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