natgillin/translations-raw huggingface dataset:
The frequency of adverse events listed below is defined using the following convention: very common (≥ 1/ 10); common (≥ 1/ 100, < 1/ 10); uncommon (≥ 1/ 1,000, < 1/ 100); rare (≥ 1/ 10,000, < 1/ 1,000); very rare (< 1/ 10,000), not known (cannot be estimated from the available data).
Pogostnost spodaj naštetih neželenih učinkov je označena v skladu z naslednjim dogovorom: zelo pogosti (≥ 1/ 10), pogosti (≥ 1/ 100, < 1/ 10), občasni (≥ 1/ 1. 000, < 1/ 100), redki (≥ 1/ 10. 000, < 1/ 1. 000), zelo redki (< 1/ 10. 000), pogostnost neznana (iz razpoložljivih podatkov se je ne da določiti).
Hypertension In controlled clinical trials for essential hypertension with losartan the following adverse events were reported
Hipertenzija V kontroliranih kliničnih preizkušanjih esencialne hipertenzije z uporabo losartana so poročali o naslednjih neželenih učinkih:
Uncommon: palpitations, angina pectoris
Srčne bolezni občasne: palpitacije, angina pektoris
Uncommon: symptomatic hypotension (especially in patients with intravascular volume depletion, e. g. patients with severe heart failure or under treatment with high dose diuretics), dose-related orthostatic effects, rash.
Žilne bolezni občasne: simptomatska hipotenzija (posebej pri bolnikih z zmanjšanim intravaskularnim volumnom, npr. bolnikih s hudim srčnim popuščanjem ali bolnikih, ki se zdravilo z velikimi odmerki diuretikov), od odmerka odvisni ortostatski učinki, izpuščaj
Uncommon: abdominal pain, obstipation 30 General disorders and administration site conditions:
Bolezni prebavil občasne: bolečna v trebuhu, zaprtje
Uncommon: asthenia, fatigue, oedema
Splošne težave in spremembe na mestu aplikacije občasne: astenija, utrujenost, edem
Hypertensive patients with left ventricular hypertrophy In a controlled clinical trial in hypertensive patients with left ventricular hypertrophy the following adverse events were reported:
26 Hipertenzivni bolniki s hipertrofijo levega prekata V kontroliranem kliničnem preizkušanju pri hipertenzivnih bolnikih s hipertrofijo levega prekata so poročali o naslednjih neželenih učinkih:
General disorders and administration site conditions: common: asthenia/ fatigue
Splošne težave in spremembe na mestu aplikacije pogoste: astenija/ utrujenost
Cardiac disorders: rare: syncope, artrial fibrillation, cerebrovascular accident
Srčne bolezni redke: sinkopa, atrijska fibrilacija, možganskožilni dogodek
Vascular disorders: uncommon: hypotension, including orthostatic hypotension
Žilne bolezni občasne: hipotenzija, vključno z ortostatsko hipotenzijo
Skin and subcutanous tissue disorders: uncommon: urticaria, pruritus, rash
Bolezni kože in podkožja občasne: urtikarija, srbenje, izpuščaj
General disorders and administration site conditions: uncommon: asthenia/ fatigue
Splošne težave in spremembe na mestu aplikacije občasne: astenija/ utrujenost
Hypertension and type 2 diabetes with renal disease
Hipertenzija in sladkorna bolezen tipa 2 z boleznijo ledvic
In a controlled clinical trial in type 2 diabetic patients with proteinuria (RENAAL study, see section 5.1) the most common drug-related adverse events which were reported for losartan are as follows:
V kontroliranem kliničnem preizkušanju pri bolnikih s sladkorno boleznijo tipa 2 s proteinurijo (študija RENAAL, glejte poglavje 5. 1) so najpogostejši z zdravilom povezani neželeni učinki, o katerih so poročali za losartan, sledeči:
General disorders and administration site conditions: common: asthenia/ fatigue 31 Investigations: common: hypoglycaemia, hyperkalaemia
Splošne težave in spremembe na mestu aplikacije pogoste: astenija/ utrujenost
The following adverse events occurred more often in patients receiving losartan than placebo:
27 Naslednji neželeni učinki so se pogosteje pojavili pri bolnikih, ki so prejemali losartan, kot pri bolnikih, ki so prejemali placebo:
Blood and lymphatic system disorders: not known: anaemia
Bolezni krvi in limfatičnega sistema pogostnost ni znana: anemija
Muscoskeletal and connective tissue disorders: not known: back pain
Bolezni mišično- skeletnega sistema in vezivnega tkiva pogostnost ni znana: bolečine v hrbtu
The following adverse events have been reported in post-marketing experience:
O naslednjih neželenih učinkih so poročali v okviru izkušenj z zdravilom v obdobju trženja:
Anaemia, thrombocytopenia
Bolezni krvi in limfatičnega sistema pogostnost ni znana: anemija, trombocitopenija
Immune system disorders: rare: hypersensitivity: anaphylactic reactions, angiooedema including swelling of the larynx and glottis causing airway obstruction and/ or swelling of the face, lips, pharynx, and/ or tongue; in some of these patients angiooedema had been reported in the past in connection with the administration of other medicines, including ACE inhibitors; vasculitis, including Henoch-Schonlein purpura.
Bolezni imunskega sistema redke: preobčutljivost: anafilaktične reakcije, angioedem vključno z otekanjem grla in glotisa, zaradi česar se zožijo dihalne poti in/ ali otekanjem obraza, ustnic, žrela in/ ali jezika – pri nekaterih od teh bolnikov so v preteklosti poročali o angioedemu v povezavi z jemanjem drugih zdravil, vključno z zaviralci ACE; vaskulitis vključno s Henoch- Schoenleinovo purpuro
Nervous system disorders: not known: migraine
Bolezni živčevja pogostnost ni znana: migrena
Skin and subcutaneous tissue disorders: not known: urticaria, pruritus, rash
Bolezni kože in podkožja pogostnost ni znana: urtikarija, srbenje, izpuščaj
32 not known: myalgia, arthralgia
Bolezni mišično- skeletnega sistema in vezivnega tkiva pogostnost ni znana: mialgija, artralgija
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function including renal failure have been reported in patients at risk; these changes in renal function may be reversible upon discontinuation of therapy (see section 4.4)
Te spremembe ledvične funkcije so po prekinitvi zdravljenja lahko reverzibilne (glejte poglavje 4. 4).
In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Losartan tablets.
Preiskave V kontroliranih kliničnih preizkušanjih so bile klinično pomembne spremembe standardnih laboratorijskih parametrov redko povezane z jemanjem tablet z losartanom.
Hyperkalaemia (serum potassium > 5.5 mmol/ l) occurred in 1.5% of patients in hypertension clinical trials.
Hiperkaliemija (kalij v serumu > 5, 5 mol/ l) se je v kliničnih preizkušanjih hipertenzije pojavila pri 1, 5% bolnikov.
In a clinical study conducted in type 2 diabetic patients with nephropathy, 9.9% of patients treated with Losartan tablets developed hyperkalaemia > 5.5 mEq/ l and 3.4% of patients treated with placebo (see section 4.4, ‘ Electrolyte imbalances’).
V klinični študiji, izvedeni pri bolnikih s sladkorno boleznijo tipa 2 in z nefropatijo, se je hiperkaliemija > 5, 5 mEq/ l razvila pri 9, 9% bolnikov, ki so prejemali tablete z losartanom, in pri 3, 4% bolnikov, ki so prejemali placebo (glejte poglavje 4. 4, "Elektrolitsko neravnovesje").
Symptoms of intoxication No experience with overdose in man is available so far.
Simptomi zastrupitve Izkušenj s prevelikim odmerjanjem pri ljudeh do sedaj ni na voljo.
Treatment of intoxication Measures are depending on the time of drug intake and kind and severity of symptoms.
Zdravljenje zastrupitve Ukrepi so odvisni od časa zaužitja ter vrste in jakosti simptomov.
Angiotensin II Receptor Antagonists, ATC code:
Farmakoterapevtska skupina: antagonisti angiotenzina II, oznaka ATC:
Angiotensin II, a potent vasoconstrictor, is the primary active hormone of the renin/ angiotensin system and an important determinant of the pathophysiology of hypertension.
Angiotenzin II, močan vazokonstriktor, je primarni aktivni hormon sistema renin/ angiotenzin in pomemben faktor v patofiziologiji hipertenzije.
Angiotensin II binds to the AT1 receptor found in many tissues (e. g. vascular smooth muscle, adrenal gland, kidneys and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone.
Angiotenzin II se veže na AT1 receptorje, ki se nahajajo v mnogih tkivih (npr. gladkih mišicah žil, nadledvični žlezi, ledvicah in srcu), in sproži več pomembnih bioloških učinkov, vključno z vazokonstrikcijo in s sproščanjem aldosterona.
Consequently, there is no potentiation of undesirable bradykinin- mediated effects.
Posledično ne potencira z bradikininom povezanih neželenih učinkov.
33 During administration of Losartan, removal of the angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA).
29 Med dajanjem losartana odsotnost negativne povratne zveze angiotenzina II na izločanje renina povzroči povečano aktivnost renina v plazmi.
The active metabolite is 10- to 40- times more active than Losartan on a weight for weight basis.
Aktivni presnovek je 10 - do 40- krat bolj aktiven kot losartan (v isti količini).
LIFE-Study The Losartan Intervention For Endpoint Reduction in Hypertension [LIFE] study was a randomised, triple-blind, active-controlled study in 9193 hypertensive patients aged 55 to 80 years with ECG- documented left-ventricular hypertrophy.
Študija LIFE Študija LIFE (Losartan Intervention For Endpoint Reduction in Hypertension; Zdravljenje z losartanom za zmanjšanje končnih opazovanih dogodkov pri bolnikih s hipertenzijo) je bila randomizirana, trojno slepa študija s primerjalnim zdravilom.
If goal blood pressure (< 140/ 90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of Losartan or atenolol was then increased to 100 mg once daily.
Če ciljnega krvnega tlaka (< 140/ 90 mmHg) niso dosegli, so najprej dodali hidroklorotiazid (12, 5 mg), potem pa so, če je bilo potrebno, povečali odmerek losartana ali atenolola na 100 mg enkrat na dan.
Other antihypertensives, with the exception of ACE-inhibitors, angiotensin II antagonists or beta-blockers were added if necessary to reach the goal blood pressure.
Za doseg ciljnega krvnega tlaka so, če je bilo potrebno, dodali še druge antihipertenzive, razen zairalcev ACE, antagonistov angiotenzina II ali beta zaviralcev.
The primary endpoint was the composite of cardiovascular morbidity and mortality as measured by a reduction in the combined incidence of cardiovascular death, stroke and myocardial infarction.
Primarni opazovani dogodek sta predstavljali srčno- žilna obolevnost in smrtnost, merjeni z zmanjšanjem kombinirane pojavnosti smrti zaradi srčno- žilnih zapletov, možganske kapi in miokardnega infarkta.
Race In the LIFE-Study black patients treated with Losartan had a higher risk of suffering the primary combined endpoint, i. e. a cardiovascular event (e. g. cardiac infarction, cardiovascular death) and especially stroke, than the black patients treated with atenolol.
Rasa V študiji LIFE so imeli bolniki črne rase, zdravljeni z losartanom, večje tveganje za primarni sestavljeni opazovani dogodek, t. j. srčno- žilni dogodek (npr. srčni infarkt, smrt zaradi srčno- žilnega vzroka) in možganska kap, kot pa bolniki črne rase, zdravljeni z atenololom.
Therefore the results observed with losartan in comparison with atenolol in the LIFE study with regard to cardiovascular morbidity/ mortality do not apply for black patients with hypertension and left ventricular hypertrophy.
Zato rezultati glede srčno- žilne obolevnosti/ smrtnosti iz študije LIFE za losartan v primerjavi z atenololom ne veljajo za bolnike črne rase s hipertenzijo in hipertrofijo levega prekata.
34 RENAAL-Study The Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan RENAAL study was a controlled clinical study conducted worldwide in 1513 Type 2 diabetic patients with proteinuria, with or without hypertension.
30 Študija RENAAL Študija RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan; Zmanjšanje števila opazovanih dogodkov z antagonistom angiotenzina II losartanom pri od insulina neodvisni sladkorni bolezni) je bila kontrolirana klinična študija.
751 Patients were treated with Losartan The objective of the study was to demonstrate a nephroprotective effect of Losartan potassium over and above the benefit of a blood lowering pressure.
751 bolnikov se je zdravilo z losartanom.
Patients with proteinuria and a serum creatinine of 1.3 – 3.0 mg/ dl were randomised to receive Losartan 50 mg once a day, titrated if necessary, to achieve blood pressure response, or to placebo, on a background of conventional antihypertensive therapy excluding ACE-inhibitors and angiotension II antagonists.
Bolnike s proteinurijo in vrednostjo kreatinina v serumu1, 3– 3, 0 mg/ dl so randomizirali tako, da so dobivali losartan 50 mg enkrat na dan (po potrebi so odmerek titrirali, da so dosegli odziv krvnega tlaka) ali placebo; poleg tega so bolniki iz obeh skupin dobivali običajna antihipertenzivna zdravila razen zaviralcev ACE in antagonistov angiotenzina II.
Investigators were instructed to titrate the study medication to 100 mg daily as appropriate; 72% of patients were taking the 100 mg daily dose for the majority of the time.
Na podlagi tega je 72% bolnikov večino časa dobivalo odmerek 100 mg enkrat na dan.
Other antihypertensive agents (diuretics, calcium antagonists, alpha- and beta-receptor blockers and also centrally acting antihypertensives) were permitted as supplementary treatment depending on the requirement in both groups.
Bolniki iz obeh skupin so po potrebi lahko dobivali druga antihipertenzivna zdravila (diuretike, zaviralce kalcijevih kanalčkov, zaviralce alfa in beta receptorjev ter antihipertenzive z delovanjem na centralni živčni sistem).
Patients were followed up for up to 4.6 years (3.4 years on average).
Bolnike so spremljali do 4, 6 let (povprečno 3, 4 leta).
The primary endpoint of the study was a composite endpoint of doubling of the serum creatinine end- stage renal failure (need for dialysis or transplantation) or death.
Primarni opazovani dogodek v študiji je bil sestavljeni opazovani dogodek podvojitve kreatinina v serumu, končne ledvične odpovedi (potreba po dializi ali presaditvi) ali smrt.
The results showed that the treatment with Losartan (327 events) as compared with placebo (359 events) resulted in a 16.1% risk reduction (p = 0.022) in the number of patients reaching the primary composite endpoint.
Rezultati so pokazali, da je bilo pri zdravljenju z losartanom (327 dogodkov) v primerjavi s placebom (359 dogodkov) tveganje za primarni sestavljeni opazovani dogodek (v številu bolnikov, ki so doživeli primarni sestavljeni opazovani dogodek) manjše za 16, 1% (p = 0, 022).
For the following individual and combined components of the primary endpoint, the results showed a significant risk reduction in the group treated with Losartan:
V skupini, ki se je zdravila z losartanom, se je pomembno zmanjšalo tveganje za naslednje posamezne komponente primarnega opazovanega dogodka in njihove kombinacije:
25.3% risk reduction for doubling of the serum creatinine (p = 0.006); 28.6% risk reduction for end-stage renal failure (p = 0.002); 19.9% risk reduction for end-stage renal failure or death (p = 0.009); 21.0% risk reduction for doubling of serum creatinine or end-stage renal failure (p = 0.01).
25, 3% zmanjšanje tveganja za podvojitev kreatinina v serumu (p = 0, 006); 28, 6% zmanjšanje tveganja za končno ledvično odpoved (p = 0, 002), 19, 9% zmanjšanje tveganja za končno ledvično odpoved ali smrt (p = 0, 009), 21, 0% zmanjšanje tveganja za podvojitev kreatinina v serumu ali končno ledvično odpoved (p = 0, 010).
ELITE I and ELITE II Study In the ELITE Study carried out over 48 weeks in 722 patients with heart failure (NYHA Class II-IV), no difference was observed between the patients treated with Losartan and those treated with captopril was observed with regard to the primary endpoint of a long-term change in renal function.
Študiji ELITE I in ELITE II V študiji ELITE, ki je trajala 48 tednov in je vključevala 722 bolnikov s srčnim popuščanjem (NYHA razred II- IV), niso opazili nobenih razlik v dolgoročni spremembi ledvične funkcije kot primarnem opazovanem dogodku med bolniki, ki so prejemali losartan, in bolniki, ki so prejemali kaptopril.
In the ELITE II Study Losartan 50 mg once daily (starting dose 12.5 mg, increased to 25 mg, then 50 mg once daily) was compared with captopril 50 mg three times daily (starting dose 12.5 m, increased to 25 mg and then to 50 mg three times daily).
V študiji ELITE II so losartan 50 mg enkrat na dan (začetni odmerek 12, 5 mg, povečan na 25 mg, nato 50 mg enkrat na dan) primerjali s kaptoprilom 50 mg trikrat na dan (začetni odmerek 12, 5 mg, povečan na 25 mg in nato 50 mg trikrat na dan).
1.5 years) in order to determine whether Losartan is superior to captopril in reducing all cause mortality.
V tej študiji so 3. 152 bolnikov s srčnim popuščanjem (NYHA razred II- IV) spremljali skoraj dve leti (povprečno 1, 5 let) z namenom ugotoviti, ali je losartan v primerjavi s kaptoprilom boljši za zniževanje celokupne smrtnosti.
An increased mortality was observed in ELITE II in the small subgroup (22% of all HF patients) taking beta-blockers at baseline.
Povečano smrtnost so opazili v majhni podskupini bolnikov iz študije ELITE II (22% vseh bolnikov s srčnim popuščanjem), ki so na začetku jemali beta zaviralce.
35 The antihypertensive effect of Cozaar was established in a clinical study involving 177 hypertensive pediatric patients 6 to 16 years of age with a body weight > 20 kg and a glomerular filration rate > 30 ml/ min/ 1.73 m2.
31 Pediatrična hipertenzija Antihipertenzivni učinek zdravila Cozaar so dokazali v klinični študiji, ki je zajela 177 hipertenzivnih pediatričnih bolnikov, starih 6 do 16 let, s telesno maso > 20 kg in hitrostjo glomerulne filtracije > 30 ml/ min/ 1, 73 m2.
Patients who weighted > 20kg to< 50 kg received either 2.5, 25 or 50 mg of losartan daily and patients who weighted > 50 kg received either 5, 50 or 100 mg of losartan daily.
Bolniki, ki so tehtali > 20 kg do < 50 kg, so prejemali bodisi 2, 5, 25 ali 50 mg losartana na dan, bolniki, ki so tehtali > 50 kg, pa so prejemali bodisi 5, 50 ali 100 mg losartana na dan.
At the end of three weeks, losartan administration once daily lowered trough blood pressure in a dose-dependent manner.
Po treh tednih se je pri uporabi enkrat dnevno losartana krvni tlak v času, ko je učinek zdravila najnižji, zmanjšal v skladu z odmerkom.
The dose-response relationship became very obvious in the low dose group compared to the middle dose group (period I: -6.2 mmHg vs. -11.65 mmHg), but was attenuated when comparing the middle dose group with the high dose group (period I: -11.65 mmHg vs. -12.21 mmHg).
Razlika v odzivu na odmerek med skupinama z majhnim in srdenjim odmerkom je bila zelo očitna (obdobje I: - 6, 2 mmHg proti - 11, 65 mmHg), in je bila med skupinama s srednjim in velikim odmerkom (obdobje I: - 11, 65 mmHg proti - 12, 21 mmHg) manjša.
The lowest doses studied, 2.5 mg and 5 mg, corresponding to an average daily dose of 0.07 mg/ kg, did not appear to offer consistent antihypertensive efficacy.
Najmanjša preizkušana odmerka, 2, 5 mg in 5 mg, ki ustrezata povprečnima dnevnima odmerkoma 0, 07 mg/ kg, nista imela dosledne antihipertenzivne učinkovitosti.
These results were confirmed during period II of the study where patients were randomized to continue losartan or placebo, after three weeks of treatment.
Ti razultati so bili potrjeni po treh tednih v drugem obdobju študije, v kateri so bolnike randomizirali tako, da so nadaljevali zdravljenje z losartanom ali pa prejemali placebo.
5.38 mmHg high dose).
Razlika v povečanju krvnega tlaka v času, ko je učinek zdravila najmanjši, v primerjavi s placebom je bila večja v skupini s srednjim odmerkom (6, 70 mmHg srednji odmerek, 5, 38 mmHg večji odmerek).
The rise in trough diastolic blood pressure was the same in patients receiving placebo and in those continuing losartan at the lowest dose in each group, again suggesting that the lowest dose in each group did not have significant antihypertensive effect.
To ponovno nakazuje, da najmanjši odmerek v obeh skupinah ni imel pomembnega antihipertenzivnega učinka.
The long-term efficacy of antihypertensive therapy with losartan in childhood to reduce cardiovascular morbidity and mortality has also not been established.
Dolgoročne učinkovitosti antihipertenzivnega zdravljenja z losartanom v otroštvu za zmanjšanje obolevnosti in smrtnosti zaradi srčno- žilnih vzrokov prav tako niso preučevali.
Both losartan and its active metabolite are ≥ 99% bound to plasma proteins, primarily albumin.
Tako losartan kot njegov aktivni presnovek sta v ≥ 99% vezana na plazemske proteine, predvsem na albumin.
About 14% of an intravenously- or orally-administered dose of losartan is converted to its active metabolite.
Približno 14% intravenskega ali peroralnega odmerka losartana se pretvori v njegov aktivni presnovek.
Plasma clearance of losartan and its active metabolite is about 600 mL/ min and 50 mL/ min, respectively.
Plazemski očistek losartana je približno 600 ml/ min, njegovega aktivnega presnovka pa 50 ml/ min.
36 Following oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially with a terminal half-life of about 2 hours and 6-9 hours, respectively.
Po peroralnem zaužitju plazemske koncentracije losartana in njegovega aktivnega presnovka padajo polieksponentno, pri čemer je končni razpolovni čas losartana približno 2 uri, njegovega aktivnega
Following an oral dose/ intravenous administration of 14C-labeled losartan in man, about 35% / 43% of radioactivity is recovered in the urine and 58%/ 50% in the faeces.
Po peroralnem/ intravenskem odmerku s 14C označenega losartana pri človeku najdemo približno 35% / 43% radioaktivnosti v urinu, 58% / 50% pa v blatu.
In patients with mild to moderate alcohol-induced hepatic cirrhosis, the plasma levels of losartan and its active metabolite after oral administration were respectively 5 and 1.7 times higher than in young male volunteers (see section 4.2 and 4.4).
1, 7- krat višje od tistih pri mladih moških prostovoljcih (glejte poglavji 4. 2 in 4. 4).
Plasma concentrations of Losartan are not altered in patients with a creatinine clearance above 10 ml/ minute.
Plazemske koncentracije losartana se pri bolnikih s kreatininskim očistkom nad 10 ml/ min ne razlikujejo.
Compared to patients with normal renal function, the AUC for Losartan is about 2-times higher in haemodialysis dialysis patients.
V primerjavi z bolniki z normalno ledvično funkcijo je pri bolnikih na hemodializi AUC losartana približno 2- krat večja.
Pharmacokinetics in paediatric patients The pharmacokinetics of losartan have been investigated in 50 hypertensive paediatric patients > 1 month to < 16 years of age following once daily oral administration of approximately 0.54 to 0.77 mg/ kg of losartan (mean doses).
Farmakokinetika pri pediatričnih bolnikih Farmakokinetiko losartana so preučevali pri 50 pediatričnih bolnikih s hipertenzijo, starih > 1 mesec do < 16 let, po enkrat dnevni peroralni uporabi približno 0, 54 do 0, 77 mg/ kg losartana (povprečni odmerki).
The results showed roughly similar pharmacokinetic parameters of losartan following oral administration in infants and toddlers, preschool children, school age children and adolescents.
Rezultati so pokazali, da so farmakokinetični parametri losartana po peroralni aplikaciji pri dojenčkih in malčkih, predšolskih otrocih, šoloobveznih otrocih in mladostnikih približno podobni.
Exposure in infants/ toddlers was comparatively high.
Izpostavljenost pri dojenčkih/ malčkih je bila sorazmerno visoka.