Pharm Quiz #7 Flashcards
Describe Sugammadex.
- Selective Relaxant Binding Agent
- Reversal for NMB
- (just like protamine neutralizes heparin, forms an inactive complex)
- Contraction of: Sugar, Gamma-cyclo dextrin
- Modified gamma-cyclodextrin that encapsulates and forms water-soluble complexes at 1:1 ratio with STEROIDAL NMB’s (Roc, Vec, pancuronium…)
- Will not work with nimbex
T or F: Once sugammadex encapsulation occurs, it does not dissociate.
- True
- sugammadex-relaxant complex is excreted in urine
Will depth of NMB affect the reversal capabilities of sugammadex?
- No
- It is independent of depth of block, it will successfully reverse 100% block!!!
- Deep blocks reverse with appropriate dose
- Concentration of free muscle relaxant falls rapidly, muscle strength reestablished
Which NMB is sugammadex most effective in reversing?
-ROCURONIUM
What’s the order of NMB that will reverse the best to the last…
- Roc
- Vec
- Pancuronium
How long will it take to reverse roc or vec using sugammadex?
3 minutes
Describe Sugammadex Pharmacokinetics.
- Complex biologically inactive
- Linear dose relationship in doses up to 8 mg/kg
- Clearance 120 L/min
- Vd: 18 liters
- Elimination 1/2 life: 2.3 hours
- Up to 80% of dose urine eliminated within 24 hours
- Does not bind to plasma proteins or erythrocytes
- Avoid with renal disease patients: HIGHLY dependent on RENAL ELIMINATION
What is the normal DOSE of Sugammadex?
-2 to 16 mg/kg (according to depth of blockade at reversal time)
What is the dose of Sugammadex for reversal of shallow or moderate block (2 twitches on TOF present)?
2 mg/kg
What is the dose of Sugammadex for reversal of deeper block with little recovery present?
-4 mg/kg or more
T or F: Sugammadex (16 mg/kg) is used when reversing high doses of rocuronium (1-1.2 mg/kg)
- True
- Used in rescue situations such as “can’t intubate, can’t ventilate”
Why has the FDA not approved sugammadex in US?
- Hypersensitivity and allergic reactions
- Effects on tooth enamel and bone healing
What are the Adverse reactions of sugammadex?
- Dry mouth
- Dysgeusia (distortion of sense of taste)
- N&V
- Allergy (rare)
- Chills
- Postural hypotension
T or F: If NMB needs to be reestablished after using sugammadex, use benzylisoquinolones.
- True
- Can also use Succinylcholine
How do anticholinergic drugs work (mechanism of action)?
- Competitively antagonize effects of acetylcholine @ cholinergic post-ganglionic sites (muscarinic receptors)
- Combine reversibly with muscarinic receptors and prevent acetylcholine from binding
- Bind to muscarinic receptors without eliciting a muscarinic response
What are the 2 types of cholinergic post-ganglionic receptors?
- Nicotinic (anticholinergic drugs will not work on these!!)
- Muscarinic
What are the 3 terms describing belladonna compounds (alkaloids)?
- Anticholinergic
- Antimuscarinic
- Parasympatholytic
Where are muscarinic cholinergic receptors found?
- Heart
- Salivary glands
- GI & GU smooth muscle
What is the neurotransmitter at post-ganglionic nicotinic and muscarinic receptors of the NM junction and autonomic ganglia?
Acetylcholine
T or F: Anticholinergics in usual doses have no effect on post-ganglionic NICOTINIC receptors.
- True
- Only specific to MUSCARINIC receptors
Where does Atropine and scopolamine come from?
- Naturally occurring tertiary amine anticholinergic drugs:
- Atropine: prototype alkaloid
- from:
- atropa belladonna (nightshade)
- Datura stramonium (jimson weed)
- Will cross BBB!!!!
Where does glycopyrrolate come from?
- Semi-synthetic congener of belladonna alkaloids
- Quaternary ammonium derivative
- Lacks CNS effects due to inability in crossing BBB
T or F: Natural anticholinergics are tertiary amines, while synthetic anticholinergics are quaternary ammonium compounds.
-True
Describe an “alkaloid” anticholinergic.
- Tertiary amine
- Occurs naturally
- Has CNS effects
- Found in loco weed
- Racemic mixture (50-50 mixture of dextrorotary and levorotary)
- Tropic acid
Describe a “synthetic” anticholinergic.
- Quaternary ammonium
- Will not cross BBB, no CNS effects
- Mandelic acid
Describe naturally occurring Anticholinergic structure.
- Esters formed by combining tropic acid and an organic base of either tropine or scopine
- Structurally, belladonna alkaloids, like atropine and scoplamine, resemble cocaine
- Atropine: weak analgesic properties like cocaine
- Racemic mixtures: dextro and levorotary forms
Which isomer of naturally occurring anticholinergic structure exerts its effects?
LEVOROTARY
T or F: Synthetic anticholinergics are NOT racemic mixtures.
True
What kind of acid does glycopyrrolate contain?
- Mandelic Acid
- (Atropine and scopolamine have: tropic acid)
T or F: Anticholinergics contain a cationic portion that fits muscarinic cholinergic receptor just like acetylcholine.
-True
How are the effects of anticholinergics overcome?
- They are competitive antagonists
- So, they can be overcome by increasing acetylcholine concentrations at muscarinic receptors
- Anticholinergics do not prevent liberation of acetylcholine or react with acetylcholine
How many muscarinic cholinergic receptor subtypes are there? What are their names?
- 5 total
- M1, M2, M3, M4, and M5
Describe M1 subtype.
- CNS
- Stomach
- Inhibits NE release
Describe M2 subtype.
- SA, AV nodes, Purkinje fibers
- Reduces myocardial O2 demands
- Relaxes bronchial smooth muscle, GI
Describe M3 subtype.
- CNS
- Bronchial smooth muscle
- Glands
- Vascular beds
- Iris
- Ciliary body
- GI
- Antisialagogue and drying of bronchial secretions
Describe M4 and M5 subtypes.
CNS
Describe Muscarinic receptors.
- G-protein coupled receptors
- Have differing sensitivities to effects of anticholinergics
- Example: M3 receptor effects (anti-sialagogue and drying of bronchial secretions) elicited with lower doses of anticholinergics than M2 receptor effects of increased HR and CNS changes
T or F: Larger doses of anticholinergics inhibit cholinergic control of GI and GU tracts, decreasing intestinal tone and inhibiting micturation.
- True
- Huge doses inhibit M1 receptor mediated H+ secretion in gastric secretions
T or F: Anticholinergic doses that inhibit H+ secretions also elicit all other muscarinic receptor effects.
True
What are the goals of pre-op use of anticholinergics?
-Antisialagogue
-Sedation
-Possibly to decrease myocardial O2 demand (coronary insufficiencies)
(these doses are too small to alter gastric volume and gastric secretions)
Which anticholinergic drug should always be avoided in glaucoma patients?
- Scopolamine
- D/T Mydriatic effect: potentially obstructing the flow of vitreous humor, raising intraoccular pressure
- Use atropine (0.4-1 mg)…will have minimal pupil size changes but…
- Glycopyrrolate is SAFEST…least effect on pupil size
T or F: Potency of anticholinergics vary from drug to drug and between cholinergic sites.
- True
- Example: greater antisialagogue and ocular effects of scopolamine compared to atropine and glycopyrrolate
- For dry mouths: (don’t need to remember doses, but that scopolamine is more potent, atropine least potent)
- Scopolamine= 5 mcg/kg
- Glycopyrrolate= 5-8 mcg/kg
- Atropine= 10-20 mcg/kg
What is the anticholinergic drug of choice with edrophonium?
- Atropine
- 7 mcg/kg
What is the dose of atropine and glyco used with 0.5-2.5 mg of neostigmine?
- Atropine: 0.6-1.2 mg
- Glycopyrrolate: 0.2-0.6 mg
Which anticholinergic has the fastest onset?
-Atropine
Why is scopolamine used for cardiac pre-ops?
- Decreases metabolic O2 requirements
- (atropine causes no change and glyco increases O2 needs)
T or F: While Atropine, Scopolamine, and Glycopyrrolate will all block the acetylcholine effects at all muscarinic receptors, they all do prefer 1 type of muscarinic receptor.
-True
Can Atropine slow heart rate?
- Yes
- Anticholinergic drugs are not pure muscarinic cholinergic antagonists
- HR slowing reflects WEAK PERIPHERAL MUSCARINIC CHOLINERGIC RECEPTOR AGONIST EFFECTS (usually with smaller doses)
- Giving an anticholinergic and getting a rise in BP may not be due solely to increased HR as anticholinergics stop inhibition of NE release
Describe Atropine Absorption.
- Oral: 90% absorbed, peak plasma levels in 1 hour
- IM: peak plasma levels in 30 min
- IV: peak plasma levels in 2-4 min
- Well distributed in the body (crosses BBB and placental barrier)
Describe Atropine Metabolism.
- Kidneys and liver
- Elimination: biphasic, terminal 1/2 life 2-3 hours
- Hepatic metabolism:
- tropic acid
- tropine
- glucuronide conjugates
- 30-50% urine excreted unchanged
- Small amounts eliminated in expired air and in feces
If an anticholinergic is orally absorbed (90%), what kind is it?
- Natural (atropine, scopolamine)
- has CNS effects
Describe Glycopyrrolate Metabolism.
- Serum levels quickly decline
- Less than 10% remains in serum after 5 min
- Excreted as unchanged drug
- Small amounts metabolized to inactive metabolites
- 85% of IV doses excreted in urine in 48 hours
Describe Scopolamine pharmacokinetics.
- Extensive metabolism with only:
- 1% excreted unchanged in urine
- 18 known metabolites: ALL INACTIVE
What are the Clinical uses of anticholinergics?
- Pre-op medication
- Treatment of reflex mediated bradycardia
- Combined with anti-cholinesterase drugs during reversal of NDMB’s
- Bronchodilation
- Biliary smooth muscle relaxation
- Ureteral smooth muscle relaxation
- Mydriasis (pupil dilation)
- Cycloplegia (paralysis ciliary muscle: affects accommodation)
- Antagonism of parietal cell H+ secretion
What are the Sedation effects of anticholinergics?
- Scopolamine: 100 x more potent than atropine in decreasing reticular activating
- Scope provides significant amnesia and depresses cerebral cortex activity in typical 0.4 mg doses
- Atropine @ 0.4 mg: minimal CNS effects compared to scope
- Atropine compared to glyco: delays arousal after anesthesia when given with neostigmine for reversal of NMB
- Scope: enhances sedative effects of concomitantly administered CNS depressants, ONLY ONE THAT WILL REDUCE MAC
- Glyco: does not cross BBB> NO SEDATIVE EFFECTS
- Scope: CNS effects vary from restlessness to somnolence, greater in elderly
- Differential Dx in patients with delayed awakening who received scope should include anticholinergic CNS effects
- Inhaled anesthetics POTENTIATE anticholinergic CNS effects
Which drug reverses restlessness/somnolence due to tertiary amine anticholinergic drugs?
-Physostigmine
What are the Antisialagogue effects of anticholinergics?
- Scopolamine>Glycopyrrolate>Atropine
- Scope 3X more potent than glyco
- Scope: good choice when sedation and potent antisialagogue actions are desired
- Glyco: 2X as potent than atropine, with longer duration of action
- In antisialagogue doses, scopolamine less likely to raise HR than atropine
- Glyco: drug of choice when sedation not desired
T or F: Anticholinergics are the drugs of choice for treating intraoperative bradycardia, esp. if resulting from vagal activity.
-True
T or F: Atropine: 15-70 mcg/kg increases HR by blocking ACh effects on the SA node.
- True
- The maximal HR increase produced by atropine shows the amount of VAGAL CONTROL ON THE SA NODE
How much can atropine increase the HR, a dose of 2mg or 10 mg?
- Will be the same
- Once vagal control of HR is completely removed by atropine, it will not increase HR.
T or F: Glycopyrrolate produces similar increases in HR, but with slower onset.
-True
What are the EKG effects of anticholinergics?
-Shortened PR intervals
T or F: Atropine influence on HR is more pronounced in youth, where vagal tone is greater. In the elderly and infants, less vagal control of heart is present, and anticholinergics treat bradycardia less effectively.
-True
Under volatile agent anesthesia, required dose of atropine may be ____, due to depression of vagal centers.
-Less
Halothane and opioids ____ central vagal tone, so _____ HR responses are seen after atropine administration.
- Increase
- Greater
IM anticholinergics can result in _____ HR, due to peripheral agonist effects on cholinergic sites.
-Slowing
Will anticholinergics alter HR in de-innervated (transplanted) hearts?
- No
- Give Beta-agonist drug, not atropine
T or F: Antagonism of NDMB with anticholinesterases requires co-administration of atropine or glyco to counteract parasympathomimetic effects of anticholinesterase drugs.
- True
- Depending on the onset of the anticholinesterase, atropine (rapid onset) or glyco (less rapid onset) is chosen
What receptors do anticholinesterase drugs work on?
- Muscarinic (agonist effect, will cause reaction)
- Nicotinic (good effects)
- Give anticholinergic drugs to prevent adverse effects of anticholinesterase drugs working at the muscarinic receptor sites
T or F: Glycopyrrolate is preferable over atropine for CV diseased patients where increased HR is harmful.
-True
T or F: Scopolamine, not combined with anticholinesterases for reversal of NDMB…patient will not wake up.
True
What is the mechanism of action of anticholinergics bronchodilator effects?
- 2nd tier drug for bronchodilator effect (Beta-2 agonist #1)
- By acetylcholine antagonism @ muscarinic receptors on airway smooth muscle that normally respond to the vagus nerve
- Resulting bronchial dilation decreases airway resistance and increases dead space
- Bronchodilation more likely when anticholinergics are aerosolized
What is the most common inhaled anticholinergic drug?
- Atrovent (Ipratropium)
- Quaternary ammonium congener of atropine
- Effective in treating from beta blockade, chronic bronchitis and COPD
- Given in combo with beta agonists
- Slower onset (30-90 min) compared to beta agonists
- Augments bronchodilating effects of beta agonists
- Due to minimal systemic absorption, atrovent causes no alterations on HR or IOP
- Tolerance to bronchodilation does not occur, as antagonists up-regulate target receptors
T or F: Atropine decreases smooth muscle tone of the biliary tract and ureters. It prevents ureter spasm produced by morphine.
-True
T or F: Iris muscles that constrict the pupil are innervated by cholinergic fibers from 3rd cranial nerve. Ciliary muscles that allow lens to become convex also controlled by cholinergic fibers from the 3rd cranial nerve. TOPICAL ANTICHOLINERGICS BLOCK BOTH OF THESE ACTIONS!!
-True
T or F: Anticholinergics placed topically on the cornea block actions of ACh, resulting in mydriasis and cycloplegia.
- True
- Complete recovery from topical atropine: 1-2 weeks
Mydriasis produced by anticholinergics may be offset by what?
-Topical administration of an anticholinesterase like pilocarpine
T or F: Glyco was originally introduced as an anticholinergic to control gastric acidity.
- True
- But, they are NOT SELECTIVE for this effect
- High doses of anticholinergics needed to decrease H+ secretion: associated with unpleasant to dangerous side effects
- High doses reduce excess peristalsis of the GI tract due to anticholinesterase drugs given for reversal of NDMB
T or F: Atropine and glyco can lower the difference in pressure between the stomach and lower esophagus.
- True
- This lowers resistance to stomach acid reflux into upper GI tract
- Lasts an hour with glyco and 40 min with atropine
Describe Transdermal Scopolamine.
- Sustained plasma concentrations
- Minimal sedation, cycloplegia, or inspissation (coughing up bronchial tree-shaped stuff)
- Apply 4 hours before needed
- For motion sickness and nausea r/t neuroaxial or systemic opioid administration
- Blocks transmission from vestibular apparatus of the inner ear to the medulla
- Blunts PONV seen with middle ear surgery alterations of vestibular apparatus function
Describe Central Cholinergic Syndrome.
- Scopolamine and atropine enter CNS producing S/S characterized as central cholinergic syndrome
- Symptoms: restlessness, hallucinations, somnolence, unconsciousness
- Symptoms due to blockade of muscarinic receptors and competitive inhibition of ACh effects in CNS
- Blockade of the central cholinergic neurotransmission
- AKA anticholinergic syndrome
- Drug of choice for treatment: PHYSOSTIGMINE
T or F: Only physostigmine, a tertiary amine anticholinesterase drug, in doses of 15-60 mcg/kg effectively treats central cholinergic syndrome.
-True
What are the classic S/S of Central Cholinergic Syndrome?
-“red as a beet”>Flushing
-dry as a bone>Dry skin and mucous membranes
-blind as a bat>Mydriasis, loss of accommodation
-mad as a hatter>altered mental status
-hot as a hare>fever
Additional manifestations:
-Sinus tachycardia
-Decreased bowel sounds
-Functional ileus
-Urinary retention
-HTN
-Tremulousness
-Myoclonus
What are anticholinergic overdose symptoms?
- produce symptoms of muscarinic cholinergic receptor blockade:
- dry mouth
- dysphagia
- dysphonia
- tachycardia
- dry and flushed skin
- rash over the blush area
- pyrexia r/t inhibition of sweat glands
- MVV is decreased d/t increased dead space and CNS stimulation
- may progress to : seizures, coma, medullary ventilatory center paralysis
T or F: Overdose of anticholinergics is more lethal in INFANTS and SMALL CHILDREN.
- True
- Antidote: PHYSOSTIGMINE 16-60 MCG/KG
