Download Advanced Pharmacology for nurse practitioner and more Study notes Pharmacology in PDF only on Docsity!
Study Guide
š§ Advanced Neuropharmacology Overview
Neuropharmacology studies how drugs cognition, and physiological function. It's divided into: influence the nervous system to modify behavior,
ļ· ļ· Molecular NeuropharmacologyBehavioral Neuropharmacology ā interactions at receptor and signaling level. ā how drugs affect behavior and mental states.
š§ 1. Neurotransmitter Systems & Key Drug Targets
Neurotransmitter Major Function Drug Classes Targeting It Acetylcholine (ACh) Memory, attention, autonomic regulation^ Cholinesterase inhibitors, anticholinergics Dopamine (DA) Reward, motivation, motor control^ Antipsychotics, stimulants, Parkinson drugs Serotonin (5-HT) Mood, sleep, pain, GI function SSRIs, SNRIs, triptans, psychedelics Norepinephrine (NE) Arousal, stress, attention, BP SNRIs, TCAs, adrenergic agonists GABA (Ī³-aminobutyric acid) Inhibitory tone, seizure control^ Benzodiazepines, barbiturates, gabapentinoids Glutamate Learning, memory, excitotoxicity^ NMDA antagonists (memantine, ketamine)
š§ 2. Drug Mechanisms by Class
š§ Cholinergic Drugs
ļ· ļ· AgonistsAnticholinesterases : stimulate muscarinic or nicotinic receptors (e.g., pilocarpine): block ACh breakdown (e.g., donepezil, neostigmine) ļ· Anticholinergics : block muscarinic receptors (e.g., atropine, scopolamine) Used in : Alzheimer's, myasthenia gravis, Parkinsonism (anti-tremor)
š§ Dopaminergic Agents
ļ· ļ· AgonistsReuptake Inhibitors : Parkinsonās (e.g., pramipexole, ropinirole): ADHD (e.g., methylphenidate) ļ· Antagonists : Schizophrenia (e.g., haloperidol, risperidone) Dopamine pathways : ļ· ļ· MesolimbicNigrostriatal ā psychosis ā motor function ļ· Tuberoinfundibular ā prolactin inhibition
š§ Serotonergic Agents
ļ· ļ· SSRIs/SNRIs5-HT1 Agonists : ā 5-HT (e.g., fluoxetine, venlafaxine): migraine (triptans) ļ· ļ· 5-HT2A Agonists5-HT3 Antagonists : psychedelics (LSD, psilocybin): antiemetics (ondansetron)
ā ļø Watch for serotonin syndrome when combining serotonergic drugs.
š§ GABAergic Agents
ļ· ļ· GABA-A AgonistsGABA analogs : gabapentin, pregabalin (modulate CaĀ²: benzodiazepines, barbiturates āŗchannels) ļ· Inhibitors : flumazenil (benzo reversal) Used for: anxiety, epilepsy, insomnia, alcohol withdrawal
ā« Glutamatergic Modulators
ļ· ļ· NMDA AntagonistsAMPA modulators : under research for depression and epilepsy: ketamine, memantine (Alzheimerās)
Excess glutamate = excitotoxicity ā seizures, stroke, neurodegeneration
š§ 3. Neurologic Disease Targets & Treatments
Direct Muscarinic Agonists
These drugs bind directly to muscarinic receptors and activate them. Drug Name Uses Pilocarpine Glaucoma, xerostomia (dry mouth) Bethanechol Urinary retention, postoperative ileus Carbachol Glaucoma (rarely used) Methacholine Diagnostic test for bronchial hyperreactivity Cevimeline (^) Xerostomia in Sjƶgrenās syndrome Muscarine Found in some poisonous mushrooms (not used clinically)
š§ Indirect Muscarinic Agonists (Cholinesterase Inhibitors)
These drugs inhibit acetylcholinesterase , increasing endogenous acetylcholine levels at both muscarinic and nicotinic receptors. Drug Name Uses Neostigmine Myasthenia gravis, postoperative ileus Physostigmine Anticholinergic toxicity (e.g., atropine overdose) Donepezil Alzheimerās disease Rivastigmine Alzheimerās and Parkinsonās dementia Pyridostigmine Myasthenia gravis Edrophonium Historically used in diagnosis of myasthenia gravis
š§ Key Muscarinic Effects ("SLUDGE-M")
These drugs mimic parasympathetic activity: ļ· S alivation ļ· ļ· LU acrimationrination ļ· ļ· DG iarrheaastrointestinal motility ļ· ļ· EM mesisiosis (pupil constriction), bradycardia, bronchoconstriction
Anticholinergicdrugs are medications that blocktheaction ofacetylcholine(ACh) at muscarinicreceptors in the centraland peripheralnervoussystem. These drugs inhibit parasympathetic activity and are used in a wide range of clinical settings.
š§ MechanismofAction ļ· Most anticholinergics are muscarinicantagonists , meaning they competitively inhibit ACh at muscarinicreceptors(M1āM5). ļ· They donotaffectnicotinicreceptors , unless specifically designed to do so (e.g., ganglionic blockers).
š§ CommonAnticholinergicDrugsbyUse š§ CNS:Parkinsonāsdisease,motionsickness Drug Use Benztropin e
Parkinsonās disease, drug- induced EPS Trihexyphe nidyl Parkinsonās disease Scopolamin e
Motion sickness (transdermal patch)
Respiratory:COPD,asthma Drug Use Ipratropiu m
COPD, asthma (short- acting) Tiotropiu m COPD (long-acting) Aclidinium COPD
ļ· "Fullasaflask" ā urinary retention Treatment: Physostigmine (crosses BBB) in severe central toxicity.
Cholinergicdrugs (also called parasympathomimetics ) are medications that mimicorenhancetheactionofacetylcholine(ACh) at cholinergicreceptors. These receptors include: ļ· Muscarinicreceptors(M1āM5) ā found in smooth muscle, heart, glands, and CNS ļ· Nicotinicreceptors(NmandNn) ā found in skeletal muscle and autonomic ganglia
š§ TypesofCholinergicDrugs 1.š§ Direct-ActingCholinergicAgonists These drugs binddirectlytoandactivate cholinergic receptors. Drug ReceptorType Use Bethanec hol Muscarinic^
Urinary retention, neurogenic bladder Pilocarpin e Muscarinic^ Glaucoma, xerostomia Cevimelin e Muscarinic (M3)^ Xerostomia in Sjƶgrenās syndrome Carbachol Muscarinic & Nicotinic Glaucoma Methachol ine Muscarinic^
Bronchial challenge test (asthma diagnosis) Nicotine Nicotinic (Nn, Nm) Smoking cessation (patch/gum) Vareniclin e
Nicotinic partial agonist Smoking cessation
2.š§ Indirect-ActingCholinergicAgonists(CholinesteraseInhibitors) These drugs inhibitacetylcholinesterase , preventing the breakdown of ACh, thus enhancingcholinergicsignaling. a.ReversibleInhibitors Drug Use Neostigmi ne Myasthenia gravis, reversal of NM blockade Pyridostig mine Myasthenia gravis Physostig mine Anticholinergic toxicity (crosses BBB) Edrophoni um
Diagnostic test for myasthenia gravis (rarely used now) Donepezil Alzheimerās disease Rivastigmi ne Alzheimerās and Parkinsonās dementia Galantami ne Alzheimerās disease b.IrreversibleInhibitors(ToxicorWarfareAgents) Agent Source Notes Organophosp hates
Insecticides (e.g., malathion)
Irreversible AChE inhibitors Nervegases Sarin, VX Military nerve agents ā”ļø Antidote: Atropine+Pralidoxime(2-PAM)
š§ Summary:CholinergicEffects Use the mnemonic "SLUDGE-M" for muscariniceffects : ļ· S alivation ļ· L acrimation
Drug Use Heroin Illicit drug (rapid CNS effect) š” Note: Heroin crosses the BBB much faster than morphine due to greater lipophilicity.
4. Antidepressants
Drug Class Examples SSRIs Fluoxetine, sertraline, citalopram SNRIs Venlafaxine, duloxetine TCAs Amitriptyline, nortriptyline MAOIs Phenelzine, selegiline
5. Antipsychotics
Drug Class Haloperidol Typical Olanzapine Atypical Risperidone Atypical Clozapine Atypical
6. Antiepileptics
Drug Notes Phenytoin Lipophilic, crosses BBB Valproic acid (^) Broad-spectrum anticonvulsant Carbamazepine Seizures, bipolar disorder Lamotrigine Seizures, mood stabilization
7. Parkinsonās Disease Drugs
Drug Notes Levodopa Crosses BBB, converted to dopamine in brain Selegiline MAO-B inhibitor, crosses BBB Amantadine Enhances dopamine release š” Dopamine itself does NOT cross the BBB ā levodopa is used instead.
8. Alzheimerās Disease Drugs
Drug Mechanism Donepezil AChE inhibitor Rivastigmine AChE inhibitor Memantine NMDA receptor antagonist
9. Anticholinergics That Cross BBB
Drug Use Atropine CNS and peripheral effects Scopolamine Motion sickness, sedation Benztropine Parkinsonism, EPS Diphenhydramine Antihistamine, causes sedation
š§ Do NOT Cross BBB Easily (unless altered) ļ· ļ· DopamineNeostigmine ā does not cross, needs levodopa ā peripheral AChE inhibitor (doesnāt cross) ļ· Ipratropium ā anticholinergic without CNS side effects
š§ Common Drug Classes to Avoid or Adjust in Renal Impairment
š§ 1. NSAIDs (Non-Steroidal Anti-Inflammatory Drugs)
Examples Why avoid? Ibuprofen, Naproxen, Indomethacin Reduce renal blood flow via prostaglandin inhibition; can cause acute kidney injury (AKI)
š§ 2. Aminoglycoside Antibiotics
Examples Why avoid? Gentamicin, Tobramycin, Amikacin Nephrotoxic; cause acute tubular necrosis, require close monitoring of levels
Drug Notes Glyburide (glibenclamide) Risk of prolonged hypoglycemia in CKD Exenatide (Byetta) Avoid in eGFR < SGLT2 inhibitors (e.g., canagliflozin) Not effective at low GFR; potential AKI risk in some
š§ 9. Contrast Agents (IV Iodinated)
ļ· Can cause contrast-induced nephropathy (CIN). ļ· Avoid or pre-hydrate in patients with low GFR.
š§ 10. Others
Drug Why avoid? Nitrofurantoin Ineffective and toxic in low GFR Bisphosphonates (e.g., zoledronic acid) Contraindicated in severe renal impairment Allopurinol Risk of allopurinol hypersensitivity syndrome in CKD Baclofen Can accumulate and cause CNS toxicity
š§ What to Do Instead? ļ· Use creatinine clearance (CrCl) or eGFR to guide dosing. ļ· ļ· ChooseMonitor hepatic-metabolism drugs drug levels , electrolytes , and when possible. renal function closely.
š§ Medications Contraindicated or Used with Caution in Thyroid Disease with Weight Loss
š§ 1. Sympathomimetic Agents
These can exacerbate hyperthyroid symptoms such as tachycardia, tremors, and anxiety. Examples Why Avoid? Pseudoephedrine Increases heart rate and BP, worsens palpitations Amphetamines Can worsen weight loss, anxiety, tachycardia Phentermine (^) Appetite suppressant; mimics hyperthyroid signs Caffeine (high dose) Stimulates CNS and metabolic rate
š§ 2. Glucocorticoids (High Dose/Chronic Use)
| Why? Can alter In weight-losing patients, may TSH secretion and mask worsen muscle wasting hyperthyroidism. and bone loss.
š§ 3. Amiodarone
| Why Avoid or Use Cautiously? ļ· Contains high iodine content ā can cause hypo- or hyperthyroidism (amiodarone- ļ· induced thyroid dysfunction)Can worsen thyroid-related weight loss or cardiac issues
š§ 4. Interferon-alpha and Lithium
| Why? ļ· May induce thyroiditis or autoimmune thyroid disease ļ· Lithium can cause may occur hypothyroidism , but if discontinued abruptly, rebound thyrotoxicosis
š§ 5. Weight-Loss Medications
Avoid in Hyperthyroidism or Unexplained Weight Loss Phentermine , Orlistat , Lorcaserin , Bupropion/naltrexone (Contrave) Can worsen or mask underlying thyroid disease or amplify weight loss risks
ā ļø Special Note: Bupropion
ļ· Used for depression and weight loss (Contrave) ļ· Caution in hyperthyroid patients due to seizure risk and metabolic stimulation
š§ Safe Alternatives (Depending on Thyroid Status)
ļ· ļ· Most commonly used cholinesterase inhibitorLonger acting and fewer side effects than neostigmine in MG ļ· ļ· DoseFormulations : Usually multiple times daily due to short duration (3ā6 hours): Oral tablets, syrup, and injectable
Benefits: ļ· Improves ptosis , diplopia , limb weakness , and bulbar symptoms Side Effects (due to muscarinic effects): ļ· ļ· GI upset (nausea, diarrhea, cramps)Salivation ļ· ļ· SweatingBradycardia ļ· Miosis š” Atropine (an anticholinergic) can be used to manage muscarinic side effects if needed.
š§ Neostigmine
ļ· ļ· Used less frequently due toSometimes used IV for diagnostic or acute settings shorter duration of action
ā ļø Important Clinical Concepts
š§ Edrophonium (Tensilon Test) (historical/less used)
ļ· Ultra-short-acting cholinesterase inhibitor ļ· ļ· UsedRapid improvement = diagnostically to confirm MG (no longer standard) positive test ļ· Rarely used now due to risks (e.g., bradycardia, arrhythmia)
š§ Cholinergic Crisis vs. Myasthenic Crisis
Myasthenic Crisis Cholinergic Crisis Cause Too little ACh (under-medicated) Too much ACh (over-medicated)
Myasthenic Crisis Cholinergic Crisis Symptoms Severe muscle weakness, respiratory distress^ Muscle weakness, symptoms^ plus^ SLUDGE Treatment Increase pyridostigmine , ICU care Stop pyridostigmine , give atropine Differentiation Test Edrophonium improves symptoms Edrophonium worsens symptoms
š§ Summary ļ· ļ· Cholinesterase inhibitors (esp. pyridostigmine) Must balance dose carefully to avoid under- or over-treatment are cornerstone treatments for MG ļ· Often used in combination with long-term management immunosuppressants , steroids , or thymectomy for
Medications Contraindicated in Thyroid Cancer / MTC
š§ 1. GLP-1 Receptor Agonists (Incretin Mimetics)
These are commonly used in type 2 diabetes and weight loss , but have a black box warning due to increased risk of thyroid C-cell tumors in animal studies. Examples Use Liraglutide (Victoza, Saxenda) T2DM, obesity Semaglutide (Ozempic, Wegovy, Rybelsus) T2DM, obesity Dulaglutide (Trulicity) T2DM Exenatide (Byetta, Bydureon) T2DM Tirzepatide (Mounjaro, Zepbound) T2DM, obesity (also GIP-GLP-1) ā ļø Contraindicated in: ļ· Patients with personal or family history of medullary thyroid carcinoma ļ· Patients with MEN2 (a genetic cancer syndrome affecting the endocrine system) š” āThese drugs caused thyroid C-cell tumors in rodents. It is unknown whether they cause thyroid Label Warning (FDA Black Box): C-cell tumors, including medullary thyroid carcinoma, in humans.ā
š§ Herbs (Botanical Supplements) Herb Common Uses Mechanism/Effect Cautions / Interactions St. Johnās Wort Depression, anxiety Increases serotonin, norepinephrine ā Effectiveness of SSRIs, warfarin, OCPs, cyclosporine Echinacea Colds, immune support Immune stimulant^ Allergic reactions (esp. in ragweed allergy), ā effectiveness with long-term use Ginkgo biloba Memory, cognitive decline^ Increases cerebral blood flow^ ā Bleeding risk (avoid with warfarin, aspirin) Ginseng Fatigue, cognitive boost^ Adaptogen, anti- inflammatory^ ā BP, insomnia; interacts with antidiabetics, warfarin Kava Anxiety GABAergic activity Hepatotoxicity riskāavoid in liver disease Valerian root Insomnia, anxiety GABA modulator Sedation, potentiates CNS depressants (e.g., benzos) Turmeric (Curcumin) Inflammation, arthritis Anti-inflammatory, antioxidant Can ā bleeding risk with anticoagulants Saw Palmetto BPH (benign prostatic hyperplasia) Anti-androgenic May interfere with PSA tests and hormonal meds Black Cohosh Menopausal symptoms Estrogen-like effects Avoid in hormone-sensitive cancers, hepatotoxicity risk
š§ Vitamins Vitamin Uses Deficiency Symptoms Toxicity / Notes Vitamin D Bone health, immune modulation Rickets, osteomalacia Hypercalcemia, kidney stones with excess use Vitamin B12 Anemia, neuropathy, memory^ Fatigue, paresthesias, macrocytic anemia^ Often low in vegans, metformin use Vitamin B (Pyridoxine) PMS, mood, nerve health Irritability, neuropathy^ High doses ā neurotoxicity Vitamin C Immune support, antioxidant^ Scurvy (bleeding gums, fatigue) GI upset with high doses Vitamin A Vision, immune, skin Night blindness Teratogenic, hepatotoxic in excess Vitamin E Antioxidant, skin, cardiovascular Rare deficiency ā Bleeding risk at high doses
Vitamin Uses Deficiency Symptoms Toxicity / Notes Folate (B9) Pregnancy, anemia, DNA synthesis^ Neural tube defects, anemia Can mask B12 deficiency
āļø Minerals
Mineral Function Too Little / Too Much Iron Hemoglobin production Anemia / GI toxicity, oxidative stress Calcium Bone health, muscle function Osteopenia / Kidney stones, constipation Magnesium Muscle, nerve, enzyme function Cramps, arrhythmia / Diarrhea, hypotension Zinc Immunity, wound healing Infections / Copper deficiency, GI upset Selenium (^) Thyroid function, antioxidant Hypothyroidism / Hair loss, brittle nails
š§ Common Supplement Interactions
Supplement May Interact With Effect St. Johnās Wort SSRIs, warfarin, cyclosporine, OCPs ā drug levels via CYP450 induction Ginkgo biloba Anticoagulants, NSAIDs ā bleeding risk Ginseng Antidiabetics, warfarin ā glucose, ā bleeding risk Vitamin K Warfarin Antagonizes anticoagulant effect Calcium, Iron Thyroid meds, tetracyclines, quinolones ā absorption of these drugs Magnesium Diuretics, PPIs Risk of hypomagnesemia
š§ ANTIBIOTICS OVERVIEW
š§ 1. Cell Wall Inhibitors
š§ Ī²-Lactams
