ___________

A

Proguanil, Chlorproguanil, cycloguanil, chlorcycloguanil

Pyrimethamine

51
Q

The Biguanides

Mode of Action
Also known as ____________

Cycloguanil inhibits _______

Active against ___________ forms of the parasite

_____cidal activity, rendering the gametocytes ________

In co-formulation with ________

A

Type 2 Antifolate

DHFR

pre-erythrocytic

Sporonto; non-infective

atovaquone

52
Q

The Biguanides

Adverse Effect

Haematological changes (__________ and ________) have been reported in patients with severe ______ impairment.

Mild gastric intolerance, diarrhoea, occasional ————- and ________ , there are few adverse effects associated with usual doses of proguanil hydrochloride

A

megaloblastic anaemia and pancytopenia

renal

aphthous ulceration and hair loss

53
Q

The Antibiotics

Mention 4

A

Tetracyclines, Doxycycline, clindamycin, fluoroquinolones

54
Q

Biguanides are in co formulation with ________

A

atovaquone

55
Q

The Antibiotics

Mode of Action

Tetracyclines are inhibitors of ___________ during protein synthesis.

A

aminoacyl-tRNA binding

56
Q

The Antibiotics

Adverse Effects
GIT effects , ________ failure, Oesophageal ulceration, Diarrhoea etc.

A

Renal

57
Q

The Naphthoquinones

Examples???

A

Atovaquone

58
Q

The Naphthoquinones

Mode of Action

Active against ________ Plasmodium species.

Inhibits _________ development in the ——-, and ———- development in the ________.

Act in synergy with ————

A

all

pre-erythrocytic; liver

oocyst; mosquito; Proguanil

59
Q

The Naphthoquinones

Act in synergy with _________

A

Proguanil

60
Q

The Naphthoquinones

Adverse Effects

Skin rashes, headache, fever, insomnia, nausea, diarrhoea, vomiting, raised liver enzymes, hyponatraemia, and, very rarely, haematological disturbances, such as anaemia and neutropenia have all been reported.

Agree?

A

Sure🍻

61
Q

The Naphthoquinones

High affinity for ____________

A

plasmaproteins

62
Q

The Peroxides

_______,________,________,________,________,___________

A

Artemisinin, Arthemeter, Artemotil, Artesunate, Artelinic acid, Dihydroartemisinin

63
Q

The Peroxides

Artemisinin, also known as _______, is a sesquiterpene lactone extracted from the leaves of _________ (__________).

A

qinghaosu

Artemisia annua

sweet wormwood

64
Q

The Peroxides

Mode of Action

Inhibits an essential _______________, PfATPase 6 (29).

Inhibits the conversion of ______ to ____

coverts ______ to _______

Potent and rapidly acting blood _______cide and is active against ____ Plasmodium species.

A

calcium adenosine triphosphatase

haem to haemozoin

haemozoin to haem; schizonto; all

65
Q

The Peroxides

Mode of Action

It has an unusually (broad or narrow?) activity against (sexual or asexual?) parasites, killing all stages from ______ to ________.

A

Broad

Asexual

young rings to schizonts

66
Q

The Peroxides

Adverse Effect
Artemisinin and its derivatives are not safe and remarkably poorly tolerated

T/F

A

F

Very safe

Well tolerated

67
Q

In P. falciparum malaria, artemisinin
Kills the ______ – including the stage _____ ————-, which are otherwise sensitive only to __________.

A

gametocytes

4 gametocytes

primaquine

68
Q

The elimination half-life of all Artemisinin is approximately _______

A

1 h

69
Q

The Peroxides

Adverse Effect

The only potentially serious adverse effect reported with this class of drugs is ________________ in approximately 1 in 3000 patients

A

type 1hypersensitivity reactions

70
Q

COMBINATION DRUGS
Can either be:

_________ based Combinations

____________ based Combinations

A

Artemisinin

Non-Artemisinin

71
Q

COMBINATION DRUGS
Artemisinin based Combinations

_________ and ______

________ and _________

Co-artem(_______ and ______)

__________ and _______

A

Artesunate and SP

Artesunate and Amodiaquine

Artemeter and lumefantrine

Artesunate and Mefloquine

72
Q

COMBINATION DRUGS
Non-Artemisinin based Combinations

Malarone (________ and ———-)

Maloprim(_______ and _________ )

LAPDAP (_______ and ________)

Mefloquine-SP

______ and ________

A

Proguanil and Atovaquone

Dapsone and Pyrimethamine

Dapsone and Chlorproguanil

Sulfalene –Pyrimethamine

73
Q

COMBINATION DRUGS
Non-Artemisinin based Combinations

________ (Proguanil and Atovaquone)

________( Dapsone and Pyrimethamine)

________ ( Dapsone and Chlorproguanil)

Mefloquine-SP

Sulfalene –Pyrimethamine

A

Malarone

Maloprim

LAPDAP

74
Q

WHO WORLD MALARIA REPORT 2020

In the WHO African Region, the first-line treatments for

P. falciparum include :

___________ (AL)

_____________ (AS- AQ) and

_______________________(DHA_x0002_PPQ).

A

artemether- lumefantrine

artesunate-amodiaquine

dihydroartemisinin-piperaquine

75
Q

WHO WORLD MALARIA REPORT 2020

The overall average efficacy rates for P. falciparum –_____% for AL, ——-% for AS-AQ and _____% for DHA-PPQ – remained consistent over time

A

98.0

98.4

99.4

76
Q

PROBLEMS WITH CHEMOTHERAPY AND CHEMOPROPHYLAXIS

Drug ______
_______ drug reaction
Cost
Limited dosage forms
Unfavorable pharmacokinetics
__________.

A

resistance

Adverse

Availability

77
Q

RATIONAL USE OF ANTIMALARIAL DRUGS

This refers to _________________ for the right indications and at the correct/adequate dosages.

A

appropriate use of antimalarials

78
Q

Antimalarial drugs will be needed for treatment of uncomplicated malaria, severe malaria and chemoprophylaxis for groups at risk.

T/F

A

T

79
Q

Appropriate use of antimalarial drug is determined by _________ and the _________ for taking the primary decision on use of the drug either at home or at the different health care levels.

A

the goal of treatment

person responsible

80
Q

Background to the Use of ACTs

___________ and _________ are Inappropriate for use in the treatment of uncomplicated malaria in Nigeria.

In line with WHO recommendation, Nigeria embarked on drug trial of some selected ________________ Therapies and found them to be very safe and effective.

This lead to the change in the first line antimalarial drug in Nigeria from ________ to _________

A

Chloroquine and Sulphadoxine-Pyrimethamine

Artemisinin-based Combination

Chloroquine to ACTs.

81
Q

Artemisinin

One of the most novel discoveries in recent medicinal plant research

1967-_________ was found to ———-

1972-_________ from the _____

1979-____________ determined by ______

A

extracts of Artemisia; have antimalarial activity

artemisinin isolated; plant

structure of artemisinin; X-ray analysis

82
Q

Artemisinin
One of the most novel discoveries in recent medicinal plant research

_____- extracts of Artemisia was found to have antimalarial activity
_____- artemisinin isolated from the plant
______- structure of artemisinin determined by X-ray analysis

A

1967

1972

1979

83
Q

QUALITIES OF ACTs

Rapid and substantial reduction of the __________,

Rapid parasite ________,

Rapid ________ of _________,

A

parasite biomass

clearance

resolution of clinical symptoms

84
Q

QUALITIES OF ACTs

Reduction of ______ carriage, which potentially reduces _________________

A

gametocyte

transmission of resistant alleles.

85
Q

ACT is ineffective against multidrug-resistant P. falciparum

T/F

A

F

Effective action against multidrug-resistant P. falciparum,

86
Q

UNIQUE QUALITIES OF ACTs

Artemisinin kills (slowly or rapidly?) and substantially most of the parasites.

Remaining are then killed by a (low or high?) conc of the companion drug.

A

Rapidly

High

87
Q

UNIQUE QUALITIES OF ACTs

The efficacy and (short or long?) half life (______) of the artemisinins offer protection against ________.

The (short or long ?) half life companion drug kills the rest of the parasites.

A

Short; < 1 hr

resistance

Long

88
Q

In ACTs

the probability that mutant parasites survive and emerge from these combined two drugs is high

T/F

A

F

It’s low

89
Q

Currently no evidence for clinically relevant artemisinin resistance

T/F

A

T

90
Q

Reasons for delay of artemisinin resistance:

(Short or long?) half-life

(Decreases or Increases?) transmission potential

Used in combination with other antimalarial drugs

A

Short

Reduces

91
Q

Use of artemisinin-based combined therapies would help delay antimalarial drug resistance

T/F

A

T

92
Q

Summary of ACT

Artemisinin induce (slow or rapid ?) killing of parasites

(Slow or Fast ?) clearance rate

Very (few or plenty ?) side effects

A

Rapid

Fast

Few

93
Q

Artemsinin-resistant parasites have not been identified

T/F

A

T

94
Q

Mechanism of Action

Killing of malaria parasite is mediated by
____________

A

production of free radicals

95
Q

Mechanism of Action

Artemisinin derivatives lacking _____________ are devoid of antimalarial activity

Addition of _______ generating compounds enhances antimalarial activity

A

endoperoxide bridge

free radical

96
Q

Antioxidants aids antimalarial activity

T/F

A

F

Antioxidants block antimalarial activity

97
Q

Mechanism of Action

Heme/iron mediates ______________

_____ chelators antagonize antiparasitic effect of artemisinin

Artemisinin-derived free radicals bind to protein through ______

A

breakage of endoperoxide bridge

Iron

alkylation

98
Q

Mechanism of Action

Iron chelators antagonize antiparasitic effect of _______

A

artemisinin

99
Q

Chloroquine antagonizes the antimalarial activity

T/F

A

T

100
Q

Mechanism of Action

Inhibit hemozoin __________ or cause hemozoin _______

Inhibit hemoglobin ________ by malaria parasites

Forms ______ adducts with malarial proteins

A

biosynthesis

degradation

Digestion

covalent

101
Q

Adverse Reactions of ACT

(Fee or Plenty?) adverse reactions

Common side effects include
Nausea Vomiting Anorexia dizziness

(Safe or Unsafe?) for pregnant women

A

Very few

Safe

102
Q

A trial conducted in northwest Thailand has found that it is safe to use artemisinin combination therapy (ACT) to treat pregnant women (_________ trimester) with malaria, but that efficacy is inferior to ___________ treatment.

A

2nd or 3rd

single-drug artesunate

103
Q

DOSAGE REGIMEN
The following ACTs are currently recommended:

Artemether-___________,

Artesunate + __________,
Artesunate + __________,
Artesunate + _______________—

A

lumefantrine

amodiaquine

mefloquine

sulfadoxine-pyrimethamine.

104
Q

DOSAGE REGIMEN
The following ACTs are currently recommended:

_________-lumefantrine,

___________ + amodiaquine,

___________ + mefloquine,

___________ + sulfadoxine-pyrimethamine.

A

Artemether

Artesunate

Artesunate

Artesunate

105
Q

DOSAGE REGIMEN

Officially adopted ACT for uncomplicated malaria in Nigeria is __________________

A

Artemether-Lumefantrine (AL)

106
Q

DOSAGE REGIMEN

The partner medicines of all other
ACTs have been previously used as monotherapies
T/F

A

T

107
Q

Lumefantrine absorption is reduced with fat

A

F

Lumefantrine absorption is enhanced with fat

108
Q

Lumefantrine absorption is enhanced with ____ hence the need to take AL with _____ or ____-containing food – particularly on the _______________ days of treatment.

A

fat

milk or fat

second and third

109
Q

AL

This is currently available as co-formulated tablets containing ____mg of artemether and ____ mg of lumefantrine.

The total recommended treatment is a ____- dose regimen of artemether-lumefantrine _____ a day for ____ days.

A

20

120

6; twice; 3

110
Q

SEVERE MALARIA

For severe malaria:

______ 2.4 mg/kg bw i.v. or i.m. given on admission (time = 0), then at 12 h and 24 h, then once a day;

________ 3.2 mg/kg bw i.m. given on admission then 1.6 mg/kg bw per day;

_________ 20 mg salt/kg bw on admission (i.v. infusion or divided i.m. injection), then 10 mg/kg bw every 8 h; infusion
rate should not exceed 5 mg salt/kg bw per hour.

A

Artesunate

Artemether

Quinine

111
Q

PREGNANCY

For severe malaria in full doses. Where available, _____ is the first, and ______ the second option in the second and third trimesters.

In the first trimester, until more evidence becomes available, _______________ may be considered as options.

A

artesunate

artemether

both artesunate
and quinine

House Pharmacology (50 decks)

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