Bio & Pharm Flashcards
Apoptosis
Apoptosis is the systematic and genetically programmed disassembly of a neuron. This is different from the accidental death, or necrosis, of cells. This process is necessary for the regular turnover of cells, including to dispose of them to prevent tumor growth. Apoptosis may be implicated in neurodegenerative disorders when it occurs too much. Apoptosis can be prevented from happening as neurotrophins can save neurons by switching off this genetic program to self-destruct.
What are critical side-effects of first and second generation antipsychotics?
First- and second-generation antipsychotics differ in age, mechanisms, and adverse effects. First-generation antipsychotics (e.g., haloperidol), also known as ‘typical’, are older and classified as low or high potency depending on how much they block dopamine D2 receptors. Extrapyramidal symptoms are more likely with these drugs because of these dopamine receptor antagonists and their potency. Other side effects result from H1 histamine blocking which can lead to sedation and drowsiness. Research states that some critical side effects of these drugs can include the lowering of the seizure threshold making them more likely, arrythmia and heart concerns, sudden cardiac death, and hypotension.
Second-generation antipsychotics (e.g., clozapine), also known as ‘atypical’, are involved with the blocking of both dopamine and serotonin receptors. These drugs are newer with typically fewer adverse effects like extrapyramidal symptoms so are more often used as a first-line treatment. However, there is a greater risk of experiencing metabolic effects like weight gain and diabetes. Some of these drugs can cause critical adverse side effects like seizures, cardiovascular issues, bone marrow suppression, and tachycardia. It is recommended that individuals on these drugs be monitored for white blood cell count if necessary.
Broca/Wernicke’s aphasia
Broca’s aphasia was coined after Paul Broca whose patient, unable to speak, died with lesions in his frontal lobe. The dominant left frontal lobe is now known as Broca’s area. Broca’s aphasia is described as a condition in which people are unable to speak but can understand language, typically characterized by anomia, or the inability to find words. Individuals with Broca’s aphasia also commonly utilize content words but few function words that connect words grammatically. This results in choppy flow of speech, repetition of words, and very short sentences. Words that can be articulated are typically well-rehearsed, like the Pledge of Allegiance. Also, they may commit paraphasic errors centered around substituting incorrect sounds or words, like purnpike instead of turnpike.
On the other hand, Karl Wernicke discovered that lesions on a specific region of the superior temporal lobe were related to poor comprehension but fluent speech. Individuals with Wernicke’s aphasia produce unintelligible speech in content but overall make correct sounds. These individuals also have poor responses to quizzing prompts, so it is unclear how much they understand of what they read or hear and are seemingly unaware of how they are speaking. Researchers hypothesize that Wernicke’s area may be related to functions of interpreting sounds to meaning and overall sound recognition.
Rough endoplasmic reticulum (vs. smooth ER)
In the cell, the rough ER is a stack of enclosed membrane dotted with dense globular structures called ribosomes. The rough ER is prevalent in neurons, is a major site of protein synthesis, and can be observed using Nissl stains. mRNA transcripts bind to the ribosomes and they translate the instructions contained to assemble a protein molecule from amino acids and peptides.
The smooth ER performs different functions in different locations and does not have ribosomes giving it a smooth appearance. The smooth ER is thought to be responsible for protein folding, regulating concentrations of calcium and glucose, detoxifying drugs, and manufacturing and metabolizing lipids.
Major processes that effect agonistic/antagonistic manner in pharmacodynamics
An agonist is a drug that binds to a receptor protein site and activates it to initiate a reaction series resulting in a specific intracellular response, typically by way of a second messenger. Typically, cells have particular receptors for particular agonists (e.g., β-adrenergic receptors that bind and respond to epinephrine or norepinephrine). Agonists may have a direct-acting effect like activating receptors or an indirect-effect by enhancing release or blocking reuptake of a neurotransmitter.
An antagonist is a drug that also binds to a receptor but does not lead to activation of the receptor, instead stabilizing its inactivity. This drug results in a lesser effect of the targeted neurotransmitter due to denying the activation of a receptor. An example of this is Naloxone, which is typically quickly administered for opioid overdoses to block opioid receptors. Antagonists can be competitive, in which they block an agonist from binding at that site, or non-competitive, in which an agonist can bind at that site but will have no effect due to the antagonist’s inhibition.
Repeated use of an agonist may influence a change in the responsiveness of the receptor; for instance, the receptor may become desensitized, and its response diminished. On the other hand, repeated use of an antagonist might result in receptor reserves being added, leading to an even greater sensitivity to agonists as well as resistance to the antagonist.
Example: Reuptake; pre-synaptic cell re-capturing its own NT. An agonist would prevent reuptake to increase concentration of NT outside cell and an antagonist would allow/force more reuptake to decrease concentration of NT outside cell.
Serotonin syndrome
Serotonin syndrome is an example of a pharmacodynamic interaction and is a potentially life-threatening medical syndrome that can occur following the co-administration of antidepressant medications, typically an MAOI or other serotonergic drug paired with an existing SSRI. For example, when taken together, MAOI’s and SSRIs will make serotonin more available as MAOIs prevent the breakdown of neurotransmitters. This might occur if the prior drug is not ‘flushed out’ for at least two weeks before taking the next.
Symptoms: hyperthermia, muscle rigidity and twitching, sweating, and changes in mental state, and untreated can lead to death, but it is rare.
Pharmacokinetics
Pharmacokinetics (PKs) refers to the study of how one’s body handles the intake of a drug and allows for one to understand dosage and treatment regimens per patient. PKs describes four stages: the absorption, distribution, metabolism, and excretion of a drug, and these all determine the onset, intensity, and duration of its effects.
Absorption involves the administration of the drug into the body’s plasma and can be taken enterally, parenterally, topically, and transdermally. Absorption can be influenced by the location of absorption, the solubility of the drug, and the amount of blood flow at the site; for instance, the first-pass effect refers to administering oral drugs that are quickly deactivated by enzymes and lead to reduced concentration.
Distribution of a drug involves the leaving of the drug from the bloodstream to the extracellular fluid where drug-receptor interactions occur and is dependent on factors including blood flow, tissue volume, and capillary permeability. One possibility is that adverse effects might occur due to the drug’s distribution to other binding sites than the target site.
Metabolism is a process by which the drug begins to be broken down chemically for excretion, and liver enzymes are heavily involved. Understanding metabolism is necessary in order to determine how much and when amounts should be administered that will appropriately be broken down in one’s body.
Excretion is a process in which the leftover parts of a drug are reabsorbed or excreted by the body (e.g., kidneys, liver), usually by urine, bile, or lungs. Understanding excretion is necessary so as not to increase toxicity of the drug if it is not fully cleared.
Hypothalamus
The hypothalamus is a structure that lies underneath the thalamus, connected to the pituitary gland, and connected to the limbic system despite not being a part of it. The hypothalamus is responsible for regulating the body’s internal environment through influencing the ANS; controlling hormone release; managing hunger, thirst, metabolism, wakefulness, and sleep; and managing emotional states like fear and anger. It also commands the body through connections with the pituitary gland, which communicates to the body through hormones released into the bloodstream. Thus, the hypothalamus is related to aspects of one’s motivation, emotion, and the internal conditions of the body (e.g., like the motivation to eat to satiate hunger), including the fight-or-flight response in stressful situations.
Hippocampus
The hippocampus is a structure contained in the limbic system deep within the medial temporal lobe that is responsible for tracking spatial location and encoding memories. The hippocampus is also involved in spatial learning with research on chickadee birds exhibiting that its size will grow the more experience these birds have on locating seeds. In a human clinical example, a patient H.M. had shown that damage to the hippocampus disrupts one’s ability to form new memories but less difficulty remembering past, long-term memories. Neuroimaging studies have also shown that greater activity in the hippocampus is related to greater later recall on tasks, indicating its role in formulating new long-term memories. The hippocampus is also involved with the hypothalamic-pituitary-adrenal (HPA) as it regulates by suppressing corticotrophin-releasing hormone (CRH) during periods where cortisol is high; consequently, chronic stress has been shown to result in lower hippocampal volumes, likely due to its difficulty maintaining.
Genotype vs. Phenotype
Genotype refers to the set of genetic material biologically inherited. For instance, in examining binary sex chromosomes, genotypes of females are denoted as XX and males as XY; the exploration of genotype has led to the discovery of X- and Y-linked chromosomal defective genes that might get passed down to children. Phenotype describes observable properties of the body and behavior as the expression of genes. Phenotype mechanisms explain why human twins might differ in regard to some body, learning, and behavior characteristics depending on what they have learned or what hormones they were exposed to over their lifetime. In another example, dogs may be genetically predispositioned to have certain muscular properties depending on their breed (e.g., pitbull); however, their behavior and muscle mass might be express differently phenotypically depending on exposure to the characteristics of a typical working pitbull. A pitbull who is neither trained nor practices working dog tasks (e.g., patrol) may appear and act differently from one that was.
Extrapyramidal Symptoms (EPS)
EPS are drug-induced movement disorders caused by certain antipsychotic and other drugs. These include involuntary or uncontrollable movements, tremors, muscle contractions. Examples of EPS’s include dystonia (sustained muscle contractions, twisting, distorted and sustained postures), Parkinson-like symptoms (motor slowing, rigidity, tremor, and reduced emotional expression), akathisia (motor restlessness), and tardive dyskinesia (short involuntary movements especially of face, tongue, lips, neck, trunk, and limbs). ESPs are often associated with first generation antipsychotics. They are thought to be the result of blocked dopamine receptors that result in an excess and imbalance of cholinergic neurons.
Major Classes of Anti-Depressants
Antidepressant pharmacological treatments are involved with neurotransmitter systems and often take multiple weeks to take a clinical effect. Four classes of antidepressants have been described with others being considered atypical antidepressants.
Tricyclic compounds (TCAs; e.g., imipramine) block the transporter reuptake of serotonin and norepinephrine to enhance their effects; tricyclic antidepressants have clinically been used to treat some chronic pain and insomnias, but it is believed that they result in adverse effects like blurry vision and cardiac effects due to blocking other receptor channels.
Selective serotonin reuptake inhibitors (SSRIs; e.g., fluoxetine) inhibit serotonin reuptake selectively, allow for greater serotonin concentration in the synaptic cleft, and tend not to block other receptors, making them more popular to prescribe; SSRIs have clinically been used for OCD and anxiety disorders, but some adverse effects like headaches and gastrointestinal issues have been reported.
Serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g., duloxetine) inhibit the reuptake of both neurotransmitters and can be used for both depression and pain relief; they are similar to TCAs but newer with fewer adverse side effects.
Monoamine oxidase inhibitors (MAOIs; e.g., phenelzine) inhibit the enzyme monoamine oxidase that typically inactivates excess neurotransmitters in nerves, allowing for neurotransmitters to remain in the synaptic cleft; this inhibition also results in MAO inactivation in the gut and liver, making drug-food effects (e.g., tachycardia & hypertension) more significant as certain toxins can build up.
G-protein coupled receptor systems (GPCRs) & the β-receptor system
G-protein-coupled receptors (GPCRs) complete slower and more complex synaptic transmissions using a variety of neurotransmitter receptors. A neurotransmitter from the extracellular environment will bind to the receptor protein, a G-protein will activate, and lastly the effector system is activated. These effector proteins can consist of G-protein gated ion channels in the membrane or activated enzymes that synthesize molecules called second messengers that diffuse away in the cytosol. GPCRs’ role in neurotransmitter communication is what makes them a focus of psychiatric drug development.
One specific GPCR contains the norepinephrine beta (β) receptor. When norepinephrine (NE) binds to this receptor, the associated G-protein activates the effector protein adenylyl cyclase. This activation converts adenosine triphosphate (ATP) to the second messenger cyclic adenosine monophosphate (cAMP) to then diffuse into the cytosol. cAMP then stimulates protein kinase enzymes to activate phosphorylation that influences protein activity. Ultimately, this process results in a more excitable cell to other neurotransmitters, and research posits this system is involved with the sympathetic nervous system’s ‘flight or fight’.
Cell-to-cell signaling
Signals between cells, also known as intercellular communication, can be mechanical, electrical and chemical through the extracellular space. These can include endocrine, paracrine, juxtacrine, and autocrine signaling.
Endocrine signaling involves long-distance communication between cells, typically from an endocrine gland, and produces hormones to travel the bloodstream and communicate in low concentrations to other cells.
Paracrine signaling involves local communication between cells through extracellular fluid, acting quickly, and are dissolved quickly.
Juxtacrine signaling, also known as direct-contact signaling, involves the binding between a ligand and receptor between cells or signaling through gap junctions between cells and is important for developmental processes.
Autocrine signaling involves binding to the ligand that the cell itself has released to stimulate its own growth; this process is believed to contribute to tumors and cancer development when this quick communication is proliferated.
Blood brain barrier
The blood-brain barrier (BBB) is made up of cells with tight junctions and wrapped in astrocytes that is responsible for the prevention of drug absorption into the central nervous system and extracellular fluid of the brain. The BBB is also responsible for maintaining the hormonal environment in the brain, repelling toxins. While potassium and ionized or polar drugs cannot pass the BBB (e.g., penicillin), lipid-soluble drugs can dissolve into the cell membranes (e.g., nicotine, anesthetics). The BBB’s restriction makes drug administration (e.g., antimicrobials) difficult in dire situations. The BBB’s permeability can also be affected by infections (e.g., meningitis). The BBB is weak in particular areas, like the circumventricular organs, to allow for the passage of some hormones.
