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34 Cards in this Set
- Front
- Back
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True or False
Barbituates are the most commonly used IV anesthetics in vet.med. |
TRUE
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Where do barbituates come from?
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Urea + Malonic Acid = Barbituric Acid
Barbituric Acid + Modifications = CNS Depressing Barbituates |
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What are the 4 subdivisions of Barbs?
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Oxybarbs
(barbital, pento/pheno-barbital) Methylated Oxybarbs (methohexital) Thiobarbs (thiopental, thiamylal) Methylated Thiobarbs (not used clinically) |
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General characteristics of the 4 groups?
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Oxybarbs - slower onset, longer duration
Methoxy - more rapid, but can have *Excitatory phenomena Thiobarbs - Rapid smooth onset, Rapid recovery Methylthios - Rapid still but *High Excitatory phenomena |
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Preparation of Barbituate Agents?
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The salts are pKa 7.0 - 8.5
but NOT stable over extended time so mixed with 6% Na2CO3 CLINICAL SOLN has pKa 9.0 - 11.0 |
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Why does the pKa of the drug matter?
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If put into an acidic solution
(LRS, most analgesics, phenothiazines, vecuronium, etc...) the non-ionized form will precipiate Outside of patient. Similarly - in patients with an acidemia - the non-ionized will more readily precipitate - therefore enhancing and prolonging the CNS suppressive effects of the drug. |
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What adverse reaction may be caused upon administration? (given the high pH of barbs)
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If administered PERIvascularly - may cause
Severe Thrombophlebitis and Sloughing of Perivascular Tissues |
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In the CNS, do barbituates mainly inhibit Presynaptic (NT release) or Postsynaptic (impulse transmission) activity?
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low doses - Presynaptic
high doses - Both Pre and Post |
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The _____ and ______ of the CNS seem to be particularly sensitive to the fx of barbs.
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Thalamus
Ascending Reticular Activating System |
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Barbs act similar to what natural CNS inhibitor?
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GABA
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Interaction with _______ has been proposed as the chief molecular mechanism of barbituate action.
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GABAa receptors
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Example:
How does Pentobarb fx GABAa? How does this compare to benzodiazepines? |
Both are ALLOSTERIC Modulators
Pentobarb - Increases open channel lifetime Benzos - increase freq. of openings |
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Do these drugs (barbs and benzodiazepines) work together at all?
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Yes
Barbs enhance benzodiazepine activity. However, at higher than therapeutic levels - Barbs can block the GABAa ion channel. |
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The hypnotic effect of barbituates results from marked enhancement of _____________ in the (CNS/PNS) and is subject to ________ by GABAa receptor antagonists.
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Inhibitory GABAergic Neurotransmission
Reversal |
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Barbituates do WHAT to the peripheral nervous system?
What effect does this have on the body? |
depress transmission in Autonomic Ganglia **esp Ach at N-ach receptors.
This contributes to an overall DECREASE in Systemic Arterial BP (and decrease skeletal m strength at high doses) |
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TRUE or FALSE
Barbituates exert an Analgesic effect. |
FALSE
thus, complete loss of consciousness is req'd before surgical procedures are tolerated |
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How can barbs help patients that have an Increased Intracranial Pressure?
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Suppress CNS activity -->
lower Cerebral metabolism/O2 consumed --> lower blood flow --> lower blood volume --> decrease in CSF (and thus intracranial) Pressure |
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What else can that nifty mechanism be helpful for?
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Protection from Ischemic Damage by lowering O2 consumption.
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What effects do barbs have on an EEG?
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Small doses - increase in low voltage fast activity
High doses - Slow, large Amp waves (loss of consciousness) Really High Doses - Neuronal burst depression (flat-line) |
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ADVERSE EFFECTS:
Respiratory System |
Depression of Medullary Resp Centers
Apnea Laryngeal reflexes depressed w/High doses |
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ADVERSE EFFECTS:
Cardiovascular |
Decrease CO
Decrease venous return (<3 filling) Decrease in BP (may increase HR) Tachycardia Tachyarrhythmia High Doses - Profound Hypotension |
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ADVERSE EFFECTS:
Hematological System |
Significant Fall in circulation RBCs and WBCs (splenic sequestration)
Increase in Coag Time |
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ADVERSE EFFECTS:
CYPs |
Most barbs metabolized by P450 - thus competitively interfering with the other shit that P450 should be worrying about
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What are the 3 Main Factors affecting the Pharmacokinetics of barbs?
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1. Degree of Ionization
2. Lipid Solubility 3. Protein Binding |
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Why does Ionization matter?
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The non-ionic form is active.
Goes back to all barbs being high pKa drugs - thus the more acidic the environment, the more pronounce the effect of the drug. |
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Why does Lipid Solubility matter?
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The non-ionized form is more lipid soluble - AND
Thios and Methoxys are much more lipid soluble than Oxys |
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Why does Protein Binding matter?
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Large portion will be bound to Albumin.
The bound drug is INACTIVE. Alkalemia increases protein binding. (thus again, alkalosis decreases fx, and acidosis prolongs fx) |
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TRUE or FALSE
The duration of central depressant effects is NOT dependent on drug metabolism. |
TRUE
Redistribution is so fast that it doesn't even make a difference. |
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Do you piss out barbs in unchanged form?
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Yes with Phenobarb (as it is not as lipophilic)
No. Even if filtered in glomerulus - the high lipophilic barbs get reabsorbed. They must go through biotransformation in the kidney to become hydrophilic and pissed out. |
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What's the deal with Greyhounds on barbituates?
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Greyhounds have slightly longer recovery from Methohexital
Thiobarbs only rapidly decline for 20 mins, then slowly decline - thus greatly Prolonging Recovery |
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Pentobarbital
(Nembutal Sodium) |
low doses can cause Excitation
Severe Resp Dep, transient Apnea, decreased BP Elimination dependent upon hepatic transformation followed by kidney excretion of INACTIVE metabolites Works FASTer in Ruminants Crosses Placental Barrier and can kill newborns in C-section. Longer Recovery - Excitatory Recovery --- thus has generally been replaced by faster Barbs. |
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Methohexital
(Brevital) |
Ultrashort Acting
Not Labeled for Animal Use Like Thio but more potent, shorter duration. Does NOT concentrate in fat, thus cumulative effects are fewer and recovery is more rapid than with thios and methoxys |
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Thiopental
(Pentothal) |
Strong Alkalinity - so perivascular adverse fx are strong.
Ultrashort Acting Not Analgesic! Unconsciousness in 30-60 seconds Increase HR, other factors remain same or slightly decrease (BP, SV, CO) Cardiac Arrhythmias common (frequently Bigeminy) Repeated IV admin greatly Prolongs Recovery - Fat stores 6-12x as much as plasma is holding and releases the drug over a long period of time. |
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Thiamylal
(Surital) |
Most Potent Thiobarb
Taken Off US market Cardiac Arrythmias twice as frequent as thio. |
