Drugs 4 Respiratory Problems

7/29/2019 Drugs 4 Respiratory Problems

1/52

Suryawati, S.Si, MSc, Apt.


2/52

A. Obat Primer efektifitas tinggi dengantoksisitas yang dapat diterima

1. Isoniazid

2. Rifampisin

3. Etambutol4. Streptomisin

5. Pirazinamid

B. Obat sekunder kurang efektif1.

Paraaminosalisilat2. Sikloserin

3. Amikasin

4. Kapreomisin

5. kanamisin


3/52

Mekanisme kerja :

- Efek utamanya ialah menghambat biosintesis

asam mikolat (mycolic acid) yang merupakan

unsur penting dinding sel mikobakterium.


4/52

Perhatikan bagian gambar yang berwarna merah:

- Isoniazid menghambat biosintesis asam mikolat (mycolicacid) yang merupakan unsur penting dinding selmikobakterium ketahanan dinding sel terganggukematian sel


5/52

Administration : taken orally,

intramuscularly or intravenously.

Adults dosage :

5 mg/kg (46 mg/kg) daily, maximum 300 mgContraindications : Known hypersensitivity

and active, unstable hepatic disease (with

jaundice)

Use in pregnancy : not known to be harmfulin pregnancy. Pyridoxine supplementation is

recommended for all pregnant (or

breastfeeding) women taking isoniazid.


6/52

Adverse effects :

- hypersensitivity reactions,

- sleepiness or lethargy,

- peripheral neuropathy,

- neurological disturbance, including opticneuritis,

- toxic psychosis and generalized convulsions, -Symptomatic hepatitis,

- lupus-like syndrome,

- pellagra,

- anaemia,

- arthralgias


7/52

Drug interactions

Isoniazid inhibits themetabolism of certaindrugs increase theirplasma concentration to

the point of toxicity. administering both

rifampicin and isoniazidcauses a reduction inplasma levels ofphenytoin and

diazepam.

Isoniazid increase thetoxicity:

- carbamazepine,benzodiazepinesmetabolized by

oxidation (such astriazolam),

- acetaminophen,

- valproate,

- serotonergic

antidepressants,- disulfiram,

- warfarin and

-theophylline.


8/52

inhibits ribonucleic acidsynthesis in a broad rangeof microbial pathogens.

FK:

lipid-soluble. Oral :rapidlyabsorbed and distributedthroughout the cellulartissues and body fluids

A single dose of 600 mgproduces a peak serum

concentration of about 10g/ml in 24 hours, a half-life : 23 hours.

It is extensively recycledin the enterohepaticcirculation, andmetabolites formed bydeacetylation in the liverare eventually excreted in

the faeces. PK : administered in

combination with othereffectiveantimycobacterial agents(to prevent resistancy).


9/52

Administration and dosage

given at least 30 minutesbefore meals (abs.isreduced when it is takenwith food).

Adults: 10 mg/kg (812mg/kg)

Contraindications

Known hypersensitivity torifamycins.

Active, unstable hepaticdisease (with jaundice)


10/52

Precautions

Serious immunological reactions resulting in

- renal impairment,

- haemolysis or thrombocytopenia (rare, RF

immediately and permanently withdrawn). Clinical monitoring (and liver function tests, if

possible) should be performed during treatment of allpatients with pre-existing liver disease, who are atincreased risk of further liver damage.

Patients should be warned that treatment may causereddish coloration of all body secretions (urine,tears, saliva, sweat, semen and sputum), and thatcontact lenses and clothing may be irreversiblystained.


11/52

Use in pregnancy

Vitamin K should be administered at birth to

the infant of a mother taking rifampicin

because of the risk of postnatalhaemorrhage.


12/52

Adverse effects Gastrointestinal reactions (abdominal pain,

nausea, vomiting) and pruritus with or withoutrash .

fever, influenza-like syndrome andthrombocytopenia

Exfoliative dermatitis is more frequent in HIV-positive TB patients.

Temporary oliguria, dyspnoea and haemolyticanaemia

Moderate rises in serum concentrations ofbilirubin and transaminases,


13/52

Drug interactions Rifampicin induces hepatic enzymes, and may

increase the dosage requirements of drugsmetabolized in the liver, including:

anti-infectives (including certain antiretroviraldrugs discussed below and in section 5.6.1,mefloquine, azole antifungal agents, clarithromycin,erythromycin, doxycycline, atovaquone,chloramphenicol);

hormone therapy, including ethinylestradiol,

norethindrone, tamoxifen, levothyroxine; methadone;

warfarin;

cyclosporine;


14/52

corticosteroids;

anticonvulsants (including phenytoin);

cardiovascular agents including digoxin (inpatients with renal insufficiency), digitoxin,

verapamil, nifedipine, diltiazem, propranolol,metoprorol, enalapril, losartan, quinidine,mexiletine, tocainide, propafenone;

theophylline;

sulfonylurea hypoglycaemics;

hypolipidaemics including simvastatin andfluvastatin;

nortriptyline, haloperidol, quetiapine,benzodiazepines (including diazepam,triazolam), zolpidem, buspirone.


15/52

RF reduces the effectiveness of oralcontraceptives- use an contraceptive pill containing a

higher dose of estrogen (50 g);

- apply nonhormonal method ofcontraception throughout rifampicintreatment

microbiological assays for folic acid and vitaminB12 disturbed.

Current antiretroviral drugs (non-nucleosidereverse transcriptase inhibitors and proteaseinhibitors) interact with rifampicin .This mayresult in ineffectiveness of antiretroviral drugs,ineffective treatment of TB or an increased riskof drug toxicity.


16/52

analogue of nicotinamide bactericidal againstM. tuberculosis,

It is highly effective during the first 2 months oftreatment while acute inflammatory changes

persist.FK

readily absorbed from the gastrointestinal tractand is rapidly distributed throughout all tissuesand fluids.

Peak plasma concentrations: attained in 2 hours

T : about 10 hours.

Metabolized in the liver and excreted in theurine.


17/52


Pyrazinamide is administered orally.

Adults (usually for the first 2 or 3 months of

TB treatment):25 mg/kg (2030 mg/kg) daily

Contraindications

Known hypersensitivity.

Active, unstable hepatic disease (with

jaundice)


18/52

Precautions

Patients with diabetes should be carefullymonitored since blood glucoseconcentrations may become labile.

Gout may be exacerbated. Clinicalmonitoring (and liver function tests, ifpossible) should be performed duringtreatment of patients with pre-existing liver

disease. In patients with renal failure, pyrazinamide

should be administered three times perweek, rather than daily


19/52

Use in pregnancy

The 6-month regimen based upon isoniazid,

rifampicin and pyrazinamide should be used

whenever possible. Although detailedteratogenicity data are not available,

pyrazinamide can probably be used safely

during pregnancy.


20/52

Adverse effects

gastrointestinal intolerance.

Hypersensitivity reactions

Moderate rises in serum transaminase Severe hepatotoxicity is rare.

Hyperuricaemia

Gout Arthralgia

anaemia

photosensitive dermatitis.


21/52

derived from Streptomyces griseus

Used for TB and treatment of sensitive

Gram-negative infections.

FK

not absorbed from the GI tract given

intramuscularly

T : 23 hours,

excreted unchanged in the urine.


22/52


administered by deep intramuscular injection andintravenous administration.

Dose : 15 mg/kg (1218 mg/kg) daily, maximum dailydose is 1000 mg.

Patients aged over 60 years may not be able totolerate more than 500750 mg daily reduce thedose to 10 mg/kg per day for patients in this agegroup.

Patients weighing less than 50 kg may not toleratedoses above 500750 mg daily.1

Contraindications

Known hypersensitivity. Auditory nerve impairment.

Myasthenia gravis.

Pregnancy.


23/52

Precautions

Hypersensitivity (rare, during the first weeksof treatment),

nephrotoxicity and ototoxicity. The doseshould be maintained at 12

15 mg/kg but at

a reduced frequency of 23 times per week serum levels should be monitoredperiodically

Use in pregnancy not be used in pregnancy (cause auditory

nerve impairment and nephrotoxicity in thefetus).


24/52

Adverse effects

Rash at injection sites.

Numbness and tingling around the mouth

Cutaneous hypersensitivity

Impairment of vestibular function (uncommon) damage to the 8th cranial (auditory) nerve

include ringing in the ears, ataxia, vertigo anddeafness ( in the first 2 months of treatment andis reversible if the dosage is reduced or the drug

is stopped ). Nephrotoxic

Haemolytic anaemia, aplastic anaemia,agranulocytosis, thrombocytopenia and lupoidreactions(rare).


25/52

Drug interactions

Other ototoxic or nephrotoxic drugs should

not be administered to patients receiving

streptomycin. These include otheraminoglycoside antibiotics, amphotericin B,

cefalosporins, etacrynic acid, cyclosporin,

cisplatin, furosemide and vancomycin.

Streptomycin may potentiate the effect ofneuromuscular blocking agents administered

during anaesthesia.


26/52

active against M. tuberculosis, M. bovis and

some nonspecific mycobacteria.

FK

absorbed from GI tract

Plasma concentrations peak in 24 hours andt1/2: 34 hours.

excreted in the urine both unchanged and as

inactive hepatic metabolites. About 20% is

excreted unchanged in the faeces.


27/52


administered orally.

Adults doses:

15 mg/kg (1520 mg/kg) daily

Dosage must always be carefully calculated on aweight basis to avoid toxicity, and the dose or thedosing interval should be adjusted in patients withimpaired renal function (creatinine clearance


28/52

Precautions

discontinue treatment when sight or

perception of colour deteriorates.

Plasma ethambutol concentration should bemonitored if creatinine clearance is less

than 30 ml/min.

Use in pregnancy

Ethambutol is not known to be harmful inpregnancy.


29/52

Adverse effects

Dose-dependent optic neuritis impairment

of visual acuity and colour vision

Signs of peripheral neuritis in the legs.Other rare adverse events include

generalized cutaneous reaction, arthralgia

and, very rarely, hepatitis.


30/52

co-trimoxazole preventive given throughout

TB treatment.

co-trimoxazole is known to prevent

Pneumocystis jirovecii and malaria and havean impact on a range of bacterial infections

in HIV-positive TB patients.


31/52

Antiretroviral therapy improves survival in HIV-positive patients

TB treatment should be started first, followedby ART within the first 8 weeks of starting TBtreatment

WHO recommends: the first-line ART regimencontain two nucleoside reverse transcriptaseinhibitors (NRTIs) plus one non-nucleosidereverse transcriptase inhibitor (NNRTI) .

The preferred NRTI: zidovudine (AZT) ortenofovir disoproxil fumarate (TDF), combinedwith either lamivudine (3TC) or emtricitabine(FTC).

For the NNRTI: either efavirenz (EFV) ornevirapine (NVP)


32/52

For those who are unable to tolerate EFV or

who have contraindications to an EFV-based

regimen, may use:

- AZT +3TC + NVP or- TDF +3TC or FTC + NVP or

- a triple NRTI regimen (AZT+3TC+ABC or

AZT+3TC+TDF)

(see: http://www.who.int/hiv/pubguidelines/en)


33/52


34/52

1. Bronkodilator (Adrenergik dan

antikolinergik, derivat xantin)

2. Kortikosteroid

3. Mukolitik dan ekspektoransia4. Antihistamin

5. Zat antileukotrien

6. Antialergi :kromoglikat, nedocromil,

ketotifen, oksatomida


35/52

Nama Obat : salbutamol, terbutalin,

tetroquinol, fenoterol, rimiterol, prokaterol,

klenbuterol, salmeterol dan formeterol.

Mek kerja: stimulasi reseptor 2 di trakea(batang tenggorok) dan bronchi aktivasi

adenil siklase pe (+) cAMP

bronkodilatasi & pe pelepasan histamin

Penggunaan: melawan serangan ataupemeliharaan dengan kombinasi bersama

kortikosteroid dan kromoglikat


36/52

Short acting agents

- Durasi aksi :4-6 jam

- Obat dengan selektifitas beta-2 lebih besar :

albuterol, levalbuterol, bitolterol, pirbuteroldan terbutalin

- Obat dengan selektifitas beta-2 lebih kecil :

isoproterenol, metaproterenol dan isoetarin

Long acting agents

- Durasi aksi :12 jam

- Contoh obat: Formoterol


37/52

Nama Obat Dosis Catatan

Salbutamol 3-4 dd 2-4 mg (sulfat),inhalasi 3-4 dd 2 semprotan

dari 100 mcg

Akut: 2 puff, diulang stlh 15

menit

Serangan hebat: im/sc 250-

500 mcg diulang ssdh 4 jam

-ES : jarang- aman utk

kehamilan & laktasi

Terbutalin 2-3 dd2,5 mg (sulfat), inhalasi

3-4 dd 1-2 semprotan dr 250

mcg, maks 16 puff sehari, sc

250 mcg, maks 4x sehari

- aman utk

kehamilan & laktasi

- &2 selektif

Fenoterol 3 dd 2,5-5 mg (bromida), supp15 mg, inh 3-4 dd 1-2

semprotan dr 200mcg

Tretoquinol 2-4 dd 3 mg(klorida), sc. 0,1-

0,2 mg, iv 50-100 mcg

Prokaterol Oral 2 dd 50 mcg

Rimiterol Inh. Maks 4 dd 2 semprotan dr


38/52

Bekerja dengan memblok asetilkolin pe (-)

cGMP bronkodilatasi (efek tidak sekuat

beta agonis dan teofilin)

FK : tidak diserap

tidak ada efek sistemik.Kadar maks: 1-2 jam dan bertahan 3-5 jam.

Onset (15-20 menit)

Sediaan: 20 g/semprotan

Dosis : 2 inhalasi/3-4 jam (maks. 12inhalasi/24 jam)


39/52

Keuntungan : dosis rendah dengan efek

samping kecil

Dilakukan pada saat perkembangan penyakit

dan gejala memburukContoh : kombinasi albuterol dan ipratropium


40/52

MK : inhibisi fosfodiesterase pe (+) kadar

cAMP inhibisi pelepasan mediator dari sel

mast dan leukosit bronkodilatasi

PK : terapi pemeliharaan PPOK ES : dispepsia, mual, muntah, diare, sakit

kepala, pusing, takikardia

Dosis : 2 x sehari 200 mg, ditingkatkan

bertahap setiap 3 hingga 5 hari Sediaan : microfine retard (sediaan lepas

lambat) memelihara kadar obat lebih

konsisten


41/52

MK : mengikat reseptor steroid di sitoplasma

mempengaruhi sintesa protein di dalam

inti sel efek

Efek : mencegah atau menekan timbulnyagejala inflamasi (menghambat udem, deposit

fibrin, dilatasi kapiler, dsb)

FK : abs oral baik

ES : gangguan cairan dan elektrolit,hiperglikemia, daya tahan tubuh rendah,

osteoporosis, dll

Sediaan : oral, aerosol


42/52

PK : terapi paliatif pada asma dan copd

bersama bronkodilator

Digunakan pada pasien pada penyakit tingkat

III atau IV (FEV1 kurang dari 50%)


43/52

Penggunaannya pada bronkhitis dilakukan jika 2

dari 3 gejala berikut tampak: pe (+) dispnea, pe

(+) volume sputum dan kandungan nanah sputum

Pemilihan AB: didasarkan pada organisme yg

paling sering yaitu : Haemophilus influenza,Moraxella catarrhalis, Streptococcus pneumonia

dan Haemophilus parainfluenza

Rekomendasi AB : makrolida (azitromisin dan

klaritromisin), sefalosporin gen-2 (sefaklor) atau3 (sefotaksim)atau doksisiklin, fluorokinolon

(levofloksasin, gatifloksasin, moksifloksasin)


44/52


45/52

Lihat kuliah farmakologi blok 5 : alergi,

imunologi dan infeksi


46/52

MK : menghambat pelepasan histamin alergi

FK : abs di sal. Cerna, eks lewat urin & tinja(utuh & metabolit)

ES : Sedasi, Vertigo, tinitus, penglihatankabur, mual atau muntah, Mulut kering,Demam, Aritmia jantung, me (+) nafsu makandan berat badan, me (-) jml trombosit (bila

(+) antidiabetik oral) PK : profilaksis asma bronkial

Sediaan : tab 1 mg, sirup 0,2 mg/ml

Dosis : 2 x 1,38-2,76 mg (dewasa)


47/52

Mek. Kerja: bekerja terhadap mast cell menghambat pelepasan mediator inflamasi spt:histamin, serotonin dan leukotrien

PK : mencegah serangan asma dan bronkitis

alergi FK : 5-10% mencapai bronki, t1/2 =1,5-2 jam,

durasi: 6 jam

ES: rangsangan lokal pd selaput lendir tenggorokdan trakea (batuk, kejang bronki)

Kehamilan : aman

Dosis: inhalasi 4 dd 1 puff (20 mg), nasal 4 dd10 mg serbuk, mata: 4-6 dd 1-2 tetes dr larutan2%


48/52


49/52

Merupakan alkaloid opium yang menghambat

refleks batuk

MK : bekerja pada reseptor opioid (, k, ) di

SSP

efek FD : analgesia, mual, muntah, depresi nafas,

dilatasi pupil mata, menghambat sekresi HCl,

memperlambat pencernaan makanan di usus

halus, dilatasi pembuluh darah kulit, pe (-)suhu badan.

PK : batuk dan sesak


50/52

Tidak berefek anagetik dan adiktif

Sediaan: tablet 10 mg dan sirup 15 mg/5 ml

Dosis dewasa: 10-30 mg diberikan 3-4 kali

sehari


51/52

Obat lokal yang dapat mengencerkan sekret

saluran nafas dengan jalan memecah benang-

benang mukoprotein dan mukopolisakarida

dari sputum

ES : mual dan pe(+) transaminase serum

Dosis oral dewasa : 3x 4-8 mg/hari

Mukolitik lain : Ambroksol dan asetil sistein


52/52

Obat lokal yang dapat merangsang

pengeluaran dahak (perangsangan N.vagus)

Dosis dewasa Amm. Klorida : 300 mg/5 ml

tiap 2-4 jam

Dosis dewasa GG : 2-4 kali 200-400 mg sehari

Drugs 4 Respiratory Problems

Documents

Transcript of Drugs 4 Respiratory Problems