Drug Delivery Via The Nasal Route

Intravenous Naloxone reaches the brain two minutes faster than intranasal Naloxone, which could be the difference between life or death. However, through an I.V., 100% of Naloxone reaches the brain. On the other hand, Strang, McDonald, Tas, and Day discovered that when intranasal Naloxone is not administered at a 90 degree angle or the nasal cavity is blocked with vomit, Naloxone gathers at the back of the throat and is swallowed by the Naloxone recipient (576). This means that when intranasal Naloxone is administered, Naloxone has to be administered repeatedly to fully reverse opioid overdose. Often times, intranasal Naloxone is followed by administration of intravenous or intramuscular Naloxone. While using intravenous and intramuscular administration, there is no way to slow the absorption of Naloxone.

The route of drug administration chosen might be dependent on a person's age because of its variants on the effects of the drugs used on them. For example, a child usually has a hard time swallowing pills so they instead would drink their medicine, it is one of those factors that would lead us to alternatives. It is the same for pregnant women and the elderly that have different effects on them, so they would have different routes of drugs.

Scientists hope they can find a possible way to safely pierce the blood-brain barrier. What they want to do next is, to all Alzheimer’s drugs to flow directly into the brain. One challenge is that the blood-brain barrier is there to protect the brain (Mills, D. 2017). If the blood- brain barrier is damaged harmful organisms can invade. The

7- Acetyl Choline – chemical messenger in the brain which makes “neurones spark better and speak to each other more clearly.” (Bryden, 2005, p. 16) Small amounts of acetyl choline when you have dementia so brain does not work as fast. Drugs called acetyl cholinesterase (AChE) inhibitors stop the breakdown of acetyl choline so you have increased amounts in

In decision point one, the choices provided are to initiate (a) rivastigmine 1.5 mg orally twice daily with an increase to 3 mg orally twice daily in two weeks, (b) donepezil 5 mg orally at bedtime, or (c) galantamine 4 mg orally twice daily. All of the medications are cholinesterase inhibitors and are considered first-line pharmacotherapy for AD (Yiannopoulou & Papageorgiou, 2012). In randomized controlled trials, rivastigmine, donepezil, and galantamine showed no significant difference in efficacy (Yiannopoulou & Papageorgiou, 2012). Donepezil was selected. Once-daily dosing has been shown to have better adherence than twice daily (Ryan et al., 2014). Galantamine and rivastigmine have a higher incidence of gastrointestinal adverse effects than donepezil (Noetzli & Eap, 2013; Yiannopoulou & Papageorgiou, 2012).

Cholinesterase inhibitors are used to breakdown the acetylcholine, which is a neurotransmitter that is connected to memory, by blocking the enzyme acetylcholinesterase. The donepezil, rivastigmine, and the galantamine are three commonly prescribed cholinesterase inhibitors. The known side effects are nausea, vomiting, diarrhea, upset stomach, and dizziness (Wattmo, Londos, & Minthon, 2014). To block the NDMA receptors, the memantine is prescribed to improve cognition and regulate the glutamate that acts as a neurotransmitter in the brain around the learning and memory area. Excessive glutamate could cause damaged, killed nerves. Common side effects of memantine consist of dizziness, confusion, and headaches (Koch, Szecsey, & Haen, 2004). Additional medication can be prescribed to patients with symptoms such as depression, psychosis, disturbed sleep, and apathy. Howes (2014) supported the commonly used drug treatments as he compared AD to the issues of the cardiovascular disease. The reduced blood flow to the brain, the reduction of oxygen, clogged arteries and vessels could damage the brain cells, making the Alzheimer’s disease worse. The treatment of AD reduces some of the effects of the cardiovascular (Howes,

Alzheimer’s disease (AD) is a complex, multifactorial neurodegenerative disease that is currently being managed by symptomatic treatment. The affected areas include the central nervous system (CNS) which is made up of the brain and spinal cord. The brain is essential in managing our thoughts, cognitive abilities, and our ability to interact with the environment. AD patients are known to experience symptoms such as memory loss in the early stages which develop into speaking difficulties to eventually hallucinations. The commonly used AD treatments include Donepezil, rivastigmine, galantamine and memantine. Only the last two will be discussed in this essay and novel treatments. The current treatments for AD focus on relieving symptoms

The areas of the brain that are opulent in cholinergic neurons are vital areas for memory and learning (Hippocampus), attention and motivation (anterior cingulate), and the control of behaviours (hypothalamus). Most drugs that are used to treat AD are cholinesterase inhibitors. Cholinesterase inhibitors act by inhibiting the job of cholinesterase, they also work as an enzyme thus metabolising acetylcholine in the synaptic cleft, leading to more activity in the cholinergic synapses. Therefore the justification of using of these types of drugs is to decrease the shortage of cholinergic in synaptic diffusion thus restoring cholinergic operations or at the very least slow down the deterioration, (Parrott A, Morinan, A, Moss, M, Scholey, A. Wiley 2004).

By CNS drug discovery we produce new CNS pharmaceutics which have the dual activity i.e. solubility of lipids and molecular size and have the capability to cross blood-brain barrier by the diffusion into endothelial plasma membranes.

Treatments of AD range from traditional cholinesterase inhibitor drugs such as Tacrine (Cognex), Donepezil (Aricept), Rivastigmine (Exelon) and Galantamine (Razadyne). Cholinesterase inhibitor drugs affect AD by inhibiting the enzyme acetylcholinesterase. Acetylcholinesterase breaks down into acetylcholine which is essential for memory and cognition. The inhibitor drugs work by slowing the progression of AD, thereby prolonging the patient’s lifespan and mental cognition (Borda 46-52).

(N/A, Treatments for Alzheimer's disease, n.d.) Prescribed medication that are being used to treat cognitive symptoms are cholinesterase inhibitors. Cholinesterase Inhibitors offer limited relief from the symptoms of Alzheimer’s disease. As the symptoms vary from each individual, the relief varies as well. Some patients will not notice the effect, others will notice their symptoms improving whilst some may experience no effect. Trials indicated that cholinesterase inhibitors, on average, delay progression of symptoms for nine to twelve

Donepezil, Tacrine, Rivastigmine and Glantamine are the four medications within the cholinesterase inhibitors (CI). CI is indicated in mild to moderate AD. These medications are not to cure but only to slow the progression of the disease process, which involves cognitive, functional, and behavioral aspects of AD. It has also shown that these medication can decrease apathy, psychosis, anxiety, depression, and agitation. It is important to titrate CI to the maximum tolerated dose to maximum efficacy

The compound already presented an interesting in vitro activity in its initial tests and currently is thought to be one of the most active benzothiadiazine-derived AMPA-PAMs reported []. Further conducted intracerebral microdialysis experiments allowed detection of micromolar concetration of 1 in mouse nucleus accumbens (NAc) dialysates. It means that the compound is able to cross blood-brain barrier (BBB) after intraperitoneal injection (ip) (see section paragraph). Intracerebral microdialysis is a known experiment that can be applied to evaluate in vivo compound’s p pharmacokinetic (PK) and pharmacodynamic (PD) profile. Nevertheless, it is crucial the compound remains in the specific brain of interest for a sufficient time and at the appropriate to evoke its function and achieve the desired effect. Therefore, examination in vivo of the novel compounds stability plays pivotal role here. In fact, chemical degradation of compound can lower its sufficient concentration below the therapeutic dose. Moreover, as explained in detail in introductory paragraphs, the AMPA-PAM activity usually resides only in one enantiomer

This Bi-Directional™ technology could be utilized to any type of dispersion technologies related to liquid and powder. When delivery of drug is required, a user exhaled into the mouthpiece of device, soft palate is elevated and the nasal cavity is isolated from the rest of respiratory system. The patient exhaled force emitted the medication from device into nostril while closure of the soft palate prevented the entry of drug to the lungs. Expended nasal passage delivered medication deep into the targeted area of the nasal cavity. When medicine is delivered to the targeted sites, air following “Bi-Directional™ flow path” flowed around to the opposite side of the nasal cavity and exit through the other side of the nose rather than into the throat or lungs, as depicted in fig 6 [129, 130]. Nasal valve is a narrow opening in the nasal cavity, created a barrier for delivery of drug to brain. Neural connection to brain is located posterior to this valve. Traditional nasal devices deliver drug in or anterior to this valve. Optinose is a biopharmaceutical company, patented closed-palate Bi-Directional™ Breath Powered® DDSs. This technology used exhale device to target the drug to upper posterior part of the nasal cavity, beyond this valve [130]. Role of oxytocin has already been explored in the treatment of autism spectrum. Higher doses

Intramuscular injection is used for the delivery of certain drugs not recommended for other routes of administration, for instance intravenous, oral, or subcutaneous. The intramuscular route offers a faster rate of absorption than the subcutaneous route, and muscle tissue can often hold a larger volume of fluid without discomfort. In contrast, medication injected into muscle tissues is absorbed less rapidly and takes effect more slowly that medication that is injected intravenously. This is favorable