Lecture 1: Neuroanatomy & Neuropsychopharmacology

• Neuropsychopharmacology is

  • the study of the effects of drugs on the nervous system adn on psychological processes
• Clinical Neuropsychopharmacology

  • incorporates the study of drug treatment in a clinical population
• A drug is

  1. A substance used in the diagnosis, treatment, or prevention of a disease or as a component of a medication
  2. A substance recognised or defined by the Food and Drug Administration
  3. A chemical substance, such as a narcotic or hallucinogen, that effects the central nervous system, causing changes in behaviour and often addiction
• Herbal medicines are not classified as drugs, yet have similar effects as them
• Foods that alter neurotransmitter levels are not drugs but again can have similar effects as them (e.g. tryptophan makes serotonin - sesame seeds; dairy; turkey
• Is there a legal or commonly accepted definition of 'drug'?

  No
• For drug scheduling information and interactions:

  • MIMS = Monthly Index of Medical Specialties
  • Australian Register of Therapeutic Goods (ARTG)
  • Goodman and Gilman’s The Pharmacological Basis of Therapeutics Textbook
• Drug Information

  • USE (MAIN EFFECT): What disorder it is used to treat
  • CONTRAINDICATIONS: drugs or disorders that this drug should not be prescribed with/for.
  • PRECAUTIONS: take care when using drugs (e.g with alcohol use)
  • ADVERSE REACTIONS: unwanted effects
  • SIDE EFFECTS: unwanted effects for one treatment yet may be wanted for another (e.g. sedative effects of antihistamines, slow GIT motility with opiates)
  • INTERACTIONS: what drug interactions will occur
  • PACK: how the drug is packaged
  • DOSE: What dose to prescribe depending on what it is used to treat
• LD50: Dose at which 50% of ‘population’ found to be lethal

  • keep below this dose!!
• ED50: Dose at which 50% of ‘population’ found drug to be Effective

  • Therapeutic (intended) dosing
• Each drug has a ‘Therapeutic Index’ {Margin of Safety}

  • Difference between LD50 and ED50
  • Keep drug dosage between here
  • Dosage may differ btwn race, height/weight etc.
  • How you take it can change it too (intravenous, orally, etc)
• • Low Therapeutic Index - little margin for dosing, easier to overdose
• • High Therapeutic Index - large margin for dosing, difficult to harm patient
• Drug Potency - ability for drug to take effect (how much is needed)
• Drug Toxicity - potential to do irreversible harm to body functions

  • poisons or excessive amount of any substance
• • Dose on x axis
  • LD on y axis
  • Responding (how much better you feel) to treat different things = curve
  • A = analgesia
  • B = respiratory depression
  • C = death

   

  Interpretation

  • This drug is working very well for headaches. It can get dangerous but only in high dosages.
  • If you have someone with a headache, follow line A (e.g. ED50)
  • If you have someone with end stage cancer, you can push the dosage higher to alleviate pain (e.g. ED75)

  
• Occipital lobe: vision

  Cerebellum: coordination

  Parietal lobe: sensation

  Frontal lobe and motor cortex: movement

  Cingulate: judgement

  Hippocampus: memory

  Thalamus and brain stem/spinal cord: pain

  Nucleus accumbens: reward

  
• Two modes of communication between brain and body

  1. Peripheral Nervous System
  2. Hormones
• Peripheral Nervous System (PNS) includes

  • Somatic (sensorimotor) -> Gets sensory info in and motor output out
  • Autonomic (parasympathetic, sympathetic)
• Places that release hormones in brain

  • Hypothalamus
  • Pituitary
  • Pineal gland
• PNS is faster than hormones as PNS is through the nerves and hormones are through blood.

  The PNS has a smaller range of effect as it targets specific organs. Hormones have a larger range of effect as it goes wherever blood is in the body.
• • Cortisol as main stress hormone
  • Is is released by the adrenal glands on kidneys
• Peripheral (Autonomic) Nervous System

  • Sympathetic
  • Arousal
  • Fight, fright, flight, fornication (4Fs)
  • Involved in anxiety
  • Parasympathetic
  • Non-emergency things (slower)
  • Growing
  • Digesting food
  • Immune system regulation
  • Energy storage
• The sympathetic and parasympathetic systems within the PNS are parallel and both always on, but move at different speeds. Sympathetic = fast; Parasympathetic = slow
• To promote homeostasis and keep cells happy, you need:

  • Oxygen
  • Rid waste products (CO2)
  • Nutrients
  • pH range 7.2
  • Temperature 37.2 C
• Oxygen

  • Respiratory system
  • Cardiovascular

  Waste

  • Renal (kidney)
  • Gastrointestinal tract (GIT) / liver
  • Cardiovascular
  • Lymphatic system
  • Cerebrospinal fluid (CSF)
  • Respiratory

  Nutrients

  • GIT
  • Cardiovascular
  • Renal (kidney)

  pH

  • CV
  • GIT
  • Respiratory

  Temp

  • Skin (sweat)
  • CV
  • GIT

  
• What is pharmacokinetics?

  What happens to the drug once it has entered the body
• Drug effect is modulated by

  1. Absorption (bioavailability - routes of administration); how much of the drug is getting to where you want it to go
  2. Distribution - blood flow, tissue permeability
  3. Metabolism (biotransformation) - liver, enzymes in tissue (how it gets broken down)
  4. Excretion - kidneys, lungs
• A drug's half-life, which is the time it takes to remove half of the active drug amount, is affected by its absorption, distribution, metabolism, and excretion.
• Half-life example

  • If you have 100mg and half life of drug is 5 minutes, in 5 minutes time, you'll only have 50mg
• Pharmacokinetics determined by chemical properties of the drug

  (e.g. liphophilicity (soluble in lipids (fats) - all cell membranes)).
• Carbons and hydrogens in drugs love fats.

  • Drugs that are lipophilic (e.g. heroine) can cross the barriers (cell membranes) very quickly
• Drug Absorption = drug pass into blood circulation
• Bioavailability: fractional extent of drug which reaches its site of

  action (or biological fluid). Once at site of action, drug may work

  for mins or hours (depending on how well it binds and how

  much is given)
• Routes of drug administration/absorption

  1. Oral (p.o) - first pass metabolism (must pass through the liver)
  2. The liver has lots of enzymes to break drugs down. If you know a certain drug is very broken down by the liver and you need 50mg to feel better, you'd maybe prescribe 100mg
  3. Parenteral injection
  4. Subcutaneous (s.c)
  5. Intraperitoneal (i.p.)
  6. Intramuscular (i.m.)
  7. Intravenous (i.v.)
  8. Pulmonary absorption (inhalants)
  9. Topical applications - transdermal, eye - via mucous membranes
• Parenteral injection: administration of medications or substances directly into the body, typically bypassing the gastrointestinal tract.

  Oral administration: must pass through GI and liver
• Oral administration (Enteral)

  • Absorption pattern: variable
  • Most convenient, economical, *safe*
  • Need patient co-operation
  • Not use for drugs that are poorly soluble, slowly absorbed, unstable or extensively metabolised by the liver
  • Emesis due to irritation of gastric mucosa
  • Emesis = vomiting
  • Drug metabolised by gut enzymes or high acidity in gut
  • *enteric coating*
  • Helps drugs last longer - extended capsules e.g. panadol with plastic like coating releases drug slower
• Oral administration (Enteral)

  • Sublingual - good for high lipophilic drugs - dissolve quickly through mucosa (eg nitroglycerin) to vena cava (no first pass)
  • E.g. like listerine strips that stick under your tongue
  • Rectal (suppository) - 50% will bypass liver - very good when patient can not take drugs orally (vomiting, unconscious). Irregular absorption and many drugs irritate rectal mucosa
• Parenteral Injections

  1. Intravenous
  2. Subcutaneous
  3. Intramuscular
  4. Intraperitoneal
• Intravenous (directly into the bloodstream = stronger)

  • Limitations of absorption reduced
  • Immediate and accurate effects (emergency use)
  • Permits titration of dose
  • Increased risk of adverse effects and overdose