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Pharma 3 > Antiprotozoal Drugs > Flashcards

Antiprotozoal Drugs Flashcards

1
Q

General concepts of protozoa

A

= single cell organism: parasites (req. vector)
Eukaryotic–> harder to selectively target

Most frequent infections
   Malaria
   Amebiasis 
  Toxoplasmosis
   Leishmaniasis
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2
Q

Malaria
Life Cycle
Strains

A

Most frequent disease in the world; spread by mosquitos
Mostly imported to Europe

Life Cycle
Malaria: sporozoites–> human. –> liver cell
development of schizont–> rupture and release
merozoites.

   Merozoites enter RBC--> asexual multiplication. Some: 
   sexual multiplication (gametocytes). Rupture of RBS

RBC Cycle continues endlessly producing symptoms
Hepatic Cycle only occurs once/infection

Strains
Plasmodium Malariae
Falciparum: most widepread and resistance. CNS malaria
Vivax: stays in liver; can reactivate post treatment
Ovale: stays in liver; can reactivate post treatment

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3
Q

Malaria

Symptoms
Drugs

A 
Can be fatal within a couple of days
Intermittant fever: erythrocytic phase
Head and muscle aches
Haemolytic anaemia, splenomegaly, jaundice
Haemoglobinuria if severe enough
Drugs
   Primary tissue schizotocidal effect
   Blood schizotocidal effect
   Gametocidal effect
   Spotontocidal effect: kill sporozoa in mosquito
   Secondary tissue schizotocidal effect
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4
Q

Plasmodia: Metabolism

A

Plasmodia can’t synth AA–> degrade Hb for AA (done in RBC vacuoles)

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5
Q

Malaria: Drug Group Names

A

Inhibitors of Heme Metabolism
Inhibitors of electron transport chain
Inhibitors of protein synthesis
Inhibitor of Folic Acid synthesis

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6
Q

Malaria: Inhibitors of Heme Metabolism

Drug Names

A 
Chloroquine
Mefloquine
Quinine
Qiunidine
Artemisinin
Artesunate
Artemether
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7
Q

Malaria: Inhibitors of Heme Metabolism

Chloroquine: Drug Characteristics

A

Ineffective against P. falciparum (can’t get into mutated
vacuoles)

MoA: Blood Schizotocidal Effect
Weak base; accumulates im food vacules (acidic)
Bind ferriprotoporphyrin IX and inhibit detoxification

T1/2: 5 Days
Req loading dose
Accumulates in various tissues
Renal excretion

Also suitable for prophylactic th

SE: limited as rel selective for infected RBC
negative cardiac effects, hair loss, neuropathy

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8
Q

Malaria: Inhibitors of Heme Metabolism

Mefloquine

A

Unknown MoA; similar to that of chloroquine

T1/2: 30 days
Strong PPB
Accumulates in RBC

Used: chloroquine resistant P. Falciparum and P. Vivax
as well as for prophylaxis

SE: Negative Cardiac

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9
Q

Malaria: Inhibitors of Heme Metabolism

Quinine and Quinidine

A

Only difference between the two: hydroxy group

MoA: Blood schizotocidal effect
Inhibition of heme polymerase
Bind to strands of DNA–> possibly inhibit transcription

Uses: acute malaria. Chloroquine resistant P. Falciparum
NOT suitable for prophylaxis

SE
Resp Depression; negative cardiac effects
SM contraction also-> splenic contraction-> fever
vasodilation

REM: Quinidine: Na Channel Inhibitor–> antiarrythmic

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10
Q

Malaria: Inhibitors of Heme Metabolism

Artemisinin
Artesunate
Artemether

A

Prodrugs, activated by free or heme bound iron

MoA: Blood schizotocidal effect
Prod of radical–> alkylation of proteins and heme

T1/2: few hours–> combine with example piperaquine

Used as first drug in acute malaria in Africa. Not for
prophylaxis

SE
Neuro and cardiotoxic
Elongation of QT

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11
Q

Malaria: Inhibitors of Electron Transport Chain

Primaquine

A

Structurally rel. to chloroquine

Secondary tissue schizotocial effect

MoA
Inhibits ubiquinone–> inhibits electron transp chain

If patient lacks glucose 6 P-> increased hemolysis with
drug

SE
Methemoglobinemia
Hemolysis (life threatening in fetus–> CI in pregnancy)

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12
Q

Malaria: Inhibitors of Electron Transport Chain

Atovaquone

A

Analogue of ubiquinone

ALWAYS COMBO: Atovaquone+ proguanil as single mutation leads to resistance
–> synergistic effect

Treatment and prophylaxis
Also effective against Toxoplasma

SE
Headache
Nausea

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13
Q

Malaria: Inhibitors of Protein Synthesis

Doxycycline

A

Tetracyclic AB

Delayed effect–> only for prophylaxis; not allowed in all countries

SE
Photosensitivity with dermal eruption

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14
Q

Malaria: Inhibitors of Protein Synthesis

Clindamycin

A

AB

Can be used for kiddies and pregnant patients

SE
can bind Ca in developing bone

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15
Q

Malaria: Inhibitor of Folic Acid Synthesis

Proguanil

A

Inhibitor of protozoal DHF acid reductase

ALWAYS COMBO
Atovaquone with Proguanil

Only for prophylaxis

SE
   macrocytic anaemia (counteract by combo with folic 
         acid)
   haematuria
   diarrhoea
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16
Q

Drugs used in the symptomatic treatment of Malaria

A 
Chloroquine
Mefloquine
Quinine
Quinidine
Artemisinin
Artesunate
Artemether
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17
Q

Drugs used only in prophylaxis of Malaria

A

Proguanil

Doxycycline

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18
Q

Amebiasis

General characteristics
Symptom

A

Caused by entameobia hystolytica
Parasite depends on metabolism gluc–> ethanol

Symptoms occur days/weeks post infection
Patients freq asymptomatic while infectious
Diarrhea/abdominal cramps/dysentry
Hepatic abscesses

19
Q

Amebiasis

Life Cycle and Infection

A

Feco-oral transmissionE
Excystation and ripening of trophozoites in interstines–>
colonic phase
Can damage barrier–>blood–>liver–>abscess-> late ph.
Excreted with feces
Trophozoites can move with their pseudopodia
Consume bacteria, other protozoa, intestinal and RBCs

20
Q

Amebiasis

Drug Names

A 
Metronidazole 
Tinidazole
Emetine
Dehydroemetin
Paramomycin
Diiodohydroxyquinolene
21
Q

Amebiasis

Metronidazole and Tinidazole
Spectrum
MoA
MoR

A 
Main Drugs used
Spectrum
   Anaerobic bacteria
   Microaerophilic bacteria (H. Pylori)
   Microaerophilic protozoa (Entam. Hyst.)

MoA
non enzymatic red: ferredoxins–> free radicals and
reactive nitroso derivatives
Metronidazole is a prodrug; req. reductive activation of
nitro group by susceptible organism
Selectively toxic towards anaerobic and microareophilic
pathogens

MoR
Low expression of ferrodoxins
NADPH dep. enzym. reduction of nitro group

22
Q

Amebiasis

Metronidazole and Tinidazole
Pharmacokinetics
SE

A

Complete GIT absorption; even distribution
Metabolites mainly excreted renally

SE
   metallic taste 
   disulfiram like effect--> no combo with alcohol 
   headache/ nausea/ dry mouth
   darkens urine
23
Q

Amebiasis

Emetine
Dehydroemetine

A

Also used as emetics and expectorants–> given IM or SC
(stim. vagal nerve–> nausea and vomiting)
Active against tissue trophozoites
Only used if metronidazole is CI due to SE

Dehydroemetine is favoured; fewer SE

MoA
Binds 40S ribosome subunit and inhibit eukaryotic
protein synthesis

SE
   May inhibit human protein synthesis in high dose
   CF
   Hepatotoxic
   Myopathy
24
Q

Amebiasis

Paramomycin

A

Is an aminoglycoside antibiotic

Only used orally; systemic admin–> severe SE

25
Q

Amebiasis

Diiodohydroxyquinolene

A

Has luminal effect
Complexes with iron; iron req by amoebas

Thyroid SE as contains iodine

26
Q

Trypanosomiasis

General
Symptoms

A

Africal Trypanosomiasis= sleeping sickness
American= Chagas Disease

Generalised lymphadenopathy
Fever
CNS involvement
--> meningoencephalitis and narcoleptic states
Primary chancre may occur at bite site
27
Q

Trypanosomiasis

Life Cycle

A

Tsetse flies are vectors–> blood meal and injects trymastigotes–> transform into trypomastigotes in blood stream–>carries to other sites.
Trypomastigotes multiply–> Tsetse fly has blood meal

28
Q

Trypanosomiasis

Drug Names

A

Pentamidine
Suramin
Melarsoprol

29
Q

Trypanosomiasis

Penamidine

A

Treatment of early phase (pre crossing BBB)
Combo with suramin

MoA
+ charged molecule–> actively transp. into parasites–>
binds - charged molecules–> inhibition of
DNA/RNA/protein synthesis

IV or IM
Accumulates in various tissues
Slow elimination

SE
Nephro-, Hepato-, Myelotoxic
Histamine releasing
Dizzyness, headache, tachycardia

30
Q

Trypanosomiasis

Suramin

A

Treatment of early phase of African Trypanosomiasis
+ and - charged
Inhibits RNA polymerase

Poorly absorbed
Strong PPB

Nephrotoxic
Neuropathy
Seizures

31
Q

Trypanosomiasis

Melarsoprol

A

Contains arsenic

For late phase treatment

Inhibits protozoal pyruvate kinase and therefore energy production

Combo with steroids to decrease occurrence of reactive encepathalopathy (5% fatality of drug)

32
Q

Toxoplasmosis

A

Toxoplasma Gondii
Animal hosts: mammals and birds
Cat is natural/ intermediate host
Crosses placenta

Lymphadenopathy
Intraocular Infection
meningitis/encephalitis

Congenital:
retinopathy/blindness and calcifying scars in brain
leading to epilepsy

33
Q

Toxoplasmosis

Drug Names

A

Pyrimethamine
Sulfadiazine
Spiramycin

34
Q

Toxoplasmosis

Pyrimethamine + Sulpadiazine

A

Both of them are sulfonamides
CI in pregnancy
Synergistic inhibition of folic acid synthesis

COADMIN folic acid to prevent myelosuppression

35
Q

Toxoplasmosis

Spiramycin

A

It is a macrolide AB

Can be used for kiddies and pregnant patients with acute infection

36
Q

Leishmaniasis

A

Intermediate hosts are sand flies; spread via saliva of insects
Live IC in macrophages

Diseases
visceral
cutaneous
mucocutaneous

37
Q

Leishmaniasis

Drug Names

A

Na Stibogluconate
Amphotericin B
Paramomycin

38
Q

Leishmaniasis

Na Stibogluconate

A

A heavy metal containing drug; cont. antimony
Reacts with -SH groups–> damages enzymes

SE
   Myelosuppression
   Circulatory shock
   Hepatotoxic
   QT elongation
39
Q

Leishmaniasis

Amphotericin B

Chemistry
Pharmacokinetics
Preparations

A

Chemistry
Polyene Macrolide; amphoteric
Water insoluble
-> Preps: complexed with sodium
encapsulated with liposomes: less nephrotoxic
IV
Strong PPB
Long T1/2
Broad spectrum, even some protozoa es leishmaniasis
Crosses BBB poorly–> intrathecal admin possible
Slow renal and biliary excretion

40
Q

Leishmaniasis

Amphotericin B

Mechanism of Action
Side Effects

A

Selectively toxic: high affinity to ergosterol
Interrupts membrane stability: forms pore in membrane
Able to integrate via hydrophobic part
Resistance due to low ergosterol content

SE
   Renal toxicity: mainly reversible
   Hypokalemia
   Anaemia (decreased EPO)
   !!Cytokine Storm!!
   Hepatotoxicity
41
Q

Leishmaniasis

Paramomycin

A

Is an aminoglycoside antibiotic

Only used orally; systemic admin–> severe SE

42
Q

Giardia

Th possibilities

A

Metronidazole

Furazolidone is resistant cases

43
Q

Trichomoniasis

Th Possibilities

A

Local suppositories/ creams may suffice

Metronidazole
Trinidazole
Nifuratel

Pharma 3 (14 decks)

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