pharmacology

• pharmacokinetics


  what the body does to the drug
• pharmacodynamics


  what the drug does to the body
• how do drugs cross the cell membrane

  aqueous diffusion

  facilitated diffusion

  passive lipid diffusion

  active transport

  pinocytosis
• bioavailability


  the fraction of a dose reaching systemic circulation after administration compared to the same dose administered IV
• oral administration


  usually absorbed in the small intestine

  low lipid soluble and strong acid and bases usually absorbed poorly

  factors affecting absorption: GI motility, blood flow, particle size and formation, physicochemical factors
• iv administration 


  fastest route of administration

  iv administration - right heart - lungs - systemic circulation

  peace concentration influenced by rate of administration
• im administration


  variable absorption - blood flow, diffusion through tissues

  can be painful

  careful with injection sites in production animals

  aspirate before administration
• subcutaneous administration


  absorption may be slower than IM

  less painful then IM

  variability in species with amount of SC available

  injection site influences rate of absorption - temperature of skin, dehydration and shock
• inhalation route


  drugs that can be vaporised

  uptake into systemic circulation/ local effect
• factors affecting drug distribution

  protein binding

  tissue binding

  organ blood flow

  membrane permeability

  drug solubility
• drug distribution: protein binding

  plasma protein binding:

  albumin binds to weak acids

  a1 acid glycoprotein bind to weed bases

  if the patients blood albumin concentration is altered ie hypoalbunaemia = less albumin available for the drug to bind do - moe of the free fraction available to act on receptors
• drug clearance


  defined as the volume of plasma from which drug is completely absorbed per unit time
• half value


  time taken for the plasma concentration to fall to 50% of its initial value
• unless the medicine indicates a withdrawal period for the species concerned, this should be no less than

  7 days for egg and milk

  28 days for meat from poultry and mammals

  500 degree days for meat and fish
• can drugs not listed on the table of allowed substances commission regulation EU no 37/2010 be given to food producing animals

  no
• category a medicines


  avoid
• category b medicines


  restrict

  refers to quinolones, 3rd and 4th generation cephalosporins and polymyxins
• category c medicines


  caution

  covers antibiotics for which alternatives in human generally exist in the EU
• category d medicines


  prudence

  antibiotics that should be used as first line treatments
• what is responsible use of antimicrobials

  only use antibiotics if appropriate

  using the right antibiotic for illness

  use the correct dose for weight of animal

  complete the course

  do not use 3rd of 4th generation cephalosporins or fluoroquinolone as first line treatment where older antibiotics would work

  use antibiotics in accordance with label

  use as little as possible and as much as necessary

  use an antimocrobial under the cascade as an exception
• apart from the misuse of antimicrobials what else accelerates the emergence of drug resistance strains

  poor infection control practices

  inadequate sanitary conditions

  inappropriate food handling
• all resistance is 


  genetic
• what are the resistance mechanisms

  intrinsic resistance

  acquired resistance

  chromosomal resistance

  transferable resistance
• antihelmintic resistance is said to exist in a population of worms if more than what % of the worms survive treatment

  5%
• why is anthelmintic resistance important

  threatens the health and welfare of grazing livestock

  has significant economic consequences

  threatens food supply chains, of global significance

  reduces production efficiency, efficiency of utilisation of resources and sustainability
• hepatic metabolism 


  phase 1: converts drug to a more polar metabolite (hydrolytic, oxidative, reductive reactions)

  phase 2: conjugation with substance

  glucoronidation (not cats)

  acetylation (not dogs)
• how are drugs normally excreted

  kidney
• renal secretion


  active: tubular secretion

  passive: glomerular filtration
• ligand


  a substance that forms a complex with a biomolecule to form a biological substance
• receptors


  receptors are proteins interacting with extracellular physiological signals converting them to intracellular effects
• what are the molecular targets for drug action


  receptors

  enzymes

  ion channels

  transportes
• receptors


  agonist and antagonists
• ion channels


  agonists: increase or decrease opening permeability

  agonists: permanently block channel
• enzymes


  antagonist: inhibits normal reactions

  false substrate: fits in hole but not quite right - produces abnormal metabolite

  prodrug/agonist: produces active drug
• transporter


  agonist

  antagonist: blocks transport

  false substrate: abnormal compound accumulates
• receptor superfamilies


  ionotrophic (receptor operated channel) fast - eg nicotinic acetylcholine receptor

  metabotrophic (G-protein coupled) medium - eg histamine receptor

  tyrosine kinase receptor, medium - eg insulin receptor

  DNA-linked receptor (intracellular) - eg glucocorticoid receptor