Dose counter

Bradshaw, D. R. S. (2006), Developing dose counters An appraisal based on regulator, pharma, and user needs, in Dalby, R. N., Byron, P. R., Peart, J., Suman, J. D., and Farr, S. J., Eds., Respiratory Drug Delivery 2006, Davis Healthcare International, River Grove, IL, pp. 121-131. 

SkyePharma multidose pocket-sized inhaler features an intelligent single dose counter to count the dose dispensed and remained in the inhaler. The built-in locking mechanism also allows no tailoff effect toward the last doses from the inhaler (Fig. 

The effects of salmeterol 50 micrograms plus fluticasone 250 micrograms delivered via a combination inhaler and via separate inhalers have been compared in 371 asthmatic patients (18). There were equivalent improvements in peak flows and asthma sjmptoms. Candidiasis, dysphonia, and throat irritation were the commonest adverse effects attributed to treatment and occurred equally in the two groups (35%). Palpitation and tremor, which may have been related to salmeterol, occurred in 2% (for each symptom) of the combination group and in 1% and under 1% of the separate inhaler group. In both of these studies compliance was measured by dose counters on the inhalers and was equivalent in the two groups. 

Device Drugs Breath- Activated Dose Counter Other Excipients Disadvantages... 

Design Requirements Customer Requirements IMPORTANCE Dose Uniformity Dose counter Aesthetic appeal Colour coded Breath actuation Actuation pressure Impact strength i OBJECTIVE TARGETS 12 3 4 ... 

With the advent of mechanically complex BAIs, the possibility of incorporating a dose counter is more likely, and these are expected to be available in the near future. Dose counters will enable parents to check if their child has taken his medicine and will enable everyone to establish when the can is empty. Patients should not be advised to float the can in water to gauge its contents, as potential water ingress is disastrous to formulation stability. 

Dose counters are already available for dry-powder inhalers (DPIs), and there is little doubt that they will also become a feature of pMDIs. 

There are also two ways to look at compliance monitors, whether they are to help the patient to follow his or her dosing regime or whether they are for the physician to check if the patient is following this regime. In the simplest case, numerical dose counters now being fitted to breath-activated inhalers enable a patient—or perhaps more importantly a child s parent—to check if the dose has been taken. This assumes the discipline of keeping track of the previous dose number. 

The primary functional parts of a dry powder inhaler are schematically shown in Fig. 6.6 and include a powder formulation, a dose (measuring) system, a dispersion principle for the powder formulation, a mouthpiece and a housing for all parts. Additionally, the inhaler may have various secondary features, including a dose counter, giving the number of doses left in the device, a compartment with desiccant to keep the powder formulation dry and a signalling to the patient that the inhalation manoeuvre is correct or has been completed. Different choices can be made for each of the functional parts and a good and compatible combination has to be chosen and developed to obtain the maximal result. 

Figure 5.21. Experimental setup (inset) showing the location of the working (WE), counter (CE) and reference (RE) electrodes and of the heating element (HE) thermal desorption spectra after gaseous oxygen dosing at 673 K and an 02 pressure of 4x1 O 6 Torr on Pt deposited on YSZ for various exposure times. Oxygen exposure is expressed in kilo-langmuirs (1 kL=l0 3 Torrs). Desorption was performed with linear heating rate, ()=1 K/s.4 S Reprinted with permission from Academic Press.

There is some evidence of a synergistic effect on reinforcement with concurrent administration of benzodiazepines and opioids (Walker and Ettenberg 2003). Cocaine abusers are less likely than opioid abusers to abuse benzodiazepines, preferring alcohol and opioids as secondary drugs of abuse. The most common pattern of benzodiazepine misuse in these individuals is intermittent use of therapeutic or supratherapeutic doses to counter unwanted effects of cocaine. 

Hydralazine 4-8 hour Up to 30 minute 5-40 mg prn dosing Headache, tachycardia, lupus like syndrome, potential nephrotoxicity Often given with beta-blocker to counter reflex sympathetic drive, may increase ICP... 

In common with neuropathy, NMDA receptor activation occurs after inflammation but here opioid actions are enhanced since CCK levels decrease. Thus, this augmented opioid actions may counter the increased excitability without the need for large increase in doses of opioid. 

Each cage contained six infrared photocell beams arranged around the base of a circular tract. Each interruption of a beam registered a count on a total-event counter and on a cumulative recorder. Cumulative IV doses at 30-minute intervals were administered over dose ranges that included the complete spectrum of effects on SLA. 

Recent data suggest that COX-2 inhibitors, including rofe-coxib, valdecoxib, and celecoxib, may increase the risk for MI and stroke.47 There is also some evidence that the non-selective NSAIDs may increase the risk for cardiovascular events.47,48 Rofecoxib was withdrawn from the market in late 2004 because of safety concerns. The FDA requested the withdrawal of valdecoxib from the market in 2005. The FDA also asked the manufacturers of celecoxib and non-selective NSAIDs (prescription and over-the-counter) to include information about the potential adverse cardiovascular effects of these drugs in their product labeling. The cardiovascular risk with COX-2 inhibitors and NSAIDs may be greatest in patients with a history of, or with risk factors for, cardiovascular disease. The American Heart Association recommends that the use of COX-2 inhibitors be limited to low-dose, short-term therapy in patients for whom there is no appropriate alternative.48 Patients with cardiovascular disease should consult a clinician before using over-the-counter NSAIDs. 

Patients should also be educated to keep track of inhaler use. Many DPIs have a built-in counter or device to notify the patient of how many doses are remaining (e.g., Diskus and Twisthaler ) or that the inhaler is approaching empty (e.g., Turbuhaler ). 

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