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PDAT6 ID > 18 - Malaria > Flashcards

18 - Malaria Flashcards

1
Q

What Drug?

A

SESQUITERPENE LACTONES

Artemisinin** & **ARTHEMETHER** & **Artesunate
artesunate is still investigational

Target
BLOOD SHIZONTS** & **YOUNG GAMETOCYTES

MoA:
Free Radical Formation = ENDEPEROXIDE
oxidative dmg to parasite’s membrane

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2
Q

Mefloquine

Class / Target / Use

A
  • *4 - Substituted Quinolines**
  • *4-chinoline-methanols**

BLOOD SCHIZONTS

Treatment for:

  • P. falciparum** or *non-ID species in areas with CQ RESISTANCE
  • *Pregnant women** = Mefloquine + Clindamycin

Prevention for:
Long Trips

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3
Q

Chloroquine RESISTANCE
4-sub-quinine
Blood Schizonts Only

A

Spontaneous Gene Mutations
pfcrt transporter protein on digestive vacuole membrane
Plasmodium falciparum CQ resistance transporter
↑drug efflux against ION TRAPPING

↑Plasmodial P450 Metabolism

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4
Q

4-Substituted Quinolones
&
Their TARGET?

A

BLOOD SCHIZONTS
can only treat the ACTIVE FORM in BLOOD, not dormant liver form

Quinine

Chloroquine

Mefloquine

Halofantrine

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5
Q

Atovaquone + Proguanil
for Prevention of Malaria

Use / Dosing / CI’s

A

Last Minute & short Trips

Prior to Travel: 1-2 DAYS

After Travel: 7 Days

250/100mg one tablet a day

CI’s
PREGNANCY / BREASTFEEDING (infant < 5kg)
RENAL Impairment

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6
Q

What Drug?

A
  • *Atovaquone**
  • *UBIQUINONE REDUCTASE INHIBITOR** –> collapse of mitochondrial membrane potential
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7
Q

What Malaria Drug?

A

ANTIFOLATE

PYRIMETHAMINE
used typically in combination with Sulfadoxine

Target only:
BLOOD SHIZONTS

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8
Q

Quinine

Class / Target / Use

A
  • *4 - Substituted Quinolines**
  • *4-chinoline-methanols**

BLOOD SCHIZONTS

Essential Stereoconfiguration
8S - 9R = Quinine
8R - 9S = Quinidine
quinidine for MORE SEVERE malaria forms

Treatment for:

  • *P. Falciparum** or non-ID species in CQ resistant areas
  • *Quinine Sulfate + Doxy/Tetra**
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9
Q

Uncomplicated vs SEVERE
Malaria

A

Uncomplicated = Severe Cold Symptoms

Severe Malaria:
Parasitemia > 5%
Hemoglobinuria / Jaundice / ANEMIA
Impaired Conciousness + Coma
Renal Failure / Respiratory Distress / HypoTension
Convulsions / Bleeding / Intravascular coagulation

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10
Q

How do we get the drug into the food vacuole of plasmodium?

4-Sub-Quinolines

A

ION TRAPPING

Food Vacoules = ACIDIC (5.5pH)

drug = BASIC –> move towards acidic pH & become protonated

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11
Q

Malaria Life Cycle

in
HUMANS

A
  1. Female anopheles –> blood meal
    1. Sporozoites enters with saliva
  2. Enter human liver & divide
    1. burst out –> MEROZITES in blood stream
  3. Merozites enter RBC’s & replicate
    1. burst out & re-infect RBCs = MALARIA FEVER
  4. ​Some intracellular merozites develop into:
    1. sexual forms = GAMETOCYTES
    2. –> ingested by ANOTHER MOSQUITO
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12
Q

What drugs can be used for the

PREVENTION OF MALARIA

A

Longer Trips
Chloroquine & Mefloquine

Short Trip
Doxycycline

Last Minute / Short
Atovaquone + Proguanil

Preventing P. Vivax
Primaquine

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13
Q

ARTEMISINS

DRUGS & TARGET

A

Artemisinin** & **ARTHEMETHER** & **Artesunate
artesunate is still investigational

Target
BLOOD SHIZONTS** & **YOUNG GAMETOCYTES

MoA:
Free Radical Formation = ENDEPEROXIDE
oxidative dmg to parasite’s membrane

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14
Q

8-Substituted Quinolines = PRIMAQUINE

MoA

A

Generation of:
ROS
via autooxidation of 8-amino group

H2O2 / Superoxide / Hydroxyl Radical
VV
Oxidative Cell Damage

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15
Q

How can P.vivax and P. ovale escape drug treatment?
(M. Tertiana)

A
  • *DORMANT LIVER FORMS**
  • *HYPNOZOITES**
  • *1st Line Quinolones –> blood schizonts only**
  • ineffective vs dormant hepatic stage*

To Prevent RELAPSE:
Primaquine = 8-subquinolone

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16
Q

Chloroquine = CQ

Class / Target / Use

A
  • *4 - Substituted Quinolines**
  • *4-chinoline-AMINE**

BLOOD SCHIZONTS

Treatment for:

  • CQ Sensitive** P. Falciparum or Non-ID species *_w/o CQ resistance_
  • *P. Malariae_ & _P. Knowlesi**
  • *P. Vivax_/_Ovale** taken with Primaquine Phos
  • *Pregnant Women**

Prevention for:
Longer Trips

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17
Q

Chloroquine
for Prevention of Malaria

Use / Dosing / CI’s

A

Longer Trips

Prior to Travel: 1-2 Weeks

After Travel: 4 weeks

600mg (300mg base) on exact same day of each week

CI’s

  • *VISON PROBLEMS**
  • irreversible retinal dmg may occur with PROLONGED treatment*
18
Q

Treatment of Malaria

P. Vivax & P. Ovale
Relapsing
M. Tertiana

A

CQ + PP

  • *ChloroQuine Phosphate_ + _Primaquine Phosphate**
  • except for certain areas*

for 2 Weeks

19
Q

Mefloquine
for Prevention of Malaria

Use / Dosing / CI’s

A

Longer Trips

Prior to Travel: 2-3 Weeks

After Travel: 4 weeks

250mg (228mg base) on exact same day of each week

CI’s
MENTAL ADR + TINGLING FEET & FINGERS
SEIZURES
cardiac conduction / PREGNANCY

20
Q

8-Substituted Quinolones
&
Their TARGET?

A

LIVER Hypnozoites & Schizonts

  • *BLOOD Gametocides**
  • does NOT work on BLOOD SCHIZONTS*
  • *PRIMAQUINE**
  • do NOT give to pregnant women*
21
Q

PRIMAQUINE
for Prevention of Malaria

Use / Dosing / CI’s

A

Preventing P. VIVAX
good for places with >90% P. Vivax

Prior to Travel: 1-2 DAYS

After Travel: 7 DAYS

30mg QD

CI’s
G6PD DEFICIENCY –> NEED TESTING
PREGNANCY & BREASTFEEDING

22
Q

PYRIMETHAMINE

Class / Target / Uses

A

DHFR Inhibitor = Antifolate
Blood Schizonts

Used in combination with:
Sulfadoxine** + **Pyrimethamine = FANSIDAR

Treatment & Prevention for:
QC-RESISTANT MALARIA
Used with quinine

23
Q

If the diagnosis of malaria is suspected and cannot be confirmed,
or
if the diagnosis is confirmed but species determination is not possible

A

treat against

  • *CQ-RESISTANT P.F**
  • *immediately**
24
Q

Treatment of Malaria

PREGNANT WOMAN

A

can NOT use PRIMAQUINE

ChloroQuine
or
Mefloquine + Clindamycin

For P.Vivax & Ovale:
maintain with CQ prophylaxis during pregnancy
then Primaquine AFTER delivery

if Severe –> use Parenteral treatment

25
Q

Treatment of Malaria

SEVERE

A

Require IV THERAPY

QuiniDINE Gluconate IV
for 24 h+ (Parasitemia < 1%)
(if not available –> Artesunate)

THEN

Oral:
QuinineorAtovaquone-GuanilorArtemether-Lumefantrine

26
Q

What organisms cause Malaria?

Vector = FEMALE ANOPHELES MOSQUITO
plasmodium genus

A

FOVM-k

  • *P. Falciparum**
  • *M. Tropica** = fulminating disease
  • *P. Vivax / Ovale**
  • *M. Tertiana** = RELAPSING
  • *P. Malariae**
  • *M. QUARTana**

P.Knowlesi = ZOONOTIC –> monkey transmition

27
Q

DHFR Inhibitor = Antifolates

TARGET

A

PYRIMETHAMINE
used typically in combination with Sulfadoxine

Target only:
BLOOD SHIZONTS

28
Q

What Drug?

A

Proguanil
inhibit the enzyme DHFR (anti-folate)

Guanidine Derivative

29
Q

Doxycycline
for Prevention of Malaria

Use / Dosing / CI’s

A

SHORT Trips

Prior to Travel: 1-2 DAYS

After Travel: 4 weeks

100mg/daily

CI’s
Pregnancy / Children <8 y/o / SUN EXPOSURE

MoA:

  • *impairs reporduction of malaria specific plastids**
  • *only Prophylaxis** not treatment
30
Q

Malaria Life Cycle

in
MOSQUITO

A
  1. Mosquito blood meal
    1. ​ –> ingest GAMETOZYTES
  2. Male + Female –> form zygote in GI of mosquito
    1. mature to mobile form = OOKINETE
  3. Ookinte –> migrates to cell wall of gut
    1. matures into OOCYST
  4. ​Oocyst replicates new sporoids
    1. ruptures –> releases SPOROZOITES
      1. SALIVA GLANDS –> human infection
31
Q

If malaria infection occurred despite use of a preventive drug…

A

that DRUG should NOT be used
in part of the
treatment regimen

32
Q

Quinidine

Class / Target / Use

A
  • *4 - Substituted Quinolines**
  • *4-chinoline-methanols**

BLOOD SCHIZONTS

Essential Stereoconfiguration
8S - 9R = Quinine
8R - 9S = Quinidine
quinidine for MORE SEVERE malaria forms

Treatment for:
SEVERE MALARIA – IV Quinidine Gluconate

33
Q

MALARONE
Atovaquone / Proguanil

MoA / Uses

A
  • *Atovaquone**
  • *UBIQUINONE REDUCTASE INHIBITOR** –> collapse of mitochondrial membrane potential
  • *Proguanil**
  • inhibit the enzyme* DHFR (anti-folate)

Target only BLOOD SCHIZONTS
for
CQ Resistant & Multidrug Resistant
P. Falciparum**&**P.Vivax

34
Q

Treatment of Malaria

CQ sensitive P. falciparum
or
species not identified in areas w/o CQ resistance

A

ChloroQuine Phosphate
CQ

600mg base @0h

300mg base @6/24/48h

35
Q

Treatment of Malaria

P. falciparum
or
species not identified in area WITH CQ RESISTANCE

A

Atovaquone - Proguanil
or
Artemether-Lumefantrine
or
Quinine Sulfate + Doxycycline or Tetracycline
or
Mefloquine

36
Q

Which Malaria drug can cause:
VISION PROBLEMS?

A

CHLOROQUINE

used for
Long Trips - Prevention of Malaria

irreversibal retinal dmg with prolonged treatment

37
Q

Which Malaria drug can cause:
Mental Side Effects & Tingling Feet/Fingers?

A

MEFLOQUINE

used for
Long Trips - Prevention of Malaria

Also:
SEUIZURES
Cardiac Conduction Problems
PREGNANCY

38
Q

Treatment of Malaria

P. malariae & P. Knowlesi

A

CQ resistance is UNUSUAL for these species

ChloroQuine Phosphate
CQ

or
same treatment for CQ resistant

39
Q

Halofantrine

Class / Target / Use

A
  • *4 - Substituted Quinolines**
  • *4-chinoline-methanols**

BLOOD SCHIZONTS

  • *Same use as Mefloquine?**
  • both are 4-chinoline methanols*
40
Q

MoA of
4- Sub Quinolines
Quinine / Quinidine
Mefloquine / Halofantrine / Chloroquine (CQ)

A
  1. Hemoglobin –> food vacuoles of Plasmodium
    1. ​digestion (protein) –> source of Amino Acids
      1. also HEME = TOXIC TO PLASMODIUM CELLS
  2. ​​HEME DETOXIFICATION
    1. Heme –> HEMOZOIN, not toxic**​

Quinolines bind to HEMAZOIN
aromatic system binds via p-bonds to porphyrin nucleus
blockage of polymer extention & ↑Toxic Heme
VVV
CELL DEATH

PDAT6 ID (31 decks)

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