💊Intro to Pharmacology Unit 5 – CNS Drugs in Pharmacotherapeutics

Key Concepts and Terminology

• Central Nervous System (CNS) consists of the brain and spinal cord responsible for processing and integrating sensory information, initiating motor commands, and regulating cognitive functions
• Neurotransmitters are chemical messengers released by neurons to transmit signals across synapses (dopamine, serotonin, GABA, glutamate)
• Receptors are specialized proteins on the surface of neurons that bind to specific neurotransmitters or drugs, triggering cellular responses
• Blood-brain barrier is a selective barrier formed by tight junctions between endothelial cells lining brain capillaries that restricts the passage of substances from the bloodstream into the brain
  • Lipophilic molecules can cross the blood-brain barrier more easily than hydrophilic molecules
• Agonists are drugs that bind to receptors and activate them, mimicking the effects of endogenous neurotransmitters
• Antagonists are drugs that bind to receptors and block the effects of endogenous neurotransmitters or agonists
• Pharmacodynamics refers to the biochemical and physiological effects of drugs on the body, including their mechanisms of action and dose-response relationships
• Pharmacokinetics describes the absorption, distribution, metabolism, and excretion of drugs in the body, which determines their onset, duration, and intensity of action

CNS Anatomy and Physiology Basics

• The brain is divided into several regions with specialized functions
  • Cerebral cortex is responsible for higher cognitive functions, sensory processing, and voluntary motor control
  • Basal ganglia are involved in motor control, learning, and reward processing
  • Limbic system regulates emotions, memory, and motivation (hippocampus, amygdala)
  • Brainstem controls vital functions such as respiration, heart rate, and consciousness
• Neurons are the primary functional units of the nervous system, consisting of a cell body, dendrites, and an axon
• Synapses are the junctions between neurons where neurotransmitters are released and bind to receptors on the postsynaptic neuron
• Neurotransmitter balance is crucial for normal CNS function, and imbalances can lead to various neurological and psychiatric disorders
  • Dopaminergic system is involved in motor control, reward, and motivation (Parkinson's disease, schizophrenia)
  • Serotonergic system regulates mood, sleep, and appetite (depression, anxiety)
  • GABAergic system is the main inhibitory system in the CNS (epilepsy, anxiety)
  • Glutamatergic system is the main excitatory system in the CNS (learning, memory)

Major Classes of CNS Drugs

• Antidepressants treat depression and anxiety disorders by modulating neurotransmitter levels (SSRIs, SNRIs, TCAs, MAOIs)
• Antipsychotics treat schizophrenia and other psychotic disorders by blocking dopamine receptors (typical and atypical antipsychotics)
• Anxiolytics reduce anxiety and promote relaxation by enhancing GABA neurotransmission (benzodiazepines, buspirone)
• Anticonvulsants prevent and control seizures by modulating neuronal excitability (valproic acid, carbamazepine, gabapentin)
• Stimulants increase alertness, attention, and energy by enhancing dopamine and norepinephrine neurotransmission (methylphenidate, amphetamines)
• Sedative-hypnotics induce sleep and sedation by enhancing GABA neurotransmission (benzodiazepines, Z-drugs)
• Analgesics relieve pain by acting on opioid receptors or modulating pain pathways (opioids, NSAIDs, gabapentinoids)
• Cognitive enhancers improve memory, attention, and executive function in conditions like Alzheimer's disease and ADHD (cholinesterase inhibitors, memantine)

Mechanisms of Action

• Modulation of neurotransmitter levels can be achieved by
  • Inhibiting neurotransmitter reuptake (SSRIs, SNRIs)
  • Blocking neurotransmitter degradation (MAOIs)
  • Increasing neurotransmitter release (amphetamines)
• Receptor agonism involves drugs binding to and activating specific receptors, mimicking the effects of endogenous neurotransmitters (opioid agonists, benzodiazepines)
• Receptor antagonism occurs when drugs bind to receptors and block the effects of endogenous neurotransmitters or agonists (antipsychotics, antiemetics)
• Modulation of ion channels can alter neuronal excitability
  • Sodium channel blockers reduce neuronal firing and are used as anticonvulsants (carbamazepine, lamotrigine)
  • Calcium channel blockers reduce neurotransmitter release and are used in neuropathic pain (gabapentin, pregabalin)
• Enzyme inhibition can affect neurotransmitter synthesis, degradation, or receptor function (cholinesterase inhibitors, MAOIs)
• Neuroprotection involves preventing or reducing neuronal damage caused by excitotoxicity, oxidative stress, or inflammation (memantine, antioxidants)

Therapeutic Uses and Indications

• Depression and anxiety disorders are treated with antidepressants, anxiolytics, and sometimes antipsychotics
• Schizophrenia and other psychotic disorders are managed with antipsychotics
• Bipolar disorder is treated with mood stabilizers (lithium, valproic acid), antipsychotics, and sometimes antidepressants
• Epilepsy and seizure disorders are controlled with anticonvulsants
• Parkinson's disease is managed with dopaminergic agents (levodopa, dopamine agonists), anticholinergics, and MAO-B inhibitors
• Alzheimer's disease and other dementias are treated with cognitive enhancers (cholinesterase inhibitors, memantine)
• Attention deficit hyperactivity disorder (ADHD) is managed with stimulants and sometimes non-stimulant medications (atomoxetine, guanfacine)
• Chronic pain conditions, such as neuropathic pain, are treated with analgesics, anticonvulsants, and antidepressants

Side Effects and Adverse Reactions

• Antidepressants can cause nausea, dry mouth, weight gain, sexual dysfunction, and rarely, serotonin syndrome
• Antipsychotics may lead to extrapyramidal symptoms (EPS), metabolic disturbances, sedation, and anticholinergic effects
  • EPS include akathisia, dystonia, and tardive dyskinesia
• Anxiolytics and sedative-hypnotics can cause drowsiness, dizziness, impaired coordination, and respiratory depression
• Anticonvulsants may cause sedation, dizziness, weight gain, and rarely, life-threatening skin reactions (Stevens-Johnson syndrome)
• Stimulants can lead to insomnia, appetite suppression, irritability, and cardiovascular effects (hypertension, tachycardia)
• Opioid analgesics may cause constipation, nausea, sedation, respiratory depression, and addiction
• Cholinesterase inhibitors can cause gastrointestinal disturbances, bradycardia, and vivid dreams
• Many CNS drugs can cause withdrawal symptoms upon abrupt discontinuation, necessitating gradual tapering

Drug Interactions and Contraindications

• Antidepressants that inhibit CYP450 enzymes can increase the levels of other drugs metabolized by the same enzymes (TCAs, SSRIs, SNRIs)
• Combining CNS depressants (opioids, benzodiazepines, alcohol) can lead to excessive sedation and respiratory depression
• MAOIs can cause hypertensive crisis when combined with tyramine-rich foods or sympathomimetic drugs
• Antipsychotics should be used with caution in patients with Parkinson's disease, as they may worsen motor symptoms
• Anticonvulsants may interact with oral contraceptives, reducing their effectiveness
• Stimulants should be avoided or used with caution in patients with cardiovascular disorders, hyperthyroidism, or history of substance abuse
• Opioids should be used with caution in patients with respiratory disorders, head injuries, or impaired liver or kidney function
• Cholinesterase inhibitors are contraindicated in patients with bradycardia, sick sinus syndrome, or gastrointestinal obstruction

Dosing and Administration

• CNS drugs are available in various formulations (oral tablets, capsules, liquids, transdermal patches, injectable solutions)
• Dosing should be individualized based on patient factors (age, weight, renal and hepatic function, comorbidities) and response to therapy
• Some drugs require dose titration to minimize side effects and achieve optimal therapeutic response (antidepressants, antipsychotics)
• Extended-release or long-acting formulations can improve adherence and reduce dosing frequency (antipsychotics, stimulants)
• Therapeutic drug monitoring may be necessary for drugs with narrow therapeutic indices or high interindividual variability (lithium, valproic acid)
• Tapering is recommended when discontinuing many CNS drugs to prevent withdrawal symptoms (antidepressants, benzodiazepines, opioids)
• Proper storage and disposal of CNS drugs, especially controlled substances, is crucial to prevent misuse and accidental ingestion

Special Considerations and Patient Education

• Pregnant and breastfeeding women should consult their healthcare providers before using CNS drugs, as many can cross the placenta or enter breast milk
• Elderly patients may be more sensitive to the effects of CNS drugs and require lower doses or more frequent monitoring
  • Increased risk of falls, confusion, and anticholinergic side effects
• Patients with hepatic or renal impairment may require dose adjustments or alternative medications
• Patients should be educated about the potential side effects, drug interactions, and the importance of adherence to the prescribed regimen
• Patients should be advised not to abruptly stop taking CNS drugs without consulting their healthcare provider
• Patients taking CNS depressants should be cautioned against driving or operating heavy machinery
• Patients should be encouraged to report any unusual symptoms or worsening of their condition to their healthcare provider
• Patients and caregivers should be provided with resources for support, education, and coping strategies (support groups, therapy, lifestyle modifications)