Pharmacodynamics and pharmacokinetics in the elderly

The paper dealswith changes in pharmacodynamics (the study ofwhat the drug does to the body) and pharmacokinetics (the study of what the body does to the drug) in the elderly. Elderly population takes 25–30 per cent of drugs taken by total population. In the elderly pharmacodynamics and pharmacokinetics are altered. According to pharmacokinetics, gastric juice pH is elevatedwhich influences drug solubility and absorption.Drug distribution is decreased in the elderly because of decreased cardiac output, increased peripheral vascular resistance, diminished blood flow in the liver and the kidneys, reduced total amount of water in the body. Drug metabolism and biotransformation mainly take place in the liver and is reduced very often. Drug elimination is reduced very often because of reduced renal reserve: creatinine clearance is reduced in the elderly in spite of the fact that the serum values remaining in the normal range. Pharmacodynamics could be altered in the elderly, as a consequences of receptor binding, of postreceptor effects, and of chemical interactions. The clinical effects of drug concentrations could be greater or smaller than those in middle-aged or younger persons

Medical and Bioethical Issues in a Pregnant Woman with Epilepsy: Case Report

A case report of a minor, pregnant girl with epilepsy caused by a brain tumour is presented. There are several aspects which make the presented case complex from medical, but also from the bioethical point of view. The decision about keeping the pregnancy or not is the most important bioethical dilemma for the patient and family. A detailed medical multidisciplinary approach and later balanced explanation of the medical situation to the patient are of extreme value for helping the patient’s decision. It is also important to enhance the activities in pregnancy counselling for a woman with epilepsy which will result in a planned pregnancy as a prerequisite for a positive pregnancy outcome

Farmakoterapijski priručnik

6. izdanj

Medical and Bioethical Issues in a Pregnant Woman with Epilepsy: Case Report

A case report of a minor, pregnant girl with epilepsy caused by a brain tumour is presented. There are several aspects which make the presented case complex from medical, but also from the bioethical point of view. The decision about keeping the pregnancy or not is the most important bioethical dilemma for the patient and family. A detailed medical multidisciplinary approach and later balanced explanation of the medical situation to the patient are of extreme value for helping the patient’s decision. It is also important to enhance the activities in pregnancy counselling for a woman with epilepsy which will result in a planned pregnancy as a prerequisite for a positive pregnancy outcome

MASSIVE CLOZAPINE OVERDOSE: WHAT TO EXPECT?

Clozapine is an atypical antipsychotic drug indicated for treatment-resistant schizophrenia. Despite its superior clinical efficacy, many deleterious adverse events, including agranulocytosis, have resulted in its more judicious use (Asenjo Lobos et al. 2010). The most frequently reported symptoms of clozapine intoxication are impaired alertness and tachycardia; other symptoms include: hyperthermia, alterations in consciousness, dysarthria, ataxia, seizures, cardiac arrhythmias, excessive bronchial mucus, hypersalivation, miosis, blood dyscrasias, pancreatitis and hepatitis (Le Blaye et al. 1992, Krämer et al. 2010). Studies that evaluated the case fatality rate with various antipsychotics concluded that clozapine was far more toxic than other antipsychotics (Ferrey 2018). To the best of our knowledge, this is the fist case report describing treatment and outcomes following a massive overdose of clozapine, amounting to 46.7 times the recommended patient’s daily dose of clozapine

Nitrates Today

Organski nitrati, poput nitroglicerina, izosorbid dinitrata i izosorbid mononitrata, u medicinskoj su uporabi već više od 150 godina. Uobičajeno se rabe u liječenju kardiovaskularnih bolesti. Mehanizam djelovanja je u otpuštanju dušik (II) oksida u glatkim mišićnim stanicama stijenke krvnih žila i endotelnim stanicama nakon bioaktivacije. U konačnici to rezultira relaksacijom glatkih mišićnih stanica i drugim staničnim učincima. Osnovni čimbenik koji ograničava primjenu ove skupine lijekova je razvoj tolerancije. Osiguravanje razdoblja bez nitrata (niske koncentracije) najjednostavniji je i najprihvatljiviji način sprečavanja tolerancije. Karakteristične nuspojave nitrata jesu glavobolja, arterijska hipotenzija i sinkopa. Zaključno, organski su nitrati i dalje skupina vrlo učinkovitih protuishemijskih lijekova koji se rabe u liječenju bolesnika sa stabilnom anginom pektoris i akutnim koronarnim sindromom (nestabilnom anginom i akutnim infarktom miokarda).Organic nitrates, such as nitroglycerin, isosorbide dinitrate and isosorbide mononitrate have been in medical use for more than 150 years. They are commonly used in therapy of cardiovascular diseases. Their mechanism of action lies in releasing nitric oxide in vascular smooth muscle cells and endothelial cells when bioactivated. This results finally in smooth muscle cell relaxation and other cellular effects. A major factor limiting the efficacy of these drugs is in the development of tolerance. Provision of a nitrate-free interval has taken on increasing significance as a strategy to avoid tolerance. Some typical side-effects of nitrates are headache, arterial hypotension and syncope. In conclusion, organic nitrates still represent a group of very effective anti-ischemic drugs used for the treatment of patients with stable angina pectoris and acute coronary syndrome (unstable angina and acute myocardial infarction)

Drugs and Pregnancy

Znanje o sigurnosti lijekova primijenjenih tijekom trudnoće vrlo je važno za sve liječnike kliničare. S obzirom na to da je 50-ak posto trudnoća neplanirano, učestalo se javlja pitanje učinka ekspozicije lijekovima u ranom i najosjetljivijem razdoblju još neotkrivene trudnoće. S druge strane, mnogo žena s bolestima koje treba liječiti kroničnom terapijom planira trudnoću. Iako je malen broj lijekova čija je primjena u trudnoći kontraindicirana zbog dokazanih štetnih utjecaja na majku i dijete, općenito postoji velik strah od primjene lijekova u trudnoći, što kao problem donosi nedovoljno ili neadekvatno ili pak pretjerano propisivanje lijekova. Neprimjerene preporuke mogu dovesti do nepotrebnog prekida ili neprimjerenog liječenja kroničnih ili akutnih bolesti tijekom trudnoće, što može povisiti rizik od njezina nepovoljnog ishoda. Kod odluke o primjeni lijekova u trudnice treba provesti ovaj pristup: 1. procijeniti potrebu za primjenom lijeka; 2. izabrati najsigurniji lijek; 3. pratiti primjenu lijeka; 4. dati specifične upute o primjeni (npr., izbjegavati određene kombinacije lijekova); 5. tražiti savjet kliničkog farmakologa ako je potrebno. U članku se daje pregled racionalne terapije najčešćih bolesti i stanja tijekom trudnoće i dojenja.Knowledge about safety and efficacy of drugs prescribed during pregnancy and lactation is important for every clinician. Due to the fact that approximately 50% of pregnancies are unplanned, there is concern about possible adverse drug reactions (ADR) of drugs taken during the early and most vulnerable stage of pregnancy. Furthermore, many women with chronic illnesses that require treatment are planning to become pregnant. Although there is limited number of drugs that are contraindicated during pregnancy due to their teratogenic or other ADR, there is much fear about prescribing drugs to pregnant women. This raises as much concern about under prescribing drugs as overprescribing them. Inadequate recommendations on drug use during pregnancy may lead to unnecessary therapy cessation or inadequate therapy of chronic or acute illnesses leading to increased risk for adverse pregnancy outcomes. When consulting on pharmacotherapy during pregnancy, physicians should take the following approach: 1. Determine if drug therapy is necessary; 2. Choose the safest drug available; 3. Monitoring drug therapy (e.g. measurement of plasma drug concentration, ADR); 4. Advice on drug use (e.g. avoiding specific drug-drug combinations); 5. Seek advice from clinical pharmacologist. This article provides a review of rational pharmacotherapy for the most common clinical conditions during pregnancy

Diuretics

Diuretici su lijekovi koji smanjuju volumen ekstracelularne tekućine povećavanjem izlučivanja soli i vode putem bubrega. Mogu se podijeliti prema kemijskoj strukturi, mehanizmu i mjestu djelovanja: diuretici Henleove petlje (furosemid, bumetanid, torasemid, etakrinska kiselina), tijazidi i tijazidima slični spojevi (hidroklorotijazid, klortalidon, metolazon, indapamid), diuretici koji štede kalij (amilorid, triamteren), antagonisti aldosteronskih receptora (spironolakton, eplerenon), inhibitori karboanhidraze (acetazolamid), osmotski diuretici (manitol) i antagonisti vazopresina (tolvaptan, liksivaptan, konivaptan). Indikacije za primjenu diuretika su široke: stanja praćena retencijom tekućine (zatajivanje srca, ciroza jetre, nefrotski sindrom), hiperkalemija, arterijska hipertenzija, nefrogeni dijabetes insipidus, hiperkalciurija, hiperaldosteronizam. U liječenju arterijske hipertenzije jedni su od osnovnih lijekova, i to primijenjeni kao monoterapija ili u kombinaciji s drugim antihipertenzivima. U zatajivanju srca primjenjuju se u svih bolesnika s kliničkim znakovima ili simptomima plućne ili sistemske venske kongestije.Diuretics are drugs that decrease the volume of the extracellular fluid by increasing renal salt and water excretion. They can be divided into several groups regarding their chemical structure, operating mechanism and site of action: loop diuretics (furosemide, bumetanide, torasemide, ethacrynic acid), thiazide and thiazide-like diuretics (hydrochlorothiazide, chlortalidone, metolazone, indapamide), potassium- sparing diuretics (amiloride, triamterene), aldosterone receptor blockers (spironolactone, eplerenone), carboanhydrase inhibitors (acetazolamide), osmotic diuretics (mannitol), and vasopressin antagonists (tolvaptan, lixivaptan, conivaptan). Indications for diuretics administration are very broad: fluid retention (heart failure, cirrhosis, nephrotic syndrome), hyperkalaemia, arterial hypertension, nephrogenic diabetes insipidus, hypercalciuria, hyperaldosteronism. In the treatment of arterial hypertension diuretics represent one of the essential drugs either as monotherapy or in combination with other antihypertensives. In patients with heart failure they are given to all patients with clinical signs or symptoms of pulmonary or systemic venous congestion

Diuretics

Diuretici su lijekovi koji smanjuju volumen ekstracelularne tekućine povećavanjem izlučivanja soli i vode putem bubrega. Mogu se podijeliti prema kemijskoj strukturi, mehanizmu i mjestu djelovanja: diuretici Henleove petlje (furosemid, bumetanid, torasemid, etakrinska kiselina), tijazidi i tijazidima slični spojevi (hidroklorotijazid, klortalidon, metolazon, indapamid), diuretici koji štede kalij (amilorid, triamteren), antagonisti aldosteronskih receptora (spironolakton, eplerenon), inhibitori karboanhidraze (acetazolamid), osmotski diuretici (manitol) i antagonisti vazopresina (tolvaptan, liksivaptan, konivaptan). Indikacije za primjenu diuretika su široke: stanja praćena retencijom tekućine (zatajivanje srca, ciroza jetre, nefrotski sindrom), hiperkalemija, arterijska hipertenzija, nefrogeni dijabetes insipidus, hiperkalciurija, hiperaldosteronizam. U liječenju arterijske hipertenzije jedni su od osnovnih lijekova, i to primijenjeni kao monoterapija ili u kombinaciji s drugim antihipertenzivima. U zatajivanju srca primjenjuju se u svih bolesnika s kliničkim znakovima ili simptomima plućne ili sistemske venske kongestije.Diuretics are drugs that decrease the volume of the extracellular fluid by increasing renal salt and water excretion. They can be divided into several groups regarding their chemical structure, operating mechanism and site of action: loop diuretics (furosemide, bumetanide, torasemide, ethacrynic acid), thiazide and thiazide-like diuretics (hydrochlorothiazide, chlortalidone, metolazone, indapamide), potassium- sparing diuretics (amiloride, triamterene), aldosterone receptor blockers (spironolactone, eplerenone), carboanhydrase inhibitors (acetazolamide), osmotic diuretics (mannitol), and vasopressin antagonists (tolvaptan, lixivaptan, conivaptan). Indications for diuretics administration are very broad: fluid retention (heart failure, cirrhosis, nephrotic syndrome), hyperkalaemia, arterial hypertension, nephrogenic diabetes insipidus, hypercalciuria, hyperaldosteronism. In the treatment of arterial hypertension diuretics represent one of the essential drugs either as monotherapy or in combination with other antihypertensives. In patients with heart failure they are given to all patients with clinical signs or symptoms of pulmonary or systemic venous congestion