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PSYD35H3 (12)
Chapter 1

Chapter 1 notes- detailed

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University of Toronto Scarborough
Nussbaum D

PSYD35- PSYCHOPHARMACOLOGY- A Primer of Drug Action, 12 Edition. (2010) CHAPTER 1 NOTES- Pharmacokinetics (ADME)  What body does to drug; 4 processes: absorption, distribution, metabolism, elimination  These processes together determine bioavailability of drug (of how much administered reaches target)  Understanding drug kinetics gives knowledge about dose, concentration at receptor, intensity of drug effect, and time course  Pharmacokinetics implies movement and time which are integral in distinguishing a drug from other related drugs  Sedative/AO drugs: Lorazepam (24h long acting) vs triazolam (6-8h short acting)  Drugs have: structural name (chemical structure in words); generic name; trade name (patent) DRUG ABSORPTION  Drug pass from world into bloodstream  Commonly admin 6 ways: Enteral (GI tract): Orally, Rectally Parenteral(non-GI): Injected, Inhaled (gas, vapour, particles in aerosol); skin, mucous membranes (nose, etc.) Oral Administration  Drug must be soluble to be effective—able to dissolve, not destroyed by gastric acid, enter intestine, go through lining and then finally enter the blood stream  Oral drugs as liquid absorb more rapidly than tablet form  If drug taken as solid form, rate it dissolves and chemistry limit rate of absorption  Prodrug: oral formulation has precursor, that undergoes chemical change (through metabolism) before become active (e.g., l-dopa to dopamine)  Tablet dissolvesmolecules carried to upper intestineabsorbed by passive diffusion (must be lipid soluble to some degree)  More fat soluble= greater absorption  ~75%+ drug orally is absorbed into blood ~1-3 h (exceptions are AD drug buspirone—rapidly broken down by enzyme which reduces absorption by over 90% (unless taken with grapefruit)  Oral disadvantages: vomiting, stomach distress, amount absorbed into blood can’t be accurately predicted, acids in stomach destroy some orally admin’d drugs (e.g., local anesthetics)  Rectal Administration: absorption is irregular, unpredictable, and may irritate rectum membranes---used if patient can’t swallow, unconscious, or vomiting  inhalation administration:  lung tissue has large surface area= rapid absorption to blood (seconds) drugs absorbed into lung capillaries are carried to pulmonary veins (during heart contraction- 02)left atrial sideaortaarteries into braind-02 is pumped to right atriumright ventriclepulmonary arteries to lungsco2 and d02 are exhaled and replaced with 02  drugs inhaled may have faster onset of effect than IV’d drugs Mucous Membranes Administration  Examples: nitroglyerine tablets dissolve under tongue are absorbed rapidly ( for heart problems); cocaine snorted—absorbed directly; nasal decongestants sprayed act/absorbed locally; nicotine gum/spray; caffeine gum; child opioid narcotic fentanyl (lollipop sucked); sublingual (under tongue) buprenorphine (opioid narcotic) and naloxone (opioid antagonist) for opioid dependency=Suboxone Skin Administration  Transdermal patches—continuous and controlled release  Examples: nicotine, fentanyl (chronic pain), nitroglycerine, estrogen…..  Slow continuous release over hours/days—minimizing side effects associated with rapid drugs Injection Administration  3 ways: IV (directly into vein); intramuscular (IM) ; subcutaneous (under skin)  IV: more prompt response than oral b/c faster absorption and more accurate dose drawbacks: rapid rate of absorption= limited time to react to OD or unexpected reaction; must use sterile techniques (hepatitis, AIDS); * drug can’t be recalled once admin’d  See page 12 for table of admin methods  IV Administration: injected directly into bloodstream, dosing extremely precise; also most dangerous (reactions, allergies); drugs must be completely solubilized to be IV’D, otherwise risk clotting  IM Administration: if injected into arm/thigh/but—absorbed more quickly than from stomach and more slowly than from IV  Rate of absorption varies depending on: blood flow to muscle, solubility of drug, volume of injection, and agent in which drug is dissolved in  Two types: 1) fairly rapid onset and short duration of action (admin’d in water) 2) slow onset and long duration admin’d in oily solution)  Subcutaneous Administration: rapid, rate depends on ease of blood vessel penetration and rate of blood through skin DRUG DISTRIBUTION  Drug absorbed in blood streamdistributed throughout bodyreach target site of action (receptors)  Most if the drug is found in areas that are remote to the drugs site of action (e.g., SSRI concentration in PNS is greater than CNS)  Once absorbed into bloodstream, rapidly distributed through whole circulatory system (~1min)  If taken orally: passes through GI lininglivercentre circulationheartthroughout body  Some occasions , drug-metabolizing enzymes in liver/GI reduce amount of drug that reaches bloodstream= FIRST PASS METABOLISM  Alcohol dehydrogenase, enzyme in GI and liver that metabolizes ethanol  If Injected: absorbed trans dermally/mucous membranesbypass intestinal absorptionenter veinscarried to right side of heartcirculates left side of heartaorta to brain and body  If Inhaled: absorbed from lungspulmonary veinleft side of heart brain Membranes that affect distribution  Cell membranes: phospholipid bilayer membrane with 2 polar heads outside and lipid chain (tail) inside that suspends large proteins Membranes consist of protein and fat; permeable to small lipid-soluble molecules but not to large Membranes are important for drug passage 1) from stomach/intestine to bloodstream; from fluid that surrounds tissue cells into the interior cell; from interior of cells back into the body water; kidneys back into bloodstream  Capillaries: drug leave bloodstream and exchanged b/w blood capillaries and body tissues  most drugs freely leave the blood though these pores in the capillary membranes, until concentration gradient is equalized  Pores in capillary membranes don’t permit large red blood cells and plasma proteins to leave blood stream—only drugs that readily penetrate capillary pores bind to proteins  BBB: capillary walls in brain don’t have pores—cells that make up capillary walls are tightly joined together and covered on outside by fatty barrier (glial sheath) To reach neuron: drug leaves capillaries and membranes of astrocytes-rate of passage into brain dependant on size of molecule and it’s lipid solubility (small= penetrate rapidly, such as O2)  Large molecules (GLU, aa, vitamins) carried by special transport systems e
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