PNP Mini Module Flashcards
Hemicholinium
Category
NMJ presynaptic blocker
Myasthenia Gravis (MG) (CP, cause, pathophys)
Antibodies against postsynaptic NMJ nicotinic ACH receptors
Scooped-out post-synaptic membrane with less scalloping (low #nAChRs)
CP: easily fatigued skeletal m. - lid ptosis, normal initial muscle strength but fatigues too easily
Fatigue due to depression of ACh release (runs out) and lacking safety factor for contraction = more likely to run out = less muscle strength
TTX
mechanism
presynaptic - blocks Na Channel in AP propagation
post-synaptic - blocks Na Channel in AP propagation
AKA tetrodotoxin
Mg2+ and other polyvalent cations
mechanism
Presynaptic NMJ competitive inhibitor for Ca2+ channel (reduces Ca entry)
Aminoglycosides ABx (side effect)
Presynaptic NMJ block of V-gated Ca Channels
Lambert-Eaton Myasthenic Syndrome (LEMS)
cause, assoc, CP
Antibodies against presynaptic Ca channels
Assoc: 50% pts suffer from small lung cell carcinoma (muscle sx present before cancer)
CP: muscles initially weak (less Ca channels impair ACh release, reduce EPPs)
ACh release and muscle contraction IMPROVES with REPETITIVE motor nerve activation (raises intracell Ca)
Black Widow Spider Venom (Iatrotoxin)
Mechanism, Effect
M: forms Ca channel in nerve presynaptic terminal
E: asynchronous muscle twitching -> flatline paralysis (run out of ACh)
Botulinum toxin Type A
Mechanism, Uses, SE, antidote
M: cleave SNAP-25 snare - reduced Ca sensitivity of secretory apparatus (cleaves near binding site of Ca to synaptotagmin), inhibits ACh secretion (less EPP without changing MEPP)
CU: Blepharospasm (Orbicularis oculi m spasm), Cosmetic (excessive facial m. contraction), Hemifacial spasms, Laryngeal Problems (Stuttering, spasmodic dysphoria - target thyroarytenoid m.), Cerebral Palsy/Stroke (reduce spasticity), Musician’s/Writer’s Cramp (reduce spasms with repetitive activity)
SE: risk weakening breathing/swallowing muscles; bioterrorism
Antidote: Heptavalent antitoxin (only works when toxin is not yet bound to nerve terminals)
How to use electrophysiology to determine mechanism (pre vs. post synaptic)?
Post-synaptic: EPP, MEPP, and response to exogenous ACh ALL DECREASE IN PARALLEL
Pre-Synaptic: EPP decrease without change in MEPP amplitudes (affects vesicle release, not amount of ACh in vesicle)
Botox B (mechanism)
cleaves synaptoBrevin - the only snare that attaches to the vesicle
Tubocurarine
Pancuronium
(Category)
NMJ Postsynaptic Non Depolarizing Blockers
-curoniums
Vecuronium
Mechanism, SE, elimination, use
M: non-depolarizing nAChR block
SE: no CV effects (tachy/hist release hypotension)
Elimination: Liver (good for pt in renal failure)
U: duration of surgery
Rocuronium
Mechanism, SE, use, eliimination
"Fast vecuronium" M: non-depolarizing nAChR block SE: no CV effects use: intubation, surgery duration (1.5 min onset) elimination: liver
Succinylcholine
structure, mechanism, use, SE, contraindications
S: 2 ACh mLc = 2 step hydrolysis by ChE
M: depolarizing nAChR block
U: early anesthesia for intubation/rapid airway (phase 1 block)
SE: low dose - bradycardia (activates mAChR), malignant hyperthermia (opens RyR in muscle - high body temp, massive skeletal muscle contraction)
CI: conditions where new AChRs form along entire muscle surface (burn pts - high serum K can cause CV collapse), pts with cardiac arrhythmias (heart block worry), liver disease/ChE deficiency, not used for duration of surgery (can cause post op muscle pain)
Nicotine (Category)
Exogenous ACh - Depolarizing nAChR blocker
Edrophonium (Tensilon)
Mechanism, use, SE
M: short acting anti-ChE
U: TEST for MG (cause sx improvement! for brief time)
SE: muscarinic mAChR effects
Sugammadex
Mechanism, SE, use
M: encapsulates curoniums and inactivates them (donut-shape)
SE: hypersensitivity rxn, and reduces steroids effect (anti-contraceptive)
Use: reverse non-depolarizing block after surgery
What is synergy?
2 drugs with same effect but different mechanism of action = compounded and enhanced effect greater than the sum of the two medications individually
Mechanism of Phase I and Phase II block
Phase I: block by receptor depolarization (Na channel inactivated, membrane depolarized at E(ACh))
Phase II: block by desensitization (Na not inactivated, but nAChR blocked)
How does rocuronium cause NMJ depression?
curonium = nondepolarizing block nAChR = removes spare receptors
now inhibited NT release via ATP in vesicles from repeated stim will cause depression in EPPs
How does SUX act in phase I and phase II block in response to high freq stim?
Phase I: depolarizing block - high freq stim = no depression, but whole response is scaled down (less nAChRs activated)
Phase II: desensitizing block - high freq stim = depression (spare receptors gone)
How do you observe full recovery from a neuromuscular block?
All 4/4 impulses in a train crease a twitch
Effects of ANS on Pupil Dilator, Bronchiolar Smooth Muscle, GI tract/Urinary Bladder, Cardiac Fx, Liver and Fat, Blood vessels, Sexual Fx, Hair, Spleen, Secretions, Pancreas, Accommodation
Symp: Mydriasis (dilation of pupils), bronchiodilation (open airway), less GI/bladder wall tone more sphincter tone, Cardiac: high HR, more contraction force, more glycogenolysis/gluconeogenesis/fatty acid release, VC via A1 = high BP (VD in skeletal muscle/liver B2 - less important for BP), Sex Fx: more smooth muscle contraction/secretions, piloerector contraction (hair), more release of erythrocytes from spleen, viscous salivary secretions, inhibits insulin secretion
Parasymp: opposite with accommodation
Acetylcholine
- effects (2)
- low dose vs. high dose
Acts on Parasymp mAChRs (parasympathomimetic)
- CV: decrease HR at SA Node
- Vessels: VD (via NO release) = low TPR = low BP
Low dose: not enough ACh in SA Node - low BP compensated by higher HR (reflex tachycardia - barostatic reflex via B1 receptors)
High dose: huge VD and lower HR (overcomes reflex)
Metacholine
-use
Parasympathomimetic (agonist mAChRs)
-use for bronchial asthma (constricts airway)
Bethanechol
- uses (2)
Parasympathomimetic (agonism mAChR)
- GI Tract - improve mobility
- Urinary Bladder - tx urinary retention
Pilocarpine
-uses (2)
Parasympathomimetic (agonist mAChR)
- tx Glaucoma: both types by increasing flow through meshwork/uncrowding angle
- tx Sjogren’s: stimulates saliva secretion to tx dry mouth from autoimmune attack on exocrine glands
What are the sx of anticholinesterase poisoning? How to tx it?
SLUD: Salivation, Lacrimation, Urination, Defecation
tx: Atropine: blocks mAChR activity; Pralidoxime (2-PAM, Protopam) - anti-ChE antagonist
Physostigmine
- type
- use
Indirect parasympathomimetic (reversible)
- anticholinesterase (more ACh)
- tx Glaucoma
- antidote for reversing NMJ blocks
Neostigmine
- type
- use
Pyridostigmine
-use
Edrophonium
-use
All are anticholinesterases (reversible)
Neo: tx MG, and GI stasis
Pyrido: main MG tx
Edro: Tensilon test for MG (short duration)
How do the following toxic gases or insecticides work:
DFP, Parathion, Malathion, Chlorpyrifos, Sarin, VX
Irreversible anticholinesterases - cause SLUD
Atropine, Homatropine, Scopolamine, Glycopyrrolate
- uses
- mechanism
General anticholinergic agents - block parasympathetic mAChR
use: cause sympathetic effects - tx GI spasm, block accommodation (cyclospasm), increase HR during anesthesia, antidote for anti-ChE poisoning, CNS depressant (anti-emetic scopolamine, sedation), block secretions
Mechanism/Uses for “-terodine” and “-fenacin” drugs and oxybutynin
Parasympathetic mAChR antagonist specific to urinary bladder - tx overactive bladder
Mechanism/Uses for Tropicamide and Cyclopentolate
Parasympathetic mAChR antagonist specific to eye
cause dilation, cycloplegia (paralyze accommodation to determine refractive errors)
Signs of anti-muscarinic toxicity (5)
tx for toxicity
DRY as a bone (less secretions) HOT as a stove (high body temp) RED as a beet (VD, high body temp) BLIND as a bat (dilation, cycloplegia) MAD as a hatter (delirium) tx: activated charcoal - salt of physostigmine (antilirium)
What are the effects of the following receptors:
A1, A2, B1, B2, B3
A1: VC (HTN) A2: Cell inhibition B1: STIM HEART (high HR, contraction) B2: RELAXES smooth muscle (bronchodilation, hypotension) B3: RELAXES bladder
What receptors are activated by the following:
EPI, NE, ISO
EPI: all receptors
NE: no B2
ISO: B only
EPI reversal:
- what happens with high dose EPI
- what happens with high dose EPI and adding an a1 blocker (ergotoxin)?
EPI: VC = high BP (a1)
EPI + a1 block: VD = low BP (b2)
Describe how TPR, HR, and BP change with NE, ISO, and EPI use
NE: act only on a1, a2, b1
- TPR: increases (a1)
- DBP: increases (a1)
- SBP: increases (b1)
- BP: increases (SBP, DBP)
- HR: decreases (barostatic reflex wins due to high MAP)
ISO: acts only b1, b2
- TPR: decreases (b2)
- DBP: decreases (b2)
- SBP: increases (b1)
- BP: decreases (DBP > SBP)
- HR: increases (b1 + reflex tachycardia)
EPI: low dose
- TPR: decreases (b2)
- DBP: decreases (b2)
- SBP: increases (b1)
- BP: little to no change
- HR: increases (b1)
EPI: high dose
- HR: initially high (b1 on SA node), then lowers (barostatic reflex takes over)
- BP: initially high (b1 contractility), then rises more (a1 VC)
Uses of Epi (4), NE (1), ISO
Epi: Cardiac arrest (a1, b1), VC (a1), Rescue inhaler (b2), anaphylaxis (b2, b1, a1)
NE: tx severe hypotension in ICU
ISO: rarely used
Phenylephrine
- type
- use
a1 agonist
use: nasal decongestant (VC), pupil dilation, raise BP during surgery (VC)
ImidaZOLINEs
- type
- use
a1 agonist
long acting nasal decongestant (reactive hyperemia - rebound congestion)
Midodrine
- type
- use
a1 agonist
tx orthostatic hypotension (VC), POTS (VC prevents further increases in HR)
Cl”ONIDINE”
- type
- use
a2a agonist
tx: anti-HTN (low TPR/HR), opioid withdrawal
alpha-methyldopa
- type
- use
a2a agonist
tx: anti-HTN during pregnancy (not used at NMH)
dobutamine
- type
- use
b1 agonist
tx: acute HF (increase CO), mimic exercise in stress echo
Albuterol Salmetrol Formoterol Terbutaline -type -use
All b2 agonists
Albuterol - SABA (rescue inhaler)
Salmeterol/Formoterol - LABA (inhaler need to use with CS)
Terbutaline: for uterine relaxation (premature labor)
Mirabegron
- type
- use
B3 agonist
tx overactive bladder (relaxes bladder)
tyramine and amphetamines
-mechanism
cause NE release!! (indirect agonist of a1/a2/b1 by kicking NE from nerve terminal)
Ephedrine-Pseudoephedrine
- type
- use
causes NE release by kicking it out of nerve terminal and b2 agonist
use: nasal decongestant (a1), anti-asthma (b2) - watch for toxicity
Phenoxybenzamine and Phentolamine
- mechanism
- use
A1 and A2 antagonists
-lower HTN, manage pheochromocytoma during surgery
“ZOSINs” and “LOSINs”
- mechanism
- use
A1 blockers
tx: benign prostatic hypertrophy (decrease resistance to urine outflow)
Yohimbine
- mechanism
- use
A2 blocker (selective) - tx impotence in DM
How can we use pharm to control sexual dysfx?
A2 blocker
- increase Ca entry to parasymp (less a2) = more NO release = more cGMP in smooth muscle = VD/erectile response
Sildenafil
-PDE5 inhibitor = blocks cGMP breakdown = more effects of NO = VD/erectile response
List the 1st gen, 2nd gen, and 3rd gen beta blockers and their selectivities
1st gen: Timolol (glaucoma) and Propanolol - both b1 block
2nd gen: Metoprolol, Atenolol, Betaxolol, Esmolol (block b1 only)
3rd gen: Labetalol (b1 and a1), Carvedilol (b1, b2, a1, CCB, antioxidant), Nebivolol (b1, NO)
