5 Nervous System Drug Overview I

1. LIPID soluble

2. POORLY bound to protein

3. NON-IONIZED at CSF pH

Something can cross the blood brain barrier best if it is:

1. *water or lipid* soluble

2. *poorly or strongly* bound to protein

3. *ionized or non-ionized* at CSF pH

Anticonvulsant drugs

Which overall drug has the MOA to stabilize neuronal membranes via hyperpolarization by either direct action on ion channels or thru active GABA gated Cl channels

Seizure

This is a sudden burst of uncontrolled electrical activity in the brain that occurs when neurons become excessively active

To stabilize nerve cell potential and decrease excitability by hyperpolarizing cells

What is the overall GOAL of using anticonvulsant drugs?

Because you want to decrease incidence, severity, and duration of seizures

Why would you use anticonvulsants overall? To hyperpolarize cells yes but like why?

Activating inhibitory

GABA and GABA-A receptor are examples of *activating inhibitory* or *inhibiting excitatory* neurons?

Inhibiting excitatory

Glutamate and NMDA receptor are examples of *activating inhibitory* or *inhibiting excitatory* neurons?

GABA inhibitory

Where do barbiturates bind, *GABA inhibitory* or *NMDA excitatory*?

GABA inhibitory

Where do benzodiazepines bind, *GABA inhibitory* or *NMDA excitatory*?

Cl influx for hyperpolarization of *post synaptic* neuron

GABA is an inhibitory neurotransmitter. When barbiturates and benzodiazepines bind (though not to the same place), what do they cause to influx into the cell for hyperpolarization?

Cl ENTERING cell = AP less likely

Cl *into or leaving* the cell makes an action potential less likely.

Barbiturates

Both barbiturates and benzodiazepines bind to GABA, an inhibitory neurotransmitter. Which one of these enhances the response to GABA, increasing the duration for which the Cl channel is open?

Benzodiazepines

Both barbiturates and benzodiazepines bind to GABA, an inhibitory neurotransmitter. Which one of these increases the affinity of the GABA and binding site, increasing the frequency of channel opening?

Benzodiazepine

Diazepam, Midazolam, Clonazepam, and Lorazepam are all what class of drug?

Benzodiazepines

What is the first choice drug for acute seizures and EMERGENCIES in horses and small animals?

Bad for long term treatment of seizures because of tolerance

Benzos are a good choice of anticonvulsant for emergencies and acute seizures. What are they bad for and why?

Yes, schedule IV

Are benzos a controlled drug?

Diazepam

Which benzo lasts longer, *midazolam or diazepam*?

Diazepam

Which benzo is highly lipid soluble, irritating IM and not good for CRI because it adheres to plastic, *midazolam or diazepam*?

Midazolam

Which benzo is water soluble, *midazolam or diazepam*?

Midazolam

Overall, which benzo is safer for liver patients because it has less active metabolites, *midazolam or diazepam*?

Midazolam (remember it does not last as long)

Which one has more rapid clearance (though both are cleared thru the kidney), *midazolam or diazepam*?

Diazepam

Which drug, when given orally, causes *acute fatal hepatic necrosis in cats*?

Because it elevates seizure threshold

Why do you want to influx Cl into the cell to cause hyperpolarization of the post synaptic membrane?

Oral absorption is high

Where is absorption high for phenobarbital? What route?

WIDE

What is the distribution like for phenobarbital, *wide or narrow*?

Liver

Where is phenobarbital metabolized?

Long

The half life of phenobarbital is *long or short*

This increases the metabolism of other barbiturates because it ramps up liver metabolism (other drugs have faster clearance)

Phenobarbital is a very strong inducer of hepatic cytochrome P450 enzyme. Why do we care?

Long term

Phenobarbital is better for *emergency* or *long term* treatment of seizures

Those with liver disease

What animals are CONTRAINDICATED to use phenobarbital in?

Hepatotoxicity, bone marrow dyscrasia, thyroid testing affected

What organs/structures might phenobarbital cause problems or toxicity in?

Potassium bromide

This old anticonvulsant can be used when phenobarbital isn't working on its own, or when you start to see liver enzymes or liver damage increase

Causes *SEVERE ASTHMA* in cats

What is the problem with using potassium bromide in cats?

Bromide enters the cell thru the Cl channel, so Br influx into the cell still works to hyperpolarize the post-synaptic neuron to elevate seizure threshold.

This drug can work synergistically with Barbiturates and Benzos, which act on the Cl channels (the same channels Bromide enters thru)

What type of effect does Potassium bromide have on the cell to stop seizures? What other drug classes might it work in conjunction with?

Oral

What route is Potassium bromide quickly absorbed thru?

EXCLUSIVELY eliminated by kidneys (no liver or plasma protein)

What is metabolism and excretion like for Potassium Bromide?

Br changes with Cl in the diet (diet high in Cl causes shorter half life)

What do you have to be really careful of with the diet in a patient receiving Potassium Bromide?

Depression, delirium, hyperexcitability, ataxia

What signs are commonly seen with Potassium Bromide toxicosis?

Levetiracetam

This antiseizure medication acts on the presynaptic neuron to stop the vesicles from releasing neurotransmitters, or "decreases GO signals"

Horses and foals

What animals can you possibly use Levetiracetam in?

Diazepam and Midazolam

What drugs should you always have available for IMMEDIATE seizure control in horses?

Sodium Bromide

If potassium bromide regulation is an issue in an animal, what close substitute can you use instead?

Phenobarbital, potassium bromide, sodium bromide, and levetiracetam

Name the seizure control options for longterm use:

Sedation and tranquilization

Phenothiazine (Acepromazine), Benozos (Diazepam), and Alpha 2 agonists (xylazine) are used for WHAT in horses?

Does NOT do analgesia

What do you need to keep in mind when using acepromazine for sedation in horses? What does it NOT do?

Acepromazine (phenothiazine)

This equine sedative is an anxiolytic but also may cause splenic engorgement, vasodilation, decreased MAP, potentially even penile prolapse and paraphimosis in male horses

Benzos (midazolam, diazepam)

This equine medication is a sedative but also is good for general anesthesia induction, muscle relaxation, and anticonvulsant properties

FALSE: Benzos ARE good because of minimal cardiovascular changes, but they do NOT DO analgesia

TRUE OR FALSE: benzos are good in foals because they cause minimal cardiovascular changes and a lot of analgesia

Alpha 2 agonists

Which equine medication can be used for sedation, anesthesia, AND ANALGESIA

Alpha 2 agonists

Xylazine and detomidine are examples of what FDA approved equine drug class?

Alpha 2 agonists

Which equine medication class has the side effects of bradycardia and arrhythmia?

Do NOT use in neonates or those with cardiac issues

What animals can you NOT use alpha 2 agonists in? What contraindications?

Butorphanol

This medication is an opioid often used in conjunction with alpha 2 agonists, used to decrease pain, coughing, and to prolong sedation in horses

Polyuria, polydipsia, polyphagia, and panting

What are the 4 P side effects of Phenobarbital in terms of behavior?