PNS and Cardio Flashcards
Acetylcholine (miochol)
Muscarinic agonist
- hydrolyzed fast by AchE
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Uses:
- cataract extraction - used to constrict circular muscle/stretch iris, good cuz hydrolyzed rapidly
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Carbamylcholine
Muscarinic agonist
- resistant to hydrolysis by AchE
- more nicotinic than muscarinic
- improves aqueous outflow in glaucoma, constricts pupil
Potent in GI, bladder and eye
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Acetyl-B-methylcholine
Muscarinic agonist
- slowly hydrolyzed by AchE
Potent in heart
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Bethanechol
Muscarinic agonist
- resistant to hydrolysis by AchE
- muscarinic selective
Potent in GI, bladder and eye
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Uses:
- post-op ileus, congenital megacolon, GERD - increases tone of GI and sphincter, don’t use for inflammatory or microbial causes
- urinary retention problems - inject into detrusor, helps pee
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Pilocarpine
Muscarinic agonist
Not charged, used for local applications, penetrates tissue
Apply topically
Uses:
- for increased intraocular pressure/narrow angle glaucoma - constricts sphinter pupillae, stretches iris to allow for drainage of aqueous humor
- xerostomia - induces salivation
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Atropine
Muscarinic antagonist
- non-selective
Penetrates tissue but not as fast as scopolamine (uncharged, can get into CNS)
Uses:
- prevent vagal reflexes induced by surgical manipulation of visceral organs
- pre-anesthesia - inhibit salivation and respiratory tract secretions
- block response triggered in parasymp system from reversal of neuromuscular blockade, can penetrate CNS cuz not charged
- ophthalmology: mydriasis
- treat anticholinesterase poisoning by organophosphates (given with oxime)
- blocks slow IPSP (muscarinic antagonists)
- blocks slow EPSP (muscarinic antagonists)
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Scopolamine
Muscarinic antagonist
- non-selective
Rapidly penetrates tissue
Uses:
- tranquilize and produce amnesia following surgery
- if gets in/used in eye: mydriasis
- anti-emetic, motion sickness
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
- more potent than anti-histamines for motion sickness (patch behind ear)
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Pirenzepine
Muscarinic antagonist - M1 selective Doesn't penetrate BBB well Uses: - peptic ulcers Contraindications - inflammatory conditions or infections, narrow angle glaucoma, cardiac arrhythmia, chronic lung disease Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Tropicamide
Muscarinic antagonist
- non-selective
Uses:
- ophthalmology: dilate pupil, rapid onset and shortest duration (2-3hrs) - cycloplegia and mydriasis
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Side effects:
- cycloplegia and mydriasis
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Glycopyrrolate
Muscarinic antagonist
- non-selective
Doesn’t cross BBB or penetrate tissue well
Uses:
- prevent vagal reflexes induced by surgical manipulation of visceral organs (IV)
- pre-anesthesia - used to dry up salivary glands and respiratory tract for trach tube
- counteract muscarinic activation that occurs due to recovery from anesthesia, block M3 in GI (neostigmine given to overcome neuromuscular blockade)
- inject into GI, used for intestinal hypermotility and diarrhea
- see dry mouth and cycloplegia
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Cyclopentolate
Muscarinic antagonist
Uses:
- ophthalmology: dilate pupil, longer lasting than tropicamide (6hrs) - cycloplegia and mydriasis
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Side effects:
- cycloplegia and mydriasis
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Tiotropium
Muscarinic antagonist
- M3 in lung selective
Uses:
- used as aerosol in lung
- chronic bronchitis and emphysema
Can use in chronic lung disease, does not effect viscosity
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Tolterodine
Muscarinic antagonist
- M3 in detrusor selective
Uses:
- overactive bladder
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Darifencin
Muscarinic antagonist
- M3 in detrusor selective
Uses:
- overactive bladder
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Ipratropium
Muscarinic antagonist
- non-selective
Uses:
- potency in lung for bronchial smooth muscle - relaxes it
- cold remedy OTC, chronic rhinitis/hay fever
- chronic bronchitis and emphysema
Can use in chronic lung disease, does not effect viscosity
Can dilate pupil if get into/touch eye
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Dimenhydrinate
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
Diphenhydramine
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
Meclinzine
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
Muscarine
Leads to cholinergic symptoms/SLUDGE (salivation, lacrimation, perspiration)
- poisoning from Amanita muscaria, Inocybe, and Clitocybe mushrooms
- treat with atropine
Pralidoxime
Oxime (2-PAM)
- displaces anticholinesterases
- treat anticholinesterase poisoning by organophosphates (given with atropine)
Edrophonium
Quaternary amine
- reversible acetylcholinesterase inhibitor (shortest lasting, seconds)
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Carbamate
Reversible acetylcholinesterase inhibitor (longer lasting, hours)
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Organophosphate
Irreversible (very long lasting) acetylcholinesterase inhibitor
- form stable covalent bond to serine group oc AchE
- pesticides usually
SLUDGE side effects
Physostigmine
Carbamate
- Reversible acetylcholinesterase inhibitor
- penetrates BBB and tissue, not charged
Uses:
- glaucoma, penetrates cornea (applied locally), constrict circular muscle and increase aqueous humour outflow (used with pilocarpine)
- poisoning by anti-muscarinic or anti-nicotinic
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Neostigmine
Carbamate
- Reversible acetylcholinesterase inhibitor
- doesn’t penetrate tissue, charged
Uses:
- paralytic ileus and atony of urinary bladder (used in conjuction with cholinomimetic bethanechol), injected into bladder
- used for MG with an antimuscarinic (glycopyrrolate/atropine)
- recovery of neuromuscular block following surgery (if nondepolaring blocker), plus an antimuscarinic
- poisoning by anti-muscarinic or anti-nicotinic
Contraindications:
- don’t use with peritonitis, inflammatory obstruction, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Pyridostigmine
Carbamate
- reversible acetylcholinesterase inhibitor
- charged, doesn’t penetrate tissue
Uses:
- used for MG with an antimuscarinic (glycopyrrolate/atropine)
- poisoning by anti-muscarinic or anti-nicotinic
- prophylaxis for nerve agent exposure - can also give galantamine (or human BuChE)
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Malathion
Anticholinesterase - organophosphate pesticide - low toxicity to man/birds - inactivated by carboxylesterase in mammals and birds SLUDGE side effects
Diazanon
Anticholinesterase
- organophosphate pesticide
- household use for cockroaches
SLUDGE side effects
Carbaryl
(Sevin) Anticholinesterase - carbamate pesticide - used in gardens SLUDGE side effects
Soman/Tabun
Anticholinesterase
- organophosphate nerve agent
- chemical warfare agent
SLUDGE side effects
Sarin
Anticholinesterase
- organophosphate nerve agent
- chemical warfare agent
SLUDGE side effects
VX
Anticholinesterase - organophosphate nerve agent - chemical warfare agent Smallest lethal dose SLUDGE side effects
Aminoglycosides and Tetracycline
Kanamycin, Neomycin, Streptomycin
- block Ca transport, reduces free Ca in presynaptic terminal
- need less neuromuscular blocker if on these cuz less Ach released
Botulinum toxin
Interferes with snare proteins, prevents vesicle release
- Botulin toxin A - cleaves SNAP 25
- Botuliln toxin B - cleaves synaptobrevin/VAMP
Uses:
- ophthalmology - strabismus, blepharospasm
- hyperhydrosis
- cervical dystonia - torticollis
- cosmetic
Hemicholinium
Blocks choline re-uptake
Succinylcholine
Depolarizing nicotinic antagonist, neuromuscular blocker
- hydrolyzed by butyryrlcholine esterase
- inactivation of Na channel produces the block
Fast onset, short acting
- used for intubation
Toxicity:
- arrest all muscles, including those of respiration
- stimulates histamine release, induces malignant hyperthermia (if RyR mutation), give dantroline
- can increase intraocular pressure
- infants need more
- hypothermia need less
- hypokalemia need more
- hyperkalemia need less
- bronchiogenic/small cell carcinoma need less
Contraindications:
- burn and truma
d-Tubocurarine
Non-depolarizing nicotinic antagonist, neuromuscular blocker
Toxicity:
- arrest all muscles, including those of respiration
- increases histamine release, causes ganglionic blockade
Physiological factors
- hypokalemia enhances effect
- hyperkalemia attenuates effect
- infants need less
- hypothermia need more
- MG needs less
- bronchiogenic/small cell carcinoma need less
Pancuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- longest lasting
Toxicity:
- arrest all muscles, including those of respiration
Vecuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- metabolism decreased in liver disease
Toxicity:
- arrest all muscles, including those of respiration
Cisatracurium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- not hydrolyzed enzymatically (Hoffman elimination), use in liver disease
Toxicity:
- arrest all muscles, including those of respiration
Rocuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- fastest onset, shortest lasting
- metabolism decreased in liver disease
Toxicity:
- arrest all muscles, including those of respiration
Hexamethonium
Nicotinic antagonist/ganglionic blocker
- blocks fast EPSP
Mecamylamine
Ganglionic blocking agent
Trimethaphan
Ganglionic blocking agent
Carbachol
Cholinergic/muscarinic agonist
- doesn’t penetrate as well as pilocarpine
Used to reduce intraocular pressure by stretching iris and opening drainage canal
Acetyl-B-methylcholine
Muscarinic agonist
- hydrolyzed by acetylcholinesterase
Neuromuscular blocking agents
Uses: - miuscle relaxants - intubation and surgery - muscle paralysis (botox) - orthopedic procedures - electroconvulsive therapy - treatment for poisoning with black widow spider venom and tetanus Drugs: - d-Tubocurarine - Pancuronium - Vecuronium - Cisatracurium - Rocuronium - Succinylcholine - Botulinum toxin - Hemicholinium - Aminoglycosides/tetracycline (block Ca transporter)
Muscarinic agonists
Ach Carbamylcholine Acetyl-B-methylcholine Bethanechol Pilocarpine Muscarine
Muscarinic antagonists
Atropine Scopolamine Pirenzepine Tropicamide Glycopyrrolate Cyclopentolate Tiotropium Ipratropium Tolterodine Darifencin Systemic side effects: - mad as a hatter, dry as bone, blind as a bat, red as a beet - dry skin/mouth, flushed face, fever, urinary retention, constipation, tachy, irrability
Antihistamines
Dimenhydrinate
Diphenydramine
Meclinzine
Anticholinesterases
Carbamates: - Physostigmine, Neostigmine, Pyridostigmine, Carbaryl (insecticide) Edrophonium - quaternary amine Organophosphates - malathion, diazanon, sarin, VX, tabun
Neuromucular blockers
Aminoglycosides - kanamycin, neomycin, streptomycin Tetracycline Botulinum toxin Hemicholinium Non-depolarizing - dTC, pancuronium, vecuronium, cisatracurium, rocuronium Depolarizing - succinylcholine
Ganglionic blockers
Mecamylamine
Trimethaphan
Hexamethonium
Catecholamines
Sympathomimetic amines, direct acting adrenergic agonists Norepinephrine Epinephrine Isoproterenol Dopamine Dobutamine
Alpha-agonists
Sympathomimetic, direct acting adrenergic agonists Non-catecholamines Phenylephrine - alpha 1 Clonidine - alpha 2 Brimonidine - alpha 2
Beta-agonists
Sympathomimetic, direct acting adrenergic agonists Non-catecholamines Beta 2 - albuterol - salmeterol - formoterol - ritodrine Beta 3 - mirabegron
NE releasers
Sympathomimetic, indirect acting Non-catecholamines Tyramine Amphetamine Ephedrine
Sympathomimetic-like drugs
Cocaine - NET inhibitor, increases synaptic NE
PDE inhibitors
- caffeine
- theophylline (asthma uses)
Reserpine
Sympatholytic - inhibits VMAT2, depletes NE in vesicles (and other monoamines) - crosses BBB and placenta Slow recovery on withdrawal Inactivates NE releasers Adrenoceptor up-regulation Higher doses - sedatives, tranquilizer Lower doses - anti-hypertensive - peripheral sympatholytic Adverse CNS effects - increased risk of clinical depression - potentiation of CNS depressants - exacerbation of parkinsonism - lowered seizure threshold
Adrenergic receptor agonist effects
Alpha 1 agonists
- vascular, iris and GU smooth muscle contraction
- viscous secretions from salivary and localized sweat glands (palms)
- K release from liver
Alpha 2 agonists
- vascular smooth muscle contraction
- decreased insulin release from pancreatic beta cells
- platelet aggregation
- decreases NE release from nerve terminals
Beta 1 agonists
- increase HR, contractile force and conduction velocity
- increase renin release from JG cells
Beta 2 agonists (NE weak)
- vascular, respiratory and uterine smooth muscle relaxation
- tremors in skeletal muscle
- increased glucose in skeletal muscle and increased K uptake
- increase glucose in liver
- decrease mast cell degranulation
Beta 3 agonists (EPI weak)
- relaxes urinary bladder
- thermogenic and lipolysis in adipose tissue
Prazosin
Alpha 1 antagonist - short half-life - vasodilation Uses: - primary hypertension (3rd/4th line) - no increase in NE release - vasodilation in peripheral vascular disease vasospasms - Raynaud's - relaxation of urinary tract smooth muscle in BPH Adverse events - orthostatic hypotension seen - nasal congestion - dry mouth - intraoperative floppy iris syndrome - retrograde ejaculation - delayed ejaculation - priapism
Yohimbine
Alpha 2 antagonist
- potentiates contraction of vascular smooth muscle cuz increases NE release
NE
Alpha 1 and 2, Beta 1 and 3 agonist - vasoconstrictor, increases MAP, increase in HR but vagal reflex decreases it Uses: - hypotension - mucosal congestion - local anesthesia (to keep it local) Adverse effects: - increased O2 demand in heart - cardiac arrhythmias - decreased organ/tissue perfusion - necrosis at infusion site - dose/concentration variable on route of administration
EPI
Alpha 1 and 2, Beta 1 and 2 agonist - vasodilator, this predominates at low doses; looks like NE at higher doses - increases CO and HR Uses: - cardiac arrest - anaphylactic shock - hypotension - mucosal congestion - local anesthesia (to keep it local) - lowers intraocular pressure via increased outflow - short term decongestant in eye - long term inflammatory in eye - mydriasis Adverse effects: - increased O2 demand in heart - cardiac arrhythmias - decreased organ/tissue perfusion - necrosis at infusion site - dose/concentration variable on route of administration - physiologic tremer via B2 receptor Metabolic effects: - B1 and B3 in adipose tissue - FFAs - B2 in muscle - increase glucose - B2 in liver - increase glucose - a2 in Beta cells - block insulin secretion - a1 in liver - K release, uptake into skeletal muscle via Na/K pump due to B2
ISO
Beta 1, 2 and 3 agonist
- vasodilator, MAP decreases, increases CO and HR
- relaxes bronchial/tracheal smooth muscle
Dopamine
Beta 1 at high doses, D1 (renal and GI vascular beds)
Uses:
- acute heart failure and circulatory shock
Dobutamine
Beta 1 selective Uses: - acute heart failure and circulatory shock - selectively increases CO Inotrope - increases CO - not much HR increase - reduces preload - decreases TPR
Lavamisole
MAO/COMT inhibitor
Can lead to neutropenia when cut in cocaine
Clenbuterol
Beta 2 agonist - promotes growth of muscle in livestock - skeletal muscle hypertrophy Adverse cardiovascular effects: - cardiac hypertrophy - beta 2 agonists illegal in athletes
Ritodrine
Beta 2 agonist - tocolytic - relaxes myometrium, inhibits contractions - used to delay preterm labor Adverse effects: - tachycardia - fetus/mom - hyperglycemia - fetus/mom - hypokalemia - fetus/mom - tremor - desensitization/tolerance - pulmonary edema in mom
Ergotamine
Alpha 1 adrenergic partial agonist
- used to abort migraines, take when experiencing the aura
- vasoconstrictor
- can lead to ergotism: vasospasm, painful extremities, peripheral gangrene
5HT 2B agonist - valvular disease
Ergonovine
Alpha 1 adrenergic partial agonist
- used to contract post-partum uterus to prevent hemorrhage
- oxytocic
Phenylephrine
Alpha 1 agonist
- decongestant, vasopressor, mydriatic