Pharm Exam 4

Nervous System Drugs: Principles of Neuropharmacology (Ch 14)

• Drugs impact transmitter synthesis in three primary ways: increasing synthesis, decreasing synthesis, or causing the synthesis of more effective transmitter molecules.
• Increasing synthesis causes receptor activation to increase.
• Decreasing synthesis of neurotransmitters will cause the transmitter content of vesicles to decline, and subsequently reduce transmitter release and receptor activation.
• Selective drugs that target specific receptors are ideal because they can alter very specific processes and leave other physiological processes unaffected.
• Non-selective drugs can alter many physiological processes.
• Example scenario with Mort: If he stays healthy, only having one receptor type is not a problem, but if he gets sick (heart failure), the drug stimulating his heart will also stimulate other organs.
• Example scenario with Merv: Selective drug action is obtainable.

Muscarinic Agonists (Ch 16)

• Muscarinic poisoning/overdose symptoms include respiratory issues (bronchospasm, excessive bronchial secretions), cardiovascular issues (bradycardia and hypotension), gastrointestinal distress (profuse salivation, nausea, vomiting, abdominal pain, diarrhea, fecal incontinence), genitourinary issues (excessive urination and incontinence), integumentary symptoms (diaphoresis), visual issues (lacrimation and miosis), and potentially severe cardiovascular collapse.
• Treatment for muscarinic poisoning/overdose involves administering atropine and providing supportive therapy.
• Anticholinergics are administered before surgery to reduce secretions and prevent bradycardia.
• Symptoms of anticholinergic toxicity include delirium, confusion, hallucinations, dry mouth, tachycardia, urinary retention, slower bowel function, hyperthermia, and flushing.
• Treatment for anticholinergic toxicity includes administering a cholinesterase inhibitor to reverse central and peripheral anticholinergic toxicity and increase acetylcholine levels.
• Scopolamine contains anticholinergic agents that block muscarinic receptors in the CNS.
• Scopolamine is used to reduce nausea, vomiting, and secretions, mainly for motion sickness.
• Scopolamine is available in oral form, taken 30-60 minutes before travel with a full glass of water, or as a patch.
• Scopolamine patch requires patient education: wash hands after applying it to avoid getting it in the eyes or mucous membranes.
• Side effects of scopolamine are sedation and drowsiness.
• Use caution with other sedatives and avoid alcohol.

Muscarinic Antagonists (Ch 17)

• In antimuscarinic poisoning, the goal is to minimize intestinal absorption of the antimuscarinic agent.
• Treatment in stages involves administering activated charcoal to promote the expulsion of the drug and giving physostigmine as an antidote.
• Cholinesterase inhibitors prevent the breakdown of acetylcholine, leading to accumulation at cholinergic junctions.
• Common treatments for overactive bladder (OAB) include behavioral therapy with scheduled voiding, timed fluid intake, Kegel exercises, and caffeine avoidance.
• Drug therapy for OAB uses anticholinergic drugs.
• Oxybutynin (1) blocks M3-receptors on the bladder detrusor but Darifenacin also blocks M3-receptors, however it does have side effects outside the bladder such as dry mouth, and constipation.
• Other drugs in this class inlcude Solifenacin, Tolterodine, Fesoterodine which are nonselective muscarinic antagonists and Trospium which is a nonselective muscarinic blocker

Cholinesterase Inhibitors and Myasthenia Gravis (Ch 18)

• Cholinergic crisis is characterized by extreme muscle weakness or frank paralysis.
• Cholinergic crisis can be accompanied by signs of excessive muscarinic stimulation.
• Myasthenia crisis is defined by extreme muscle weakness caused by insufficient acetylcholine at the NMJ.
• Myasthenia crisis can result in death from paralysis of the muscles of respiration if left untreated.
• Distinguishing between the two crises involves assessing medication history and looking for signs of excessive muscarinic stimulation.
• In myasthenia crisis, a provider may administer edrophonium, an ultrashort-acting cholinesterase inhibitor, to alleviate symptoms.
• In cholinergic crisis, edrophonium intensifies the symptoms.
• If you increase activity you can combat the effects of acetylcholine availability. By taking supplemental doses of cholinergic drugs.
• Pyridostigmine (Mestinon) is the drug of choice for managing myasthenia gravis.
• Pyridostigmine is available in syrup and tablet form.
• ER tablets should be taken whole.
• Syrup and IR tablets should be spaced to provide optimal functioning.
• Use caution in patients with GI tract obstruction, urinary tract obstruction, peptic ulcer disease, asthma, coronary insufficiency, and hyperthyroidism.
• Drug interactions include muscarinic antagonists, competitive neuromuscular blockers, and depolarizing neuromuscular blockers.
• Adverse side effects of cholinesterase inhibitors stem from excessive muscarinic stimulation which can cause excessive salivation, increased gastric secretions, increased tone and motility of the GI tract, urinary urgency, bradycardia, sweating, miosis, spasm of accommodation.
• With an overabundance of Ach in the synapse can lead to overactivity of the PNS.
• Neuromuscular blockade is caused by accumulation of acetylcholine in amounts sufficient to produce depolarizing neuromuscular blockade.
• NMBAs can interrupt the transmission of nerve signals at the neuromuscular junction to prevent muscle contraction.

Nicotinic Cholinergic Blockers (Ch 19)

• Nicotinic blocking agents prevent acetylcholine from activating nicotinicM receptors on skeletal muscles, resulting in muscle relaxation.
• Side effects of nicotinic blocking agents include muscle weakness, paralysis, possible respiratory failure, hypotension, and tachycardia.
• Nicotinic blocking agents do not control pain.
• Examples of nicotinic blocking agents include atracurium, cisatracurium, mivacurium, pancuronium, rocuronium, and vecuronium.

Adrenergic Agonists (Ch 20)

• Adrenergic agonists are drugs that activate adrenergic receptors and mimic the effects of the sympathetic nervous system to respond to catecholamines.
• Alpha 1 receptors in blood vessels, eyes, and the bladder cause vasoconstriction, pupil dilation, and urinary retention.
• Alpha 2 receptors on presynaptic nerve terminals inhibit norepinephrine release.
• Beta 1 receptors in the heart and kidneys increase heart rate, force of contraction, and renin release.
• Beta 2 receptors in the lungs, blood vessels of skeletal muscles, uterus, and liver cause bronchodilation, vasodilation, decrease uterine contractions, and increase glycogenolysis.
• Beta 3 receptors in adipose tissue and the bladder cause lipolysis and relaxation of the detrusor muscle.
• Albuterol is highly selective and acts on beta 2 receptors only for receptor specificity.
• Isoproterenol is less selective and acts on beta 1 and beta 2 receptors.
• Epinephrine is even less selective and acts on all four adrenergic receptor subtypes: alpha1, alpha2, beta1, beta2.
• Epinephrine is used for anaphylactic shock because it activates alpha1, beta1, and beta2 adrenergic receptors.
• It can reverse the most severe manifestations of the anaphylactic reaction.
• Epinephrine is sometimes used with local anesthetics to cause alpha1-mediated vasoconstriction to delay absorption, control superficial bleeding, and elevate blood pressure.
• Physiological effects of dopamine are dose-dependent.
• Activation of peripheral dopamine receptors causes dilation of the renal vasculature, increased heart rate and cardiac contractility, and vasoconstriction.

Adrenergic Antagonists (Ch 21)

• Beta-adrenergic antagonists (beta blockers) work for angina by blocking beta1 receptors in the heart, decreasing cardiac workload, reducing oxygen demand, and preventing ischemia and pain.
• Beta blockers reduce the frequency and intensity of migraine attacks but cannot abort a migraine once it has begun.
• Primary neurotransmitters of the autonomic nervous system are acetylcholine (ACh), norepinephrine, and epinephrine.

Indirect-Acting Antiadrenergic Agents (Ch 22)

• Common side effects of clonidine (Catapres) include drowsiness, xerostomia (dry mouth), rebound hypertension, embryotoxicity, and abuse (euphoria, sedation, hallucinations).
• Patient education for clonidine includes avoiding hazardous activities if alertness is impaired, chewing gum or sucking hard candy for dry mouth, withdrawing clonidine slowly over 2-4 days to prevent rebound hypertension, and ruling out pregnancy before use.

Central Nervous System Pharmacology (Ch 23)

• Adaptation is a hypothesized mechanism of CNS drug actions that has received wide acceptance.
• With increased therapeutic effects, antipsychotics and antidepressants must be taken for several weeks before full therapeutic effects develop.
• With decreased side effects, the intensity of side effects may decrease with long-term use, even if therapeutic effects remain undiminished.
• Tolerance and physical dependence requires continued drug use for the brain to function "normally."
• Medical applications of CNS drugs include relief of pain, suppression of seizures, production of anesthesia, and treatment of mental health conditions.

Drugs for Parkinson Disease (Ch 24)

• Carbidopa inhibits decarboxylation of levodopa in the intestine and peripheral tissues, making more levodopa available to the CNS.
• It does not cross the blood-brain barrier.
• There is no drug to stall, cure, or prevent progression of Parkinson's disease.
• "Off" times refer to the loss of symptom relief in Parkinson's disease.
• "Off" times can be reduced by prescribing DAs, COMT inhibitors, MAO-B inhibitors (dopaminergic drugs), or adenosine antagonists.
• MAO-B inhibitors block the activity of the enzyme monoamine oxidase B (MAO-B), which is responsible for breaking down dopamine in the brain.

Drugs for Alzheimer Disease (Ch 25)

• Cholinesterase inhibitors enhance transmission by central cholinergic neurons that have not yet been destroyed.
• Cholinesterase inhibitors do not cure or stop the progression of AD, but they may slow down progression by a few months.
• Mild to moderate AD is treated with cholinesterase inhibitors like donepezil, rivastigmine, and galantamine.
• Moderate to severe AD is treated with NMDA receptor antagonists like memantine and aducanumab.

Drugs for Multiple Sclerosis (Ch 26)

• Mitoxantrone (Novantrone) is used for the treatment of MS in patients with decreased neurologic disability and clinical relapse with worsening RRMS and SPMS.
• It may delay the time to relapse and the time to disability progression.
• Side effects include hair loss, injury to GI mucosa (stomatitis, GI distress), nausea, vomiting, menstrual irregularities, and allergy-like symptoms.
• Other side effects include blue-green tint to the skin, sclera, and urine.
• Adverse side effects include myelosuppression, cardiotoxicity, fetal harm, and tissue injury with extravasation.
• It is administered as an IV solution every 3 months.
• Patient education includes monitoring for myelosuppression with CBCs and cardiac impairment with LVEF. Additionally, they need to be aware of the possibility of fetal harm.
• Subtypes of MS include Clinically isolated syndrome, Relapsing-remitting MS, Primary progressive MS, and Secondary progressive MS. In RRMS there are recurrent episodes of neurological disfunction sperated by periods of partial or full recovery. SPMS Occurs when a pt with RRMS develops steadily worsening dysfunction with or without occasional plateaus, acute exacerbation, or minor remissions.
• Recognize drugs used to treat muscle spasms in MS Baclofen (Lioresal) and tizanidine (Zanaflex)

Drugs for Seizure Disorders (Ch 27)

• The drug Dilantin is used to treat seizures
• Dilantin side effects: CNS effects, gingival hyperplasia (excessive growth of gum tissue), dermatologic effects (rash), teratogen, cardiovascular (dysrhythmias and hypotension), purple glove syndrome (swelling and discoloration of hands/arms), hirsutism.
• If patients have the human leukocyte antigen (HLA)-B*1502 gene take it.
• Do not use in preganancy
• Give Dilantin slow IV push
• Try to monitor antiseizure drug therapy through a trial period to determine its effectiveness or by monitoring plasma levels

Drugs for Muscle Spasm and Spasticity (Ch 28)

• The drug baclofen [Lioresal], is used to treat muscle spasms and spasticity.
• Baclofen relieves spasm related to conditions such as MS or trauma (spinal cord).
• Baclofen acts within the spinal cord to suppress hyperactive reflexes involved in the regulation of muscle movement by reducing flexor and extensor spasms.
• Adverse effects include CNS effects (drowsiness, dizziness, weakness, and fatigue), nausea, vomiting, constipation, and urinary retention.
• Abrupt discontinuation can cause visual hallucinations, paranoid ideation, and seizures if administered orally.
• Contraindications for tizanidine [Zanaflex] include not taking with metaxalone (liver damage) and caution for hallucinations and psychosis.
• Cyclobenzaprine [Flexeril] is a centrally acting SM relaxant that works in the brainstem to reduce tonic motor activity.
• Cyclobenzaprine is most efficacious of the drugs used to treat muscle spasms and associated pain.
• Cyclobenzaprine can cause CNS effects as side effects (drowsiness, dizziness, fatigue), anticholinergic effects (dry mouth, blurred vision, photophobia, urinary retention, constipation), and cardiac rhythm disturbances (sinus tachy, and significant conduction delays).
• Drugs used to treat spasticity include baclofen, diazepam, dantrolene, and tizanidine.
• *Important notes Baclofen, diazepam, tizanidine act on CNS and Dantrolene acts directly on skeletal muscle.