**<p style="text-align: center;">Odjel za biotehnologiju</p>** **<p style="text-align: center;">Sveučilište u Rijeci</p>**
*<small><p style="text-align: center;">Informatika BIL103</p></small>*
# **<p style="text-align: center;">Azitromicin</p>**
<small><p style="text-align: center;">Vanja Tomašević</p>
<p style="text-align: center;">Rijeka</p>
<p style="text-align: center;">30.6.2023.</p></small>
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---
## Povijest
* Prvi plivin [originalni](https://www.plivazdravlje.hr/aktualno/clanak/8920/Originalni-ili-genericki-lijek.html) lijek
* Patentiran 1981. godine
* FDA ga odobrava 10 godina kasnije
* Pliva ušla u partnerstvo sa Pfizerom
* U SAD-u i zapadnoj Europi poznat pod nazivom Zithromax, a u istočnoj Europi pod nazivom Sumamed
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## Priča o uspjehu
* Zithromax jedan od najprodavanijih antibiotika u SAD-u
* više od $2 milijarde prihoda u 2005. godini
* Pliva postaje jedna od najvećih farmaceutskih kompanija u Europi
* Plivini znanstvenici koji su otkrili azitromicin 2000. godine proglašeni su [„Herojima kemije 2000“](https://hrcak.srce.hr/file/30040)
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## Prodaja
* Azitromicin i dalje ostvaruje nevjerojatnu prodaju
* Zarada je 2022. godine iznosila $7 mlrd.
* Prognozira se >$10 mlrd. zarade za 2030. godinu
```mermaid
pie
title Antibiotici na recept (Indija 2020.)
"Azitromicin": 24
"Doksicilin": 10
"Faropenem": 1
"Hidroksiklorokin": 8
"Ostali": 57
```
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---
## Što je azitromicin?
* [Makrolidni antibiotik](https://www.hemed.hr/Default.aspx?sid=18177)
* Posjeduje dugi poluživot
* Dobro prodiranje u tkivo
* Visoka razina sigurnosti
<div align="left">
<img src="https://5.imimg.com/data5/SELLER/Default/2022/6/KS/GX/RW/125278182/azithromycin-tablet-500-mg-500x500.jpg" width="200" height="200">
<small>
*[Azitromicin tablete](https://www.indiamart.com/proddetail/azithromycin-250-mg-tablets-i-p-24679843162.html)*
</small>
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----
<style>
.reveal {
font-size: 35px;
}
</style>
## O azitromicinu
|Trgovačko ime|Klasa lijeka|Masa|Formula|
|-----|-----|-----|-----|
|Sumamed, Zithromax|Makrolidni antibiotik|748.996|C<sub>38</sub>H<sub>72</sub>N<sub>2</sub>O<sub>12</sub>|
|**Primjena**|**Poluživot**|**Legalni status**|**Struktura**|
|[Oralno, intravenozno](https://reference.medscape.com/drug/zithromax-zmax-azithromycin-342523)|11-14 sati|Rx^1^||
*<small>
1 --> lijek je dostupan samo na recept
</small>*
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----
## Primjena
* Tretiranje respiratornih bolesti
* Uspješan u liječenju genitalurinalnih infekcija
* Pogodan za korištenje kod djece teže od 45 kilograma
* Dolazi u obliku [tableta](https://mediately.co/hr/drugs/XClY0TrQiPKe5gk0qdpdHyAhJ6V/sumamed-125-mg-filmom-oblozene-tablete), [kapsula](https://mediately.co/hr/drugs/YmJ0VfrbQ4YmGUW52Ar4eJuCNk6/sumamed-250-mg-tvrde-kapsule), [prašaka za oralnu suspenziju](https://mediately.co/hr/drugs/66RcB0vL03hH6YyVogi8l0EfbA6/sumamed-100-mg-5-ml-prasak-za-oralnu-suspenziju)
<div align="left">
<img src="https://i.guim.co.uk/img/static/sys-images/Guardian/Pix/pictures/2014/11/10/1415649777215/Woman-taking-pills-and-wa-012.jpg?width=620&quality=85&auto=format&fit=max&s=59f101dfdbaf2bdd1d9e48a297e87ad5" width="280" height="250">
*<small>
[Postupak oralne primjene lijeka](https://www.massgeneral.org/children/how-to-swallow-a-pill/learning-how-to-swallow-a-pill-step-by-step)
</small>*
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---
## Sinteza azitromicina
```mermaid
graph TD;
A[Eritromicin A] -- H<sub>2</sub>NOH, pufer --> B[Eritromicin oksim];
B -- R-SO<sub>2</sub>Cl, baza --> C[Eritromicin-6,9-imino-eter];
C -- HCOOH, CH<sub>2</sub>O, H<sub>2</sub> kataliza --> D[Azitromicin];
D --> E[Filtracija];
E --> D;
D --> F[Kristalizacija];
F --> D;
D --> G[Kromatografija];
G --> D;
```
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----
## Kemijske reakcije
1. Eritromecin A u reakciji sa hidroksilaminom u puferskom okruženju:
$C_{37}H_{67}NO_{13} + NH_2OH \to C_{37}H_{68}N_2O_{13}$
2. Eritromicin oksim u reakciji sa sulfonil kloridima u lužnatom okruženju:
$C_{37}H_{68}N_2O_{13} + TsCl \to C_{37}H_{66}N_2O_{12} + TsOH$
3. Završni proces dorade eritromicin-6,9-imino-etera u azitromicin:
$C_{37}H_{66}N_2O_{12} + H_2 + RCOX^1 \to C_{38}H_{72}N_2O_{12}$
*<small>
1 --> [Acil halid](https://en.wikipedia.org/wiki/Acyl_halide), ovisi o postupku dobivanja azitromicina
</small>*
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----
## Eritromicin
* Makrolidni antibiotik
* Formula: $C_{37}H_{67}NO_{13}$
* Koristi se za tretiranje infekcija kože i gornjih dišnih puteva
* Baza za izradu azitromicina
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----
## Azitromicin 3D_1
* Prikaz 3D strukture azitromicina programom Avogadro
<div align="left">
<img src="https://hackmd.io/_uploads/r1ZKhC9un.png" width="600" height="550">
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----
## Azitromicin 3D_2
* Prikaz 3D strukture azitromicina (zelena boja) i MPH-E proteina (plava boja) Acinetobacter baumannii bakterije programom PyMOL
<div align="left">
<img src="https://hackmd.io/_uploads/HJHCnkoOh.png" width="420" height="450">
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---
## Nuspojave
* 1 u 100 ljudi:
* Mučnina
* Glavobolja
* Vrtoglavica
* Gubitak apetita
* 1 u 1000 ljudi:
* Aritmija (abnormalni otkucaji srca)
* Tinitus (zujanje u ušima)
* Upala gušterače
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## 112
* Hitnu pomoć potrebno je kontaktirati prilikom ovih nuspojava:
* Bol u prsima (mogući srčani udar)
* Stezanje u prsima i grlu
* Crvena, iritirajuća koža
* Oticanje jezika, lica i usana
* Poteškoće prilikom disanja ili pričanja
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---
## Hvala na pažnji! :smiley:
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---
## Izvori
1. [Mediately baza lijekova](https://mediately.co/hr)
2. [EMA](https://www.ema.europa.eu/en)
3. [NHS](https://www.nhs.uk/)
4. [FDA](https://www.fda.gov/)
5. [Total synthesis of azithromycin](https://pubmed.ncbi.nlm.nih.gov/19173267/)
6. [From Erythromycin to Azithromycin and New Potential Ribosome-Binding Antimicrobials](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039525/#B31-antibiotics-05-00029)
7. [Pliva](https://www.pliva.hr/)
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----
## Kemijske strukture (dokumenti)
* [Google colab-Azitromicin](https://colab.research.google.com/drive/152oW1xE-vEUF4dMWl0Tp6qijqcTA7dl4?usp=sharing)
* [Google colab-Eritromicin](https://colab.research.google.com/drive/1t_O_80vUKept97JHBaWhhpVgk48605Ps?usp=sharing)
* [Avogadro-Azitromicin](https://drive.google.com/file/d/17qJdJ2e35VIQmun_V-KTpQ_BQ4How6SL/view?usp=sharing)
* [PyMOL-Azitromicin](https://drive.google.com/file/d/17vHBd29Ew6jdcBuACzIglL8tg8pJItoN/view?usp=sharing)
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