ANS Flashcards
M1,M2,M3: G-protein activation
M1 and M3: Gq - Phospholipase C
M2: Gi
Sympathetic vs. parasympathetic
Sympathetic: t1-L2, short preganglionic (ACh nicotinic), long post (Epi)
Parasympathetic C1-C8 + L3-S5, long preganglionic (ACh) short post (muscarinic ACh)
M2 receptor locations
M2 is the heart of med school) M2 - Gi (decrease cAMP) - SA node - AV node - cardiac myocytes
M1/M3: location and activation
Phospholipase C
- vascular sm. muscle
- sm. muscle of GI (walls, sphincters)
- GI secretions
- urogenital: bladder walls, sphincters, uterus, seminal vesicles
- eye: iris, ciliary muscle, lacrimal glands
- M1 are CNS
Direct muscarine agonists
Non-selectively activates M1,2 and 3. Cevimaline is more selective for M3 (civilized people drive M3s)
Choline esters:
- methacholine: asthma diagnosis
- carbachol: glaucoma(constricts pupils) meiosis induction
- bethanachol: urinary retention/GI dysmotility
Alkaloids:
- pilocarpine (muscarine analog) xerostomia
- cevimaline - glaucoma, miosis induction
Cholinergic effects:9 DUMBBELLS
Blurred vision N/V/D Sweating Hypersalivation Flushing Bradycardia Reflex tachycardia Bronchoconstriction
Natural alkaloid amines:
in NAAM the AK shot (antagonize) AT you with a SCOPE)
Direct muscarinic antagonists: nicotinic ACh poisoning, N/V (motion sickness)
Atropine, scopolamine
Tertiary amines : high CNS penetrance
Quaternary amines: lower CNS penetrance than tertiary
Atropine
No selective muscarinic antagonist
- antidote for muscarinic ACh toxicity
- bronchi, salivary and sweat glands most effective
- ACLS algorithm
Scopolamine
Nonselective muscarinic antagonist
- Substantial CNS effects
- prevention of motion sickness N/V
Benzotropine and triphenidyl
- M1 selective
- decrease tremor in early Parkinson’s (park your benz, with the triprop logo, benzs are thrilling cars)
- treat extra pyramidal symptoms
hyoscyamine and dicyclomine
- Nonselective muscarinic antagonist (hyoscyamine)
- M1/3 selective (dicyclomine)
- decreases GI motility in IBS
(hyo rode a cycle back from the bathroom)
Tertiary and quaternary amines: indications for urinary incontinence
Urinary incontinence
- high M3 selectivity tertiary amines:
~ Darifenacin
~ solifenacin
- low M3 selectivity tertiary amines:
~ oxybutynin
~ tolterodine
~ fesoterodine
- quaternary amines
~ Trospium
(Don't Soil (high) Old Trousers For (low) the 4th Time (quaternary))Quaternary amines for COPD/asthma
- Nonselective muscarine antagonists
- first line for COPD
- not first line for emergency management of airways
Ipratroprium (brats are short and high energy: short acting, muscarinic agonist) and tiotropium (long acting)
Direct nicotinic agonist
Acetylcholine/nicotine: agonists (Varen Succed DAN: direct nicotinic agonists)
- varenicline (partial nicotinic agonist)
- succinylcholine (paradoxical action: brief fasiculation followed by flaccid paralysis)
Direct nicotinic agonist toxicity: cause
nicotine and varenicline
Nicotine:
- acute
~ N/V/D
~ Cardiac (HTN, arrythmias)
~ CNS: seizures, depolarizing blockade
- chronic CV and GI risk
Varenicline
- nausea
- CNS: insomnia, abnormal dreams psychDirect nicotinic agonist toxicity: succinylcholine
- paralysis (prolonged)
- malignant hyperthermia
- myopathy
- hyperkalemia (continue depolarization causes continuous efflux of K)
(Hypnotize My Mind Please)
AChE inhibitors: general
Indirect cholinergic agonist (inhibits degradation in the synapse)
- treatment for myasthenia gravis (edro, neo and phyo caused ester agony)
- edrophonium (short acting: non-covalent bond)
- neostygmine
- phyostigmine
~ stigmines: nonlabile covalent bond long lasting (Stygmines styck around)
Organophosphate poisoning: MOA and trt
- Covalent bonding
- muscarinc and nicotinic toxicity
- trt: atropine and pralidoxamine (ACH antagonism and AChE regeneration)
(spray at toxic at bugs: atropine + pralidoxamine)
Central AChE inhibitors (DRG): examples (3), indications, toxicities
- indicated in dementia esp. Alzheimer’s
- relatively selective for CNS AChE (DRG)
- toxicity: GI, dizziness, bradycardia, hepatotoxicity
- e.g.
~ Donepezil
~ galantamine
~ rivastimine
Adrenergic receptor: general
G-protein linked
- a1: Gq (Phospholipase C)
- a2: Gi (decrease cAMP)
- B1/2: Gs (increase cAMP)
Dopamine pathway
Tyrosine -THB-> L-dopa -pyridoxal phosphate-> dopamine -vitamin C-> norepi -s-adenysylmethionine-> epi
Catecholamine affinity
NE: high for a1/2 and lower for B1 Epi: dose dependent - low dose B predominates - high dose a predominates DA: also dose dependent - low dose: dopamine - moderate dose: high affinity to B1, lower for a1 and dopamine - high dose: a1 over B1
Alpha Agonists
a1: vasoconstriction
- systemic: phenylepherine, midorine
- local: phenylepherine, oxymetazoline, tetrahydrazoline
a2: negative feedback on central and peripheral adrenergic *note-even though its adrenergic, stimulating it decreases symp.
- neurons - decrease NE release/sympathetic outflow
- Clonadine, methyldopa, dexmedetomidine, tizanidine
AA is for potheads) (sMoking local POT causes agony, Come To My Drugstore: drugstore will help you take less)
Non-selective alpha antagonists
Phenoxybenzamine (irreversible)
Phentolamine (reversible)
- pro-op pheo management
(NSAA popt into space to get iron from a meteor)
a1-antagonists
- inhibit vasoconstriction (a1med) and prostate sm. muscle contrxn.
- terazosin
- tamulosin
Alpha An: a ninja
Clinical indications for a1 inhibitors
- blockade of a1 vasoconstriction, vascular and prostatic for BHP and 2nd line for HTN
- terazosin, doxazosin, prazosin
- a1a antagonist: tamulosin for BHP
- risk of hypotension
alpha: elite ninjas Put Tangos Down)
a2 antagonists:
Minimal clinical utility: increases sympathetic outflow
- mirtazapine (antidepressant) exhibits central a2 antagonism as one MOA
Non-selective B agonist: 1
Isoproteronol (terrornol)
- B1: increases HR/contractility (B1)
- B2: induces vascular and bronchial sm. muscle realaxation
- rarely clinically used: tachyarrythmias, palpitations
Doberman causes terror
B1 adrenergic AGonist
Dobutamine:
- enatiomers have competing B1 and a1 effects -> B1 antagonism
- causes positive inotropy with minimal increase in HR and without vasoconstriction (Doberman causes terror, less hr increase/vasodilation)
BAG): they put 1BAG over the dobermans head to make it less frightening)
Clinical indications for dobutamine and toxicity
Phamacological Cardiac stress test
Acute decompensating heart failure
Cardiogenic shock
Toxicity: arrythmias, HTN and tremors
B2 adrenergic agonists: short and long acting
(2 Bags of alcohOL) Short: albuterol et al - 5-15 min onset; 3-4 hour duration - acute asthma trt (1st line) - COPD, hyperkalemia (2nd line) (IV albuterol)
Long: salmeterol et al
- 15-50 minute onset; 12-24 hour duration
- chronic asthma trt (prevents bronchospasm)
B3 - adrenergic agonists
Mirabegron (miraBegron, Bladder, Beta = 3)
- over active bladder
- toxicity: HTN, Tachycardia
- drug interactions: CYP3A4, 2D6
B blockers: 4 types
Non-selective
B1 selective
Selective vasodilators
Sympathomimetics
Non-selective B antagonists
Tim antagonized the Pro and got kicked in the Nads. The boys (beta) lolled)
LOLs: propranolol, nadolol, timolol
- B1 blockade: decreases heart contractility
- decrease in renin release
- B2 blockade: many non-cardiac symptoms, tremor and glaucoma
- highly lipophilic, on the way out for CV indications
Vasodilation B blockers:
a/B blockers: carvedilol, labetalol
- vasodilation
- more commonly used for CV indications
B blockers with NO (nitrous oxide) effect: Nebivolol
- B1 selective
- increases NO release from endothelium
- NO B Nebivolol
B- sympathomimetics
they pinned a medal on the ace mime
Acebutolol, pindolol
- partial B1 agonist with or without B2 activity
- for PTs. With CV indications who can’t tolerate Beta blockade
- rarely used (less effective than full antagonists)
Indications for B blockers
HTN: 1st line only for PTs. With additions CV indications
Ischemic HD
Chronic HF
Arrythmias
B blocker toxicity
CV: - bradycardia, or block - hypotension - worsening of acute HF Peripheral - bronchospasm - masked hypoglycemia - worsening PVD - impotence CNS - fatigue - depression (assoc with lipophilicity) Decreaseed exercise tolerance Management of overdose: IsoproTERRORnol, glucagon
Catecholamine storage inhibitor: use, MOA, toxicities
Reserpine
- irreversible inhibitor of VMAT
- depletes: norepi, epi, serotonin and dopamine
- used to be used for HTN
- toxicities: depression, anxiety, psychosis
Catecholamine Storage inhibitors
MOA: promotes release of stored catecholamines
clinical indication: ADHD, narcolepsy, obesity (phentermine only)
False neurotransmitters:
Tyramine: many food and drug interactions with MAOIs
- in beer, wine, aged cheese, live, fave beans
- displaces NE -> can lead to HTN crisis
Tyr is a false god, but encountering him will raise your BP
Storage inhibitors: mixed action sympathomimetics; MOA, Indications (mimics are false: pseudo)
Ephedrine, pseudoephedrine
- MOA: Nonselective a/B agonist
- enhanced norepi release
- MOA: decongestant (Sudafed)
Catecholamines reuptake inhibitors
Amy and Velna were a pain when they cockblocked atom from picking up Sarah Tonin because atom was hyper) Cocaine: potent NET inhibitor - c-II controlled substance Atomoxerine - less potent that cocaine - used to trt ADHD - minimal CV risk (Clonadine like effect) SSRIs/SNRIs - amitriptyline (SS) - venlafaxine (SN) - for depression and neuropathic pain
MAOIs: function, interactions, SE
MOA: inhibition of MAO increases available catecholamines for release
- effects both a and B receptors
- interaction with tryramine -> HTN crisis
- serotonin syndrome
~ anti-depressants and seretonergic meds (tramadol, meperidine, dex, St. John wort)
~ hyperthermia, HTN, myoclonus, rigidity, autonomic instability, and mental status changes
Chol
Direct ACh agonist: choline esters
- carbachol
- bethanachol
Receptor locations: a1
Iris radial smooth muscle
Vascular smooth muscle; skin, mucosa, viscera
GI/UG sphincters, (contraction: pressure builds)
Pilomotor
- Gq (act Phospholipase C - IP3/DAG)
Receptor locations: a2
GI walls: activation (auto receptors decrease sympathetic flow)
Sympathetic preganglionic auto receptors (decrease NE) (MAIN)
Pancreatic islet cells (decrease secretion)
- Gi (decrease cAMP)
B1 receptor locations
Heart (increase contractility, CO)
Kidneys: (increase renin release-> increase BP)
- Gs (increase cAMP)
B2 receptor locations
- AIRWAY: vaso/bronchodilation
- All other Sm. muscle
- Gs (increase cAMP)
M1: receptor location
CNS, parasympathetic
- Gq (Phospholipase C-> IP3/DAG)
M2 receptor locations
Heart
-Gi (decrease Phospholipase C - IP3/DAG)
M3 receptor locations
Et al
- Gq (act Phospholipase C - IP3/DAG)
Zosin
Alpha-1 antagonists
Cycloplegia
- Loss of parasympathetic accommodation reflex
- blurred vision sans Diplopia
ANS receptor for which there are no drugs (or of little clinical significance)
Nonspecific alpha agonist
Alpha-2 Antagonist
Beta-2 Antagonist
