Wk1 Mental

separator:tab

html:true

What is the definition of a psychotropic drug?

Any drug capable of affecting the mind, emotions and behaviour.

According to the Aged Care Quality and Safety Commission (2020), what are the broad categories of psychotropics?

1. Antidepressants
   2. Anxiolytic/Hypnotics
   3. Antipsychotics
   4. Mood Stabilisers
   5. Anticonvulsants
   6. Psychostimulants
   7. Cognitive Enhancers
   8. Hallucinogenics/psychedelics
   9. Dissociatives
   10. Entheogenic compounds
   11. Cannabinoids
   12. Deliriants
   13. Nootropics
   14. Melatonergics
   15. Opioids

In the context of psychotropic categories, what does an asterisk (*) typically indicate regarding novel psychiatric therapeutics?

It indicates drugs that are currently in the drug pipeline (novel therapeutics).

How do psychotropics generally function at a physiological level?

They function by modulating neurotransmitter activity within the Central Nervous System (CNS), typically the brain.

What is the mechanism of action for SSRIs (Selective Serotonin Reuptake Inhibitors)?

They block 5HT (serotonin) reuptake transporters, resulting in an increase of synaptic serotonin concentrations (( \uparrow ) synaptic [serotonin]).

What is the mechanism of action for Benzodiazepines?

They allosterically modulate ( \text{GABA}_\text{A} ) receptors, leading to neuronal depression.

How does Ketamine function mechanistically in the CNS?

It acts as an NMDA receptor antagonist.

What is the primary mechanism of action for Antipsychotics?

They antagonise dopamine receptors.

What are two key clinical effect characteristics of psychotropic drugs?

1. Delayed onset: Often taking weeks to months to manifest.
   2. Highly variable between individual patients.

According to literature (Efinger V, et al., 2021), what must antidepressants cross to exert intracellular action?

They must cross the blood-brain barrier (BBB) to enter neurons.

What is the primary mechanism of action for Antidepressants?

Inhibit reuptake of monoamines (SERT, NET, DAT) and/or inhibit monoamine metabolism; downstream receptor modulation.

Which neurotransmitter systems are primarily targeted by Antidepressants?

Serotonin, Noradrenaline, and Dopamine.

What are the core clinical effects of Antidepressants?

Mood elevation, anxiolysis, and emotional regulation.

Provide examples of Antidepressant drugs.

Fluoxetine, Sertraline, Venlafaxine, Amitriptyline, and Moclobemide.

What is the primary mechanism of action for Anxiolytics / Hypnotics?

Enhance inhibitory neurotransmission (positive allosteric modulation of ( \text{GABA}_\text{A} ) receptors) or reduce arousal pathways.

Which neurotransmitter system is primary for Anxiolytics / Hypnotics?

GABA (primary).

What are the core clinical effects of Anxiolytics / Hypnotics?

Reduced anxiety, sedation, and sleep induction.

Provide examples of Anxiolytic / Hypnotic drugs.

Diazepam, Alprazolam, Temazepam, Zolpidem, and Buspirone.

What is the primary mechanism of action for Antipsychotics?

Dopamine \( \text{D}_2 \) receptor antagonism or partial agonism; additional serotonergic receptor modulation.

Which neurotransmitter systems are primarily targeted by Antipsychotics?

Dopamine (primary) and Serotonin.

What are the core clinical effects of Antipsychotics?

Reduction of psychosis and mood stabilisation.

Provide examples of Antipsychotic drugs.

Haloperidol, Chlorpromazine, Risperidone, Olanzapine, and Aripiprazole.

What is the primary mechanism of action for Mood Stabilisers?

Modulate intracellular signalling pathways and neuronal excitability; reduce glutamatergic activity.

Which neurotransmitter/signalling systems are targeted by Mood Stabilisers?

Glutamate, Dopamine, and Second messenger systems.

What is the core clinical effect of Mood Stabilisers?

Prevention of mood swings and relapse.

Provide examples of Mood Stabiliser drugs.

Lithium, Valproate, Carbamazepine, and Lamotrigine.

What is the primary mechanism of action for Anticonvulsants?

Stabilise neuronal membranes; reduce excitatory transmission or enhance inhibitory signalling.

Which neurotransmitter systems are primarily targeted by Anticonvulsants?

GABA and Glutamate.

What are the core clinical effects of Anticonvulsants?

Seizure control and mood stabilisation.

Provide examples of Anticonvulsant drugs used in psychiatry.

Valproate, Carbamazepine, Lamotrigine, and Topiramate.

What is the primary mechanism of action for Psychostimulants?

Increase synaptic monoamines via release promotion and/or reuptake inhibition.

Which neurotransmitter systems are primarily targeted by Psychostimulants?

Dopamine and Noradrenaline.

What are the core clinical effects of Psychostimulants?

Increased alertness, attention, and executive function.

Provide examples of Psychostimulant drugs.

Methylphenidate, Dexamphetamine, and Lisdexamfetamine.

What is the primary mechanism of action for Dissociatives?

NMDA receptor antagonism leading to reduced excitatory neurotransmission.

Which neurotransmitter system is primary for Dissociatives?

Glutamate.

What are the core clinical effects of Dissociatives?

Dissociation, altered perception, and rapid antidepressant effects.

Provide examples of Dissociative drugs.

Ketamine, Esketamine, and Phencyclidine (PCP).

In terms of clinical implications, what usually appears before therapeutic benefits are realized?

Side effects.

What phrase describes the common patient experience during the early stages of psychotropic therapy?

" ""Worse before better""."

Why is the early stage of psychotropic therapy a challenge for patient management?

It creates hurdles regarding patient adherence, expectations, and establishing trust in the therapy.

What are the three direct functions of Pharmacists regarding psychotropics?

1. Translators of complex pharmacological information.
   2. Managers of drug interactions and adverse effect profiles.
   3. Support pillars for long-term adherence and medicine use.

What is the AMH safety warning regarding SSRIs and Suicidality?

Increased suicidal thoughts and behaviour can occur soon after starting antidepressants, particularly in young people; frequent monitoring is required early in treatment.

What are Common Adverse Effects (>1%) associated with SSRIs?

Nausea, diarrhoea, agitation, insomnia, drowsiness, tremor, dry mouth, dizziness, headache, sweating, weakness, anxiety, sexual dysfunction, rhinitis, myalgia, and rash.

What are Infrequent Adverse Effects (0.1–1%) associated with SSRIs?

Extrapyramidal reactions (tardive dyskinesia, dystonia), sedation, confusion, palpitations, tachycardia, hypotension, hyponatraemia (SIADH), and abnormal platelets/bleeding.

What are Rare Adverse Effects (<0.1%) associated with SSRIs?

Elevated liver enzymes, hepatitis, hepatic failure, hyperprolactinaemia, blood dyscrasias, akathisia, paraesthesia, and taste disturbance (especially paroxetine).

How does chemical structure influence drug behavior?

It directly dictates both pharmacokinetics (ADME) and pharmacodynamics (molecular targets).

What three things does chemical structure govern regarding a drug's journey to the brain?

1. ADME (Absorption, Distribution, Metabolism, Excretion).
   2. Successful reach to the brain.
   3. Molecular targets it can interact with inside the CNS.

What are the four chronological milestones a psychotropic drug must achieve to function successfully?

1. Survive formulation and administration (compound stability).
   2. Be absorbed and distributed (pharmacokinetics).
   3. Cross the blood–brain barrier (BBB) (pharmacokinetics).
   4. Interact with selected CNS targets (pharmacodynamics).

What is the primary function of the Blood–Brain Barrier (BBB)?

To protect the CNS from potentially harmful circulating substances.

What are the four key structural and functional features of the BBB?

1. Tight endothelial junctions.
   2. Low paracellular permeability.
   3. Active efflux transporters.
   4. High selectivity.

Describe Tight Junctions in the BBB.

Fused adjacent endothelial cells that physically seal the interendothelial cleft to eliminate paracellular permeability and establish a continuous vessel wall.

Describe Adherens Junctions in the BBB.

Situated below tight junctions, they mechanically anchor adjacent endothelial cells together to maintain overall junction integrity.

What is the mechanism of Efflux Transporters like P-glycoprotein at the BBB?

They act as active defense pumps that remove drug molecules from brain tissue and pump them back into circulation.

What is the clinical impact of Efflux Transporters at the BBB?

They reduce overall CNS drug concentrations and directly contribute to clinical treatment resistance.

What five physicochemical properties must be balanced and optimized in psychotropic drug design?

1. Lipophilicity
   2. Molecular size and shape
   3. Degree of ionisation
   4. Plasma protein binding
   5. Stereochemistry

What are the three primary effects of increasing the lipophilicity of a drug?

1. Increases Volume of Distribution (( V_{\text{D}} ))
   2. Improves passive membrane permeability
   3. Enhances blood–brain barrier (BBB) penetration

What are the risks associated with excessive lipophilicity in drug design?

1. Increases retention and duration of action in non-target peripheral organs
   2. Causes the molecule to become physically lodged inside the lipid bilayer
   3. Prolongs elimination half-life
   4. Raises overall toxicity risk and promotes fat accumulation (adipose deposition)

Why are CNS drugs typically small molecules?

Smaller molecules cross cellular membranes and navigate the blood–brain barrier with greater ease.

What three aspects of drug action are directly impacted by the shape of a molecule?

1. Exact receptor fit (lock-and-key model)
   2. Binding selectivity
   3. Likelihood of off-target binding

Most psychotropic medications are chemically classified as what?

Weak bases

How does the degree of ionisation affect a drug's behavior in vivo?

Unionised Drug Form: Promotes crossing of biological membranes.
Ionised Drug Form: Improves aqueous solubility.

What is considered the ideal outcome for the ionisation state of a CNS drug?

That the drug exists dynamically in equilibrium between both ionised and unionised forms in vivo.

Why are amine functional groups frequently incorporated into psychotropic drug structures?

To modulate ( \text{p}K_{\text{a}} ) and manipulate the ionisation state to balance solubility against membrane crossing.

List three examples of psychotropic drugs where ( \text{p}K_{\text{a}} ) and ionisation are critical to their function.

Any three of: Escitalopram, Amitriptyline, Levodopa, Metoclopramide, Cocaine, Ketamine, Psilocin.

What are enantiomers?

Mirror-image molecules that share an identical chemical formula but exist as distinct spatial formulations.

Despite having the same chemical formula, enantiomers can differ in what three clinical parameters?

1. Potency and specific receptor affinity
   2. Intrinsic efficacy
   3. Adverse effect profiles

In a racemic mixture like Citalopram, how do the two enantiomers functionally interact?

One enantiomer (often ( (S) )) drives the therapeutic benefit, while the opposing enantiomer (( (R) )) may contribute negligible benefit or disproportionately drive adverse effects.

Compare the potency of ( (S) )-citalopram and ( (R) )-citalopram.

( (S) )-citalopram is highly selective for the serotonin transporter (SERT), while ( (R) )-citalopram is 20-fold less potent and actually antagonises the positive actions of the ( (S) )-enantiomer.

What are the clinical benefits of Escitalopram (the pure ( (S) )-enantiomer) over the racemic mixture Citalopram?

Fewer side effects, improved response rates, and higher clinical remission rates.

How does acetylation change the properties of Morphine when it becomes Diacetylmorphine?

Acetylation of the hydroxyl groups enhances blood–brain barrier (BBB) permeability.

Why can Levodopa cross the blood–brain barrier while Dopamine cannot?

The addition of a carboxyl group to create Levodopa allows it to be actively transported across the BBB via amino acid transporters.

What structural change is used to create Haloperidol Decanoate, and what is the clinical result?

Esterification; it creates a highly lipophilic, long-acting injectable depot formulation.

How is Olanzapine Pamoate modified to achieve slow release?

Through salt formation, which produces a slow-release long-acting injectable antipsychotic.

What structural modification in Glycopyrrolate prevents it from crossing the BBB compared to Atropine?

Structural quaternization; it introduces a permanent charge, restricting its actions to peripheral tissues.

How does the structure of Lorazepam differ from Diazepam in terms of metabolism?

The inclusion of a hydroxyl group on lorazepam facilitates rapid conjugation and direct metabolism, shortening duration and removing active metabolites.

How is Lisdexamfetamine (a prodrug) converted into active amphetamine?

Amphetamine is covalently bound to the amino acid L-lysine; active amphetamine is slowly released only after enzymatic cleavage by red blood cells.

What are the four main pillars of protein targets that psychotropic drugs interact with?

1. Receptors
   2. Transporter Proteins (e.g., SERT, NAT, DAT)
   3. Ion Channels (e.g., ( \text{Na}^+ ), ( \text{Ca}^{2+} ))
   4. Enzymes (e.g., AChE, MAO, COX)

Contrast Direct Actions vs. Indirect Actions in neurotransmitter modification.

Direct: Drug acts as a key directly inside target receptors (e.g., \( \text{D}_2 \) antagonists).
Indirect: Drug alters the pool of endogenous neurotransmitter without directly targeting the receptor binding site (e.g., SSRIs blocking SERT).

Define Inverse Agonism in receptor interaction.

The drug binds to the receptor and shuts down baseline constitutive activity, inducing the exact opposite biological response.

What is Allosteric Modulation?

When a drug binds to a secondary site (separate from the orthosteric site) to either amplify (PAM) or dampen (NAM) the receptor's response to its natural ligand.

What are the two primary ways CNS medications indirectly increase chemical signals?

1. Blockade of Neurotransmitter Reuptake: Inhibiting transporter proteins (e.g., SSRIs).
   2. Blockade of Neurotransmitter Metabolism: Inhibiting metabolic enzymes (e.g., MAOIs, AChEi).

What are the three advantages of using indirect mechanisms for neurotransmitter modulation?

1. Preserves natural spatial and temporal patterns of neuronal signaling.
   2. Prevents extreme, artificial over-activation of target receptors.
   3. May significantly improve patient tolerability profiles.

"Differentiate between Highly Selective and Broad-Spectrum (""Dirty"") drugs. "

Highly Selective: Engage targeted receptors with precision (e.g., Escitalopram).
Broad-Spectrum: Bind indiscriminately across a wide array of receptor types (e.g., Amitriptyline).

Why does Amitriptyline cause more side effects than Escitalopram?

" Amitriptyline is a ""dirty"" drug that cross-reacts with histamine, muscarinic, and alpha receptors, while Escitalopram is engineered to precisely bind only the SERT transporter."

What is the chronological mismatch in the time course of receptor effects for antidepressants?

Receptor binding and transporter inhibition occur almost immediately, yet clinical improvements are characteristically delayed by weeks.

What is the underlying mechanism for the delay between drug administration and clinical benefit?

Therapeutic benefit requires down-stream, long-term neuroplastic adaptation changes in response to sustained receptor modulation.

What are the four core biological reasons side effects arise in psychotropic treatment?

1. Receptors are widely distributed across multiple anatomical brain regions.
   2. Target receptors are active in non-CNS systems (periphery).
   3. Drugs lack perfect, absolute selectivity for a single receptor type.
   4. Side effects can be a direct, unavoidable outcome of modulating the target receptor.