Lectutre 19 CNS drug delivery Flashcards
Describe the role of ion regulation in maintaining optimal ionic composition for synaptic signaling. How does the concentration of potassium differ between plasma and cerebrospinal fluid (CSF)?
Ion regulation and homeostasis involve specific ion channels and transporters to maintain the ideal ionic composition for synaptic signaling. For example, potassium levels are around 4.5 mM in plasma but 2.5-2.9 mM in CSF, ensuring proper neuronal function.
How does the blood-brain barrier (BBB) protect the brain from harmful substances like plasma proteins? What are the potential consequences of these substances crossing a leaky BBB?
The BBB shields the brain from harmful macromolecules like certain plasma proteins. If these substances breach a leaky BBB, they can lead to severe pathological outcomes, underscoring the importance of the BBB’s selective permeability.
Define the concept of segregation of neurotransmitters and its significance in minimizing ‘cross-talk’. Why is it crucial to keep central and peripheral transmitters separate?
Segregation of neurotransmitters involves keeping central and peripheral transmitters distinct to reduce interference or ‘cross-talk.’ This separation is vital for maintaining the specificity and efficiency of neuronal communication.
How do different mechanisms facilitate the transport of molecules across the BBB? Explain the processes of paracellular aqueous pathway, transcellular diffusion, carrier-mediated transport, receptor-mediated endocytosis, and active efflux transport.
Various mechanisms enable molecule transport across the BBB, including paracellular aqueous pathway, transcellular diffusion, carrier-mediated transport, receptor-mediated endocytosis, and active efflux transport. Each mechanism plays a crucial role in regulating the passage of substances into the CNS.
Describe the significance of saturable carrier-mediated transport at the BBB. How do these highly selective transport systems ensure an adequate supply of nutrients to the brain? Provide examples of nutrients transported through this mechanism.
Saturable carrier-mediated transport systems at the BBB are crucial for selectively transporting essential nutrients like glucose and amino acids to the brain. These systems ensure a sufficient supply of nutrients by facilitating the passage of specific molecules critical for brain function.
Describe the structure and function of the choroid plexus in to the Blood-CSF Barrier (BCSFB)
The choroid plexus consists of cuboidal epithelial cells with microvilli surrounding fenestrated capillaries. It acts as the BCSFB by secreting cerebrospinal fluid (CSF) and allowing movement of substances across endothelial cells.
How does the Blood-Brain Barrier (BBB) influence drug delivery to the central nervous system (CNS)?
The BBB ensures short diffusion distances for drugs to reach neurons and glial cells once crossed. Targeting drugs across the BBB is preferred for global delivery to all brain cells.
Discuss different approaches to targeting drugs to the brain for systemic drug delivery.
Approaches include intravenous, intra-arterial, transnasal delivery, chimeric peptides, cationic proteins, prodrugs, chemistry-based methods, liposomes, nanosystems, biotechnology-based techniques like mAbs and genomics.
Explain the concept of direct CNS delivery and the methods involved in circumventing the Blood-Brain Barrier (BBB).
Direct CNS delivery involves intracerebral or intraventricular injection to bypass the BBB. It includes intracerebral implants for controlled drug release and instillation of drugs into the cerebral ventricle, although it is highly invasive with limited drug distribution.
Define the role of the Blood-CSF Barrier (BCSFB) in drug and solute entry into the brain compared to the Blood-Brain Barrier (BBB).
The BCSFB allows some substances to enter the brain via the choroid plexus into CSF, while others enter through both the BBB and BCSFB. It provides an alternative route for drug delivery to the CNS.
Describe the process of intrcal injection and its advantages and disadvantages compared to other routes of drug administration.
Intrathecal injection involves delivering drugs into the spinal fluid space, offering a less invasive alternative to intraventricular administration. However, it lacks drug accumulation in deep brain structures, risking spread along the spinal canal leading to side effects like ataxia. It is best for spinal diseases but not large parenchymal diseases like glioblastomas.
How does the autonomic nervous system serve as a potential route for drug delivery to the central nervous system, and what discovery led to this realization?
The autonomic nervous system has emerged as an ideal route for CNS drug delivery, following research on prion diseases like CJD, scrapie, and BSE in 1998. Prions were found to use a distinct pathway from the BBB, entering the brain via infected blood cells through nerve fibers, paving the way for targeted drug delivery.
Define the roles of intravenous and intra-arterial routes in drug administration, highlighting their advantages and limitations.
Intravenous administration allows direct drug delivery into the body but faces challenges like drug half-life, rapid metabolism, and BBB permeability. Intra-arterial route enhances intra-tumoral drug concentrations when combined with BBB-disrupting agents. Both routes have specific advantages and limitations in drug delivery.
Describe the concept of transnasal drug delivery, including the mechanism involved and its limitations.
Transnasal drug delivery is a non-invasive method bypassing the BBB by moving drugs from the nasal submucosa space to the brain’s CSF cavity. This method leverages the olfactory region’s cells extending into the cranial cavity. However, limitations include drug absorption variability and the risk of drainage into the pharynx if large volumes are used.
Explain the significance of drug accumulation in parenchymal structures in the deep brain for sustained drug release, and why intrathecal administration may not be suitable for large parenchymal diseases like glioblastomas.
Accumulation in deep brain structures is crucial for sustained drug release, which intrathecal administration may lack. This route, while less invasive, may not be suitable for large parenchymal diseases like glioblastomas due to the risk of drug spread along the spinal canal, potentially causing ataxia and muscle coordination loss.
