Cluster headache je primární bolest hlavy patřící mezi trigeminové autonomní cefalgie. Její léčba vychází z empirických doporučení a zahrnuje akutní, preventivní a přemosťující přístupy, které jsou doplňovány neuromodulačními metodami. Verapamil je považován za preventivní lék první volby, ačkoliv se u cluster headache jedná o off-label použití. Léčba verapamilem má být zahájena co nejdříve na začátku clusterové periody dávkou 240 mg/den, podmínkou je vyloučení kontraindikací a normální elektrokardiografický nález. Již v prvním týdnu léčby je pak dosažena obvyklá účinná dávka 360 mg/den. Další navyšování probíhá postupně dle individuálních potřeb pacienta a za pravidelných kontrol elektrokardiogramu. Léčba vysokou (≥ 480 mg/den) a velmi vysokou dávkou (≥ 720 mg/den) verapamilu probíhá pod dohledem specialisty a souběžně vyžaduje kardiologické sledování. Maximální doporučená dávka k preventivní léčbě cluster headache je 960 mg/den. Preventivní léčba probíhá několik týdnů až měsíců a ukončuje se postupně.
Cluster headache is a primary headache disorder classified under trigeminal autonomic cefalalgias. Its treatment is based on empirical recommendations and includes acute, preventative and bridging treatment strategies, and complemented by neuromodulatory methodes. Verapamil is considered first-line preventative medication, although its use in cluster headache is off-label. The treatment should be started at the very beginning of the cluster period with an initial dose of 240 mg/day, prior it is mandatory to rule out contraindications and confirm that patient ́s echocardiographic finding is normal. During the first week of treatment, the typical effective therapeutic dose of 360 mg/day is achieved. Further increase of the dose is provided stepwise according the needs of the patient and with routine electrocardiogram monitoring. If high (≥ 480 mg/day) or very high doses (≥ 720 mg/day) of verapamil are necessary, treatment should be administered under the specialist ́s supervision with close cardiological follow-up. The maximu recommended dose for preventative treatment of cluster headache is 960 mg/day. Preventative treatment usually continues for several weeks or months and must be withdrawn gradually.
- MeSH
- Atrioventricular Block diagnostic imaging classification MeSH
- Cluster Headache * diagnosis drug therapy prevention & control MeSH
- Electrocardiography methods MeSH
- Contraindications MeSH
- Humans MeSH
- Pain Management methods MeSH
- Drug-Related Side Effects and Adverse Reactions classification MeSH
- Verapamil * administration & dosage pharmacokinetics pharmacology adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The solubility of weakly basic drugs in passage through gastrointestinal tract leads to their pH-dependent release from extended release formulations and to lower drug absorption and bioavailability. The aim of this study was to modulate the micro-environmental pH of hypromellose/montanglycol wax matrices and to observe its influence on the release of weakly basic drug verapamil hydrochloride (VH) with a pH-dependent solubility with respect to gel layer formation and its dynamics. For this study, malic and succinic acids differing in their solubility and pKa were selected as pH modifiers. The dissolution studies were performed by the method of changing pH. Within the same conditions, pH, thickness, and penetration force of the gel layer were measured as well. From the PCA sub-model, it is evident that a higher acid concentration ensured lower gel pH and conditions for higher drug solubility, thus creating larger gel layer with smaller rigidity, resulting in higher VH release during the dissolution test. Incorporation of stronger and more soluble malic acid (100 mg/tablet) created the most acidic and the thickest gel layer through which a total of 74% of VH was released. Despite having lower strength and solubility, matrices containing succinic acid (100 mg/tablet) released a comparable 71% of VH in a manner close to zero-order kinetics. The thinner and less rigid gel layers of the succinic acid matrices allowed an even slightly faster VH release at pH 6.8 than from matrices containing malic acid. Thus acid solubility is more parametrically significant than acid pKa for drug release at pH 6.8.
- MeSH
- Hypromellose Derivatives * MeSH
- Gels MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Delayed-Action Preparations chemistry MeSH
- Malates chemistry MeSH
- Multivariate Analysis MeSH
- Solubility MeSH
- Succinates chemistry MeSH
- Tablets MeSH
- Drug Liberation MeSH
- Verapamil administration & dosage chemistry metabolism MeSH
- Waxes * MeSH
- Publication type
- Journal Article MeSH
- Keywords
- biologický poločas, esmolol, magnesium sulfuricum, vernakalant,
- MeSH
- Acetanilides administration & dosage pharmacology adverse effects MeSH
- Adenosine administration & dosage pharmacology adverse effects MeSH
- Amiodarone administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Anti-Arrhythmia Agents * administration & dosage pharmacokinetics pharmacology classification metabolism adverse effects MeSH
- Atropine administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Adrenergic beta-Antagonists administration & dosage pharmacokinetics pharmacology classification adverse effects MeSH
- Potassium Channel Blockers administration & dosage pharmacokinetics pharmacology classification adverse effects MeSH
- Calcium Channel Blockers administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Sodium Channel Blockers administration & dosage pharmacokinetics pharmacology classification adverse effects MeSH
- Dronedarone administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Phenytoin administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Cardiovascular Diseases * drug therapy MeSH
- Drug Interactions MeSH
- Humans MeSH
- Metoprolol administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Liver Diseases complications MeSH
- Kidney Diseases complications MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Prajmaline administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Propafenone administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Sotalol administration & dosage pharmacokinetics pharmacology adverse effects MeSH
- Verapamil administration & dosage pharmacokinetics pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Arteriální hypertenze je v České republice stále nejčastějším kardiovaskulárním onemocněním. Její prevalence roste, v posledních deseti letech se odhaduje na téměř 40 % a ve věkové skupině 65–75 let se vyskytuje ve více než 60 %. Bohužel monoterapie arteriální hypertenze je dostatečně účinná pouze asi v jedné třetině případů. Špatně dodržovaná doporučená léčba hypertenze má výrazně negativní prognostický dopad, dochází až přibližně k 15% nárůstu výskytu akutních infarktů myokardu a ke zhruba 28% nárůstu výskytu cévních mozkových příhod. Jednou z nejvýhodnějších kombinací antihypertenzní léčby jsou v současné době inhibitory angiotensin konvertujícího enzymu (event. sartany) a blokátory kalciových kanálů. Velmi příznivá je kombinace verapamilu a trandolaprilu, která udržuje pokles krevního tlaku po dobu 24 hodin (o 14 mm Hg systolického a o 11 mm Hg diastolického tlaku) a také účinně zabraňuje rozvoji hypertenzní mikrovaskulární dysfunkce.
Arterial hypertension is the most common cardiovascular disease in the Czech Republic. Prevalence of arterial hypertension is increasing with age, approaching 40% in the last years and affecting above 60% of people aged 65–75 years. Monotherapy of arterial hypertension is sufficiently effective in about 1/3 of cases only. Poor adherence to the recommended treatment has a negative prognostic impact – increasing the incidence of acute myocardial infarction by about 15% and that of stroke by about 28%. One of the most preferred combinations are calcium channels blockers and angiotensin converting enzyme inhibitors. The combination of verapamil and trandolapril is very favorable, maintaining the blood pressure reduction over 24 hours (reducing the systolic pressure by about 14 mm Hg and the diastolic by about 11 mm Hg). It also effectively prevents the progress of hypertension‑related microvascular dysfunction.
- Keywords
- TRANDOLAPRIL,
- MeSH
- Antihypertensive Agents * pharmacology therapeutic use MeSH
- Calcium Channel Blockers administration & dosage pharmacology therapeutic use MeSH
- Drug Combinations MeSH
- Hypertension * drug therapy MeSH
- Indoles administration & dosage pharmacology therapeutic use MeSH
- Angiotensin-Converting Enzyme Inhibitors administration & dosage pharmacology therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Verapamil * administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Srdeční selhání je časté onemocnění se závažnou morbiditou a mortalitou. Článek shrnuje nová doporučení farmakologické léčby chronického srdečního selhání. Základem léčby je ovlivnění neurohumorální aktivace, která hraje klíčovou roli s patofyziologii srdečního selhání – především tedy betablokátory a ACE inhibitory, při trvající symptomatologii blokátory mineralokortikoidních receptorů. Nadějně se jeví výsledky studií s inhibitorem angiotensinových receptorů a neprilysinu. Nově se v doporučeních objevuje ivabradin.
Heart failure is a frequent disease with a serious morbidity and mortality. The article summarizes new recommendations for pharmacological therapy for chronic heart failure. The mainstay of treatment is to interfere with neurohumoral activation that plays a crucial role in the pathophysiology of heart failure, in particular with beta blockers and ACE inhibitors; in the case of persistent symptomatology with mineralocorticoid receptor blockers. The results of studies of the angiotensin receptor neprilysin inhibitor appear promising. The recommendations newly include ivabradine.
- Keywords
- Látky ovlivňující neurohumorální aktivaci,
- MeSH
- Anticoagulants administration & dosage adverse effects therapeutic use MeSH
- Aspirin administration & dosage adverse effects therapeutic use MeSH
- Benzazepines administration & dosage adverse effects therapeutic use MeSH
- Adrenergic beta-Antagonists administration & dosage adverse effects therapeutic use MeSH
- Angiotensin II Type 1 Receptor Blockers administration & dosage adverse effects therapeutic use MeSH
- Chronic Disease * drug therapy prevention & control MeSH
- Digoxin administration & dosage adverse effects therapeutic use MeSH
- Diuretics administration & dosage adverse effects therapeutic use MeSH
- Eplerenone MeSH
- Drug Therapy * methods trends utilization MeSH
- Angiotensin-Converting Enzyme Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Ivabradine MeSH
- Humans MeSH
- Neprilysin antagonists & inhibitors administration & dosage therapeutic use MeSH
- Spironolactone administration & dosage adverse effects therapeutic use MeSH
- Heart Failure * etiology drug therapy prevention & control MeSH
- Statistics as Topic MeSH
- Verapamil administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
P-glycoprotein (P-gp) inhibition represents a promising therapeutic strategy for oncologic patients. The inhibition by naturally occurring anthocyans would bring certain benefits. Unfortunately, due to the low bioavailability and consequently low blood level, they cannot be used for cancer therapy. However, due to the food supplementation, significant concentration can raise up in the intestine, where P-gp is abundantly expressed. As many drugs are orally taken, simultaneous administration might affect the concentration of these drugs in the blood. Here, we found that anthocyanidins (aglycons) but not anthocyanins (glycosides) can significantly inhibit P-gp up to 60% of positive control, verapamil. This inhibitory activity was observed for 500 μm concentrations of malvidin and pelargonidin. We conclude that these compounds may be the source of food-drug interactions either for orally taken drugs or for intravenously administered drugs eliminated via biliary excretion which are the substrates of P-gp.
- MeSH
- Anthocyanins administration & dosage metabolism MeSH
- Administration, Oral MeSH
- Fluoresceins administration & dosage metabolism MeSH
- Food-Drug Interactions * physiology MeSH
- Humans MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 antagonists & inhibitors metabolism MeSH
- Dietary Supplements * MeSH
- Swine MeSH
- Verapamil administration & dosage metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Srdeční selhání je časté onemocnění se závažnou morbiditou a mortalitou. Článek shrnuje nová doporučení farmakologické léčby chronického srdečního selhání. Základem léčby je ovlivnění neurohumorální aktivace, která hraje klíčovou roli s patofyziologii srdečního selhání – především tedy betablokátory a ACE inhibitory, při trvající symptomatologii blokátory mineralokortikoidních receptorů. Nadějně se jeví výsledky studií s inhibitorem angiotensinových receptorů a neprilysinu. Nově se v doporučeních objevuje ivabradin.
Heart failure is a frequent disease with a serious morbidity and mortality. The article summarizes new recommendations for pharmacological therapy for chronic heart failure. The mainstay of treatment is to interfere with neurohumoral activation that plays a crucial role in the pathophysiology of heart failure, in particular with beta blockers and ACE inhibitors; in the case of persistent symptomatology with mineralocorticoid receptor blockers. The results of studies of the angiotensin receptor neprilysin inhibitor appear promising. The recommendations newly include ivabradine.
- Keywords
- Látky ovlivňující neurohumorální aktivaci,
- MeSH
- Anticoagulants administration & dosage adverse effects therapeutic use MeSH
- Aspirin administration & dosage adverse effects therapeutic use MeSH
- Benzazepines administration & dosage adverse effects therapeutic use MeSH
- Adrenergic beta-Antagonists administration & dosage adverse effects therapeutic use MeSH
- Angiotensin II Type 1 Receptor Blockers administration & dosage adverse effects therapeutic use MeSH
- Chronic Disease * drug therapy prevention & control MeSH
- Digoxin administration & dosage adverse effects therapeutic use MeSH
- Diuretics administration & dosage adverse effects therapeutic use MeSH
- Eplerenone MeSH
- Drug Therapy * methods trends utilization MeSH
- Angiotensin-Converting Enzyme Inhibitors administration & dosage adverse effects therapeutic use MeSH
- Ivabradine MeSH
- Humans MeSH
- Neprilysin antagonists & inhibitors administration & dosage therapeutic use MeSH
- Spironolactone administration & dosage adverse effects therapeutic use MeSH
- Heart Failure * etiology drug therapy prevention & control MeSH
- Statistics as Topic MeSH
- Verapamil administration & dosage adverse effects therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Anti-Arrhythmia Agents pharmacology adverse effects therapeutic use MeSH
- Antidepressive Agents, Second-Generation pharmacology therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal pharmacology therapeutic use MeSH
- Adrenergic beta-Antagonists * pharmacology therapeutic use MeSH
- Calcium Channel Blockers administration & dosage adverse effects therapeutic use MeSH
- Cholinesterase Inhibitors adverse effects MeSH
- Hypoglycemic Agents pharmacology therapeutic use MeSH
- Insulin pharmacology therapeutic use MeSH
- Cardiovascular Diseases * drug therapy MeSH
- Drug Therapy, Combination * MeSH
- Drug Interactions * MeSH
- Humans MeSH
- Selective Serotonin Reuptake Inhibitors pharmacology therapeutic use MeSH
- Sotalol adverse effects therapeutic use MeSH
- Verapamil administration & dosage adverse effects therapeutic use MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Článek v přehledu popisuje klinické obrazy a současnou léčbu méně častých primárních bolestí hlavy. Mezi tyto bolesti hlavy patří podle mezinárodní klasifikace trigeminové autonomní bolesti hlavy a tzv. další primární bolesti hlavy. Uvedeny jsou všechny klinické jednotky z obou těchto skupin, důraz je kladen zejména na cluster headache, která se vyskytuje relativně nejčastěji. Přehled má za cíl zlepšit znalosti o bolestech hlavy a urychlit diagnostiku a léčbu těchto nemocných.
This paper describes clinical manifestations and current treatment of less common primary headaches. According to the international classification, these include trigeminal autonomic cephalgias and so called other primary headache disorders. All clinical entities from both these groups are presented, the emphasis is on cluster headache that occurs most frequently. The goal of this review is to improve knowledge on headaches and to facilitate timely diagnosis and treatment. Key words: cluster headache – paroxysmal hemicrania – primary cough headache – primary thunderclap headache – primary stabbing headache – hypnic headache The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.
- Keywords
- primární thunderclap headache, hypnická bolest hlavy, primární bodavá bolest hlavy,
- MeSH
- Calcium Channel Blockers therapeutic use MeSH
- Chemoprevention methods MeSH
- Cluster Headache * drug therapy physiopathology prevention & control MeSH
- Indomethacin administration & dosage therapeutic use MeSH
- Cough complications MeSH
- Humans MeSH
- Lidocaine administration & dosage adverse effects therapeutic use MeSH
- Methylprednisolone administration & dosage therapeutic use MeSH
- Paroxysmal Hemicrania * drug therapy physiopathology prevention & control MeSH
- Headache Disorders, Primary * diagnosis etiology drug therapy physiopathology MeSH
- SUNCT Syndrome drug therapy physiopathology MeSH
- Verapamil administration & dosage therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
The solubility of weakly basic drugs within passage though GI tract leads to pH-dependent or even incomplete release of these drugs from extended release formulations and consequently to lower drug absorption and bioavailability. The aim of the study was to prepare and evaluate hydrophilic-lipophilic (hypromellose-montanglycol wax) matrix tablets ensuring the pH-independent delivery of the weakly basic drug verapamil-hydrochloride by an incorporation of three organic acidifiers (citric, fumaric, and itaconic acids) differing in their concentrations, pK a, and solubility. The dissolution studies were performed by the method of changing pH values, which better corresponded to the real conditions in the GI tract (2 h at pH 1.2 and then 10 h at pH 6.8). Within the same conditions, pH of matrix microenvironment was measured. To determine relationships between the above mentioned properties of acidifiers and the monitored effects (the amount of released drug and surface pH of gel layer in selected time intervals-360 and 480 min), the full factorial design method and partial least squares PLS-2 regression were used. The incorporation of the tested pH modifiers significantly increased the drug release rate from matrices. PLS-components explained 75% and 73% variation in the X- and Y-data, respectively. The obtained results indicated that the main crucial points (p < 0.01) were the concentration and strength of acidifier incorporated into the matrix. Contrary, the acid solubility surprisingly did not influence the selected effects except for the surface pH of gel layer in time 480 min.
- MeSH
- Algorithms MeSH
- Calcium Channel Blockers administration & dosage chemistry MeSH
- Electrodes MeSH
- Factor Analysis, Statistical MeSH
- Gels MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Pharmaceutical Preparations administration & dosage chemistry MeSH
- Methylcellulose analogs & derivatives MeSH
- Drug Design MeSH
- Solubility MeSH
- Tablets MeSH
- Particle Size MeSH
- Verapamil administration & dosage chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
