Pharm FINAL

RAHHHHH

List common symptoms of depression

-Presence of depressed mood

– Anhedonia

– Insomnia or hypersomnia

– Change in appetite or weight (>5%)

– Psychomotor retardation or agitation

– Low energy

– Poor concentration

– Thoughts of worthlessness or guilt

– Recurrent thoughts about death or suicide

Describe the first general theory of depression

Monamine Hypothesis: Depression results from reduced levels or impaired function of monoamine neurotransmitters (serotonin, dopamine, norepinephrine), leading to decreased monoaminergic signaling in the brain

• Antidepressants often work by increasing monoamine availability

Describe the second general theory of depression

Neurotrophic Hypothesis: Depression is caused by decreased brain-derived neurotrophic factor (BDNF) and dysregulated cortisol, leading to reduced neuroplasticity (learning capability), impaired synaptic maintenance, and decreased neuronal resilience

Recall the major classes of antidepressants

Monoamine oxidase inhibitors (MAOI)

Tricyclic antidepressants (TCA)

Selective serotonin reuptake inhibitors (SSRI)

Selective serotonin-norepinephrine reuptake inhibitors (SNRI)

Atypical antidepressants

Novel antidepressants

Which monamines come from the precursors Tyrosine vs tryptophan?

Tyrosine → dopamine → norepinephrine

Tryptophan → serotonin

Compare and contrast characteristics of depression and anxiety

• Depression: Characterized by persistent low mood, loss of interest or pleasure, low energy, feelings of hopelessness, and withdrawal from activities. It is often focused on the past or present and feels like emotional “shutdown.”

• Anxiety: Characterized by excessive fear, worry, and physiological arousal (like racing heart, tension, restlessness). It is typically focused on the future, involving anticipation of threat or danger.

Differentiate between types of anxiety disorders

Generalized Anxiety Disorder (GAD)

• Persistent, excessive worry about many different aspects of life that occurs most days for at least 6 months

Social Anxiety Disorder

• Intense fear of social or performance situations due to worry about embarrassment, judgment, or rejection

Panic Disorder

• Recurrent, unexpected panic attacks followed by ongoing fear of having more attacks

Specific Phobias: Flying, dentist, heights, blood

• Strong, irrational fear of a specific object or situation that leads to avoidance behavior

PTSD

• Anxiety disorder that develops after trauma and involves intrusive memories, avoidance, negative mood changes, and hyperarousal lasting over a month

Recall the major classes of anxiolytics

Fluoxetine (SSRI)

Venlafaxine (SNRI)

Buspirone (Azapirones)

Amitriptyline (Tricyclic)

Diazepam (Benzodiazepines)

Gabapentin (Antiepileptics)

Risperidone (Atypical Antipsychotics)

Mirtazapine (Alpha-2 antagonist)

Propranolol (Beta-blockers)

What are the positive symptoms of psychotic disorders?

An addition to perception

• Hallucinations, delusions, feelings of persecution, agitation, combativeness, hyperactivity 

What are the negative symptoms of psychotic disorders?

A subtraction to perception

• Diminished emotional expression, decreased motivation, reduced speech, diminished ability to experience happiness, diminished interest in social interactions

What are the cognitive symptoms of psychotic disorders?

Disorganized thinking; derailment/unconnected tangents, answers to questions do not relate to the question, speech is incomphrensible

Explain which dopaminergic pathways contribute to which psychotic symptoms

Mesocortical Tract

• Negative symptoms of schizophrenia

• cort = cut out = negative

Mesolimbic tract

• Positive and cognitive symptoms of schizophrenia

• limb sounds like lit = positive (and cognitive)

Nigrostriatal Tract

• Responsible for motor control

• We don’t try to target this, accidentally targeted with drugs that target the above two

• stri = stride = motor control

Tuberoinfundibular Tract

• Increased prolactin release associated with side effects of antipsychotics

• Antipsychotics increase prolactin release = many side-effects

• tube = boob = prolactin

Medullary-periventricular Tracts

• Change eating patterns, make patients gain weight

• vent = need snacks = eating patterns

Explain the primary mechanism of action of antipsychotics, including dopamine D₂ receptor blockade and the role of serotonin receptor antagonism

Most antipsychotics are dopamine receptor antagonists

• ↓ dopamine activity, especially in mesolimbic pathway → improves positive symptoms (hallucinations, delusions)

Serotonin (5-HT₂A) antagonism (mainly atypicals):

• Blocking 5-HT₂A → ↑ dopamine release in nigrostriatal pathway

• This helps reduce EPS (motor side effects)

• Also improves negative + cognitive symptoms

Explain typical antipsychotics in terms of what they treat and side effects

Treats: Treat positive symptoms

Side effects: High EPS risk, Low sedation, weight gain

• Why EPS?

  • Dopamine regulates motor control, antagonizing it leads to less motor control

Explain atypical antipsychotics in terms of what they treat and side effects

Treats: Treat positive + negative + cognitive symptoms

Side effects: Low EPS, High metabolic effects (weight gain, diabetes-like issues), sedation, hypotension

• IMPORTANT: Agranulocytosis can occur with weak D2 receptor antagonists and strong serotonin receptor antagonists like clozaine and olazapine

Identify the major adverse effects (and receptors responsible) of antipsychotics, including extrapyramidal symptoms and metabolic effects

D₂ Antagonism

• Nigrostriatal pathway → EPS

  • Acute dystonia (early, painful spasms)

  • Tardive dyskinesia (late, often irreversible)

• Tuberoinfundibular pathway → ↑ prolactin

  • Galactorrhea (milk production)

  • Breast swelling, endocrine disruption

• Mesolimbic → ↓ pleasure

• Mesocortical → worsens negative symptoms

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H₁ (Histamine) Antagonism

• Sedation

• Weight gain

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M₁ (Muscarinic) Antagonism

• “Dry” effects:

  • Dry mouth

  • Constipation

  • Blurred vision

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α₁ (Alpha-1 Adrenergic) Antagonism

• Vasodilation

• Postural hypotension

• Dizziness, fainting

Explain how typical antipsychotics reduce their symptoms

Reduce positive symptoms via strong D2 antagonism of overactive dopamine release in the mesolimbic tract

Explain how atypical antipsychotics reduce their symptoms

Reduce positive symptoms via weak/partial D2 antagonism of overactive dopamine release in the mesolimbic tract

Reduce negative symptoms via serotonin antagonism to increase the amount of dopamine in the mesocortical tract

Reduce cognitive symptoms via serotonin antagonism to increase the amount of dopamine which is a smooth movement regulator in the nigrostrital tract

Differentiate between general anesthesia, local anesthesia, and analgesia

General Anesthesia: Induces temporary unconsciousness and affects whole body

Local Anesthesia: Numbs a small, specific area

Analgesia: Acts as pain relief without losing consciousness or total sensation

Explain the primary goals of general anesthesia

• Analgesia: Loss of response to pain

• Amnesia: Loss of memory

• Immobility: Loss of motor, sensory, autonomic reflexes

• Unconsciousness: Loss of consciousness

• Skeletal muscle relaxation: Facilitates surgery

Explain the stages of anesthetic depth

Stage I (Analgesia): conscious, pain reduced, reflexes intact

Stage II (Excitement): unconscious but unstable, reflexes + movement + irregular breathing

Stage III (Surgical anesthesia): stable unconsciousness, reflexes gone, muscle relaxation, controlled breathing (goal stage)

Stage IV (Medullary depression): respiratory/cardiac failure, no reflexes, life-threatening overdose level

Explain blood:gas partition coefficient

Blood:Gas Partition Coefficient: How much anesthetic dissolves in blood vs stays in gas

• High: More soluble in blood, dissolves and less reaches brain

• Low: Less soluble in blood, more stays in blood as a gas and more reaches brain

Explain Minimal Alveolar Concentration (MAC)

Minimal Alveolar Concentration (MAC): % inhaled anesthetic needed to prevent movement/pain in 50% of patients

Explain how blood:gas partition coefficient and MAC relate to onset, recovery, and potency

• Onset & recovery:

  • Controlled by blood:gas coefficient

  • High: Less reaches the brain, onset is longer, faster recovery

  • Low: More reaches the brain, faster onset, slower recovery

• Potency:

  • Controlled by MAC

  • Low MAC = strong anesthetic (needs less drug)

  • High MAC = weaker anesthetic (needs more drug)

Differentiate between inhaled and intravenous anesthetics based on their mechanisms of action and pharmacokinetic properties.

• Inhaled anesthetics: act mainly by enhancing CNS inhibition (↑GABA, ↓excitatory signaling); given via lungs; onset/recovery depend on blood:gas solubility; eliminated mostly unchanged via exhalation

• IV anesthetics: directly act on CNS receptors (mainly ↑GABA); given IV for rapid brain delivery; duration depends on redistribution and metabolism (liver/plasma) rather than exhalation

Explain how intravenous anesthetics produce their effects, duration control, and time-sensitive half-time

IV anesthetics act directly on CNS receptors, inhibiting GABA-A receptors. This causes rapid loss of consciousness; effect is immediate because the drug goes straight to the brain via blood

• Duration control: Emergence is due to redistribution (brain → muscle → fat) + metabolism via liver

• Context-sensitive half-time:

  • Time for plasma concentration to drop by 50% after stopping an infusion

  • Increases with longer infusions because peripheral tissues (fat/muscle) become saturated and “leak” drug back into blood

  • So: short infusion = fast wake-up; long infusion = slower wake-up even for the same drug

Differentiate local anesthetics, neuromuscular junction blockers, and general anesthetics by their mechanisms and clinical effects

Local

• Mechanism: Block voltage-gated Na⁺ channels → prevent action potential propagation in peripheral nerves

• Clinical Effects: Cause localized loss of pain/sensation without affecting consciousness

NMJ:

• Mechanism: Block nicotinic ACh receptors at NMJ (either depolarizing or competitive antagonism) → prevent muscle contraction

• Clinical Effects: Cause skeletal muscle paralysis (no sedation, no analgesia)

General:

• Mechanism: Depress CNS activity (↑ GABA_A receptor activity, ↓ excitatory signaling) → global neuronal inhibition

• Clinical Effects: Cause unconsciousness, amnesia, analgesia, and muscle relaxation for surgery

Explain how local anesthetics block voltage-gated sodium channels to prevent action potential propagation and produce loss of sensation

• Bind and block voltage-gated Na⁺ channels in peripheral nerves

• Prevent Na⁺ influx → stop depolarization and action potential formation

• No signal propagation along pain fibers → loss of sensation

• Preferentially affect rapidly firing pain pathways first

Predict how drug properties and tissue conditions influence the onset, potency, and duration of local anesthetics.

• ↑ Lipid solubility → ↑ potency (better membrane penetration)

• ↑ Protein binding → ↑ duration (longer tissue retention)

• Basic tissue → faster onset/more effective

• Acidic tissue → slower/less effective

• Vasoconstrictors ↓ blood flow → prolong duration

Compare depolarizing and non-depolarizing neuromuscular junction blockers based on their actions at the NMJ

Depolarizing: Binds and activates ACh receptor, causing persistent depolarization, leading to muscle twitches then paralysis

Non-Depolarizing: binds and does not activate Ach receptor, prevents depolarization leading to flaccid paralysis

• Depolarizing = Short duration (rapid onset)

• Non-depolarizing = Long duration

• Neither provides sedation or analgesia

What are the mirtazapine sedation effects due to?

Increased norepinephrine/serotonin and antihistamine effects

What is the ion responsible for Benzodiazepin-induced neuronal inhibition?

Chloride

• Benzos increase GABA which allows more chloride to enter neurons, neurons fire less and anxiety/seizures/insomnia back off