Anesthesia Drugs Flashcards
1
Q
Atropine
A
- Class: Anticholinergic
- MOA: Competitivley anatagonize Ach at postganglionic muscarininc cholinergic receptor in PNS
- Onset 1-5 min, duration 30
- Rapid hydrolysis to inactive metabolites, some renal excretion
- Increased HR, contractility; bronchodilation; mydriasis
- Crosses BBB
- Used as premed before reversing NM blockade (neostig, edrophonium)
2
Q
Glycopyrrolate
A
- Class: Anticholingeric
- MOA: Competitively antagonize Ach at postgang muscarinic cholinergic receptor in PNS
- Onset several minutes, duration ~1h
- 4 times potency of atropine
- Poorly lipid soluble, does not cross BBB; excreted unchanged in urine
- No mydriasis, increase HR/contractility, bronchodilation
3
Q
Epinephrine
A
- Class: Natural catecholamine
- MOA: Non-selective agonist of a1, a2, b1, & b2 adrenergic receptors
- Low dose = beta - inc CO, myocardial O2 consumption,; decrease diastolic BP, dec PVR
- High dose = a1 - marked increase SVR
- Dec threshold for ventricular arrhythmias, esp with halothane
4
Q
Norepinephrine
A
- Class: Natural catecholamine
- MOA: a1, a2, b1 agonist
- Alpha effects predominate at clinically used doses (B1 at very low dose)
- Coronary vasodilation
- Similar arrhythmogenic effects to epi
5
Q
Dopamine
A
- Class: Natural catecholamine
- MOA: D1, D2, a1, a2, b1, b2 - dose-dependent; release of endogenous norepi
- Low dose (1-2ug/kg/min): D1/2 - vasodilation renal/mesenteric vasculature, increase UOP
- Intermediate (<10): Beta effects inc contractility, HR, CO
- High (>10) - alpha effects - inc SVR, splenic contraction
- Discontinue in stepwise manner
6
Q
Dobutamine
A
- Class: Synthetic catecholamine
- MOA: Primarily B1, a1 and B2 at high doses (no a2)
- Primarily used to inc CO in poor myocardial function
- Possibly cause seizures in conscious cats
7
Q
Isoproterenol
A
- Class: Synthetic Catecholamine
- MOA: Potent B1, B2 agonist, no alph
- Positive inotrope/chronotrope
- Potent bronchodilator - increase anatomic deadspace and V/Q mismatch
- Increase renal & splanchnic bloodflow via selective vasodilation
8
Q
Phenylephrine
A
- A1 adrenergic receptor agonist
- Increase SVR and BP, may decrease CO via inc afterload
- No CNS effects, dec renal & hepatic bloodflow
9
Q
Clenbuterol/albuterol/terbutaline
A
- Primarily used for management of bronchospasm
- Cause tachycardia at high dose (B1), dec BP at lower dose (B2)
- Drive K+ intracellular via stimulation of Na/K ATPase
- B adrenergic agonist
10
Q
Ephedrine
A
- Direct & indirect sympathomimetic - a1/2, b1/2
- Inhibit monoamine oxidase on norepi - tachyphylaxis due to depletion in indirect effect
- Used to manage anesthetic hypotension - longer duration of action = bolus
11
Q
Prazosin
A
- Quinazoline derivative, highly selective A1 antagonist
- blocks A1 adrenergic receptors create functional UO via contraction of bladder neck/urethra
- Vasodilation and dec SVR/BP
12
Q
Phenoxybenzamine
A
- Long-acting, non-selective alpha andrenergic blocker, a1 > a2
- Irreversible receptor blockade, inhibits neuronal & extraneuronal uptake of catecholamines
- Usually used for pre-operative management of pheochromocytoma
13
Q
Beta-blockers
A
- Competitive antagonists of B1 & B2 receptors; some have sympathomimetic effect/partial agonist
- Negative inotropic effect - decrease myocardial O2 demand, inhibit RAAS via blockade of JGA
- Bronchospasma at high doses
- Atenolol - B1 selective, used for cats with HCM
- Esmolol - very B1 selective, lipophilic (rapid onset) - BB of choice for GA
- Propanolol - non-selective, control HR/BP in hyperthyroid cats, presurgical mgmt pheo
- Sotalol - non-selective; class III anti-arrhythmic, K+ channel blocking effects; decrease VPC in boxer/ARVC
14
Q
Acepromazine
A
- Phenothiazine tranquilizer
- Sedation primarily via blockade of D2 receptors
- Also blocks a1, muscarinic, and H1 receptors
- Decreases SV, CO, and BP by 20-30%, decreases PVC
- Little pulmonary effects, MAC reducer, decreases platelet aggregation
- Does NOT lower seizure threshold
15
Q
Diazepam
A
- Benzodiazepine - enhance GABAa receptor affinity for GABA (primary inhibitory NT in CNS); hyperpolarize post-syn cell membrane via Cl-
- Light-sensitive & binds to plastic
- Rapid absorption via nasal or rectal route
- Unreliable sedative but good central muscle relaxant and anti-convulsant
- No CV or resp depression
- Metabolized to active compounds
16
Q
Midazolam
A
- Benzodiazepine - enhance GABAa receptor affinity for GABA (primary inhibitory NT in CNS); hyperpolarize post-syn cell membrane via Cl-
- Rapid IM absorption
- Unreliable sedative but good central muscle relaxant and anti-convulsant
- Minimal CV depressant effects, 10-20% HR/CO reduction
- Inactive metabolite - better for hepatic dz
17
Q
Alpha-2 agonists
A
- Sedative and supraspinal analgesic effects via decreased norepi release and binding in cerebral cortex & brainstem; also centrally mediated bradycardia/hypotension
- Receptors in spinal cord and vascular endothelium - spinal analgesia, vasoconstriction, peripheral bradycardia
- Variably some A1 agonist effect - excitation, increased motor activity
- Normal to slightly decreased cerebral bloodflow/ICP
- Blood gas parameters normally maintained, can decrease respiratory drive
- Bradycardia via peripheral (reflex due to inc SVR) and central (dec sympathetic outflow) mechanisms. CO decreased and selectively decrease tissue blood flow
- Reversal: yohimbine (xylazine), atipamezole
18
Q
Xylazine
A
- Alpha2-agonist
- 160:1 a2/a1 specificity
- Persistent bradycardia due to central effects outweighing peripheral: hypertension progresses to hypotension (20-30%)
- CO decreases up to 50%
- Contraindicated for C-section - increased neonate mortality
19
Q
Dexmedetomidine
A
- Alpha2-agonist, dextrorotatory isomer of medetomidine
- 1620:1 a2/a1
- Similar CV effects as xylazine/other A2
- Neuroprotective effects, minimal effect on ICP, blunting of response to intubation, etc, - good for intracranial surgery
20
Q
Opioids - MOA/Pk/Pd
A
- G-protein coupled receptors - dec cAMP, inhibit Ca2+ channels presynaptic (decrease release of excitatory NT), increase K+ outflow postsynaptic (hyperpolarization/inc activation threshold)
- Three receptors - u (b-endorphin), k (leucine- & methionine- enkephalin), d (dynorphin A)
- Lipophilic so high Vd, cross BBB (variable efflux by P-gylcoprotein)
- Receptors in brain, spinal cord, CTZ, GI, synovium, leukocytes, etc.
- Easily cross placenta - naloxone for fetuses if given during c-section
21
Q
Opioids - systemic effect
A
-Analgesia is main effect: spinal and supraspinal (inhibit GABA interneurons in PAG), more effective on C-fibers than A-delta fibers; peripherally have anti-hyperalgesic effects
-Generally dose-dependent sedation (synergistic with other sedatives) , can see excitation (rapid IV administration)
-Dose-dependent resp depression - mediated by
supraspinal mu receptors; usually minor in vet species (inc PaCO2)
-Central anti-tussive effects (u and K at cough center in medulla oblongata)
-Clinical doses have minor CV effects - mild bradycardia (central enhanced parasympathetic activity), usually CO/BP maintained
-Emetic/anti-emetic depending on drug/route/rate: CTZ - delta emetic, u/k anti-emetic. IV generally anti, SQ/IM pro; morphine emetic low/1st dose (not with inc ICP)
-Inhibit release of motility-modifying neurotransmitters (5HT-2, NO, VIP, Ach) - ileus
-Urinary retention due to spinal cord inhibition of micturition with epidural (longer with morphine)
-Thermoregulation: act on preoptic anterior hypothalamus - alter setpoint and compensatory mechanisms: hyperthermia in cats, hypo due to panting in dogs
-Dose dependent MAC reduction; full-u more than others
22
Q
Morphine
A
- Full-u agonist, kappa agonist at high doses
- Baseline of opioid potency - 1
- Less lipophilic - slower entry into and diffusion from CNS -> ideal for epidural administration
- Histamine release after IV administration in dogs
- 50% hepatic/50% extrahepatic metabolism (most opioids near 100%)
- Can be given intra-articular
23
Q
Oxymorphone
A
- Full-u, 10x potent as morphine
- No histamine release, generally less GI side-effects
- Expensive
24
Q
Hydromorphone
A
- Full-u, 8x morphine potentcy
- No histamine release, most associated with hyperthermia in cats (though documented in many)
25
Fentanyl
- Full-u, 100x morphine
- Less GI side effects, antiemetic
- Short duration (30m - 2h depending on dose)
- Transdermal solution - effective within 4 hours, last 3-4d
- Trandermal patch: 12h to SS in cat, last 3-4d; 24h in dogs, last 2-3d
26
Methadone
- U-agonist (2x morphine) with NMDA antagonist effects - better for chronic pain
- Synergistic with some other mu (morphine)
- Metabolism inhibited by chloramphenicol
27
Meperidine
- U (0.1x morphine), serotonergic effects (not with monoamine inhibitors)
- More histamine release IV than morphine
- Negative inotropic effects, anti-muscarinic effects
- Basically sucks, no one uses in small animal
28
Hydrocodone
- U-opioid
- Poor bioavailability in dog but variably metabolized to hydro
- Antitussive
29
Codeine
- Classified as u-opioid
| - 4% bioavailability in dogs (no morphine metabolite); codeine-6-glucuronide may have some effects along with norcodeine
30
Fentanyl derivaties (su- remi- alf-)
- Full-u
| - Remifentanil: metabolized by plasma-esterases (6min T1/2)
31
Etorphine/carfentanil
-Used for wildlife capture, will kill you if you poke yourself with needle
32
Buprenorphine
- Partial-u (will partially reverse full); 25-40x morphine
- pH of cat mouth yields could OTM absorption
- Simbadol - SID (x3) SQ for cats
- SR bup - up to 72h, not approved
33
Butorphanol
- U-antagonist/partial agonist; kappa-agonist
- Anti-tussive and sedative PO but not analgesic
- Dose reduce with MDR1
34
Nalbuphine/Pentazocine
- U-antagonist/kappa-agonist
| - Like butorphanol but not as good
35
Tramadol
- Centrally acting analgesic; codeine analogue with some activity at u-receptor
- Not metabolized to M1 (active form in humans). Of dubious efficacy in dogs (LJ agrees with this, JT says it is good orally in dogs)
- Activity as serotonin and norepi reuptake inhibitors (likely method of analgesia in dogs according to LJ)
- Cats do make M1, may be effective
- Metabolized in liver and kidney
36
Opioid antagonists
- Naloxone - primary antagonist, mostly mu but some kappa/delta; convulsions d/t GABA antagonism
- High naloxone dose with antagonize central opioid effects - acute pain, sympathetic stimulation - titrate slowly to effect
- Low-dose naloxone block TLR4 allodynia from morphine
- Naltrexone - mu/kappa/delta; longer duration used for wildlife reversal
- Methylnaltrexone - low lipid solubility - does not reverse CNS effects
37
Dantrolene
- Ryanodine receptor antagonist - peripherally acting muscle relaxant
- Treatment for malignant hyperthermia & rhabdomyolysis
38
Doxapram
- Analeptic (central nervous system stimulant)
- Respiratory stimulant via combination of central and peripheral effects
- Dose-dependent with activation of peripheral aortic & carotid receptors
- Increase RR and TV to increase minute ventilation but very short-lived - used to assess laryngeal function
- Dose in one study: 1.1mg/kg for lar-par (no change in glottal size; different study increased
39
Famotidine
- H2 receptor antagonist (~5x more potent than ranitidne, 20-50 more than cimetidine)
- Demonstrated to be superior in prevention of gastric ulcer to no treatment (saline) or ranitidine, but inferior to PPI
40
Omeprazole
- Proton-pump inhibitor - prevents acid secretion by parietal cells (gastrin, H2, M3)
- Acts on proton-pump on luminal side of cell
- Theoretical concern about changing gastric fauna/bacterial overgrowth
41
Maropitant
- Neurokinin (NK1) receptor antagonist - reduces binding of Substance P in brainstem nuclei, centrally acting anti-emetic
- Extensive hepatic metabolism by CYP3A
- Possible analgesic properties related to NK1 receptors on sensory afferents in CNS and PNS
- MAC reduction of 16-30%
42
Methocarbamol
- Centrally acting muscle relaxant - inhibits spinal & supraspinal polysynaptic reflexes via action on interneurons; no direct effect on skeletal muscle
- Use for tetanus, pyrethrin/permethrin toxicity, acute muscle strain
43
Metoclopromide
- Multiple sites of action: serotonin antagonism in CNS, D2 antagonism in CNS and GI
- Anti-emetic (weak), increases GE sphincter tone and promotes duodenal peristalsis
- Reduction in risk of GE reflux in orthopedic surgeries
44
Ondansetron/dolasetron
- Serotonin (5HT-3) receptor antagonist
- Often used as an antiemetic prior to chemo: effective at preventing vomiting from cisplatin (acts on gastric mucosa stimulating 5HT3)
45
Procainamide
- Class 1a antiarrhythmic, effective at treating SVT and VT
- Na+ channel blockade to slow rise of phase 0 of cardiac action potential, raise threshold, prolong refractory period
- Often 2nd line for VT refractory to lidocaine, similar efficacy as sole agent
46
Sodium Nitroprusside
- Potent arterial and venous dilation through liberation of NO
- Risk of inadvertent hypotension, tachycardia.
- If overdose or hepatic/renal insufficiency, potential for cyanide or thiocyanate toxicity
47
Vasopressin (ADH)
- Vasoconstrictor - acts on V1a receptor on smooth muscle (also V1b pituitary and V2 renal collecting duct)
- Alternative to epineprhine, works in acidic environment & in CIRCI
- No b1 effects so less risk of myocardial ischemia
48
Desmopressin (DDAVP)
- Synthetic analogue of vasopressin with reduced vascular effects
- Used to manage central DI, peri-operative management of Von Willebrands
49
Amantadine
- Dopamine agonist & NMDA antagonist
- Used in Parksinson's and possible role in TBI (in people, being studied in rats)
- Some evidence for use in chronic arthritic pain in dogs/cats
50
Amitriptyline/Notriptyline
- Tricyclic antidepressant used for behavioral disorders/FLUTD, possible use for neuropathic pain
- SSRI but also Na+ channel blockade, NMDA antagonism, antihistamine activity
- Caution in animals with renal insufficiency
51
Gabapentin/pregabalin
- Structural analogues of GABA but no action at GABA receptors (or NMDA, Dopamine)
- Suggested inhibition of N-type voltage-dependent neuronal calcium channels
- Historically used as anticonvulsant, currently used for neuropathic pain
52
Tapentadol
- Higher mu receptor affinity (50x) than tramadol but lower than M1 metabolite
- Similar potency as tramadol for norepi reuptake inhibition, less (5x) for serotonin reuptake inhibition
- Low oral bioavailability in dogs, extensive hepatic metabolism (glucuronidation) to inactive metabolite
53
Succinycholine
- Depolarizing NMBA
- Structurally is two Ach molecules combined
- Rapidly degraded in plasma by pseduocholinesterase - can give large doses and get rapid onset without prolonged duration
- Not broken down in cleft by acetylcholinesterase - channel remains open, no repolarization of postjunctional membrane
- Pseudocholinesterase synthesized in liver - decreased by liver disease, chronic anemia, pregnancy, reglan, burns, etc
54
Atracurium (and other non-depolarizing NMBA)
- Non-depolarizing NMBA
- Dose-dependent onset of ~5min and duration of 30 min in dog
- Competitively binds to alpha subunit blocking Ach binding and depolarization
- About 1/2 undergoes Hoffman elimination - not prolonged in hepatic/renal disease; pH and temperature dependent
- Potential for histamine release (not seen with cisatracurium isomer)
- Also affect muscarinic receptors on cardiac muscle (arrythmias, inc or dec HR) and parasymp NS in ganglia, less CV effects with newer NMBA
- Large, hydrophilic - do not cross placenta, may gain entry into CSF
- Reversal with anticholinesterase drugs - edrophonium, neostigmine, pyridostigmine; edrophonium shorter duration and less muscarinic cholinergic effects (do not need to premed with anticholinergic)
55
Barbituates (thiopental, pentobarbital, phenobarbital)
- CNS depression via activation of GABAa, hyperpolarization of post-synaptic membrane
- Lipophilic so rapid onset, quick redistribution from CNS to tissues; can have prolonged recovery was tissue equilibrate if multiple boluses/CRI given
- CNS: CBF and ICP decreased, cerebral 02 consumption decreased by up to 55%; cerebral perfusion pressure maintained d/t ICP dec more than MAP
- CV: dec SV and contractility, sensitizes to epi related arrhythmias; mild dec in MAP but inc HR
- RESP: Dose-dependent dperession of resp centers, dec responsiveness to low O2/high CO2
- Modest decrease renal and hepatic bloodflow
- Crosses placenta, more effect on neonates than propofol
- Avoid use in sighthounds - deficient in microsomal enzyme to metabolize
56
Propofol
- Exerts effects through GABAa receptors and inhibits NMDA receptor
- Chemically distinct from all other anesthetics, rapid awakening
- Rapidly moves into CNS, quickly redistributes. Extensive hepatic and extrahepatic metabolism so short half-life
- CNS: reduces ICP and CMRO2, can have significant decrease in CPP in patients with elevated ICP
- CV: Dec arterial BP, SVR, and CO. No compensatory inc HR
- RESP: Dose-dependent ventilatory depression, postinudction apnea, dec responsiveness to O2 and CO2
- No adverse effect on heaptic blood flow or GFR.
- Crosses placenta but rapidly cleared from neonatal circulation
- Oxidative injury to cat RBC with repeated administration
57
Dissociatives (ketamine, tiletamine)
- MOA: NMDA, opioid, monoaminergic, and muscarinic receptors, voltage gated Ca channels; NOT GABA
- Rapid onset, short duration, also effective IM unlike other injectable anesthetics
- Metabolized in liver, biotransformed to norketamine in cat - extrectd unchanged in urine
- CNS: cataleptic state by dissociation of limbic and thalamocortical systems via NMDA antagonism; increase CBF and CRMO2, inc ICP; does not lower sz threshold, may be neuroprotective
- CV: Negative inotrope, overcome by sympathetic stimulation; inc HR, systemic & pulm BP, CO, myocardial O2 (can see decrease if catecholamine stores exhausted - eg CIRCI)
- Resp: No respiratory depressant effects; bronchodilator/decrease airway resistance
- No hepatic, renal, GI effects
- Little muscle relaxation, can have inc tone and spontaneous movement
- Crosses placenta, most depression of neuro reflexes in neonates of injectable induction drugs
- Good analgesic
58
Etomidate
- Imidazole derivative, acts at GABA receptor enhancing inhibitory effects
- Rapid penetration to CNS, rapid, redistribution to inactive tissues. 75% albumin bound.
- CNS: cerebral vasoconstriction, dec CBF and CRMO2. CPP unchanged due to maintenance of MAP, dec ICP. May precipitate sz in p with hx.
- CV: No cardiovascular effects, ideal for p with severe cardiac dz
- Resp/renal/GI/hepatic: No resp depression, no reduction in hepatic blood flow or GFR
- Endocrine: adrenocortical supression via dose-dependent inhibition of convernsion of cholesterol to cortisol; contraindicated with Addison's
- Pain on IV injection; myoclonus, dystonia, tremors; intravascular hemolysis d/t hyperosmolality
59
Alfaxalone
- Neuroactive steroid; acts on GABA, modulate ion currents at low dose, agonist at high dose
- CyP450 and conjugation-dependent metabolism
- CNS: CBF, ICP, CRMO2 all decreased
- CV: HR, CO, BO decrease in dose-dependent fashion
- RESP: dose-dependent depression
- (CV and RESP effects not as significnat at lower clinical doses)
- Can be used as a CRI for TIVA; longer-recovery with minor adverse events
