Cholinergic Medications: Types and Uses

• Compendium Pharmacologia, Summa Pharmacologica Medicamenta include drug names written in a tabular format.

Cholinergic Medications

• Cholinergic medications are drugs that mimic or affect acetylcholine (ACh), which is the primary neurotransmitter of the parasympathetic nervous system.

Cholinergic Agonists - Parasympathetic

• Direct-acting cholinomimetic agents bind directly to cholinergic receptors.
• Indirect-acting cholinomimetic agents inhibit acetylcholinesterase (AChE), which normally breaks down ACh.
• Carbachol treats wide-angle glaucoma, and contracts the sphincter of the iris, M3 receptor agonist.
• Pilocarpine treats glaucoma and Sjogren's syndrome, M1, M2, M3 agonist and contracts ciliary muscle.
• Bethanechol treats urinary retention by acting as a M2, M3 agonist, increasing bladder contraction and GI motility.
• Edrophonium diagnoses Myasthenia Gravis, inhibits AChE, and is contraindicated in hypersensitivity Gl/Urinary obstruction
• Physostigmine treats glaucoma and is an antidote for atropine.
• Neostigmine is used to manage glaucoma, and is contraindicated in peritonitis.
• Pyridostigmine helps to treat MG, and is an irreversible anticholinesterase agent.

Cholinergic Antagonists

• Antimuscarinic agents block muscarinic receptors, working on M1,M2, M3 receptors.
• M1 primarily affects the gastrointestinal system causing constipation.
• M2 primarily affects the heart by increasing heart rate.
• M3 affects exocrine glands, leading to dryness.
• Atropine blocks DUMBBELS, antidote for cholinesterase poisonings and is found in urinary incontinence medication.
• Scopolamine primarily treats motion sickness by blocking M1 & interfering with vestibular communication to the vomiting center.
• Ipratropium and Tiotropium treat COPD, asthma and Rhinitis blocking M3 in the lungs and causing bronchodilation.
• Oxybutynin treats urinary incontinence and hyperhidrosis by blocking M3, increasing bladder sphincter contraction+ M3.
• Hexamethonium, Mecamylamine and Trimetaphan treat hypertensive emergencies.

Cholinergic Antagonists

• Used to reduce skeletal muscle contraction for endotracheal intubation facilitation.

Non-depolarizing Agents

• Competitively bind to nicotinic receptors at the neuromuscular junction.
• Cisatracurium, Pancuronium, Rocuronium, Atracurium are in this class of drugs.

Depolarizing Agents

• Reversibly bind to nicotinic receptors, resulting in prolonged depolarization.
• Succinylcholine is in this class of drugs.
• High risk inducing malignant hyperthermia with halothane

Sympathomimetics, Adrenergic Agonists (Alpha And Beta)

• Affect the autonomic sympathetic system act by activating adrenergic receptors, mimicking the effects of sympathetic nervous system stimulation.
• Epinephrine is used during cardiac arrest to increase blood pressure and bronchodilation in asthma and anaphylaxis; treats wide-angle glaucoma.
• Norepinephrine treats severe hypotension and shock via vasoconstriction and increased cardiac contractility.
• Dopamine treats severe hypotension and shock; at low doses, it causes vasodilation, and at high doses, it vasoconstricts.
• Oxymetazoline and Phenylephrine treat severe hypotension and shock, nasal congestion, and produces mydriasis for retinal exams, a1-selective.

Sympathomimetics, Adrenergic Agonists (Alpha And Beta) - Autonomic Drugs

• Albuterol is a ẞ2-selective agonist used to treat asthma, bronchospasm, and hyperkalemia.
• Mirabegron is a ẞ3-selective agonist used for overactive bladder, relaxing the bladder.
• Cocaine and Amphetamine are indirect-acting agonists.
• Pseudoephedrine is a mixed-action agonist used as a nasal decongestant and for stress incontinence in women.

Adrenergic Antagonists - Alpha Blockers

• Phenoxybenzamine and phentolamine are non-selective alpha-blockers used to treat pheochromocytoma.
• Phentolamine is also used to detect pheochromocytoma.
• Prazosin, terazosin, and doxazosin are selective alpha 1-blockers for hypertension.
• Tamsulosin, Alfuzosin, and Silodosin are for benign prostatic hyperplasia and improve urinary flow by relaxing bladder neck contraction

Adrenergic Antagonists - Beta Blockers

• Propranolol, Pindolol, Nadolol, Sotalol and Timolol are 1st Generation, non-selective.
• Atenolol, Bisoprolol, Esmolol, Acebutolol, Metoprolol (A-BEAM) are 2nd Generation, selective.
• Carvedilol and Labetalol are 3rd Generation, nonselective, CHF.
• Nebivolol and Betaxolol are 3rd Generation, selective.
• Beta-blocker use should be cautious in patients with pre-existing cardiac disorders like left ventricular hypertrophy.

Alzheimer Drugs

• Donepezil, Rivastigmine, and Galantamine are cholinesterase inhibitors used as first-line treatments for Alzheimer's, improving congnition.
• Memantine is an NMDA-receptor antagonist for moderate to severe Alzheimer's disease.

Phosphodiesterase Inhibitors

• Milrinone is a PDE-3 inhibitor for acute decompensated HF by increasing cardiac contractility and pulmonary vascular resistance.
• Sildenafil, Vardenafil, Tadalafil and Avanafil are PDE-5 inhibitors used for erectile dysfunction and pulmonary arterial hypertension.
• Tadalafil is also used for BPH

Parkinson Drugs

• Levodopa is the first-line treatment for Parkinson's disease, which converts into dopamine in the CNS.
• Selegiline and Rasagiline are MAO-B inhibitors, increase dopamine availability.
• Bromocriptine, Ropinirole, Pramipexole, Rotigotin, and Apomorphine are dopamine mimics that stimulate dopamine receptors.
• Benztropine, Biperiden, Procyclidine, Trihexyphenidyl, Amantadine are muscarinic receptor antagonists used to treat Parkinson's that improve tremor and rigidity.
• Monitor side effects and make adjustments accordingly for optimal management.

Diabetes

• Pramlintide is a synthetic amylin analog used in type 2 diabetes to reduce glucose production and slow gastric emptying.
• Liraglutide, Exenatide are GLP-1 receptor agonists that mimic incretins and upregulate insulin secretion
• Alogliptin, Linagliptin, Saxagliptin and Sitagliptin are DPP-4 inhibitors, which inhibit the enzyme DPP-4 to increase insulin secretion
• Chlorpropamide, Tolbutamide, Tolazamide, Glyburide, Glipizide, Glimepiride are Sulfonylureas stimulate insulin release from beta-cells
• Metformin is a biguanide that reduces glucose levels by inhibiting hepatic gluconeogenesis and increasing glucose utilization.

SGLT-2 Inhibitors

• Canagliflozin, Dapagliflozin, Empagliflozin are SGLT-2 inhibitors used in type 2 diabetes to decrease renal glucose reabsorption, glycosuria and blood glucose

Antihypertensive Drugs

• The a1-blockers like doxazosin and prazosin act by orthostatic hypotension and are helpful in benign prostatic hypertrophy.
• The ẞ1-selective drugs like atenolol and metoprolol can contribute to depression and asthma.
• Carvedilol and labetalol, nonselective beta-blockers, are used in chronic congestive heart failure.

Antihypertensive Drugs 2

• Clonidine and methyldopa are centrally acting adrenergic drugs that lower vasoconstriction SVR, CO and BP.
• Amlodipine, felodipine, nicardipine and nifedipine are calcium channel blockers (dihydropyridines) that cause peripheral edema.
• Verapamil and diltiazem are nondihydropyridines effective in both hypertension and angina.

Diuretics

• Loop diuretics (furosemide, butenamide, torsemide) reduce NaCl reabsorption in the thick ascending loop of Henle.
• Thiazides (hydrochlorothiazide, metalazone, indapamide) reduce NaCl reabsorption in the early distal convoluted tubule reducing peripheral resistance.
• Potassium-sparing diuretics (triamterene, spironolactone, eplerenone) avoid potassium loss.

Renin-Angiotensin-Aldosterone System

• Aliskiren inhibits renin to lower angiotensin I and II, reducing vasoconstriction and SVR, use if hyperkalemia.
• Benazepril, captopril, enalapril, lisinopril, quinapril and ramipril are ACE inhibitors that prevent angiotensin I converting into angiotensin II.
• Candesartan, irbesartan, losartan, olmesartan and valsartan block angiotensin II receptors, causing vasodilation and lowered SVR

Hyperlipidemia

• Statins (atorvastatin, fluvastatin, rosuvastatin, simvastatin) block HMG-CoA reductase to lower cholesterol production, causing liver toxicity..
• Niacin, or nicotinic, acid works on adipose tissue blocks hormones and blocks lipases to help treat hyperlipidemia.
• Fibrates (fenofibrate, gemfibrozil) activate PPAR-alpha to reduce APO-CIII and increase APO-A1 / A2.
• Bile acid sequestrants bind to negative bile salts forming insoluble complexes reducing A, D, E, K absorption.
• Ezetimbe block cholesterol absorption by binding to Cholesterol NPC1LI reducing chylomicrons.

Antihistamines

• First-generation H1 blockers (promethazine, meclizine, clemastine, cyclizine, hydroxyzine,) block H1 receptors and are sedating.
• Second-generation H1 blockers (cetirizine, loratidine, ketoifen, desloratidine) block H1 and lower selectivity leading to less side effects.
• H2 blockers / antagonists (cimetidine, ranitidine, famotidine, nizatidine) decrease acid secretion by blocking H2 receptors, leads to gynecomastia.

NSAIDS (nonsteroidal anti-inflammatory drugs)

• COX1 inhibitors: (ketorolac, flurbiprofen, ketoprofen and low dose aspirin), block PGE2 and PGI2 + TXA2 contributing to GI upset and reduced clotting for pain and fever.
• Non-selective: (naproxen, ibuprofen, piroxicam and diflunisal) non-selective blocking of COX1 and COX2.
• COX2 inhibitors: (meloxicam, diclofenac, celecoxib, etodolac) blocking of PG12 and mild nausea, causing risk of myocardial infarction.

Antidepressants

• SSRIs: (citalopram, escitalopram, duoxetine paroxetine, fluoxetine and sertaline) block SERT to increase serotonin and create sexual dysfunction.
• SNRIs: (venlafaxine, devenlafaxine, milnacipran levomilnacipran and duloxetine) block SERT and NET-
• TCAs: (amatryptyline, nortryptyline, protryptyline, imipramine, clomipramine and doxepine) blocks SERT, NET, H1 and muscarinic.
• MAOIs: (isocarboxazide, tranylcypromine, phenelzine and selegeline) block MAO.

Schizophrenia

• First-generation antipsychotics (haloperidol, fluphenazine, prochlorperazine, trifluoperazine and chlorpromazine) used for positive symptoms.
• Second-generation antipsychotics (clozapine, olanzapine, quetiapine and risperidone) used for both.

Anti HIV

• Entry inhibitors (enfuvirtide, maraviroc and ibalizumab), entry inhibitors stop HIV absorption at the CD4
• NRTIs (abacavir, tenofovir, didanosine, emcrititabine, stavudine, zidovudine and lamivudine).
• NNRTIs (nevirapine, delavirdine and efavirenz).
• Integrase inhibitors (bictegravir, dolutegravir, elvitegravir, raltegravir) inhibit integrase enzyme.
• Protease inhibitors (atazanavir, darunavir, fosamprenavir, indinavir and ritonavir) works against protease

Anti-Influenza

• M2 ion-channel blockers includes Amantadine and Rimantidine, Influenza type A.
• Endonuclease inhibitors is Balovaxir, influenza type A&B.
• Neuroaminidase inhibitors include Oseltamivir, Peramivir and Zanamivir, types A&B.

Anti HBV

• Entecavir is a nucleoside/nucleotide analog.
• Adefovir, Lamivudine and Tenofovir are NRTIs.

Anti HCV

• Ledipasvir, Ombitasvir and Velpatasvir are NS5A inhibitors.
• Sofosbuvir and Dasabuvir are NS5B inhibitors.
• Grazoprevir and Simeprevir are NS3/4A inhibitors to prevent RNA splicing.

Anti Herpes Drugs (HSV)

• Acyclovir, Famciclovir and Valacyclovir are an analogue of dGTP which inhibits DNA synthesis by chain.

Immunosuppresants

• Cyclosporine binds to cyclophilin and reduces activation of T Cells and inhibit IL-2 to limit further inflammation.
• Tacrolimus binds to FK506 BP causing IL-T to be disrupted and inhibit T Cells to help stabilize inflammation.
• Cyclophosphamide blocks immunity.
• Azathioprine damages DNA and inhibits proliferation at the induction phase.

Immunosuppresants 2

• Mycophenolate blocks B&T lymphocytes .
• Sirolimus forms a potent complex to prevent cell transition.
• Glucocorticoids limits gene expression.
• Methotrexate suppress cell synthesis and cell immune mediated immunity

Antifungal Drugs

• Amphotericin B binds to ergosterol in fungal cell membranes and alters permeability resulting in renal toxicity.
• Nystatin is same as Amphotericin B treatment
• Naftifine and Terbinafine are allylamines that interfere with integrity.
• Butenafine is also allylamine derivative
• Clotrimazole, Fluconazole, Itraconazole, Miconazole, Voriconazole and Ketoconazole are Azoles that cause liver dysfunction and inhibit testostererone synsthesis.
• Anidulafungin, Caspofungin and Micafungin are Echincondins, they upset the GI system and can cause flushing.

Antifungal Drugs 2

• Flucytosin causes BM suppression.
• Griseofulvin interferrs with microtubules and alters the development of Tinea.

Local Anaesthesia

• Blocks Na channel to prevent Na influx.
• Can cause blurry vision and headache.

General Anesthesia

• Bind to GABA-A receptors on post synaptic neurons cause adrenal depression,
• Etomidate/Propofol/Thiopental is a short acting anesthetic can be used only for a quick procedure such as placing/removing a bronchoscopy.
• Ketamine/NO/Cyclopropane/Xenon: Selectively blocks NMDA receptors.
• Desflurane/Halothane/Enflurane/Isoflurane decrease a patients awareness and creates more memory effects.
• Dexmedetomidine produce pain and causes short term hypertension and bradycardia,

Antibiotics - Beta Lactam Abs

• Penicillinase sensitive: Uses gram+ cocci
• Penicillinase sensitive + beta-lactamase : hhelp, h influenzae
• Penicillin resistant: staphylococcus aureus
• Antipseuodomonal: pseudomaonas
• Monobactam: Gram- only

Beta Lactam Abs

• Cephalosporins, binds to beta-lactam, inhibits cell wall synthesis
• 1st generation: Treat prevent Staphylococcus auteus in wound.
• 2nd and 3rd Generation: treats H influenza, Enterobactet, Neisseria
• 4 -5 th generation: broad gram +

Beta Lactam Abs 2

• Carbapenems: Life-threatening infections (G+ -)
• PBP binds to the beta-lactam ring, disrupt cell synthesis

Disrupts Cell Wall

• Fosfomycin treats urinary infection and irreversibly blocks MurA.
• Cycloserine is TB drug
• Vancomycin treats gram(+)
• Bacitracin: Topical on open wounds

Mycobacterial Cell Wall Inhibitors

• INH block mycolic acid (liver/ neurotoxic)
• Ethambutol block arabinosyl transferase (optic neuritis)

Cell Membrane Integrity Disruptors

• Daptomycin: Forms transmembrane channels, disrupts membrane polarity
• Polymyxin damages gram(-) bacteria cell membranes (neuphrotoxic)

Nucleic Acid Synthesis Inhibitors

• Metronidazole (anti-parasite/bacteria)
• fluroquinolones: (interfere with DNA)
• Rifamycins: (DNA/RNA polymerase)

Metabolic Pathway Inhibitors

• Sulfonamindes
• Trimetroprim

30S Subunit Inhibitors

• aminoglycosides -severe infections (-anaerobes)
• Tetracyclines: Pneumonia with acne

50S inhibitors

• Amphenicol: broad spectrum
• Macrolides: atypical pneumonia
• Lincosamides: Anaerobes, lung

50S Inhibitors

• Oxazelidindes: gram +

Thyroid Drugs

• Levothyroxin: synthetic T4
• Propothiourac and Methimazole: inhibit Thyroid hormone, granulocytosis

hormonal Drugs

• Contraception, Multiphase (bind preg receptors)
• Syn estrogenic or combined (inhibits ovulation)

Controceptives

• Progesterone
• NuvaRing
• SC Injections
• Intreauterine

Hormonal Drugs 2

• Laber : (B2 Action): increase heart Hypo, dilates

Anit Progestants,

• Mifepristone: Inhibits receptor
• Sex Characteristics (Stimulates anabolism )

Anticoagulation

• Hepararin: Blocks clotting factors
• NOACs : Anticoagulation
• Warefrin: inhibit k
• Aspirin: Analgestic effects . platelets are effecte

Anticoagulation and Phosphodiesterase

• DIPYRIDAMOLE
• CILOSTAZOL

Paracetamol

• Used for antipyretics and analgesic
• Fatal liver damage

Benxodiazepines:

• Anxiety, seziure to stop activity

Barbiturates

• Anti ansiety drug
• increase C1 Channels

Opioids

• Anagestics
• Morphibe to surpress pain

Insulin

• NPH: Intermediate treatment
• Analogs : fast acting treatment

Additional

Releases DHT. Treats hair loss/ hypertroposohy