Autonomic Drugs – Cholinergic Antagonists PDF

Autonomic Drugs -- Cholinergic Antagonists Overview: - Cholinergic antagonists -- general term for the agents that bind to cholinoceptors (muscarinic or nicotinic) and prevent the effects of ACh and other cholinergic agents - 3 groups: - Muscarinic blockers = anticholinergic ag...

Autonomic Drugs -- Cholinergic Antagonists Overview: - Cholinergic antagonists -- general term for the agents that bind to cholinoceptors (muscarinic or nicotinic) and prevent the effects of ACh and other cholinergic agents - 3 groups: - Muscarinic blockers = anticholinergic agents = antimuscarinic agents = parasympatholytics Block parasympathetic activity, leave sympathetic activity unopposed - Ganglionic blockers - Show preference for nicotinic receptors at sympathetic and parasympathetic ganglia - Neuromuscular blocking agents - Interfere with efferent impulse to skeletal muscles -- used in surgery and critical care Antimuscarinic Agents: - Commonly known as anticholinergic drugs -- block muscarinic receptors. Including the few sympathetic cholinergic neurons (for sweating and salivation) - Do not block nicotinic receptors and have no activity on NMJ +-------------+-------------+-------------+-------------+-------------+ | **Drug** | **Mechanism | **Pharmacok | **Therapeut | **Adverse | | | of Action** | inetics** | ic | Effects** | | | | | Uses / | | | | | | Actions** | | +=============+=============+=============+=============+=============+ | Atropine | Tertiary | Acts both | Eye: Action | Dose | | | amine | centrally | = mydriasis | dependent; | | (ophthalmic | extracted | and | and may | can cause | | and | from | peripherall | cause | dry mouth, | | injection) | belladonna | y | dangerous | blurred | | | alkaloid | -- crosses | elevation | vision, | | *Hyoscyamin | | the BBB | in | sandy eyes, | | e* | High | | intraocular | tachycardia | | | affinity | General | pressure | , | | *\[hi-oh-SY | for | actions | for pt with | urinary | | E-uh-meen\] | muscarinic | last 4hrs | glaucoma | retention, | | - | receptors | | | constipatio | | active | -- prevents | Ocular | -Use: can | n. | | isomer of | ACh from | effects may | be used for | | | atropine- | binding | persist for | mydriatic | CNS effects | | GI | | days | effects, | include | | antispasmod | | | but | restlessnes | | ic* | | Neuroeffect | generally | s, | | | | or | replaced by | confusion, | | | | organs vary | other | hallucinati | | | | in | agents | on | | | | sensitivity | allow | and | | | | -- greatest | measurement | delirium | | | | effects | of | | | | | seen in | refractive | Low doses | | | | bronchial | errors | of | | | | tissues and | without | cholinester | | | | sweat | interferenc | ase | | | | glands and | e | inhibitors | | | | the heart | by | can be used | | | | | accommodati | to overcome | | | | Readily | on | toxicity | | | | absorbed, | capacity of | | | | | half-life | the eye | Geriatric | | | | of about 4 | | pts are at | | | | hours | GI: Action | high risk | | | | | = | of | | | | | antispasmod | confusion, | | | | | ic | disorientat | | | | | to reduce | ion, | | | | | activity of | and | | | | | the GI | depressed | | | | | tract. | cognitive | | | | | | fxn | | | | | -Use: Relax | | | | | | the GI | Dangerous | | | | | tract | in | | | | | | children- | | | | | Cardiovascu | sensitive | | | | | lar: | to rapid | | | | | Action = | increase in | | | | | divergent | body temp | | | | | effects | (occurs | | | | | depending | with | | | | | on dose -- | decreased | | | | | at low | sweating) | | | | | doses, | | | | | | effect is a | | | | | | slight | | | | | | decrease in | | | | | | HR, higher | | | | | | doses | | | | | | increase HR | | | | | | | | | | | | -Use: treat | | | | | | bradycardia | | | | | | | | | | | | Secretions: | | | | | | Action = | | | | | | block | | | | | | muscarinic | | | | | | receptors | | | | | | on salivary | | | | | | glands, | | | | | | producing | | | | | | dry mouth. | | | | | | Similar | | | | | | effects on | | | | | | tear | | | | | | production | | | | | | and sweat. | | | | | | | | | | | | -Use: can | | | | | | be used to | | | | | | block | | | | | | secretions | | | | | | in | | | | | | respiratory | | | | | | tract prior | | | | | | to surgery | | | | | | | | | | | | Antidote | | | | | | for | | | | | | cholinergic | | | | | | agents -- | | | | | | used for | | | | | | treatment | | | | | | of | | | | | | organophosp | | | | | | hate | | | | | | poisoning, | | | | | | anticholine | | | | | | sterase | | | | | | overdose, | | | | | | and some | | | | | | types of | | | | | | mushroom | | | | | | poisoning | | | | | | -- CNS | | | | | | activity | | | | | | | | | | | | Anti-SLUD | | +-------------+-------------+-------------+-------------+-------------+ | Scopolamine | Tertiary | Peripheral | Effective | | | | amine plant | effects | for motion | | | (patch) | alkaloid | similar to | sickness | | | | | atropine, | used in the | | | | | has greater | prevention | | | | | CNS | of motion | | | | | activity | sickness | | | | | | and | | | | | (CNS | postoperati | | | | | affects | ve | | | | | occur at | n/v (PONV) | | | | | therapeutic | | | | | | doses -- | Blocks | | | | | atropine | short term | | | | | usually | memory | | | | | requires | | | | | | higher | Causes | | | | | doses) | sedation | | | | | | but at high | | | | | Longer | doses can | | | | | duration of | produce | | | | | action | excitement | | | | | | and | | | | | | euphoria | | | | | | susceptible | | | | | | to abuse | | +-------------+-------------+-------------+-------------+-------------+ | **Drug** | **Mechanism | **Pharmacok | **Therapeut | **Adverse | | | of Action** | inetics** | ic | Effects** | | | | | Uses / | | | | | | Actions** | | +-------------+-------------+-------------+-------------+-------------+ | Inhaled | | | | | | agents -- | | | | | | used as | | | | | | bronchodila | | | | | | tors | | | | | | and for | | | | | | maintenance | | | | | | treatments | | | | | | of | | | | | | bronchospas | | | | | | m | | | | | | associated | | | | | | with COPD | | | | | +-------------+-------------+-------------+-------------+-------------+ | Ipratropium | Short | All agents | Used in the | | | | acting | are | acute | | | | muscarinic | delivered | management | | | | antagonist | via | of | | | | (SAMA) | inhalation | bronchospas | | | | | where | m | | | | | effects are | in asthma | | | | | restricted | | | | | | to the | | | | | | pulmonary | | | | | | system and | | | | | | they do not | | | | | | enter the | | | | | | systemic | | | | | | circulation | | | | | | or the CNS | | | +-------------+-------------+-------------+-------------+-------------+ | Aclidinium | Long acting | | | | | | muscarinic | | | | | \[a-kli-DIN | antagonist | | | | | -ee-um\] | (LAMAs) | | | | +-------------+-------------+-------------+-------------+-------------+ | Glycopyrrol | | | Has some | | | ate | | | systemic | | | | | | uses as | | | | | | well when | | | | | | given by | | | | | | injection | | | | | | used for | | | | | | excessive | | | | | | sweating | | | | | | (genetic | | | | | | issue), | | | | | | reduction | | | | | | of preop | | | | | | secretions, | | | | | | reduction | | | | | | of | | | | | | end-of-life | | | | | | secretions, | | | | | | reversal of | | | | | | bradycardia | | | | | | , | | | | | | reversal of | | | | | | cholinergic | | | | | | agents | | +-------------+-------------+-------------+-------------+-------------+ | Umeclidiniu | | | | | | m | | | | | | | | | | | | \[ue-ME-kli | | | | | | -IDN-ee-um\ | | | | | | ] | | | | | +-------------+-------------+-------------+-------------+-------------+ | Tiotropium | | | Used in the | | | | | | acute | | | | | | management | | | | | | of | | | | | | bronchospas | | | | | | m | | | | | | in asthma | | +-------------+-------------+-------------+-------------+-------------+ | Tropicamide | | Duration of | Used as | | | & | | action is | ophthalmic | | | | | shorter | solutions | | | Cyclopentol | | than | for | | | ate | | atropine | mydriasis | | | | | | and | | | | | | cycloplegia | | | | | | | | | | | | Tropicamide | | | | | | -- | | | | | | mydriasis | | | | | | for 6 hours | | | | | | | | | | | | Cyclopentol | | | | | | ate-- | | | | | | mydriasis | | | | | | for 24 | | | | | | hours | | +-------------+-------------+-------------+-------------+-------------+ | Benztropine | | | Useful as | | | & | | | adjuncts w/ | | | | | | other | | | Trihexyphen | | | antiparkins | | | idyl | | | on | | | | | | agents to | | | | | | treat | | | | | | Parkinson | | | | | | disease and | | | | | | antipsychot | | | | | | ic-induced | | | | | | extrapyrami | | | | | | dal | | | | | | symptoms | | +-------------+-------------+-------------+-------------+-------------+ | Oral | | | | | | Antimuscari | | | | | | nic | | | | | | agents for | | | | | | overactive | | | | | | bladder | | | | | +-------------+-------------+-------------+-------------+-------------+ | Oxybutynin | Competitive | Nonselectiv | Management | Dry mouth, | | | ly | e | of | constipatio | | \[ox-i-BYOO | blocking | -- binding | overactive | n, | | -ti-nin\] | muscarinic | to other | bladder and | blurred | | | (M~3~) | muscarinic | urinary | vision -- | | | receptors | receptor | incontinenc | limits | | | in the | subtypes | e | tolerabilit | | | bladder, | may | | y | | | intravesica | contribute | Used in | | | | l | to adverse | patient | Trospium is | | | pressure is | effects | with | preferred | | | lowered, | | neurogenic | in | | | bladder | Oral doses, | bladder | geriatric | | | capacity id | long ½ life | | patients, | | | increased, | | | especially | | | and the | | | those at | | | frequency | | | risk of | | | of bladder | | | cognitive | | | contraction | | | dysfunction | | | s | | | , | | | is reduced | | | d/t fewer | | | | | | CNS effects | | | | | | -- | | | | | | minimally | | | | | | crosses BBB | +-------------+-------------+-------------+-------------+-------------+ | Fesoterodin | | | Management | | | e | | | of | | | | | | overactive | | | \[fes-oh-TE | | | bladder and | | | R-oh-deen\] | | | urinary | | | | | | incontinenc | | | | | | e | | +-------------+-------------+-------------+-------------+-------------+ | Tolterodine | | | | | | | | | | | | \[tol-TER-o | | | | | | h-deen\] | | | | | +-------------+-------------+-------------+-------------+-------------+ | Trospium | | | | | | | | | | | | \[TROSE-pee | | | | | | -um\] | | | | | +-------------+-------------+-------------+-------------+-------------+ | Darifenacin | | More | | | | | | selective | | | | \[dar-e-FEN | | M~3~ | | | | -a-sin\] | | muscarinic | | | | | | receptor | | | | | | antagonist | | | | | | | | | | | | Oral doses, | | | | | | long ½ life | | | +-------------+-------------+-------------+-------------+-------------+ | Solifenacin | | | | | | | | | | | | \[sol-ee-FE | | | | | | N-a-sin\] | | | | | +-------------+-------------+-------------+-------------+-------------+ Ganglionic Blockers: - Most agents are used for research -- have no therapeutic use - Nicotine - Has effects on both sympathetic and parasympathetic ganglia - Used for smoking cessation  Neuromuscular blocking Agents: - Block cholinergic transmission b/w motor nerve endings and nicotinic receptors on skeletal muscle - Have some similarities to ACh and act as antagonists (nondepolarizing) or as agonists (depolarizing) at receptors at the NMJ - Used to facilitate rapid intubation (RSI) and as adjunctive therapy to mechanical ventilation - Used in surgery to facilitate endotracheal intubation and provide complete muscle relation at lower anesthetic doses - Using lower anesthesia doses id safe and allows patients to recover more quickly - Not ok to use agents to mask inadequate anesthesia - The first known NMB was curare \[kyoo-RAH-ree\], which Amazon hunters used to paralyze prey +-------------+-------------+-------------+-------------+-------------+ | **Drug** | **Mechanism | **Pharmacok | **Therapeut | **Adverse | | | of Action** | inetics** | ic | Effects** | | | | | Uses / | | | | | | Actions** | | +=============+=============+=============+=============+=============+ | Nondepolari | | | | | | zing | | | | | | (competitiv | | | | | | e) | | | | | | blockers | | | | | | (antagonist | | | | | | s) | | | | | +-------------+-------------+-------------+-------------+-------------+ | Cisatracuri | Low doses: | Injections | Muscles | Cholinester | | um | | -- given as | have | ase | | | -competitiv | IV or | differing | inhibitors | | | ely | occasionall | sensitivity | -- can | | | block ACh | y | to blockage | overcome | | | at this | IM | | effects of | | | nicotinic | | Small, | nondepolari | | | receptors | Do not | rapidly | zing | | | without | enter cells | contracting | blockers, | | | stimulating | or cross | muscles of | but at high | | | the | BBB | the face | doses can | | | receptor, | | and eyes | cause | | | this | Each have | are most | depolarizin | | | preventing | different | susceptible | g | | | depolarizat | methods of | and are | blockade | | | ion | metabolism | paralyzed | | | | of the | | first, | Halogenated | | | muscle cell | | followed by | hydrocarbon | | | membrane | | fingers, | anesthetics | | | and | | limbs, neck | -- enhance | | | inhibiting | | and truck | neuromuscul | | | muscular | | muscles and | ar | | | contraction | | lastly the | blockade by | | | | | diaphragm | sensitizing | | | -effects | | | the NMJ to | | | can be | | The muscles | the effects | | | overcome by | | recover in | of NMBs | | | admin of | | reverse | | | | AChE | | order | Aminoglycos | | | inhibitors | | | ide | | | | | | abx -- | | | -muscle is | | | inhibit ACh | | | still able | | | release | | | to respond | | | from | | | to | | | cholinergic | | | electrical | | | nerves and | | | stimulation | | | synergize | | | | | | with | | | High Doses: | | | competitive | | | | | | blockers, | | | -AChE | | | enhancing | | | inhibitors | | | neuromuscul | | | are less | | | ar | | | effective | | | blockage | | | at | | | | | | reversing | | | Calcium | | | effects | | | channel | | | | | | blockers -- | | | -Muscle | | | increase | | | foes not | | | the | | | respond to | | | neuromuscul | | | electrical | | | ar | | | stimulation | | | blockade of | | | | | | competitive | | | | | | blockers | +-------------+-------------+-------------+-------------+-------------+ | Rocuronium | | | | | +-------------+-------------+-------------+-------------+-------------+ | Vecuronium | | | | | +-------------+-------------+-------------+-------------+-------------+ | Depolarizin | | | | | | g | | | | | | blockers | | | | | | (agonists) | | | | | +-------------+-------------+-------------+-------------+-------------+ | Succinylcho | Depolarize | Short | As with | Hyperthermi | | line | the plasma | duration of | other | a | | | membrane of | action d/t | agents, | -- can | | | the muscle | plasma | respiratory | induce | | | fiber, | cholinester | muscles are | malignant | | | similar to | ase | paralyzed | hyperthermi | | | ACh | | last | a | | | | | | | | | Resist | | Brief | Prolonged | | | degradation | | muscle | muscular | | | by AChE and | | fasciculati | weakness -- | | | can more | | ons | may | | | persistentl | | result in | experience | | | y | | severe | prolonged | | | depolarize | | muscle | paralysis | | | the muscle | | soreness | in patients | | | fibers | | | who are | | | | | Uses: | deficient | | | The | | | is plasma | | | receptor is | | -rapid | cholinester | | | depolarized | | endotrachea | ase | | | until the | | l | or have an | | | receptor is | | intubation | atypical | | | incapable | | (RSI) | dorm of the | | | of | | | enzyme | | | transmittin | | -used | | | | g | | during | Hyperkalemi | | | further | | electroconv | a | | | impulses | | ulsive | -- | | | | | shock | increases | | | Process | | treatment | potassium | | | that causes | | | release | | | transient | | | from | | | twitching | | | intracellul | | | (fasciculat | | | ar | | | ions) | | | stores -- | | | and later | | | avoid in | | | paralysis | | | burn | | | | | | patients | | | -Phase I | | | and | | | receptor | | | patients | | | membrane | | | with renal | | | depolarizes | | | failure -- | | | , | | | can lead to | | | producing | | | cardiac | | | transient | | | arrythmias | | | fasciculati | | | or cardiac | | | ons | | | arrest | | | followed by | | | | | | flacid | | | | | | paralysis | | | | | | | | | | | | -Phase II | | | | | | membrane | | | | | | repolarizes | | | | | | , | | | | | | but the | | | | | | receptor is | | | | | | desensitize | | | | | | d | | | | | | to the | | | | | | effect of | | | | | | acetylcholi | | | | | | ne | | | | | | -- | | | | | | sustained | | | | | | paralysis | | | | +-------------+-------------+-------------+-------------+-------------+ \*Review article on last 3 slides\*