Pharmacokinetics Pharmacodynamics Drug distribution Target tissues and stimulation (CNS: depression or stimulation

Week 5 - Analgesics Flashcards by Christine Parascandola

CNS Pharmacology:

how drugs alter brain activity and offset pathology

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NeuroPharmacology:

how drugs act on neurons at cellular/molecular level

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PsychoPharmacology:

how drugs modify behavior, perception, affect a thought

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In the last three decades, dramatic advances have been made in ?

CNS pharmacology

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Regrettably, recent developments are not that good. Why?

Large pharm companies severely restricting
neuropsychiatric drug development efforts citing

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Drug is defined as

A substance used to prevent or treat conditions associated with stimulation or depression
of the brain associated with both mental and physical processes

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Describe the therapeutic Importance of drugs.

Relieve pain and fever
Suppress disorders of movement or seizures
Induce sleep or arousal
Reduce desire to eat
Inhibit motion sickness
Treat anxiety, mania, depression

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Prescription Drug is defined as

A drug that is limited to use under the supervision of a veterinarian
because of potential danger, difficulty of administration, or other indications

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Controlled Drug is defined as

Drugs that have a potential for abuse or dependence;
classified into schedules according to their level of abuse potential

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Drugs act like ________, transferring _____-______ messages
between ______ in the brain and spinal cord.

neurotransmitters, electro-chemical, neurons

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Drugs can _____-___ the transfer of these signals and are called ?

speed - up, CNS stimulants

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Drugs can slow - down the transfer and are called ?

CNS depressants

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CNS drugs act on ______ receptors that modulate
_______ ______.

specific, synaptic transmission

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Some nonspecific agents (such as ______, ________) have
____-______-mediated actions that result in
alterations in synaptic transmission

alcohol, anesthetics, non-receptor

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DRUGS can alter the function of CNS to provide:

Analgesia: narcotic (opioids) and non-narcotic (NSAIDs & NMDA receptor antagonists)
* Tranquilization (sedation) effects
* Anticonvulsant effects
* Antiemetic effects
* Anxiolytic, sedative, and hypnotic
* General anesthetic effects
* Behavior changes: CNS stimulants
CNS Depressants (antidepressants, anxiolytic drugs)

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CNS Drugs
Actions

Pharmacokinetics
Pharmacodynamics
Drug distribution
Target tissues and stimulation (CNS: depression or stimulation

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Agonists:
* Bind to and ______ target tissue (CNS)

stimulate

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Antagonists:
* Bind to target tissue but

don’t stimulate

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Different things can happen to result in drug action.
5. Release of NT into synapse cleave?
After communciation with receptor on post-synaptic neuron

The action potential in the presynaptic fiber
Synthesis of the NT
Storage
Metabolism
Release
Reuptake
Degradation
Post-synaptic receptor

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Drugs can act on synthesis, storage, metabolism, uptake, release. Retrograde signalling we won’t be discussing.

Glial cells can also participate in some functions of the synapse communication.

Cocaine blocks uptake of catecholamine which are dopamine, serotonin, and norepinephrine. Adrengeric synapses?
ACh is ?
Post-synaptic region provides primary site of drug action and things can happen here to interfere with real signaling.

Action potential in presynaptic fiber
Synthesis of neurotransmitter (NT)
Storage
Metabolism
Release
Reuptake into the presynaptic neuron or glial cell
Degradation
Receptor for the NT
Receptor-induced increase/decrease in ionic conductance
Retrograde signaling

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Main targets for neuro-active drugs:

 Ion channels
 Receptors
 Enzymes
 Transport proteins

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Most of the targets occur in several different _______ _____,
giving rise to subtle differences in function and pharmacology

molecular isoforms

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Slowly developing secondary responses to the primary interaction of the drug
with its target are often important (delayed efficacy of antidepressants,
tolerance and dependency with opioids).

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The term BBB denotes the highly-selective barrier separating the brain tissue from the blood circulation.

A lot of drugs are unable to pass the BBB.

The main function of the BBB is the ?

protection of CNS against toxins, pathogens and even NTs (glutamate)

The BBB consists of a _______ layer of _______ cells joined by _____ ______ and surrounded by _______l.

continuous, endothelial, tight junctions, astrocytes

Circulating drugs must cross BBB in order to gain access to the neurons of the brain

DRUGS that can cross the BBB:  ____ in molecular size (Examples?)  Lipid ____ (________)  _____ bound to protein  Non- ______ at the ___ of cerebrospinal fluid (CSF)  _____ or ____-mediated transfer (L-DOPA)

Small, CO2, caffeine, nicotine, heroin, soluble, lipophilicity, Poorly, ionized, pH, Diffusion, carrier

The BBB tends to increase in ________ in the presence of ________ or at the site of ____

permeability, inflammation, tumor

The BBB is poorly developed in ______; hence, chemicals can easily gain access to the ________ _____.

neonates, neonatal brain

Analgesic drugs are used to inhibit ______ processing at different levels

pain

Goal of therapy: ?

reduction of transduction, transmission, modulation, and perception of pain

Pain: is an unpleasant ____ and _____ experience associated with ____ or ____ tissue damage. Pain has been recognized for its contribution to ____ and _____

sensory, emotional, actual, potential, morbidity, mortality

Classes of Pain Duration

Classes of Pain Location

Pain processing System

1. Transduction 2. Transmission 3. Modulation 4. Perception

Pharmacological Intervention of Pain Processing

Opioids are?

Derivatives of opium (poppy plant)

Opium: extract from the ______ ______ ____ of unripe bulbs of the _____ plant contains morphine and codeine.

white milky sap, poppy

The active chemical compounds in opium are _____ and _____

Morphine,Codeine

Difference between morphine and codeine are their chemical structure. Pay attention to this.

Opiates: _____ drugs derived from opium ____ or semi- ______ derivatives with narcotic properties. Opiates can be ____ or ____. Representatives: ?

narcotic, poppy, synthetic, Natural, unnatural opium, morphine, heroin (3x > potent)

Opioids: ___-synthetic or ___-synthetic ____ drugs that mimic the natural ____. Not found in ____. Representatives: ?

fully, semi, narcotic, opiate, nature hydrocodone, oxycodone, fentanyl, tramadol

Endogenous opioid neuropeptides: ?

endorphins, enkephalins, dynorphins are release by the neuroendocrine cells to activate receptors

CH2 methyl group allows it to be lipophyllic and can cross BBB.

Opioids are _______ substances except for _____ and ______ (partial agonist)

Controlled, antagonists, nalbuphine

Administering Opiods: Routes of Administration: ?

IV, IM, SC, oral, rectal, transdermal, subarachnoid, and epidural

PK: Metabolized in the liver and excreted in the urine * Wide margin of safety (dogs don’t ask for prescription or go to black market)  Cats are deficient in the metabolic pathway, the t1/2 of most opioids in cats may be prolonged  The elimination t1/2 is 1 hr in dogs, 3 hr in cats, and 1.5 hr in horses

Opiods * Produce _____ and _____ * _____ induction when combined with other drugs * Classified as ____ agonists, _____ agonists, mixed ?

analgesia, sedation, Anesthetic, full, partial, agonist-antagonists

Opiod Uses: Analgesia

Analgesia * Prevent and treat postoperative pain * Used with tranquilizers to produce neuroleptanalgesia

Opiods Pre-anesthetic

agonists, partial agonists, or mix agonist-antagonists (agonistic effect on one receptor, antagonistic on another receptor) * May be used alone or in combination with - Tranquilizers - Anticholinergics She said this was VERY important.

Opiods mimic ? * May be used ____ or in combination with?

agonists, partial agonists, or mix agonist-antagonists alone - Tranquilizers - Anticholinergics

Opioids Pharmacological effects: _____ and ____ but depend on many factors

Analgesia, sedation

Opioids in dogs ---> ?

Dogs: sedation narcosis

Opioids in cats, horses, and ruminants ---> ?

Cats, horses, and ruminants: may cause CNS stimulation bizarre behavior patterns or dysphoria

Opioids MOA * Bind to the receptors in the ____ and ____ _____ and mediate the ____ of _______ and ______ secretion * Stimulate ____ receptors [?] * Each opioid has a different ____ at each receptor * Receptors are present in ?

brain, spinal cord, inhibition, neurotransmission, endocrine, opioid, mu (μ), kappa (κ), and delta (Δ), action, numerous cells/ tissues

Name the analgesics that are agonists

Morphine, hydromorphone, oxymorphone (10 times >), fentanyl (75-125 times > potent), tramadol (<)

Name the analgesics that are Partial Agonists

Buprenorphine, Butorphanol (μ-receptor)

Name the analgesics that are Mixed Agonist-Antagonists

Butorphanol (partial μ-receptor agonist and agonist for k-receptor) Nalbuphine (agonist for k-receptor and antagonist for the μ-receptor) Buprenorphine (μ-partial, k-antagonist)

Name the analgesics that are antagonists

Naloxone and Naltrexone

All opioid receptors are __-____ receptors that mediate the inhibition of _______ and ______ secretion.

G-coupled, neurotransmission, endocrine

μ-receptors are present in the brain, spinal cord and, when bound, lead to?

Spinal and supraspinal analgesia euphoria mild sedation miosis respiratory depression chemical dependence inhibition of Ach and dopamine release decrease in GI motility

κ-receptors are present in the cerebral cortex, spinal cord and other brain regions and, when bound, lead to?

Spinal and supraspinal analgesia sedation dysphoria diuresis miosis

Δ-receptors are present in the limbic system, cerebral cortex, and spinal cord and, when bound, lead to ?

Spinal and supraspinal analgesia inhibition of dopamine release cardiovascular depression

_____ agonist binds to receptors.

Full

Red = ____ effect Green = allows ____ events to occur

blocks, normal

Adverse Effects of Opioids on CNS

Adverse Effects of Opioids on Cardiovascular system

Adverse Effects of Opioids on Respiratory system

Adverse Effects of Opioids on GI

Adverse Effects of Opioids (cont)

Emergencies: Reverse undesirable effects  CNS and respiratory depression  Overdose  Reverse neuroleptanalgesia  Reviving neonates delivered by C-section Wake up patient following sedation

Naloxone hydrochloride * ____ or ______ ___ administration * Used in what species?

IM, slow IV, Dogs, horses, cats, exotic mammals

Naltrexone * Used in ___ animals (___, ___ against ______ effects) * Orally in ____ for behavioral problems (?) * ______ lasting

wild, IV, IM, carfentanil, dogs, constant licking, tail chasing, Longer

What is the MOA of Naloxone hydrochloride?

Unknown

Describe the PK of Naloxone hydrochloride

Describe the adverse effects of Naloxone hydrochloride

N-methyl-D-aspartate (NMDA) receptor is a _____ receptor and ___ channel * Ligands: _____ and ____ * Mediating ______ and _____ functions

Glutamate, ion, Glutamate, Glycine, learning, memory

Amantadine is an antagonist that can be used on ____ and ____ for ____ and ____ pain.

dogs, cats, acute, chronic

Ketamin is used in?

hospital settings

Gabapentin is used to treat what type of pain?

neuropathic pain, cancer-related pain

Amitriptyline is an ?

antidepressant

Lidocaine patch is a form of veterinary ______ _____________

pain management

Non-Opiod Analgesic Drugs

Tylenol can damage liver Ibuprofen can cause GI ulcers in certain dogs, even at very low doses and at high doses can lead to severe liver damage. NSAIDs are used as pain killers. Make cards for rest of info on this

What is the MOA of NSAIDs?

Carprofen is an ______ and can be used on what species?

NSAID, dogs, cats, reptiles, and birds

Deracoxib is an ______ and can be used on which species? For what reasons?

NSAID, dogs, after surgery

Firocoxib is an ______ and can be used on which species? For what reasons?

NSAID, dogs, horses, osteoarthritis and surgery

Meloxicam is an ______ and can be used on which species? For what reasons?

Dogs, cats, osteoarthritis

What are the side effects of NSAIDs

Usually safe but some common side effects are: kidney, liver, and GI problems, drug to drug interaction