NUR 2047 Pharmacology Lecture 4 PDF

NUR 2047 Pharmacology Lecture 4 Drugs affecting the Autonomic and the Central Nervous System; Analgesia  Learning Objectives After this lecture, students should be able to:- ❖Understand the functions of the ANS and CNS ❖Understand the receptors of the ANS ❖Understand the...

NUR 2047 Pharmacology Lecture 4 Drugs affecting the Autonomic and the Central Nervous System; Analgesia  Learning Objectives After this lecture, students should be able to:- ❖Understand the functions of the ANS and CNS ❖Understand the receptors of the ANS ❖Understand the drugs for depression, anxiety and insomnia ❖Understand the drugs for degenerative diseases ❖Understand the drugs for seizures ❖Understand analgesics Nervous System  Basic functions and subdivisions of the Nervous System ❖Recognizes stimuli in the internal and external environments ❖Process and integrate the environmental stimuli ❖React to the environmental stimuli with a series of actions or responses Structural subdivisions ❖Sensory subdivisions ❖Motor subdivisions Somatic nervous system ✓ Consists of nerves that provide voluntary control over the skeletal muscles Autonomic nervous system ✓ Nerves exert involuntary control over the smooth muscle, cardiac muscle and glands  Branches of the Autonomic Nervous system Sympathetic Nervous System ❖Activated under conditions of stress ❖Results in fight or flight response Parasympathetic Nervous System ❖Activated under non-stressful conditions ❖Rest and digest response Effects of PSNS and SNS https://www.youtube.com/watch?v=m2GywoS77qc https://www.youtube.com/shorts/l9XD6QgGBUk  Synapse ❖Area at the end of the neuron Synaptic cleft ❖Space between neurons ❖Nerve impulses must cross to reach the next neuron Presynaptic neuron ❖Generates original impulse Postsynaptic neuron ❖Nerve on the other side of the synapse waiting to receive impulse  Receptors in the ANS PSN pathway ❖ACh is released at both ganglia (nicotinc ❖receptor) and effector organ (cholinergic ❖(muscarinic) receptor) SN pathway ❖ACh is released at the ganglia (nicotinic ❖receptor) and NE at the effector organ ❖(adrenergic receptor)  Autonomic Nervous System drugs ❖These are classified according to the receptors that they stimulate or block Activation of the SNS ❖Adrenergic drugs or sympathomimetics Activation of the PNS ❖Cholinergic drugs or parasympathomimetics Inhibition of SNS ❖Adrenergic blockers or sympatholytics Inhibition of PNS ❖Cholinergic blockers or anticholinergics Autonomic Nervous System drugs CNS General mechanism of the drugs that act on the CNS Depression and serotonin  Depression, anxiety and insomnia ❖Treated with many types of central nervous system (CNS) drugs CNS depressants Anti depressants ❖SSRIs, SNRIs, TCA Benzodiazepines ❖Diazepam, Alprazolam  Indications Indications of antidepressants Depressive disorders Generalized anxiety Panic disorders  SSRI Antidepressants Selective serotonin reuptake inhibitors (SSRIS) Depression (MoA) Blocks the reuptake of serotonin at the presynaptic terminals, thus leading to an increased concentration of Serotonin in the synaptic cleft ✓ Paroxetine ✓ Sertraline (Zoloft) ✓ Citalopram ✓ Escitalopram ✓ Fluoxetine Side effects ✓ Feeling agitated, shaky or anxious ✓ Orthostatic hypotension, Indigestion, diarrhea, constipation, dizziness, ✓ Headache, tremor, blurred vision, ✓ Dry mouth, cough, Dyspnea, painful menstruation  SSRIS Nursing considerations SSRIS ❖Monitor for effects (?reduction in depressive mood) and side effects (any side effects) ❖Realization of full therapeutic effect is up to 6-8 weeks ❖Take in the morning ❖Take with food to reduce stomach upset ❖Use with caution for patients with liver and renal failure (reduced dose and careful monitoring) ❖Monitor for serotonin syndrome (high levels of serotonin) – BP, P, shivering, diarrhea to muscle rigidity, fever, seizures ❖Increased risk of suicide in patients with suicidal ideas (This especially happens in the early weeks of treatment and subsides gradually) ❖Avoid taking with grapefruit juice (affects the bioavailability of the medication) ❖Abrupt cessation causes withdrawal symptoms – anxiety, insomnia, increased nervousness. Need gradual withdrawal ❖Cautious use in pregnant and lactating women due to the potential adverse effect to fetus and baby  SNRI Antidepressants Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) Depression, anxiety (MoA) Blocks the reuptake of serotonin and norepinephrine at the presynaptic terminals, thus leading to an increased concentration of these neurotransmitters in the synaptic cleft ✓Venlaflexine ✓Duloxetine Side effects ✓Hypertension, Nausea, loss of appetite, dry mouth, tiredness, constipation, Hyponatremia, increased risk of bleeding, somnolence  SNRIS Nursing considerations SNRIS ❖Monitor for effects (?reduction in depressive mood) and side effects any side effects) ❖Realization of full therapeutic effect is up to 6-8 weeks ❖Take in the morning ❖Take with food to reduce stomach upset ❖Use with caution for patients with liver and renal failure (reduced dose and careful monitoring) ❖Monitor for serotonin syndrome (high levels of serotonin) – BP, P, shivering, diarrhea to muscle rigidity, fever, seizures ❖Increased risk of suicide in patients with suicidal ideas (This especially happens in the early weeks of treatment and subsides gradually) ❖Abrupt cessation causes withdrawal symptoms – anxiety, insomnia, increased nervousness. Need gradual withdrawal ❖Cautious use in pregnant and lactating women due to the potential adverse effect to fetus and baby  TCA Antidepressants Tricyclic antidepressants (TCAs) Depression, anxiety (MoA) Block the reuptake of serotonin and norepinephrine at presynaptic terminals, thus leading to an increased concentration of these neurotransmitters in the synaptic cleft ✓Amitriptyline ✓Nortriptyline ✓Doxepin Side effects ✓Hypertension, arrhythmias, palpitations, MI, Constipation, dry mouth, blurred vision, dizziness, drowsiness, Weight gain, excessive sweating at night, urinary retention  TCAs Contraindications for TCAS ❖Myocardial infarction (It can reoccur because of the cardiac effects of the drug) ❖Seizures (seizures threshold is decreased due to stimulation of receptor sites) ❖Liver and renal disease as it may interfere with metabolism and excretion ❖Myelography within previous 24 hours or the next 48 hours (possible interaction with the dye) ❖Glaucoma, urinary retention as the condition will be exacerbated by the anticholinergic effect of the drug ❖Pregnant and breast-feeding as it will cause adverse effects on the fetus and breast-fed infants  TCAs Nursing considerations TCAS ❖Usually administered before bed due to sedating effects ❖Monitor BP, P, angina, palpitations ❖Monitor vision ❖Monitor for urinary retention ❖Assess history of seizures, suicidal ideas ❖Abrupt cessation causes withdrawal symptoms – nausea, headache, vertigo, malaise, nightmares ❖Drug-drug interactions Oral anticoagulants – increased risk of bleeding https://www.youtube.com/watch?v=xQM-gn8jgQM  Benzodiazepines ❖One of the most widely prescribed drug classes ❖Benzodiazepines are useful for the short-term treatment of anxiety and insomnia ❖Used for Panic disorders Generalized anxiety Phobias Insomnia ❖They act by facilitating the binding of the inhibitory neurotransmitter GABA at various GABA receptors throughout the CNS ❖GABA binds at special sites called GABA-a receptors on the outside of the receiving neuron. Benzodiazepines also bind to their own receptors situated on the GABA receptors. This allow more Cl- to enter the neuron, making it even more resistant to excitation ❖The effect is reduced neuronal excitability  Benzodiazepines GABA receptors ❖Lessens the ability of a nerve cell to receive, create or send chemical messages to other nerve cells ❖Produces a calming effect ❖GABA binds at special sites called GABA-a receptors on the outside of the receiving neuron. Benzodiazepines also bind to their own receptors situated on the GABA receptors. This allow more Cl- to enter the neuron, making it even more resistant to excitation https://www.youtube.com/watch?v=4ZHudeMho8g https://www.youtube.com/watch?v=JAhmh2-jCdY  Benzodiazepines Sedatives/hypnotics ❖Flunitrazepam (Rohypnol) ❖Midazolam ❖Nitrazepam Anxiolytics ❖Alprazolam (Xanax) ❖Bromazepam ❖Clobazam (Frisium) ❖Clonezepam (Rivotril) ❖Diazepam (Valium) ❖Lorazepam (Ativan) Benzodiazepines Side effects ❖Drowsiness ❖Dizziness ❖Slurred speech ❖Confusion ❖Muscle weakness ❖Memory problems ❖Constipation ❖Nausea ❖Dry mouth Seizures and drugs  Antiseizure pharmacotherapy ❖It is directed at controlling the movement of electrolytes across neuronal membranes or affecting neurotransmitter balance Goal ❖to suppress neuronal activity just enough to prevent abnormal or repetitive firing Action ❖Three general mechanisms by which antiseizure drugs work Stimulating an influx of chloride ions, an effect associated with neurotransmitter gamma-aminobutyric acid (GABA) Delaying an influx of sodium ions Delaying an influx of calcium ions Results in hyperpolarization inhibition (reduce firing) Antiseizure pharmacotherapy and GABA  GABA receptor-chloride channel ❖The chloride selectivity filter allows the channel to open exclusively to chloride ions when GABA, benzodiazepines or barbiturates bind to the cellular receptor. Some antiseizure drugs are similar to the structure of GABA, or they may potentiate GABA indirectly. After the influx of chloride ions, the net result is inhibition of the neuron’s action potential and suppression of the neuron’s firing rate https://www.youtube.com/watch?v=xFUHE9gX6W8  Degenerative diseases of the CNS Disease Description Parkinson’s Disease Progressive loss of dopamine in the CNS causing tremor, muscle rigidity and abnormal movement and posture  Parkinson’s disease ❖An imbalance in the levels of acetylcholine and dopamine. The body needs this balance to control movements well ❖Decrease in dopamine Dopamine helps move electrical signals through the brain. Hence, it is responsible for the smooth, controlled movements of the body Decrease in dopamine presents the loss of smooth, controlled movements and is replaced by tremor and stiffness Drop in dopamine in turn allows acetylcholine to take over. When this occurs, muscles become too excited which leads to symptoms such as jerking and tremors Goal of pharmacotherapy ❖Increase the ability of the patient to perform normal ADL such as eating, walking, dressing and bathing ❖Restore the balance of dopamine and ACh within the corpus striatum of the brain ❖Drugs include dopaminergic agents (replace dopamine) and anticholinergics (cholinergic blockers)  Dopamine cannot cross the blood-brain barrier ❖ Levodopa (its precursor) can. Once levodopa crosses the blood-brain barrier and enters neurons, it is converted into Dopamine, which normally inhibits firing of the next neuron. Natural Ach in the brain stimulates the same postsynaptic neuron. ❖ Thus, to restore normal neuron activity, drug therapy attempts to either restore Dopamine inhibitory action or block Ach stimulatory activity Dopaminergic drugs for Parkinsonism Analgesia  Pain drugs ❖Nociceptors Free nerve endings located throughout the entire body that initiate the sensation of pain ❖Two major classes of drugs to manage pain NSAIDs act at peripheral level Opioids act within the CNS Neural pathways for pain  Analgesics Medications to relieve pain ❖Opioids (narcotics) Responsible for reducing moderate to severe pain Narcotic substance – produce numbness or stupor-like symptoms Opioid receptors  Opioids Action ❖Acts both pre-synaptically and post-synaptically to produce analgesic effect ❖Pre-synaptic – block Ca2+ channels on nociceptor afferent nerves to inhibit the release of neurotransmitters (substance P and glutamate) which contribute to nociception (detection of painful stimuli) ❖Post-synaptic – open K+ channels which hyperpolarize cell membranes, increasing the required action potential to generate nociceptive transmission ❖Morphine, oxycodone, hydrocodone, methadone https://www.youtube.com/watch?v=XHLANzO6hSQ  Effects of opioids Positive effects ❖Moderate to severe pain relief ❖Cause sedation ❖Cough suppressant Adverse effects ❖Respiratory depression ❖Bradycardia ❖Sedation ❖Slow GI motility ❖Nausea, Vomiting ❖Constipation  Opioids Nursing considerations ❖Monitor Glasgow Coma Scale to monitor for over sedative effect ❖Monitor BP, P, RR, SpO2 to monitor for hypotension, bradycardia, respiratory depression ❖Monitor pain score to monitor the effect of the drug ❖Monitor for side effects (nausea, vomiting, constipation) ❖Monitor for overdose, look out for respiratory depression and over sedation ❖Overdose – Naloxone (opioid antagonist) centrally acting pure opioid antagonist with high affinity at mu-opioid receptors Quickly counteracts opioid action  References ❖ Holland, L.N., Adams, M., and Brice, J., ( ). Core concepts in Pharmacology. Pearson. ❖ Karch, A. M. (2020). Lippincott Pocket Drug Guide for Nurses (p.115). Wolters Kluwer Health. Kindle Edition. ❖ Skidmore-Roth, L. (2009). Mosby’s nursing drug reference (22nd edn.). St. Louis: Mosby. Q&A