Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CHLORPROPAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1989

Simple high-performance liquid chromatographic method for the determination of tolbutamide and its metabolites in human plasma and urine using photodiode-array detection.

A high-performance liquid chromatographic method has been developed for the determination of tolbutamide and its metabolites in human plasma and urine. The compounds examined were extracted with diethyl ether from the acidified biological fluid. Chlorpropamide was used as internal standard, and 235 nm was chosen as the wavelength for diode-array detection. A study of the relationship between the capacity factor and the mobile phase composition and pH showed that acetonitrile-2-propanol-0.1% orthophosphoric acid (17: 17: 66, v/v) was the best eluent on a C8 reversed-phase column. The method is precise, sensitive and suitable for pharmacological investigations.

Chromatography, High Pressure Liquid↗
PubMed2003

Analysis of synthetic anti-diabetic drugs in adulterated traditional Chinese medicines by high-performance capillary electrophoresis.

Four synthetic anti-diabetic drugs, acetohexamide (ACE), chlorpropamide (CHL), glibenclamide (GLI) and tolbutamide (TOL), which can be found as adulterants in traditional Chinese medicines (TCMs) were assayed simultaneously using high-performance capillary electrophoresis (HPCE) in 4 min with UV detection at 200 nm. The electrolyte was a buffer solution containing 100 mM phosphate buffer (NaH2PO4/Na2B4O7, pH 7.5). Applied voltage was 15.0 kV and temperature was 30 degrees C. 2-(4-Hydroxyphenyl) ethyl ammonium chloride (HEA) was used as an internal standard. The effects of buffer concentration, pH and supplied voltage on separation were investigated. The relative standard deviations (R.S.D.) of these anti-diabetic drugs for intra-day and inter-day analyses were 0.23-4.27 and 1.23-6.33%, respectively. The recoveries of the synthetic drug adulterants in traditional Chinese medicinal formula ranged from 81.3 to 105.5%. GLI was found and determined in a real sample of TCM.

Buffers↗
PubMed1997

Inhibiting effects of antioxidants on drug-induced phototoxicity in cell cultures. Investigations with sulphonamide-derived oral antidiabetics and diuretics.

The sulphonamide-derived oral antidiabetics chlorpropamide, glibenclamide, glipizide, gliquidone, glymidine, tolazamide and tolbutamide, and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide and xipamide were investigated for phototoxicity in a cell culture model. Cell death dependent on ultraviolet A (UVA) radiation fluence and test substance concentration was observed in the presence of the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, hydrochlorothiazide, hydroflumethiazide, piretanide, polythiazide and trichlormethiazide. Bendroflumethiazide was phototoxic at concentrations of 0.05 mM and above; bemetizide, benzylhydrochlorothiazide, bumetanide and hydroflumethiazide were phototoxic at concentrations of 0.25 mM or more; the oral antidiabetics glibenclamide and gliquidone, as well as the diuretics butizide, hydrochlorothiazide, piretanide, polythiazide and trichlormethiazide were phototoxic at concentrations of 0.5 mM. To evaluate the effects of antioxidants, ascorbic acid, alpha-tocopherol, beta-carotene or ubiquinone was added to the tissue culture flasks before irradiation. The phototoxic inhibition of the colony-forming ability was largely reduced by the addition of ascorbic acid and alpha-tocopherole, indicating the involvement of reactive oxygen species in the phototoxic process.

Antioxidants↗
PubMed2003

Sulfonylureas and cardiovascular effects: from experimental data to clinical use. Available data in humans and clinical applications.

OBJECTIVES: 33 years after the UGDP study, the question of deleterious effects of the sulfoylurea (SU) is still raised. We have made a systematic review of the literature from experimental studies to clinical and epidemiological studies. RESULTS: The main molecule studied is glibenclamide (GB). In vitro and in animal studies, GB is both deleterious for ischemic preconditionning (IPC) and protective for arrhythmia during acute ischemia. Glimepiride (GM) and gliclazide (GCZ) do not seem to have effect on IPC. These effects have been few studied in diabetic animals. In human, according to the investigations used, the GB seems nil or suppressing for IPC, it seems elsewhere decreases ventricular arrhythmias during periods of acute ischemia. It is possible that these two actions account for the non-appearance of concordant deleterious effects between short and long-term studies. With regards to other drugs, only the GM has been specifically studied in human and appears to be nil on IPC. The only prospective clinical study available, although not having for objective to answer to this question, is the UKPDS study. This trial demonstrates the absence of deleterious cardiac effects of GB compared to chlorpropamide and particularly compared to insulin. CONCLUSION: In conclusion, in experimental studies the cardiac effects of SU differ: both deleterious and protective for GB, nil for GM and GCZ on IPC. In all cases the clinical consequences seems to be nil.

Animals↗
PubMed1995

Detection of hypoglycemic drugs in human urine using micellar electrokinetic chromatography.

Micellar electrokinetic chromatography (MEKC) is evaluated as a potential analytical method for the separation and detection of a series of sulfonylurea drugs used in the treatment of hyperglycemia. These drugs are often surreptitiously abused, producing extremely low blood glucose levels and symptoms indistinguishable from those associated with an insulin-secreting tumor. Separation buffer containing 50 mM sodium dodecyl sulfate (SDS) was found to be adequate for the MEKC separation of the third generation drugs (glipizide and glyburide) but not the second generation drugs (acetohexamide chlorpropamide, tolazamide, and tolbutamide). At a pH of 8.5 in the presence of 20 mM borate/20 mM phosphate and 150 mM SDS, all seven components were adequately resolved with an analysis time of 17 min. Altering the concentration of the buffering components to either 5 mM borate/5 mM phosphate or 40 mM borate alone reduced the analysis time to less than 10 min with no observable loss in resolution. A series of other micelle-forming surfactants were evaluated, and only sodium cholate provided an improvement over the SDS-based system. Optimal separation was obtained with 75 mM sodium cholate and led to complete analysis with baseline resolution of all seven components in less than 8 min. These conditions were shown to be adequate for the detection of the hypoglycemic drugs spiked into normal urine and in patients taking these drugs. The precision associated with nine consecutive injections of six samples (n = 54) was found to be acceptable with percent coefficient of variance for absolute migration times (MTabs) for all peaks averaging 0.89 with peak area and peak height being 8.49 and 8.26, respectively. The between-sample precision was found to average 0.92% for MTabs and 8.56% and 8.45%, respectively, for the relative peak area and peak height. With a detection limit for the drugs in urine (following extraction) in the 50 ng/mL range, the potential exists for an MEKC-based assay for the detection of sulfonylurea drugs in urine.

Chromatography, High Pressure Liquid↗
PubMed1992

Prodrugs of nitroxyl as inhibitors of aldehyde dehydrogenase.

In the preceding paper, analogs of chlorpropamide with an OMe substituent on the sulfonamide nitrogen were shown to inhibit aldehyde dehydrogenase (AlDH), and it was postulated that these compounds were bioactivated by O-demethylation to release nitroxyl (HN = O, nitrosyl hydride), which is an inhibitor of AlDH. Further evidence for the production of nitroxyl from compounds with O-acyl instead of OMe on the sulfonamide nitrogen is now presented. Thus, nitrous oxide (N2O), the end product of nitroxyl dimerization and disproportionation, was found to be generated on alkaline or enzymatic hydrolysis of N,O-diacylated N-hydroxyarylsulfonamides. Since the latter compounds strongly inhibit yeast AlDH in vitro after bioactivation by an esterase intrinsic to this enzyme, nitroxyl generated from these compounds must be the common intermediate that inhibits AlDH.

Aldehyde Dehydrogenase↗
PubMed1987

Synthesis of N-(3,6-dihydro-1(2H)-pyridinyl)benzamides with hyperglycemic-hypoglycemic activity.

A group of N-(3,6-dihydro-1(2H)-pyridinyl)benzamides 7 were synthesized to determine the effect that the position and physicochemical properties of substituents attached to the heterocyclic ring have on blood glucose levels. 5-Methyl-N-(3,6-dihydro-1(2H)-pyridinyl)benzamide 7b was the most active hyperglycemic agent, elevating blood glucose 124% and 116% at 2 and 4 h, respectively, after a 100 mg/kg po dose. The most active hypoglycemic agent was the 4-acetyl analogue 7o, which was about 50% as active as chlorpropamide, lowering blood glucose 19% at 4 h after a 100 mg/kg po dose. A correlation between blood glucose levels and the partition coefficient P was not observed.

Animals↗
PubMed1965

The development of hepatic glucokinase in the neonatal rat.

1. Glucokinase and hexokinase activities have been determined in the livers of newborn rats and attempts made to influence in vivo the development of the glucokinase. 2. Glucokinase first appears in rat liver about 16 days after birth and adult activities are reached 10-12 days later. Evidence is presented which indicates that this represents synthesis of new protein. Hexokinase activities remain constant throughout the period of glucokinase development. 3. Both exogenous glucose and insulin are necessary for the natural development of glucokinase, for this is retarded in starved and alloxan-diabetic neonatal rats. 4. The absence of glucokinase during the first 2 weeks of extrauterine life in the rat is not due to lack of insulin. 5. Attempts to advance the time at which glucokinase first appears by infusions of glucose, insulin and chlorpropamide alone and in various combinations have resulted in marginal effects only. 6. When rats are starved for 3 days during the period of glucokinase development and then re-fed, glucokinase is more rapidly synthesized, indicating that the potential ability to synthesize glucokinase continues to develop throughout the period of starvation. 7. Some possible reasons for the comparatively late development of glucokinase are discussed.

Animals↗
PubMed1999

A five-year evaluation of intervention in diabetes care in Trinidad and Tobago.

AIMS: To evaluate an intervention to improve diabetes care in government-run heath centres in Trinidad and Tobago over 5 years. METHODS: A cross-sectional survey of 690 subjects with clinical diabetes attending nine health centres was carried out in 1993. The intervention was: reports to the Ministry of Health, dissemination of management guidelines and annual training workshops for healthcare staff. Re-evaluation was through a survey of 1579 subjects with diabetes, attending 23 health centres in 1998. RESULTS: Comparing 1993 with 1998, foot examinations in the previous year increased from 38 (6%) to 346 (22%) and fundoscopy from 6 (1%) to 139 (9%). For subjects attending for 1 year or less, 34/96 (35%) had dietary advice recorded in 1993 compared with 77/143 (54%) in 1998. Exercise advice was recorded for 3/96 (3%) in 1993 and 48/143 (34%) in 1998. In 1993, 329 (48%) were taking chlorpropamide but this fell to 57 (4%) in 1998. Glibenclamide use increased from 214 (31%) to 856 (54%) and gliclazide from four (1%) to 205 (13%). In 1993, 198/338 (56%) of hypertensive subjects were taking Brinerdin, this fell to 56/829 (7%) in 1998 while use of thiazide diuretics, methyldopa and angiotensin-converting enzyme (ACE) inhibitors increased. There were no changes in indicators of metabolic control, blood pressure control or body weight. CONCLUSIONS: Use of audit data to inform health policy and practice, linked with educational interventions, may modify patterns of care in government-run primary care health centres in a middle-income country with a high prevalence of diabetes.

Antihypertensive Agents↗
PubMed1995

Perioperative management of the diabetic patient.

Patients with diabetes mellitus are at a higher risk to undergo surgical intervention compared with the non-diabetic population, and additionally, they have an increased perioperative morbidity and mortality. Insulin deficiency and insulin resistance are aggravated by surgery and anaesthesia. The consequences of hyperglycemia are glycosuria, volume depletion from osmotic diuresis, impairment of wound healing and leucocyte function and exacerbation of ischemic brain damage. Depending on the extent of hypoinsulinemia, lipolysis and ketogenesis are enhanced which may result in metabolic acidosis with subsequent electrolyte disturbances. Protein catabolism is increased because of increased breakdown and decreased synthesis. Insulin administration reverts or overcomes most of these disturbances. The preoperative assessment includes the diagnoses of the long-term complications to judge the intraoperative risks. Long-acting insulins, such as ultralente of animal origin should be stopped preoperatively and substituted by protamine and lente insulins. In type-2-diabetic patients, long-acting sulfonylurea drugs such as chlorpropamide should be stopped and substituted by short-acting agents. Metformin must always be stopped. Type-2-diabetic patients with marked hyperglycemia under oral treatment should be switched to insulin before operation. The insulin requirements in diabetic patients during surgery vary from 0.25-0.40 U per gram glucose in normal weight patients, 0.4-0.8 U per gram glucose in case of obesity, liver disease, steroid therapy or sepsis, to 0.8-1.2 U per gram glucose in patients undergoing cardiopulmonary bypass surgery. Therefore, the appropriate dose has to be determined individually. The regimen nowadays preferred by most authors is based on variable rate insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1996

Pharmacokinetic basis for the safety of glimepiride in risk groups of NIDDM patients.

The pharmacokinetics of the sulfonylurea, glimepiride, in risk groups of NIDDM patients are reviewed with regard to pharmacokinetic-effect relationships. A variety of factors, such as regulatory processes, glucose absorption, insulin sensitivity, might prevent the definition of a clear concentration-effect relationship for sulfonylureas. However, when these processes are minimized, as with the glucose clamp technique, such relationships can be defined. This is true for glibenclamide or glimepiride, for which saturation of effect is apparent in the upper therapeutic dose range in healthy subjects. However, pharmacokinetic-pharmacodynamic relationships are less readily defined during long-term treatment of NIDDM patients. In kidney or liver disease, the hypoglycemic effect of sulfonylureas can be increased and prolonged, mainly due to a decrease in insulin metabolism or of hepatic glucose output; the risk of hypoglycemia is increased. The pharmacokinetics of most sulfonylureas have not been well characterised in patients with kidney or liver disease. Generally, sulfonylureas are eliminated by renal excretion of metabolites, some of which have similar pharmacological activity to the parent drug e.g. glibenclamide, chlorpropamide, tolbutamide. In renal disease, elimination of these metabolites can be impaired. In 31 NIDDM patients with kidney disease, elimination of unchanged glimepiride was greater in patients with more severe renal disease, probably due to a decrease in the plasma protein-bound fraction. Elimination of the renally excreted metabolites was also impaired in the same group of patients. 12 of 16 NIDDM patients with kidney disease who continued glimepiride treatment for three months maintained fasting blood glucose levels of less than 9.99 mmol/l at a daily dose of 1-6 mg, the typical dose range for patients with normal renal function. Pharmacokinetic data on sulfonylureas are generally inconsistent in cirrhotic patients. In 11 patients with liver disease, the pharmacokinetics of glimepiride were similar to those of healthy volunteers. In conclusion, pharmacokinetics, pharmacodynamics and their relationships can be defined for glimepiride under controlled conditions. Such information is lacking for many commonly used sulfonylureas in risk group NIDDM patients. Studies described here show that the pharmacokinetics of glimepiride are altered in renal disease but may not be seriously affected in patients with liver disease.

Adult↗
PubMed1987

Non-insulin-dependent diabetes mellitus. Current status of oral hypoglycemic therapy.

Proper treatment of non-insulin-dependent (type II) diabetes presents the physician with a number of choices. Diet and exercise should be tried first in many patients; if this regimen is unsuccessful, treatment with either insulin or a first- or second-generation sulfonylurea must be considered. Theoretically, second-generation agents are more advantageous than first-generation agents because they do not interact with other drugs. I do not believe that they are more efficacious, however, and they probably do not have fewer side effects if chlorpropamide (Diabinese) is eliminated from consideration. Future well-designed crossover studies may help to clarify this issue. Combined insulin and sulfonylurea therapy can be tried in obese patients resistant to large doses of insulin, although results are not dramatic. In all patients the goal is to reach acceptable fasting glucose levels and near-normal glycosylated hemoglobin values.

Blood Glucose↗
PubMed1999

Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists.

In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies. The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based. Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered. Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit. Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy. The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning. Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenytoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies. Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics should not be administered to young children because of the propensity of laxatives to cause fluid and electrolyte imbalance. In conclusion, based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline.

Acute Disease↗
PubMed1991

Lack of knowledge of symptoms of hypoglycaemia by elderly diabetic patients.

The knowledge of symptoms of hypoglycaemia of 45 consecutive elderly diabetic patients was assessed during a structured interview and compared with that of an age-matched non-diabetic control group. Twenty-three (88%) patients taking oral hypoglycaemic agents (OHAs) and six (32%) insulin-treated patients denied any knowledge of hypoglycaemia. There was no significant difference in knowledge of 14 symptoms of hypoglycaemia between the non-diabetic controls and the combined diabetic (OHA and insulin) groups, but insulin-treated patients were slightly more knowledgeable than patients taking OHAs. Fourteen (54%) of the OHA group were taking either glibenclamide or chlorpropamide which have been associated with severe and prolonged hypoglycaemia. Elderly diabetic patients are unlikely to respond to the warning symptoms of hypoglycaemia and caution should therefore be exercised when prescribing for these patients.

Administration, Oral↗
PubMed1988

Overview of drug interactions with the quinolones.

Drug interactions with the quinolones are of two types: pharmacokinetic and pharmacodynamic. Pharmacokinetic interactions include inhibition of absorption of quinolones by aluminium and magnesium containing antacids and inhibition of metabolism of other drugs by quinolones. Norfloxacin and ofloxacin are not extensively metabolized and do not inhibit drug metabolism; ciprofloxacin and enoxacin reduce theophylline clearance in normal subjects by less than 50% and greater than 50% respectively. Ciprofloxacin inhibits the metabolism of caffeine, theophylline and antipyrine. The latter is a marker of broad substrate specificity and, until proved otherwise, it would be prudent to avoid combination of ciprofloxacin with drugs which are metabolized and have a low therapeutic index. In addition to theophylline, these include cyclosporin, phenytoin and warfarin. There is evidence that the elderly and patients with liver disease are particularly susceptible to kinetic interactions with ciprofloxacin. In contrast, there is no evidence to suggest that ofloxacin is likely to impair hepatic drug elimination. Enoxacin does not impair the metabolism of chlorpropamide or glibenclamide, it is therefore unlikely that any of the quinolones will interact with sulphonylurea hypoglycaemic drugs. A pharmacodynamic interaction has been demonstrated in vitro between quinolones and non-steroidal anti-inflammatory drugs (NSAIDS) or theophylline. All of these drugs inhibit binding of radio-labelled gamma-amino-butyric acid to mouse synaptic membranes and combinations of quinolones with NSAIDS or theophylline are synergistic. Convulsions have been reported in patients who received a combination of enoxacin with either fenbufen, a NSAID, or theophylline. Like theophylline, NSAIDS undergo hepatic metabolism, so the clinical interaction may be the result of combined pharmacokinetic and pharmacodynamic interactions. Drug-interactions with quinolones are a clinically important problem. Drugs, such as ofloxacin, which do not impair hepatic metabolism of other drugs, have a clinically significant advantage over other quinolones. The pharmacodynamic interaction between quinolones and other GABA inhibitors is extremely poorly documented; further in-vitro, animal and clinical studies are urgently required.

4-Quinolones↗
PubMed1975

The emergency management of diabetes mellitus.

Some of the acute metabolic derangements of unstable diabetes have been discussed. The management of patients undergoing surgical operations has also been considered. No problems are usually encountered in diabetic patients treated with diet alone or with oral hypoglycaemic compounds, although chlorpropamide may need to be stopped sometime before operation. Patients receiving insulin therapy should be stabilised pre-operatively on a regimen which will allow more flexible management during operation and in the postoperative period; this can be readily performed by placing the patient on soluble insulin and giving spaced dosages. Other routines may be used for minor procedures. Adequate supplies of carbohydrate should be given in the form of intravenous dextrose and under no circumstances should oral glucose be given in the 6 hours before operation.

Administration, Oral↗
PubMed1983

Effects of therapeutic drugs on lymphocyte transformation.

1 Over 40 non-steroidal drugs, routinely given on a long term therapeutic basis, were tested in lymphocyte transformation cultures at high therapeutic concentrations, or in serum cultures after short term oral drug administration. Lymphocyte transformation was assessed by measuring thymidine and 2-deoxyuridine incorporation into DNA. 2 When added in vitro, salicylate significantly inhibited thymidine (48%, n = 35) and deoxyuridine incorporation (20%, n = 12). Thymidine incorporation was specifically inhibited by phenylbutazone (39%, n = 6) and chlorpropamide (48%, n = 5). Specific inhibition of deoxyuridine incorporation, indicative of impaired lymphocyte folate metabolism, was obtained following the addition of pyrimethamine (51%, n = 3) and to some extent by carbimazole (30%, n = 2). In serum cultures, pyrimethamine inhibited deoxyuridine incorporation (30%, n = 3) and chloroquine inhibited the incorporation of both thymidine (37%, n = 3) and deoxyuridine (46%, n = 3). 3 Most classes of drugs used long term are unlikely to cause any significant clinical effect, by impairing lymphocyte function. Caution may be warranted when high doses of salicylate, phenylbutazone, chloroquine, pyrimethamine, chloropropamide or combinations of these drugs are prescribed.

Deoxyuridine↗
PubMed1982

Alcohol-induced rosacea flushing blocked by naloxone.

We evaluated the roles of endogenous opioid peptides and histamine in the pathophysiology of alcohol-induced facial flushing in rosacea. Non-diabetic patients with rosacea ingested 360 ml of 6% ethanol after receiving either subcutaneous naloxone hydrochloride or oral chloropheniramine maleate. Only pretreatment with naloxone blocked the alcohol-induced rosacea flushing (AIRF), suggesting an active role of endogenous enkephalin and/or endorphin in this vascular reactivity. In this respect, AIRF is similar to chlorpropamide alcohol flushing and menopausal flushing.

Adult↗