Anti-Malarial Drugs Flashcards
Malaria is a/an (acute or chronic?) infectious disease caused by 4 species of the protozoa genus _____.
Acute
plasmodia
P.________ is the most dangerous species.
Others are _______,______,_______
falciparum
P. malariae, P.ovale, P.vivax
One ______ of the world population is at risk of malaria more than 300 million cases each year. (WHO 1998).
•
fifth
Malaria kills more than a million people annually
T/F
T
Majority of mortality due to malaria are children under _____ who die cause they do not receive treatment quickly enough. (Alnwick 2000).
five
Nigeria is a malaria-endemic area
T/F
T
_______ is the principal cause of childhood mortality.
malaria
At least 20% of all childhood deaths are due directly to malaria
T/F
F(10)
_____-_____ children die from malaria each day! (FMOH)
300 – 500
________ countries accounted for 95% of malaria cases globally.
Twenty-nine
Nigeria (_____%), and _____ other countries accounted for about 51% of all cases globally. Similar stats for death
■
27
4
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
sporozoites
liver; merozoites
released; red blood cells
Rupture; merozoites; can
Female; gametocytes
Signs and symptoms of UNCOMPLICATED MALARIA
______
_______
____________ pains
_________
Malaise
_______
___________
Nightmares
Fever
Headache
Joint and body
Weakness
Vomiting
Diarrhea
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)
consciousness or unrousable coma
prostration; weakness
feed; convulsions
two; 24 h
acidotic
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)
circulatory; shock
jaundice
haemoglobin
bleeding
pulmonary
circulatory collapse or shock, in severe malaria may be characterized by systolic blood pressure < ____ mm Hg in adults
and < _____ mm Hg in children
70
50
SEVERE MALARIA
Laboratory findings:
– _____glycaemia
– (metabolic or respiratory ?) (acidosis or alkalosis?)
– severe ______cytic anaemia (Hb < 5 g/dl, packed cell volume < 15%)
hypo
metabolic; acidosis
normo
SEVERE MALARIA
Laboratory findings:
– __________uria
– hyper ___________
– hyper_________
–______ impairment (serum creatinine > 265 μmol/l).
haemoglobin
parasitaemia
lactataemia
renal
Malaria in Pregnancy
Despite _________________________, women living in endemic areas suddenly become _____________ when they become pregnant.
being clinically immune from P. falciparum malaria
susceptible to the disease
Malaria during pregnancy is characterised by very ___________ of the placenta.
heavy parasitization
Protection against P. falciparum malaria acquired prior to the first pregnancy works against the parasites
T/F
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.
Malaria in Pregnancy
The severity and prevalence of parasitaemia both rapidly decline with ______________
increasing parity
The Available Antimalarial Medicines
List them allllll
NAPS BAA (sleep and mosquitoes bite you)
The Naphthoquinolines
The Antibiotics
The Peroxides
Sulphones
The Biguanides
The Arylaminoalcohol
4-Aminoquinolines
8-Aminoquinolines
The Arylaminoalcohols
Divided into 2
________ methanols
___________ methanols
Quinoline
Phenanthrene
The Arylaminoalcohols
Quinoline methanols (______,______,______)
Phenanthrene methanols ( ________,_______)
Quinine, Quinidine, Mefloquine
Halophanthrene, Lumefantrine
The Arylaminoalcohols: Mefloquine
Aka: _______________
Mode of Action
Activity on the ____________.
Alters the binding affinity of the parasite through the _____-binding _______
4-quinoline methanol
mid- to late trophozoite
ATP; cassette transporter.
The Arylaminoalcohols: Mefloquine
Mode of Action
Is a ———- ________cide active against _____,_______,________
Blood schizonticide
P.falciparum, P.malariae, P.vivax
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.
neuropsychiatric; cardiovascular
Quinoline methanols :Quinine, Quinidine
Efficacy
Is a ______ ————cide effective against P.__________
Blood schizonti
Falciparum
Quinoline methanols : Quinine, Quinidine
Mode of Action
Acts like CQ
_______________ stage of the parasite.
Mid to late trophozoite
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
Tinnitus, muffled hearing; vertigo
hypo; injected too rapidly
cardiac; mefloquine
Quinidine is cardiotoxic
T/F
T
4-Aminoquinolines
________ ,________ ,_________, _________, Mepacrine (______), Pyronaridine (benzonaphthyridine)
Chloroquine
Amodiaquine
Piperaquine; Naphthoquinoline
acridine
4-Aminoquinolines
Mode of Action
Activity on _____________ stage
Prevents ____________ by ________ or _____
mid- to late trophozoite
detoxification of haem by polymerization to haemozoin or malaria pigment.
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.
schizonti
P.falciparum, P.malariae, P.ovale and P.vivax
Gametocyto; an antipyretic and anti inflammatory
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.
visual; pruritus; dark
Irreversible; visual
Retinopathy
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 _________.
leucopaenia and agranulocytosis
chloroquine
Itching is more common with which
AQ or CQ
Itching is less common with AQ.
Itching is more common with CQ
8-Aminoquinolines
Examples
______,_________
Primaquine, Pamaquine
8-Aminoquinolines
Mode of Action
The mechanism of action is ____________.
unknown
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. ________).
intrahepatic
All types
P. V and P. O,
Falciparum
vivax; falciparum
8-Aminoquinolines
Efficacy
For radical cure of _____________
Gametocytocidal against _______
significant blood stage activity against P. ________ (and some against asexual stages of P. ________).
P. V and P. O
Falciparum
vivax; falciparum
8-Aminoquinolines
Adverse Effect
________ in individuals with _________
Haemolysis
G6PD Deficiency
Sulfones
Examples
•Sulphonamides (_____,________,_________),
•_________
sulphadoxine, sulphalene, co- trimoxazole
Dapsone
Sulfones
Mode of Action
Works synergistically with ________ against the parasite specific enzymes, _____ and _____.
Activity on ________ to _________ stage.
Inhibits ___________, which is essential for _______ synthesis
pyrimethamine
DHPS
DHFR
mature trophozoite to early schizont
parasite synthesis of folate; pyrimidine
Sulfones
Adverse Effects
Serious adverse reactions to sulfa drugs include severe _______ reactions, such as _________ and __________.
cutaneous
Stevens Johnson syndrome and TEN
DHPS acts as __________
PABA analogues
Severe cutaneous reactions to sulfones are Commoner amongst the ______ and _______ taking the drug for ———-.
Europeans and North Americans
prophylaxis
TEN appears to be more common in ____________ patients.
Dapsone causes varying degree of ———— and _________
HIV infected
haemolysis
Methemoglobinemia
The Biguanides
Examples
_______,__________,______,_____ and , ___________
Proguanil, Chlorproguanil, cycloguanil, chlorcycloguanil
Pyrimethamine
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 ________
Type 2 Antifolate
DHFR
pre-erythrocytic
Sporonto; non-infective
atovaquone
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
megaloblastic anaemia and pancytopenia
renal
aphthous ulceration and hair loss
The Antibiotics
Mention 4
Tetracyclines, Doxycycline, clindamycin, fluoroquinolones
Biguanides are in co formulation with ________
atovaquone
The Antibiotics
Mode of Action
Tetracyclines are inhibitors of ___________ during protein synthesis.
aminoacyl-tRNA binding
The Antibiotics
Adverse Effects
GIT effects , ________ failure, Oesophageal ulceration, Diarrhoea etc.
Renal
The Naphthoquinones
Examples???
Atovaquone
The Naphthoquinones
Mode of Action
Active against ________ Plasmodium species.
Inhibits _________ development in the ——-, and ———- development in the ________.
Act in synergy with ————
all
pre-erythrocytic; liver
oocyst; mosquito; Proguanil
The Naphthoquinones
Act in synergy with _________
Proguanil
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?
Sure🍻
The Naphthoquinones
High affinity for ____________
plasmaproteins
The Peroxides
_______,________,________,________,________,___________
Artemisinin, Arthemeter, Artemotil, Artesunate, Artelinic acid, Dihydroartemisinin
The Peroxides
Artemisinin, also known as _______, is a sesquiterpene lactone extracted from the leaves of _________ (__________).
qinghaosu
Artemisia annua
sweet wormwood
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.
calcium adenosine triphosphatase
haem to haemozoin
haemozoin to haem; schizonto; all
The Peroxides
Mode of Action
It has an unusually (broad or narrow?) activity against (sexual or asexual?) parasites, killing all stages from ______ to ________.
Broad
Asexual
young rings to schizonts
The Peroxides
Adverse Effect
Artemisinin and its derivatives are not safe and remarkably poorly tolerated
T/F
F
Very safe
Well tolerated
In P. falciparum malaria, artemisinin
Kills the ______ – including the stage _____ ————-, which are otherwise sensitive only to __________.
gametocytes
4 gametocytes
primaquine
The elimination half-life of all Artemisinin is approximately _______
1 h
The Peroxides
Adverse Effect
The only potentially serious adverse effect reported with this class of drugs is ________________ in approximately 1 in 3000 patients
type 1hypersensitivity reactions
COMBINATION DRUGS
Can either be:
_________ based Combinations
____________ based Combinations
Artemisinin
Non-Artemisinin
COMBINATION DRUGS
Artemisinin based Combinations
_________ and ______
________ and _________
Co-artem(_______ and ______)
__________ and _______
Artesunate and SP
Artesunate and Amodiaquine
Artemeter and lumefantrine
Artesunate and Mefloquine
COMBINATION DRUGS
Non-Artemisinin based Combinations
Malarone (________ and ———-)
Maloprim(_______ and _________ )
LAPDAP (_______ and ________)
Mefloquine-SP
______ and ________
Proguanil and Atovaquone
Dapsone and Pyrimethamine
Dapsone and Chlorproguanil
Sulfalene –Pyrimethamine
COMBINATION DRUGS
Non-Artemisinin based Combinations
________ (Proguanil and Atovaquone)
________( Dapsone and Pyrimethamine)
________ ( Dapsone and Chlorproguanil)
Mefloquine-SP
Sulfalene –Pyrimethamine
Malarone
Maloprim
LAPDAP
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).
artemether- lumefantrine
artesunate-amodiaquine
dihydroartemisinin-piperaquine
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
98.0
98.4
99.4
PROBLEMS WITH CHEMOTHERAPY AND CHEMOPROPHYLAXIS
Drug ______
_______ drug reaction
Cost
Limited dosage forms
Unfavorable pharmacokinetics
__________.
resistance
Adverse
Availability
RATIONAL USE OF ANTIMALARIAL DRUGS
This refers to _________________ for the right indications and at the correct/adequate dosages.
appropriate use of antimalarials
Antimalarial drugs will be needed for treatment of uncomplicated malaria, severe malaria and chemoprophylaxis for groups at risk.
T/F
T
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.
the goal of treatment
person responsible
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 _________
Chloroquine and Sulphadoxine-Pyrimethamine
Artemisinin-based Combination
Chloroquine to ACTs.
Artemisinin
One of the most novel discoveries in recent medicinal plant research
1967-_________ was found to ———-
1972-_________ from the _____
1979-____________ determined by ______
extracts of Artemisia; have antimalarial activity
artemisinin isolated; plant
structure of artemisinin; X-ray analysis
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
1967
1972
1979
QUALITIES OF ACTs
Rapid and substantial reduction of the __________,
Rapid parasite ________,
Rapid ________ of _________,
parasite biomass
clearance
resolution of clinical symptoms
QUALITIES OF ACTs
Reduction of ______ carriage, which potentially reduces _________________
gametocyte
transmission of resistant alleles.
ACT is ineffective against multidrug-resistant P. falciparum
T/F
F
Effective action against multidrug-resistant P. falciparum,
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.
Rapidly
High
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.
Short; < 1 hr
resistance
Long
In ACTs
the probability that mutant parasites survive and emerge from these combined two drugs is high
T/F
F
It’s low
Currently no evidence for clinically relevant artemisinin resistance
T/F
T
Reasons for delay of artemisinin resistance:
(Short or long?) half-life
(Decreases or Increases?) transmission potential
Used in combination with other antimalarial drugs
Short
Reduces
Use of artemisinin-based combined therapies would help delay antimalarial drug resistance
T/F
T
Summary of ACT
Artemisinin induce (slow or rapid ?) killing of parasites
(Slow or Fast ?) clearance rate
Very (few or plenty ?) side effects
Rapid
Fast
Few
Artemsinin-resistant parasites have not been identified
T/F
T
Mechanism of Action
Killing of malaria parasite is mediated by
____________
production of free radicals
Mechanism of Action
Artemisinin derivatives lacking _____________ are devoid of antimalarial activity
Addition of _______ generating compounds enhances antimalarial activity
endoperoxide bridge
free radical
Antioxidants aids antimalarial activity
T/F
F
Antioxidants block antimalarial activity
Mechanism of Action
Heme/iron mediates ______________
_____ chelators antagonize antiparasitic effect of artemisinin
Artemisinin-derived free radicals bind to protein through ______
breakage of endoperoxide bridge
Iron
alkylation
Mechanism of Action
Iron chelators antagonize antiparasitic effect of _______
artemisinin
Chloroquine antagonizes the antimalarial activity
T/F
T
Mechanism of Action
Inhibit hemozoin __________ or cause hemozoin _______
Inhibit hemoglobin ________ by malaria parasites
Forms ______ adducts with malarial proteins
biosynthesis
degradation
Digestion
covalent
Adverse Reactions of ACT
(Fee or Plenty?) adverse reactions
Common side effects include
Nausea Vomiting Anorexia dizziness
(Safe or Unsafe?) for pregnant women
Very few
Safe
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.
2nd or 3rd
single-drug artesunate
DOSAGE REGIMEN
The following ACTs are currently recommended:
Artemether-___________,
Artesunate + __________,
Artesunate + __________,
Artesunate + _______________—
lumefantrine
amodiaquine
mefloquine
sulfadoxine-pyrimethamine.
DOSAGE REGIMEN
The following ACTs are currently recommended:
_________-lumefantrine,
___________ + amodiaquine,
___________ + mefloquine,
___________ + sulfadoxine-pyrimethamine.
Artemether
Artesunate
Artesunate
Artesunate
DOSAGE REGIMEN
Officially adopted ACT for uncomplicated malaria in Nigeria is __________________
Artemether-Lumefantrine (AL)
DOSAGE REGIMEN
The partner medicines of all other
ACTs have been previously used as monotherapies
T/F
T
Lumefantrine absorption is reduced with fat
F
Lumefantrine absorption is enhanced with fat
Lumefantrine absorption is enhanced with ____ hence the need to take AL with _____ or ____-containing food – particularly on the _______________ days of treatment.
fat
milk or fat
second and third
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.
20
120
6; twice; 3
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.
Artesunate
Artemether
Quinine
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.
artesunate
artemether
both artesunate
and quinine
