Benzodiazepines, azapirones, barbiturates and antihistamines fall under what classification of behavior modification drug?
What class of drug facilitates GABA in the CNS, is commonly used to reduce urine spraying in cats and noise phobia, fear and separation anxiety in dogs?
What benzodiazepine is particularly used to treat thunderstorm phobia in dogs, has a slow onset and is less sedating than diazepam?
Clorazepate dipotassium (Transxene)
What benzodiazepine is used to treat fearfulness in dogs and cats, and is also used in humans to treat panic disorder?
What benzodiazepine is used in older, debilitated animals with anxiety (dogs) and is biotransformed with no active metabolites?
Name four benzodiazepines used to behavior modification? (clad)
Clorazepate, Lorazepam, Alprazolam, Diazepam
What drugs are steronergic and dopaminergic, treat urine spraying, separation anxiety and fear, but are ineffective for humans?
Azapirones (example: Buspirone)
What are two side effects of azapirones?
GI tract (uncommon)
Changes in social relationships
What class of behavior modification drugs block the uptake of serotonin and norepinephrine, and are used to control aggression, urine spraying, excessive grooming, anxiety and hypervocalization?
Name three tricyclic antidepressants. (cia)
What are the side effects of tricyclic antidepressants?
-Anticholinergic effects (dry mouth, urine/feces retention, reduced tear flow, mydriasis)
-Lower seizure threshold
-Cardiac conduction disturbances at high doses
What antidepressant is used for urine marking in dogs and cats?
What antidepressant is more steronergic than Amitriptyline and is used for human problems (bedwetting, narcolepsy, ADD, depression, panic)?
What antidepressant is used in dogs for separation anxiety, canine compulsive disorder, acral lick dermatitis, tail chasing and flank sucking.
What antidepressant is used in cats for urine spraying, stereotypic behavior hyperesthesia syndrome and anxiety states?
How do you avoid GI side effects (anorexia, nausea, diarrhea) with Selective Serotonin Reuptake Inhibitors?
Start at low doses for one week then increase with time.
Name four examples of SSRIs.
What SSRI should you not use in beagles or beagle crosses at high doses? What could it cause?
Paroxetine - fatalities due to cardiac abnormalities!
What SSRI may cause constipation in cats?
What is the action of Monoamine oxidase-B inhibitors?
Irreversible inhibition of MAO
Inhibition of catecholamines (Dopamine)
What class of behavior mod drugs is used for cognitive dysfunction and sleep disorders in older dogs?
What drug interaction risks are there with MAO-B inhibitors?
With TCAs and SSRIs, may cause serotonin syndrome.
What inhibits Cytochrome oxidase P450 which is required to metabolize tricyclic antidepressants?
____ and ____ may inhibit learning necessary for behavior modification, but ___ may facilitate it.
Benzodiazepines and phenothiazines
What are some possible drug interactions that are helpful because of affects on different NT systems, but may put at risk for serotonin syndrome?
TCAs and benzodiazepines
Benzodiazepines and MOIs
TCAs and SSRIs may be used with ___ or ____ to enhance treatment.
Buspirone or trazodone
What are some side effects of benzodiazepines?
Sedation, ataxia, muscle relaxation, memory deficit, hepatic necrosis in cats.
Most of these behavior mod drugs are extra-labeled. Which two are FDA approved?
Clomipramine and Selegiline
What includes the date prescription order was written, name, address, weight, age of patient and Rx?
What is the body of the prescription and contains the name and amount/strength of the drug or of each ingredient?
What is the instruction to the pharmacist, usually consisting of a short sentence, "make a solution" or "dispensed into capsules"?
What are the instructions to the patient as to how to take the prescription?
Signa or 'Sig'
Is "take as directed" satisfactory for the Signa?
No - avoid.
What is a written order prepared by someone other than the prescriber (must be registered with DEA if for a controlled substance)?
When clients request a written prescription, are you obliged to give it to them?
Yes, or else you are guilty of restricting free trade.
Elements of a prescription?
DVM info, client info, date, DEA# if CS, directions, animal name and species, drug name/strength/quantity, withdrawal times, signature, authorized refills.
To avoid confusion, do you use q24h or QD?
What are three essentials in a valid veterinary client patient relationship in terms or prescription drugs?
Agreement, examination, follow-up
What is not considered a drug as long as the manufacturer does not make therapeutic claims on the label, and is available without prescription?
How often can Controlled Substances be refilled?
5 times or 6 months, whichever comes first.
What CS have a high potential for abuse, and is not accepted for medical use in US (only research)?
What CS have high potential for abuse, is accepted for medical use in US, and abuse may lead to severe psychological/physical dependence?
What CS has is currently accepted for medical use in the US, and abuse may lead to moderate or low physical dependence, or high psychological dependence?
Can compounded drugs be purchased in bulk from compounder and resold to clients?
What is the difference between compounded drugs and investigational?
Barbiturates: as lipid solubility increases, duration of CNS depressant effect _______, onset of effect _____, metabolism and potency _______.
Decreases, decreases, increases
Barbiturates are administered PO or IV. Why not intra-arterially, IM or SC?
Intra-aterial can cause endothelial damage and vasospasm, and will distribute entirely (think of pregnancy).
IM/SC is irritating and damaging.
What are two highly lipid soluble barbiturates (meaning they can enter tissue easily, including the brain)?
Why does physical/emotional state of the animal matter when giving barbiturates?
Epinephrine release, which causes B2-mediated vasodilation in skeletal muscle. Less blood going to the brain and a higher dosage is required.
Barbiturates are P450 inducers. What irreversibly inhibits liver P450 in dogs and cats?
What is the mechanism of barbiturates, which are generally considered CNS depressants?
Exact mechanism unknown. Inhibits Ach release, NorEp and glutamate.
At high doses, inhibits Ca uptake at nerve endings
How are barbiturates GABA-mimetic, reducing neuronal excitability?
Increasing GABA-mediated inhibition at GABA-A receptors (increases time Cl channels stay open)
Which is safer: barbiturates or benzodiazepines?
Benzodiazepines - less GABA enhancing action
Name four uses of barbiturates.
Treat seizure disorders.
Decrease intracranial pressure + cerebral edema
Are barbiturates analgesic?
No, they are hyperalgesic at sub-anesthetic dose
What mechanisms do barbiturates employ other than GABA-A?
Antagonist at AMPA receptor (glutamate).
Phenobarbital as anesthetic decreases the activity of voltage-dependent Na+ channels.
What is the correct order of events that occur with increasing barbiturate doses?
Sedation, hypnosis, anesthesia, coma, death.
What is the state of calmness, sleepiness in which the patient is awake?
What is the state of normal sleep in which the patient is easily aroused?
What is the deep state of CNS depression where the patient cannot be easily aroused?
What is the state where the patient cannot be aroused and basic physiological drives are severely depressed?
What barbiturates have a duration of action of 5-15 minutes, therefore used for anesthesia induction and short-term maintenance?
What barbiturates have a duration of action of 3-8 hours, therefore used to treat insomnia, preoperative sedation and emergency seizure treatment?
What barbiturate is long acting (days) and therefore used for the treatment of seizures and status epilepticus?
Phenobarbital (used as anticonvulsant)
How can you administer pentobarbital?
PO, IM, IV, rectal
Which suppresses spontaneous neuronal activity the best: pentobarbital or phenobarbital?
How can phenobarbital be administered?
PO, IM, IV
What action do benzodiazepines have on GABA-A receptor both in the presence and in the absence of GABA?
In the presence - enhance channel gating
In the absence - activates mutant receptors (weak allosteric agonists)
As lipid solubility increases, what happens to duration of action, latency between admin. and effect, extent of metabolism and hypnotic potency?
Duration of action decreases, latency between admin. and effect decreases, extent of metabolism increases and hypnotic potency increases.
What occurs in acute barbiturate intoxication?
Serious deficits on cardiovascular and other peripheral functions
Do barbiturates have true analgesic activity?
No, they depress the sensory cortex, lessen motor activity and produce sedation.
Use barbiturates cautiously with CATS! What are they sensitive to?
What are the factors affecting distribution of barbiturates?
Lipid solubility, extent of plasma protein binding, and emotional/physical state of the animal.
Which sites on the barbiturate molecule most influence lipid solubility?
C2 and C5
Barbiturates bind reversibly to plasma albumins in what relation to lipid solubility?
Direct proportion - testing liver function useful!
How does epinephrine release (stress) affect barbiturate pharmacokinetics?
Epinephrine causes B2 mediated vasodilation in skeletal muscles, so higher cardiac output to muscles. Desired effect calls for increased dose, could lead to overdose.
What effect do barbiturates have on cardiovascular?
(Pentobarbital) - tachycardia, decreased myocardial contractility and stroke volume, and decreased arterial pressure and TPR.
What effects do barbiturates have on GI tract?
Reduced tone and motility
Thiobarbiturates, after initial depression, there is an increase in tone and motility.
How can barbiturates affect skeletal muscle?
Reduced sensitivity of motor endplate to ACh = relaxing of muscle somewhat.
Basal metabolic rates reduced
What does the termination of effects on barbiturates depend on?
*Redistribution from brain to highly perfused areas
Can barbiturates cause fatal CNS depression? How about benzodiazepines?
Barbs - yes
Benz - no
What feature of barbiturate action causes an increased rate of metabolism of many drugs?
That they induce liver microsomal enzymes
What is Acetylcholine, a quaternary amine with a positive charge, inactivated by?
What are the effector organs of ACh?
Cholinergic drugs are often associated with the stimulation of what?
Parasympathetic nervous system
Which receptors are located postsynaptic to preganglionic neurons (~postgang ??) in all autonomic ganglia, including Chromaffin cells of adrenal medulla?
What receptors are located at neuromuscular junctions, on pre-synaptic nerve terminals and in the CNS?
Which nicotinic receptor subtype is found in neuromuscular junction, its activation opening cation channels resulting in end plate depolarization and skeletal muscle contractions?
Nm: Nicotinic muscular receptors
Which Nicotinic receptor subtype is found in the autonomic ganglion, adrenal medulla and CNS?
Nn: Nicotinic neuronal receptors
What receptors can be found on post-synaptic membrane of the neuro-effector junction innervated by postganglionic parasympathetic and sympathetic neurons?
What receptors can be found in non-innervated areas like vascular epithelium, in autonomic ganglia, on pre-synaptic nerve terminal and in CNS?
What muscarinic subtype is located in autonomic ganglia, CNS and some secretory glands?
What muscarinic subtype is located in the heart (SA node, atria, AV node, ventricle)?
What muscarinic subtype is located in the smooth muscle and secretory glands?
Activation of M2 receptor leads to what kind of signal transduction pathway?
Decrease in adenyl cyclase.
Increased K+ channel.
Causes decreased conduction rate -> decreased heart rate
Activation of M1 and M3 receptor leads to what kind of signal transduction pathway?
Phospholipase C stimulation -> increased cytosolic Ca+
Smooth muscle contraction
Secretion of exocrine gland
Does Ach cause a contraction or a relaxation of smooth muscles?
(think bronchioles, urinary tract, uterus)
What direct-acting cholinergic agonist shows some limited selectivity to the cardiovascular system?
What direct-acting cholinergic agonist shows some limited selectivity to smooth muscles of the GI tract and urinary bladder?
What is a mild nicotinic, strong muscarinic agonist, with a longer duration of action than ACh since its hydrolized at a slower rate by AChE and almost totally resistant to hydrolysis by other cholinesterases?
What is a very potent nicotinic and muscarinic agonist and is totally resistant to hydrolysis by AChE and other cholinesterases?
What pure muscarinic agonits is totally resistant to hydrolysis by AChE and other cholinesterases and is used to treat GI tact atony and detrusor atony in cats and dogs?
What are the main side effects of Bethanechol?
Intense contraction of the GI tract, salivation, nausea, and vomiting. Use with caution!
Name three direct acting cholinergics which are alkaloids producing parasympathetic effects?
What direct acting cholinergic alkaloid is used to reduce intraocular pressure in canine glaucoma therapy?
All indirect cholinergic agonists are cholinesterase inhibitors, divided into what two groups?
What indirect cholinergic agonists are hydrolyzed slower than ACh?
Physostigmine and neostigmine
What indirect cholinergic agonist competes for binding to the anionic subsite, is given IV and has a short duration of action?
What are indirect and irreversible cholinergic agonists, which are mainly OP compounds (di-isopropyl-phospho-fluorodate) used for?
Insecticides, nerve gases, dichlorvos
Drugs that interfere with actions of ACh by blocking cholinergic receptors, known as cholinergic antagonists, are grouped into what three categories?
How can indirect and irreversible cholinergic agonists be treated?
Administer pralidoxime (2-PAM)
What are two stipulations in using 2-PAM to treat indirect and irreversible cholinergic agonists?
Its only effective against organophosphate inhibitors.
Must be given within hours of exposure.
What are four reversible cholinesterase inhibitors (aka indirect agonists)?
Which penetrates the blood-brain barrier easily: Physostigmine or Neostigmine?
What cholinesterase inhibitor has been used in the past for glaucoma because it is mainly parasympathomimetic, and as an anticholinergic?
At therapeutic doses, where does Neostigmine have an effect?
Nicotinic receptors at the neuromuscular junction and autonomic ganglia.
What makes Neostigmine a therapy of choice for Myasthenia gravis?
Selectivity for nicotinic receptors at neuromuscular junction and its poor penetration into CNS.
What cholinesterase inhibitor is primarily used as an anti-curare agent and in the diagnosis of myasthenia gravis, and is similar to Neostigmine but with a short duration of action?
What is an alternative cholinesterase inhibitor that can be used in the treatment of Myasthenia gravis?
What compounds are irreversible cholinesterase inhibitors which interact with the esteratic subsite, forming extremely stable complexes?
What cholinesterase reactivator is used clinically?