week 2. Antiviral, antifungal, intro to parasites Flashcards Preview

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Flashcards in week 2. Antiviral, antifungal, intro to parasites Deck (190)
1

what was the first antiretrovural drug produced and when?

AZT in 1987

2

explain the progression of HIV after infection?

you get primary infection --> where there is a rapid rise in viral load with a stark decrease in CD4 account.
However the immune system responds and there is a clinical latency where there the viral load is in balance.
However after some time the level of viral load increase while the CD4 count reduces --> opportunistic infection occurs

3

what are the two types of Virus?

ones based on RNA and ones with DNA

4

viruses that cause acute infection what are they based on?

RNA --> short lasting

5

give examples of acute infection caused by virus

Influenza, measles, mumps, hepatitis A virus

6

what are chronic infection based on?

DNA --> long lasting --> more stable and theredfore last a long time

7

what are the two types of chronic infection by a virus?

latent and persistant

8

give example of chronic latent virus's?

Herpes simplex, Cytomegalovirus

9

give example of persistant virus?

HIV, Hepatitis B virus, Hepatitis C virus

10

what is a characteristic of persistant virus?

it replicates all the time

11

how does HIV convert its RNA to DNA?

using reverse transcriptase

12

what type of genetic information does Hep C have?

purerly RNA

13

how does Hep C overcome the immune system and cause chronic infection?

it affects the liver and therefore evades the immune system and constantly evolving --> beating the immune system

14

will you 100% die from hep B/C if you have it

no

15

what does a virus consist of?

Nucleic acid (DNA or RNA)
Protein (coat - structural, enzymes-non-structural)
+/- Lipid envelope

16

HIV is Obligate intracellular parasites. What does this mean?

it cannot reproduce outside a host --> needs intracellular resources

17

what is important about envelope structural proteins of HIV?

it is what allows HIV to invade cells

18

what is the sequence of viral replication?

1)Virus attachment to cell (via receptor)
2)Cell Entry --> find the cell they can enter without harming it
3)Virus Uncoating  ready for replication
4)Early proteins produced – viral enzymes
5)Replication
6)Late transcription/translation – viral structural proteins
7)Virus assembly
8)Virus release
9)Some virus kill the cell by lysis but not all do this and go and affect other cells

19

what do virus's encode and why are they important for treatment?

viruses encode unique proteins that are vital for virus replication and infectivity --> antiviral drugs target this for molecular inhibition

20

what are the different types of polymerases involving VIrus's?

DNA to DNA -->Eukaryotes , DNA viruses
DNA to RNA --> Eukaryotes ,DNA viruses
RNA to RNA--> RNA viruses
RNA to DNA --> Retroviruses (HIV), Hepatitis B virus

21

what is azidothymidine?

Nucleoside Reverse Transcriptase Inhibitor (NRTI

22

what does AZT do?

it inhibits reverse transcriptase in HIV and other retroviruses

23

what was AZT first used for?

as a cancer drug but was to toxic

24

what year was AZT used as a HIV treatment?

1985

25

what is AZT analogue of?

thymidine --> Oh is replace with 3 nitrogen atoms

26

what are the two types of NRTI analogue?

Purine analogue
Pyrimidine analogue

27

what are the pyrimidine?

thymine and cytosine

28

give examples of pyrimidine analogue?

Thymidine analogues --> Zidovudine
Cytosine analogues -->Lamivudine

29

what are the purines?

adenine and Guanidine

30

give example of purine analogue?

Abacavir
Tenofovir

31

why is NRTI effective for hep B virus?

The virus contains reverse transcriptase enzyme

32

what NRTI are effective against hep B infection?

Lamividine
Tenofovir

33

how does NRTI work?

by competing with reverse transcriptase for their interaction site with HIV genetic material

34

what is the difference between NRTI and NNRTI and how do NNRTI work?

NRTI looks similar to necleotides but NNRTI doesn't look like anything like nucleotides.

NNRT block reverse transcriptase by binding to a different part of the protein

35

name all the different protease inhibitors for HIV treatment?

Atazanavir
Darunavir
Fospamprenavir
Lopinavir
Nelfinavir
Ritonavir*
Saquinavir

36

which of the protease inhibitors increase the affect of other drugs?

ritonavir

37

what is the importance of protease in HIV?

HIV virus cuts proteins--> to form specific enzymes needed for it to function and replicate

38

what three parts of the HIV genome can be targeted in treatment?

core structural protein, envelope structural protein and viral enzymes

39

give example of the newer HIV drugs?

Fusion inhibitor
Integrase Inhibitors
Chemokine receptor antagonsits (

40

give an example foa fusion ihibitor and how it functions in respect to HIV treatment?

Enfuviritide (T20, given by IM injection as it is a peptide

41

give an example foa Integrase Inhibitors in respect to HIV treatment?

Raltegravir

42

how does Chemokine receptor antagonsits work?

it blocks the ability for HIV to bind to co receptors such as CCR-5 and CXCR4 --> which prevents the HIV virus to bind to CD4

43

what are the different combinations of Highly Active Antiretroviral Therapy (HAART)?

2 NRTIs + NNRTI
2 NRTIs + boosted PI

44

when is HAART given?

Started when CD4 falls
Aim to switch off virus replication
Taken life long
Suppression >10yrs achieved

45

what toxicity can be caused by HAART?

liver and kidney toxicity

46

in HAART why is 3 drugs used?

reduce the chance of the virus to become resistant --> very highly unlikely that the virus will mutate in such a way to become resistant to 3 different drugs

47

what mutation takes place in HIV to become resistant to Lamivudine?

M184V mutation

48

how many nucleotides does HIV contain?

9000

49

what mutation can make someone more resistant to HIV infection?

having a mutation to the gene that codes for CCR5 and CxCr4 will give someone greater resistance to HIV

50

what are inteferons?

are naturally occurring antivirals that are within the human body

51

what is the treatment of Hep C?

use of exogenous interferon --> can boost peoples antiviral affect

52

for howlong do you have to give interferons to treat Hep c?

3 to 12 months

53

what are the side effects of interferons?

make you feel depressed, flu like and is a injection

54

when will antivirals work on acute infection?

only if given very soon after infection --> as the bodies own immune system will start to kick in

55

what is Aciclovir used for?

For Rx of Herpes Simplex Virus (HSV) and Varicella Zoster Virus (VZV)

56

what is the structure of Aciclovir

Nucleoside analogue (phosphorylated by herpesvirus thymidine kinase)

57

what is Ganciclovir used for?

treatment of Cytomegalovirus (CMV)?

58

what is the treatment of influenza?

Oseltamivir and Zanamavir (neuraminidase inhibitors)

59

what is Ribavirin used for?

Hepatitis C virus and RSV

60

what is Interferons used for?

Hep B and C

61

what is a parasite?

An organism which lives in or on another organism (its host) and benefits by deriving nutrients at the other's expense.

62

DOES A PARASITE always cause disease?

no

63

what does Symbiosis mean?

living together; close, long term interaction between two different species

64

what does Mutualism mean?

an association in which both species benefit from the interaction

65

what does parisitism mean?

an association in which the parasite derives benefit and the host gets nothing in return but always suffers some injury

66

what does Commensalism mean?

an association in which the parasite only is deriving benefit without causing injury to the host

67

what is a definitve host in parasites?

Either harbours the adult stage of the parasite or where the parasite utilizes the sexual method of reproduction

68

what is the intermediate host in parasites?

Harbours the larval or asexual stages of the parasite

69

what is teh Paratenic host in parasites?

Host where the parasite remains viable without further development

70

what are the two types of parasites?

Protozoa --> Micro-parasites
Helminths -->Macro-parasites

71

what does P.Falciparum cause and where is it found?

cause malaria and found in blood smears

72

what are the two types of helminths?

Platyhelminths-->(Flatworms)
Nematodes --> (Round worms)

73

give example of Cestode and what is causes?

Taenia sp and it is tapeworm

74

what does Tissue nematode cause?

 found in the bowel  cause elephantiasis inflammation of the lymphatic system  extreme swelling of arm and leg

75

what are the two types of parasite life cycle?

direct and indirect

76

what is direct life cycle?

invoves one type of species --> transmission through same species

77

how does indirect cycle work?

involves more than one specie --> there is a intermediate host

78

what is a complex indirect life cycle?

where there is more than one intermediate host

79

What type of parasite is Ascaris?

Macro-parasite (Helminth) - intestinal nematode

80

in what area is Ascaris most prevelant and what age group?

between ages of 3-8yr olds and also in areas of poor sanitation

81

how is Ascaris transmitted?

1 worm produces 200,000 eggs -> feaces of humans that contains eggs that contaminate water and ground.

82

how does Ascaris worm develop from a egg into a worm?

THe life cycle

Has a direct life cycle Worm in human intestine, eggs shed into the environment in faeces, eggs are then ingested, they travel in the portal circulation to the lungs where they then hatch and the worms are they swallowed and enter the intestine

83

what are the 2 different clinical stages of Ascaris?

lung migration and intestinal phase

84

In the lung migration of Ascaris what are the syptoms? (6)

Loefflers syndrome- dry cough, dyspnea, wheeze, haemoptysis, eosinophilic pneumonitis

85

what does eosinophilic pneumonitis mean?

is a disease in which a certain type of white blood cell called an eosinophil accumulates in the lung

86

what symptoms are present in the intestinal phase of AScaris?

Malnutrition
Migration – into hepatobiliary tree and pancreas
Intestinal obstruction
Worm burden

87

what is the treatment of Ascaris?

Albendazole and Benzimidazole
Prevents glucose absorption by worm

88

what are the controls for AScaris?

Improve sanitation
Education
Community targeted deworming

89

what type of parasite are Schistosomiasis?

macro-parasites --> worms

90

where does Schistosomiasis occur and why?

predominantly in Africa because of the presence of Fresh water snails

91

What are the 4 stages of disease following schistosomiasis infection?

1) Swimmers itch (at sight of entry) 2) Katayama fever (can last a couple of weeks) 3) Chronic schistosomiasis (can persist for years) 4) Effects of eggs in distant sites: spine, lung

92

what does Schistosomiasis cause?

Causes chronic disease resulting in bladder cancer and liver cirrhosis

93

what is the intermediate host of Schistosomiasis ?

fresh water snails

94

what is the life cycle of Schistosomiasis ?

Eggs are shed in human stools or urine, the eggs hatch and the organism infects freshwater snails by penetrating snail tissue, organism matures in snail then released into water and penetrates human skin.
Pass into human circulation, migrate to portal blood in liver and mature into adults which migrate to the mesenteric venules of the bowel/rectum (laying eggs that circulate to the liver and shed in stools) and venous plexus of the bladder.

95

what is Katayama fever?

infection of the unirary tract and intestines --> through the blood --> weight loss --> loss of appetite

96

what specie of schistosomiasis affects the unirary tract and what is the symptoms?

S. haematobium
Haematuria
Bladder fibrosis and dysfunction
Squamous cell CA bladder

97

what specie of schistosomiasis affects the intestinal tract and what is the symptoms?

Hepatic/Intestinal (S. mansoni; S. intercallatum, S. japonicum; S. mekongi)
Portal Hypertension
Liver cirrhosis

98

how do you diagnose schistosomiasis that affects the urinary tract?

Terminal Stream Microscopy
Serology

99

how do you diagnose schistosomiasis that affects the intestinal tract?

Stool Microscopy
Rectal Snip Microscopy
Serology

100

what is the treatment for schistosomiasis ?

Praziquantel (parazinoisoquinoline derivative) and treatment of long term complications

101

how does Praziquantel work?

40-60 mg/kg with food 3 doses 8-hourly
Mechanism unknown- increased ionic permeability tetanic contraction, detachment, death
Well absorbed, extensive 1st pass metabolism, inactive metabolites excreted in urine

102

how is schistosomiasis controlled?

Chemical treatment to kill snail intermediate hosts

Chemoprophylaxis
Avoidance of snail infested waters
Community targeted treatment, education and improved sanitation

103

what type of parasite causes Hydatid ?

Macro-parasite (Platyhelminth- Cestode-Tapeworm

104

what is the host of Hydatid?

human are accidental hosts
usual host are sheep and dog

105

what causes Hydatid?

Echinococcus sp. (E. granulosus- cystic and E. multilocularis- alveolar)

106

what are the main point in the life cycle of Hydatid?

Dog has adult worm in intestines and sheds eggs in faeces These are ingested by a sheep, they hatch and the organism penetrates the sheep intestinal wall and travels to the liver or lungs where it forms a hyatid cyst. Cyst in sheep is ingested by a dog and cycle continues

107

what is the clinical signs of Hydatid?

Cysts: 70% liver, 20% lungs
May remain asymptomatic for years
Secondary bacterial infection
Cyst rupture- hypersensitivity
Aliphatic shock
Can see death

108

how is Hydatid diagnosed?

imaging and serology?

109

how to control Hydatid?

Regularly worm dogs to reduce egg production
Hand hygiene
Safe disposal of animal carcasses/products of conception

110

what type of parasite causes malaria?

Micro-parasite (protozoa- sporozoan

111

what are the species that cause malaria?

P. falciparum
P. vivax
P. ovale
P. malariae

112

which specie caues the most severe type of malaria?

P. falciparum

113

how is malaria transmitted?

by Anopheles (mosquito) as a vector

114

What is the life cycle of malaria?

Organism infected mosquito takes a blood meal from a human injecting the organism This travels to liver cells where it replicates until the cell bursts and the organism then infects RBCs, it can continue in a cycle in which it replicates in RBCs causing them to burst and release further organisms to infect further RBCs. It can also form gametocytes in RBCs which are ingested by another aedes mosquito when it takes a blood meal to form a new organism

115

what is the clinical presentation of malaria?

Fever & Rigors (alt. days with falciparum malaria, every 48hrs or 72hrs with benign malaria)
Cerebral malaria (confusion, headache, coma)
Renal failure (black water fever)
Hypoglycaemia
Pulmonary oedema
Circulatory collapse
Anaemia, Bleeding and DIC

116

what does the malaria parasite affect?

rupture red cells, block capillaries and cause inflammatory reaction

117

how do you diagnose malaria?

Thick and Thin Microscopy --> at least 3 to rule it out
Serology- detection of antigen in blood
PCR- detection of malarial DNA

118

what are the controls for malaria?

Insecticide spraying in homes
Larvicidal spraying on breeding pools
Filling in of breeding pools
Larvivorous species introduced in to mosquito breeding areas
Use of insecticide impregnated bed nets
Chemoprophylaxis

119

what is Cryptosporidiosis caused by?

Caused by Cryptosporidium parvum and hominis (micro-parasite, sporozoan)

120

what does Cryptosporidiosis cause?

diarrhoeal disease

121

how is Cryptosporidiosis spread?

human to human transimission --> faecal-oral spread.

122

what animals act as reservoir of Cryptosporidiosis?

cattle, sheep, goats

123

what conditions promote Cryptosporidiosis?

warm and tropical places

124

what is the clinical presentation of Cryptosporidiosis?

Watery diarrhoea with mucus (no blood)
Bloating, cramps, fever, nausea, vomiting

125

how long does Cryptosporidiosis last for and when is it severe?

Usually self-limiting (last up to 2 weeks)
Can be severe in:
very young
very old
Immuno-compromised (60% HIV patients infected go on to chronic infection- can loose up to 25 litres fluid/day)

126

who are at risk of human to human spread of Cryptosporidiosis ?

Regular users of swimming pools (can be resistant to chlorine)
Child care workers and parents
Nursing Home residents/carers
Healthcare workers
Travellers

127

who are at risk of animal to human spread of Cryptosporidiosis ?

Backpackers, Campers, Hikers
Farm workers
Visitors to farms/petting zoos
Consumers of infected dairy products

128

what is the diagnosis of Cryptosporidiosis- ?

Faeces sample:
Acid fast staining

Antigen detection by EIA Enzyme Immunoassays

129

what are the treatments for Cryptosporidiosis?

Symptomatic:

Rehydration etc.
Nitazoxanide

For immunocompromised:

Paromomycin (to kill parasite)
Nitazoxanide (effectiveness is unclear)
Octreotide (reduce cramps and frequency)
HIV patients, HAART should be quickly initiated

130

how can Cryptosporidiosis be controlled?

Human-Human:

Hand hygiene
Filter or boil drinking water (cf. chlorination)
Isolate symptomatic patients in healthcare setting
Ensure symptomatic children are kept away from school

Animal-Human:

Pasteurise milk and dairy products
Boil or filter drinking water if camping

131

what are the two main types of fungi?

Filamentous fungi
Yeasts

132

what characterstic does Dimorphic fungi have?

can be a in a yeast form or the filmanetous form depending on the environment they are in

133

what does Pneumocystis jiroveci cause?

it causes pneumonia in immunesupressed patients

134

what are all the possible targets of antifungals?

cell wall
DNA synthesis
mitosis
cell membrane
protein synthesis

135

what is the cell membrane of a fungus made up of and why is this key to antifungal agents?

it is made up of Ergosterol --> human cell mebrane contain cholesterol. Therefore antifungal agents can target Ergosterol without damaging human cells

136

what is the cell wall of antifungals made up of?

ß-1,3 glucan

137

where is Ergosterol found and what does it regulate?

Forms clusters within the phospholipid bilayer of the cell membrane
Has a role in the regulation of membrane permeability

138

what is the importance of ergosterol?

Required for normal growth and function of the fungal cell wall, hence fungal viability

139

what is the route of the formation of ergosterol?

squalene --> lanosterol --> ergosterol

140

what are the two main enzymes involved in the formation of ergosterol? At what point do they act?

Squalene epoxidase --> involved in squalene converting to lanosterol
Lanosterol 14a demethylase --> involved in lanosterol converting to ergosterol

141

what is ß-1,3 glucan mae up of?

large polymer of UDP glucos

142

how much of the cell wall is made up of ß-1,3 glucan

50-60% of the dry weight of fungal cell wall is made up of ß-1,3 glucan

143

what synthesises ß-1,3 glucan?

ß-1,3 glucan synthase

144

what does ß-1,3 glucan form?

forms a fibrous network on the inner surface of the cell wall

145

what are the antifungal classes?

Polyenes
Allylamines
Azoles
Echinocandins

146

what is the mode of action of polyenes?

Association with ergosterol  in a physical way
Formation of pore-like molecular aggregates
Loss of membrane integrity and leakage of K+
Cell death --> don’t have a proper cell membrane integrity

147

give exampls of polyenes?

Amphotericin B
Nystatin

148

what is the problem of Nystatin ?

it is very toxic and can't be given by Iv --> only orally and small amounts

149

what is the spectrum of activity of Amphotericin B?

Most fungi of medical importance
Aspergillus spp., Candida spp., Cryptococcus spp.

150

what are the adverse affects of Amphotericin B?

allergic reaction and nephrotoxicity
It is not 100% selective to fungal cells can affect human cells --> if patient is ill then can also damage the kidneys

151

why is the Lipid-associated AmB?

it is less toxic to kidney cells

152

what are the different formations of AmB?

Liposomal AmB (L-AmB)
AmB lipid complex (ABLC)
AmB colloidal dispersion (ABCD)

153

how is AmB used clinically? How is it administrated?

Not absorbed orally so it is administered parenterally  IV
Used for Serious/systemic infections
e.g. aspergillosis, candidiasis, cryptococcosis
Not used, if possible, in patients with existing nephrotoxicity

154

what is Nystatin used for?

Superficial infections
e.g. oral/vaginal candidiasis
tropical administration

155

how does Allylamines work? Give a example of Allylamines.

Mode of action --> Inhibit ergosterol synthesis (Squalene epoxidase)
Examples
Terbinafine

156

what is the spectrum of terbinafine?

Broad spectrum of activity in vitro but in practice only one type of infection

157

what is the adverse affects of terbinafine?

Liver toxicity
Jaundice, hepatitis – rarely fatal

158

what is the clinical use of terbinafine?

Dermatophyte infections (superficial fungal infections)

159

what is the tropical use of terbinafine?

Athletes foot (tinea pedis), tinea corporis, tinea cruris

160

what is the systemic (oral) use of terbinafine?

Scalp ringworm (tinea capitis), onychomycosis

161

what is onychomycosis?

nail infection

162

what is 1)tinea corporis, 2)tinea cruris?

1)infection of the arms and legs
2)infection of the groin

163

what is the structure of azoles?

Synthetic compounds containing a 5-membered azole ring

164

what are the two types of azoles and state how many nigrtogen atoms they have

Imidazoles --> Two nitrogen atoms
Triazoles --> Three nitrogen atoms

165

which azoles type is the new one?

imidazoles --> is old one
Triazoles --> new one

166

how dos azoles work?

Inhibit ergosterol synthesis
Lanosterol 14α-demethylase -->inhibit this enzyme
Build up of non-ergosterol 14α-sterols in cell membrane --> don’t function properly and therefore fungus can’t become functioning fungal

167

what is the spectrum of azoles?

Complex, varies between drugs
Essentially broad spectrum
Yeasts and filamentous fungi

168

what azole is ineffective against Aspergillus?

Fluconazole

169

what type of drug is Ketoconazole and why was it stopped?

it is a imidazoles --> very toxic and causes hepatitis

170

give examples of imidazoles --> state the most common one?

Clotrimazole--> most common and used for vaginal thrush
Miconazole
Ketoconazole --> shampoo format

171

give examples of Triazoles--> state the most common one?

Fluconazole --> common
Itraconazole--> common
Voriconazole --> common
Posaconazole
Isavuconazole

172

what is the adverse effect of azoles?

Hepatotoxicity  liver problem
Mild liver enzyme abnormalities (e.g. 7% with fluconazole)
Life-threatening hepatitis (e.g. 1/10 000 patients with ketoconazole)

173

what drug interaction does azole have?

Inhibition of cytochrome P-450 enzymes
Increases concentration of all drugs metabolised by Cy P-450 enzymes

174

what is the antifungal spectrum for triazoles drugs?

Fluconazole --> only yeast
Itraconazole/ voriconazole --> yeast and Aspergillus spp.
Posaconazole/isavuconazole --> yeast, Aspergillus spp and Mucoraceous moulds

175

what is the clinical use of Imidazoles?

Superficial infections (topical administration)
Candidiasis --> vaginal thrush ( treatment -->Clotrimazole)
Dermatophyte infections

176

what is the clinical use of triazole?

Systemic infections (oral/parenteral administration)
Aspergillosis (used in treatment and occasionally as prophylaxis)
Candidiasis (fluconazole)

177

what is the mode of action of Echinocandins ?

Inhibition of β-1,3-glucan synthase
Construction of severely abnormal cell wall

178

give examples of Echinocandins ?

Anidulafungin --> most common
Caspofungin
Micafungin

179

what is the spectrum of actiity of Echinocandins?

Aspergillus and Candida spp.

180

what are the adverse affects of Echinocandins?

Minimal
e.g. skin rash, nausea, vomiting, headache, diarrhoea in common with any other drug

181

what is the clinical use of Echinocandins?

Parenteral formulations only --> only IV
only treat serious fungal infection --> so really only treat Aspergillus
and Candida spp

182

what is 5-fluorocytosine (5-FC)?

Synthetic analogue of cytosine (nucleotide) --> initially anti cancer drug but now used as a antifungal agent
Pyrimidine nucleoside

183

what is the mode of action of 5-fluorocytosine (5-FC)?

Entry into cell requires fungal cytosine permease--> selective toxicity
Converted to 5-fluorouracil and 5-fluorodeoxyuridine monophosphate --> Inhibit RNA/protein synthesis and DNA synthesis

184

spectrum of activity of 5-fluorocytosine (5-FC)?

yeast only --> Candida and Cryptococcus spp.

185

what is the adverse affect of 5-fluorocytosine (5-FC)?

Bone marrow suppression
Selective toxicity is incomplete ( gets to human a bit)
5-fluorouracil (5FU) is an anti-cancer drug

186

clinical use of 5-fluorocytosine 5-FC?

clinical use is exteremly limited -->
Cryptococcal meningitis (in combination with AmB)

187

what is the mode of action, spectrum of activity, adverse affect and clinical use of Griseofulvin?

Mode of action -->Inhibition of fungal mitosis
Spectrum of activity --> Dermatophytes
Adverse effects -->Minimal
Clinical use --> Dermatophyte infections in children requiring systemic treatment --> e.g. kerion, onychomycosis

188

what are the reasons for therapeutic drug monitoring

To minimize toxicity -->Level should remain below a threshold value
To maximize efficacy --> Level should exceed a threshold value

189

what are the antifungal agents that need therapeutic drug monitoring TDM?

Itraconazole
5-fluorocytosine
Voriconazole

190

why does Itraconazole, 5-fluorocytosine and Voriconazole needs TDM?

itraconazole --> if given to low of a dose then won't have a affect
5-fluorocytosine --> V. toxic if have a build up
Voriconazole --> liver toxicity but also a level of use beneath it which it is not effective