Animal Behaviour - Introduction to Psychopharmacology
Sedatives – Drugs that depress the central nervous system, reducing anxiety and inducing calmness or sleep (e.g., benzodiazepines, barbiturates, azapirones).
What are the major drug psychoactive classes?
- Sedatives-
Benzodiazepines
Barbituates
Azapirones
- Antidepressives and anxiety -
TCA
SSRI
MAO inhibitors
- Neuroleptic/Antipyschotics eg. ACP, chlorpromazine, haloperidol
- epilepsy and mania
Anti-convulsants
-Sedative
Antihistamines
B Blockers
Key Terms
What are the major drug psychoactive classes?
- Sedatives-
Benzodiazepines
Barbituates
Azapirones
- Antidepressives and anxiety -
TCA
SSRI
MAO inhibito...
When may B blockers be used?
Combat the somatic signs of aniety which could be detected by body -> feelings of fear
Which drugs are used as anti depressive in humans/ anxiety in animals? Which other condition may one of these be useful for?
TCAs
SSRIs
MAO Inhibitiors
- may also be useful in age related cog decline (dementia)
Give examples of drugs acting at the cell membrane
Adrenaline
Give examples of drugs acting at a nuclear receptor and impacting protein synthesis
Sex hormones, GH (Steroids)
Give examples of drugs acting on intracellular enzymes
MAO inhibtiors
Related Flashcard Decks
Study Tips
- Press F to enter focus mode for distraction-free studying
- Review cards regularly to improve retention
- Try to recall the answer before flipping the card
- Share this deck with friends to study together
| Term | Definition |
|---|---|
What are the major drug psychoactive classes? | - Sedatives- Benzodiazepines Barbituates Azapirones - Antidepressives and anxiety - TCA SSRI MAO inhibitors - Neuroleptic/Antipyschotics eg. ACP, chlorpromazine, haloperidol - epilepsy and mania Anti-convulsants -Sedative Antihistamines B Blockers |
When may B blockers be used? | Combat the somatic signs of aniety which could be detected by body -> feelings of fear |
Which drugs are used as anti depressive in humans/ anxiety in animals? Which other condition may one of these be useful for? | TCAs SSRIs MAO Inhibitiors - may also be useful in age related cog decline (dementia) |
Give examples of drugs acting at the cell membrane | Adrenaline |
Give examples of drugs acting at a nuclear receptor and impacting protein synthesis | Sex hormones, GH (Steroids) |
Give examples of drugs acting on intracellular enzymes | MAO inhibtiors |
Define drug | A substance that induces a biological response |
Define receptor | A cellular drug target |
Define pharmacokinetics and pharmacodynamics | Kinetics - What the body does to the drug Dynamics - What the drug does to the body |
Define affinity, efficacy and specificity | Affinity - ability to interact with a receptor Efficacy - ability to induce a biological response Specificity - NO drug is truly specific - as the conc^ will exert other actions |
How do antagonists and agonists differ in functionality? | Agonist - affinity and efficacy Antagonist - has affinity but NEVER efficacy (always =0) |
What are the different types of agonist? | Full Partial Inverse |
What is digoxin used for? | Congestive heart failure - +inoptrope |
Define threshold concentration | Lowest dose to give an effect |
Define max dose | Maximum dose before side effects begin to majorly increase |
Give examples of a partial agonist | Buspirone - 5-HT modulator used for feline urinary issues, separation anxiety and feather pecking Buprenorphine - partial opioid agonist -> less risk of reparatory depression associated with analgesia and harder to OD |
What is the outcome of a partial agonist dependant upon? | The [endogenous agonist] - if ^ -> antagonism - if v -> agonism Therefore acts as a MODULATOR of neurotransmission |
What are the 6 types of antagonism? | Competitive (reverisble) Competitive (Irreversible) - usually enzymes (enzyme “suicide”) Non-competitive - inhibits the way enzymes function Physiological Pharmacokinetic Chemical |
Give a use of an antagonist | Dexometodine -> Aneasthesia Competitive antagonist shifts concentration of active anaesthetic and stops it from working, thus reversing effects of anaesthesia (Shifts dose response curve to the right) |
How does non-competitive antagonism affect the shape of the dose-response curve? | MAY shift curve -> right Decreases gradient of slope Decreases maximum possible response |
What are the two types of receptor adaptation that occur in response to drug use? | Short term - desensitisation -> rapid uncoupling from effector mechanism eg. G protein internalisation of receptor inactivation of ion channels temporary efect rapidly reversed Long term - down-regulation -> slow changes in protein expression levels adaptive response to long term agonist activation secondary to other mechanisms eg. chronic stress influenced by multiple factors slow to reverse |
What phenomena may receptor adaptation underlie? | Antidepressants Antipyschotics Mood stabilising drugs Tolerance Side effect profiles -> May also be the therapeutic action of the drug!! |
Give an example of receptor adaptation? | Exogenous steroid use -> endogenous steroid production by negative feedback (can occur with any long term medication) |
Outline the different aspects of pharmacokinetics | What the body does to the drug Administered-> Absorption-> Systemic blood circulation-> Distribution-> Tissues -> Elimination (metabolised or excreted) |
Which factors can affect absorption? | Route, frequency of dosing, half life |
Which factors can affect distribution? | Plasma protein binding, lipid solubility, rate of blood flow |
Which factors can affect elimination? | Half life, frequency of dosing, disease |
Why do heavy metal and DDT poisoning occur? | The elimination pathway of their pharmacokinetics is not functional! |
When do drug interactions occur? | Build up of substrate and insufficient enzyme -> interactions eg. dysfunctional P450 hepatic enzyme system which can occur genetically |
What must be remembered about psychiatric drugs? | Many have active metabolites which can build up Most drug interactions are more for academic or marketing interest than clinically relevant Some have low Tis eg. TCAs like clomipramine |
Give 5 pharmacological targets for neurotransmission | Post-synaptic receptors eg. buspirone (5-HT1a), diazepam (GABAa) Auto/hetero receptors - negative feedback from the synapse stimulated by tonic NT levels eg. mirtazipine (a2-adrenoceptor) appetite stimulus, antidepressant and sleep disorder drug Enzymes eg. selegeline (MAOb inhibitor) neuroprotective action Reuptake transporters eg. clomipramine (TCA), fluvoxetine (SSRI) Ion channels |
What actions do successful/effective drugs tend to have? | Broad effects at multiple sites (this -> ^risk of side effect though) |
Give a psychoactive drug with a low TI | Clomipramine (TCA) for separation anxiety cardiotoxicity with arrythmias no antidote delayed onset |
Give the 6 drug classes used in the treatment of anxiety | 1- Benzidiazepines - amnesic, anxiolytic, hypnotic, NOT LONGTERM, tolerance and dependence) 2- Barbituates - anticonvulsant, anaesthetic, v TI (Petabarbitone = euthanasia) CNS depressant 3- Azapirones - antipyschotic, motor sedative (voluntary movement only, reflexes still work) DA antag. eg. Stresnil (pig aggression,) Fluoperidol SHORT TERM behaviour control 4-Buspirone - nonsedating anxiolytic 5-HT1a partial agonist 5- Antihistmines (sedative) eg. piritone 6- B-blockers - treat somatic signs of anxiety |
What are the actions of ACP | Sedative but REFLEXES ARE NOT AFFECTED - give analgesia too |
What are the 3 GABA receptors? | GABAa - ligand gated ion channel, pentameric, Cl- channel GABAb - G-protein coupled receptor, activting K+ channels GABAc - ligand gated ion channel Cl- |
What is the mechanism of action of benzodiazepines? | Enhance response of GABA - facilitate opening of GABA activated Cl- channel Bind to regulatory site ^affinity for GABA ^frequency of opening Do not affect conductance or mean opening time potentiates GABA effectiveness essentially |
What ar the effects and uses of Benzodiazepines? | -v anxiety and aggression sedation, hypotic reduced muscle tone and coordination anticonvulsant retrograde amnesia paradoxical increase in irritability and aggression (DISINHIBITION) unwanted effects acute overdose tolerance and dependance side effects during therapy eg. sedation when wanted as an anxiolytic |
What may underlie anxiety neurologically? | Distribution of GABA receptors (potentially) Serotonin -Dense 5-HT input to locus coerulus and amygdala which spark a fear response before visual recognition of the stimulus itself -Low 5-HT activity may -> dysregulation of other neurotransmitters eg. NA -Reciprocal interactions eg. medial PFC connected wit hamygdala, allowing regulation of affect and modulation of autonomic and neuroendocrine function allowing cognitive control of anxiety response -STEIN'S theory suggests ^5-HT -> anxiety disorders |
What is the main use of Azaperones? | Anxiolytic and aggression |
What is the pharmacological activity of azaperones like? | Chemical straightjacket! - Multiple actions at multiple receptors |
Give an example of an azaperone | Buspirone - partial 5-HT1a agonist |
How does endogenous ligand concentration affect the actions of partial agonists? | If endogenous ligand conc is high, acts as an antagonist by competing for receptors (thus moves curve -> right) If endogenous ligand conc is low, acts as an agonist but can only produce a sub maximal response |
Following the onset of a shock or fear response, what should happen? | NA and 5-HT increase, then are Downregulated by prefrontal cortex |
How is histamine related to the brain? | Present in low levels in the CNS hypothalamc neurones with widespread axonal innervations H1 in cortex and reticular activating system aontribute to arousal and wakefulness (therefore H1 antags are sedative) Also involved in emesis, regulation of food and water intake, thermoreg |
What pathological state occurs when the serotonin system fails to function correctly? | Depression |
Which are the monoamine NTs? | Serotonin (IMPULSE,) Noradrenaline (VIGILANCE,) Dopamine (DRIVE) - interactions as outlined by Healy and MacMonagle 1997 implicated in the control of mood, emotion and behavioural responses regulate and are influenced by endocrine systems |
Which part of the neurone does buspirone act on? | The cell body (usually in the brainstem) Downregulates 5-HT system |
Why is dopamine not usually targeted for drug use in antidepressant field? | Link with cocaine/amphetamine |
Give 7 drugs used in the treatment of affective disorders (OCD, depression, anxiety disorders) | TCAs eg. clomipramine, amytryptaline SSRIs eg. Fluoxetine, paroxetine 5HT and NA reuptake inhibs eg. Venlafaxine 5HT and NA repecific antagonist eg. Mirtazapine both of these ^NA and 5HT NA SRIs eg. Reboxetine Mixed uptake inhibitors and antagonists eg. nefazedone MAO inhibitors eg. Selegeline ALL ACT TO INCREASE MONOAMINE TRANSMISSION |
What does the increased [synaptic monoamine] act to do? | Activation of somatodendritic autoreceptors - v firing rate -> hippocampal neurogenesis Receptor adaptation up/down regulation (plasticity) -> ^[synaptic] and cognitive effects Activation of pre-synaptic auto receptors - v NT release -> Post-synaptic receptor adaptation Remember there are multiple causes of anxiety |
Which drugs are safer, TCAs or SSRIs? | SSRIs! TCAs have a sedative muscarinic effect and give you dry mouth and blurred vision |
How selective are most uptake inhibitors for 5HT or NA? | Ranges from Citalopram (most selective for 5HT) to Reboxetine (most selective for NA) VENLAFAXINE VERY GOOD DRUG EQUAL NA AND 5HT SELECTIVITY |
What are antipyschotics/neuroleptics used for? | controlling aggression (scizophrenia in humans) - chemical straight jacket |
What are the two classes of antipyschotics/neuroleptics? | Typical - DA untags (Extrapyramidal, muscarinic and Motor side effects) Treat + symptoms of schizophrenia, multiple sites of action all D2 receptors, multiple side effects (may induce depression and parkinsons or catalepsy in animals) Atypical - DA and 5HT antags (No motor side effects, but weight gain, insomnia, sedation side effects) More selective targeting D2 and 5HT2 Rs, reduced side effects and therapeutic profile |
Outline the antiphyschotic drug D2 R blockade | mesolimbic - reduces positive symptoms Mesocortical - Incresases negative symptoms, cognitive deficits Nigrostriatal - induces motor side effects (parkinsons) Tuberoinfundibular - Effects on hormone secretion (hyperPRLeamia) |
High doses of what type of drug can provide chemical restraint? | Antipyschotics eg. Aceptapromazine |
What is another name for Atypical antipyschotics? | 2nd generation D2 and 5HT antagonists (hypothesised improved efficacy and reduced side effects compared to typical antipyschotics but limited evidence) Fast off theory (fast kinetics) R5HT2a receptors expressed in cortical, hippocampal regions especially |
How can the best efficacy be achieved when formulating a drug? | Multiple therapeutic mechanisms, without multiple extra mechanisms which will evoke side effects |
What physiological use do anticonvulsants have? | Mood stabilising - eg. for bipolar enhanced GABA action eg. phenobarbital Inhibition of sodium channels eg. Carbamazepine, phenytoin Inhibition of calcium channels eg. Ethosuximide, gabapentin reduce electrical excitability of cell membranes through USE DEPENDANT Na channel blockade |
What type of drug is Selegeline? | MAOb inhibitor enhance DA reelase and blockade of reuptake does not induce food interactions |
Where does MAob predominate? | DA rich areas of CNS |
How may MAOb be neuroprotective? (i.e. for use in dementia in dogs and cats) | Reduces oxygen free radical production (up regulates superoxide dismutase) Delays apoptosis sows decline, does NOT prevent |