| Question | Answer |
| What is a drug? | -natural or artificial
-if medicinal can be used as a substance to treat, prevent or diagnose a disease
-any chemical agent (other than food) |
| What is pharmacology? | -study of drugs or poisons |
| What is pharmacokinetics? | -study of what the body does to the drug
-movement in , through and out of body
-absorption, metabolism, distribution and excretion |
| What is pharmacodynamics? | -what the drug does to the body
-mode of action
-dose-response/effect relationship |
| Routes of administration two types? | -enteral-to do with the GI tract
-parenteral-other than GI |
| Enteral examples of administration? | -oral-OP
-rectal |
| Parenteral examples of administration? | -spinal
-IV, SC, IP, IM, IC
-intra-dermal (only goes into dermal layer of skin
- intra-arterial (joints)
-intra-osseous (into bone like tibia)
-epidural (into the small of the back) |
| Advantages of Oral administration? | -cheaper
-convenient for owner
-easy to administer
-safest option
-pain free
-no need for sterile equipment
-variety of dose forms
-systemic distribution |
| Disadvantages of Oral administration? | -absorption is varied
-gastric irritability in some causes vomiting
-not used if animal is vomiting or unconscious
-patient cooperation and unpleasant taste
-slow onset
-diluted
-may be destroyed by gastric pH, liver enzymes etc. |
| Rectal Administration? | -Suppositories
-suspension
-good for unconscious or vomiting animals
-can cause irritability to rectal mucosa
-often erratic and incomplete
-if inserted at the terminal end it by passes the portal vein and therefore the 1st part of metabolism |
| Topical Administration? | -to the surface of the mucous membranes or skin (transdermal) |
| Other Enteral Administration? | -endo/intra tracheal (inhalation)
-inhalation into the lungs
-intramammary-teats or udder |
| Parenteral Considerations? | -injection other than GI
considerations:
-volume to administer
-drug concentration
-tonicity
-pH
-viscosity
-particle size
-temp
-sterility
-adjuvants and vasoconstrictions |
| IV injection benefits and disadvantages? | -can deliver large doses
-can achieve high concentrations
-can titrate "to effect"
-100% bioavailable
-most hazardous
-applicable for some irritant ones
-not good for suspensions or oils
-use the smallest needle |
| SC and IM considerations? | -speed
-duration
-pain
-complications-swelling
-IM don't use unless necessary |
| Intra-dermal injections? | -allergy tests
-can only inject small volumes |
| Intra-osseous injections? | -direct into bone marrow
-give if cant use IV |
| Intra-cardiac? | -only use for emergencies, e.g. like adrenaline |
| Intra-articular? | -e.g. arthritis for horses
-morphine
-corticosteroids
-local anaesthesia
-(relates to joints) |
| Intra-peritoneal advantages? | -larger absorptive area
-better bloody supply than IM & SC
-in small animals can give crystalloids and anesthetic drugs through |
| Intra-peritoneal disadvantages? | -may cause peritonitis
-too much may restrict breathing
-potential for discomfort
-damage to organs by needles
-cant use for euthanasia |
| Epidural injections? | -can give local anesthesia or opioids like morphine
-space between L7-sacrum with no vertebrae |
| Spinal injections? | -injected into the cerebrospinal fluid
-local anesthetics and opioids
-smaller volume
-faster onset
-shorter duration |
| Other routes for injections? | -intra-tracheal-through tube, local or systemic effect like adrenaline
-inhalation-absorption through lungs, e.g. anti-asthmatics, inhalation anesthesia
-sublingual-under the tongue, not oral, goes into mucosal layer and directly into blood |
| Topical Administration? | -mucous membranes-local effects, ear nose eye, desensitization of laryx with lignocaine, vagine uterus or urethra
-skin/transdermal: ointment or lotion, local action, e.g. neomycin, transdermal-absorption through skin e.g. fentanyl patch, hormones |
| Drug absorption? | -movement of the drug from the site of administration to the body by blood, lymph or extra/intra cellular environment
-absorption rate constant (ka) is the amount of drug that is absorbed into the body as a set amount of time |
| Factors affecting rate of absorption? | -physiological-associated with route of administration
-for oral-membrane physiology and GI physiology
-factors associated with properties of drug-molecular weight, pH, solubility, ionization
-membrane permeability
-dosage form |
| More factors affecting rate of absorption? | -whether it goes into blood or lymph
-whether it is a weak acid (absorption best in stomach)or weak base (absorption best in intestine)
-oral-goes into blood and then portal vein or lymph (if lipid soluble) then to the liver where some/all metabolised |
| Rate of Absorption-parenteral? | depends on:
-condition of injected site
-degree of tissue perfusion
-properties of the drug-IM is quicker, ID-slower |
| Rate of Absorption-other routes? | -topical-less absorption-increases if broken
-rectal and sublingual-absorption fast due to vascularity mucosa |
| Passive diffusion?-drug transport | -goes down concentration gradient
-weak acids/bases are either ionized or non-ionized
-non ionized are lipid soluble and diffuse |
| Drug transport-facilitated diffusion and active transport? | -facilitated same as passive but with the help of a carrier protein
-active-needs help of carrier protein and ATP-as goes against concentration gradient, e.g. transport of drug to urine or transport of bile-drug |
| pinocytosis and phagocytosis-drug transport? | -engulf drug
-needs ATP |
| First Pass effect? | -intestine/hepatic metabolism when delivered by portal circulation
-greater-less drug that reaches systemic circulation |
| Drug Distribution? | -process by which it leaves injection site (parenteral) or liver (enteral) and circulates in body |
| Types of Drug Distribution? | -stays in vascular system-large or bound-plasma proteins
-distributed body water-small gases
-concentrates specific tissue-iodine thyroid
-throughout body/tissue-common, determined by ability to pass through membrane, highest in organs of elimination |
| What is drug distribution influenced by? | -local blood flow
-ability to bind to plasma/tissue proteins
-some can change their own distribution-anesthetics
-ability to cross biological membranes |
| Why do drugs bind to plasma proteins and what are the important ones? | Drugs bind to proteins to be transported and distributed.
-important ones: albumin, acid glycoproteins and beta globulins |
| Drug binding to Protein? | -reversible
-forms a reservoir (inactive)
-obeys law of mass action
-KD<1- high affinity
-KD>1-low affinity |
| Disease or pregnant patients in relation to protein bound drugs? | -need to adjust level of protein bound drugs due to changes in plasma protein levels |
| Overdose risk with drugs? | -too much free drugs, when they compete for the same plasma protein they displace each-other and re-bounce |
| Drug Elimination-2 processes? | -metabolism and excretion
-aim to increase their polarity (water solubility) as most are lipophilic-poorly excreted by kidney and liver |
| Organs involved in drug metabolism? | -liver
-small intestine
-kidneys
-skin
-lungs
-plasma
-other |
| Cytosol involved in drug metabolism? | -mitochondria
-lysosomes
-smooth ER |
| Phase 1 Metabolism?- drugs | -oxidation (with oxidases)
-reduction (with reductases)
-hydration (with hydrolases)
-polar drugs are excreted and non polar are made more polar
-reduces therapeutic activity of drugs-some still active, some toxic, pro-drugs bio-activated |
| Phase 2 Metabolism?- drugs | -involves transferase enzymes
-drugs undergo conjugation (ionized molecules added e.g. acetyl, methyl) to form a conjugate (polar molecule) which can then be excreted |
| Some drugs can alter their metabolism, how? | -by inhibiting or inducing enzyme synthesis
-so dose rates then need to be increased or decreased to maintain effective plasma concentrations. |
| factors that affect liver metabolism? | -age
-disease
-diet
-environment
-physiological status
-other drugs
-genetics
-route of administration |
| Metabolism & entero-hepatic circulation? | -metabolized drug is excreted in bile
-goes into intestinal lumen (where bacteria deconjugate it into a free drug)
-is re-absorbed across intestinal mucosa
-portal circulation goes back to liver
-this delays its elimination and it can accumulate |
| What does bioavailable mean? | -measure of drug absorption, the rate that it is taken up in an active form |
| Drug Secretion? | -urine (kidney,renal), active process
-bile (liver), active process
-other (saliva, tear, sweat), minor, passive diffusion
-lungs (for volatile drugs)
-excretion in milk (dairy animals) |
| Renal secretion? | -nephron
-glomerular filtration
-tubular secretion
-tubular reabsorption |
| Glomerular filtration? | -small molecules that dissolve in plasma water are excreted by passive elimination
-free drugs <20kDa are sieved in water, ionized or unionized
-plasma protein bound cannot be filtered |
| Tubular Secretion? | -active transport
-acid and basic carriers
-excreted by proximal tubule
-slower elimination
-competition between drugs for same transporters
-separate transport system for acids/bases
-acid-penicillin
-base-dopamine |
| Tubular Reabsorption-active? | -involves energy
-mainly occurs in the proximal tubule
-endogenous compounds-AA, glucose, Na, K
-renal tubule to the blood
-drugs-similar to AA are reabsorbed
-induces passive reabsorption of water |
| Tubular Reabsorption-passive? | -goes into blood
-down concentration gradient
-non ionized drugs and H20 reabsorbed
-ionizing stay in urine
-depends on pKa and pH
-elimination can be modified by urine pH
-e.g. phenobarbital elimination increased by alkalizing urine as pKa 7.2 |
| Excretion in bile? | -large polar molecules >300kDa
-as they cannot pass the membrane
-may enter entero-hepatic circulation
-good (dogs), moderate (cats), poor (humans) |
| Pharmacokinetic important parameters? | -bioavailability (F)-absorption
-volume of distribution (Vd)-distribution
-plasma half life (T1/2)-elimination
-clearance (CL)-elimination |
| Bioavailability? | -plots plasma concentration vs. time
-is the amount of dose that can reach the bloodstream and is physiologically active
-for IV is 100%
-for oral is % under curve compared to that under IV curve |
| Bioavailability example? | e.g. cyclosporine
bioavailable IV = 100%
bioavailable PO = 0.25/25%
so oral dose = 4 * IV dose |
| Factors influencing bioavailability? | -route of admin
-differences in species e.g. mono vs poly gastrics |
| Volume of Distribution? | -volume of fluid into which the drug is dispersed to the body at a uniform concentration
-fluids tissues-highly perfused by blood
-Vd = dose of drug/concentration of drug
small-high conc plasma retention
large-low conc plasma retention outside plasma |
| Vd examples? | Vd-3-restricted to plasma eg heparin
Vd-11-distributed in ECF but cant go into cells e.g. mannitol
Vd-42-penetrate most barriers, total water body both ECF and ICF e.g. alcohol
Vd>24-extensively stored in specific areas eg. chloroquine |
| Drug half life, what does this mean? | -time it takes for the amount of drug in the body to be reduced by half
-T 1/2 = 0.693/kei
-kei is elimination rate constant
-depends on Vd and CL
-dose does not change
-varies between individuals as each has their own T1/2 for each drug |
| What is body clearance? | -rate of elimination in relation to drug conc in plasma
=rate of elimination/concentration
-vol plasma cleared of drug/unit time
-factor influence-urine pH, diseases & plasma protein binding |
| Clinical Pharmacokinetics? | -studies time course of a drug concentration in the body
-drug conc can be measure in urine, plasma, cerebrospinal fluid etc.
-if know dose and conc, can measure the parameters |
| What is a steady state-drug? | -amount of drug entering body=to amount of drug leaving body
-steady after 4 half lives
-accumulates if not eliminated before next dose |
| Why do we need to know pharmacokinetic parameters? | -bioavailability-measures unchanged drug that goes to circulation
-Vd-measure amt of drug in body fluid
both determine dose size
-T 1/2- determines steady state and dosing interval
-CL- determines dose rate |
| Dosage form? | -formulation of the prepared drug |
| Dose? | -amt of drug given per time unit |
| daily dose? | -calculated from dose and no. per day |
| dosing rate? | -dose/time |
| dosage regimen? | -freq. drug doses including time period and intervals |
| Initial/loaded or priming dose | -large single dose before later smaller doses |
| Maintenance doses | smaller, equal doses given at intervals |
| prophylactic doses | given to prevent getting a disease |
| therapeutic doses | given after exposure to an illness |
| Pharmacodyamic considerations? | -mode of action (action site and mechanism)
-drug effect (final effect) |
| Why are we concerned about how drugs work? | -when applying QLD health drug and poisons regulations 1996
-to know adverse effects and contraindications
-approved uses |
| How do drugs work? | -non receptor-by its properties
-receptor-binds in or on cells
-by enzymes-target and blocks reactions |
| Non-receptor drugs method? | -chemical action e.g. antacids neutralize gastric acid secretion
-physical-osmosis (mannitol), purgatives, lubricant (paraffin), adsorbent (charcoal), demulcent |
| Receptor mediated drugs? | -bind to membrane receptors-on cell surfaces
-intracellular receptors-in nucleus or cytoplasmicorganelles
-receptors are molecules that bind to specific molecules (ligands)
-cellular receptors (membrane)
-nuclear receptors (intracellular) |
| Drug-Receptor interactions? | -lock and key
-depends on drug structure
-if weak-h bonds & van der waal-short acting
-if strong-covalent bonds-long acting |
| Examples of receptor drugs | -fentanyl-acts on membrane receptors
-local anesthetics-on ion channels
-erythromycin & aminoglycosides-on cytoplasmic structures
-steroids & thyroid hormones-on intracellular receptors |
| Enzyme drugs? | -inhibit enzymes and stop their biochemical processes
-aspirin stops prostaglandins act in inflammation |
| Drugs that inhibit carrier proteins? | -e.g. loop diuretics-furosemide inhibits on Na/K/Cl pump, causes loss of water and sodium and they are not reabsorbed |
| What are agonists? | -they bind to and activate receptors to cause an effect |
| What are antagonists? | -bind and block receptors from agonist activity |
| Competitive Antagonist? | -competes with the agonist/ligand for the same binding site, reversible if give a large dose of agonist |
| Non Competitive Antagonist? | -binds to a different site to the agonist and inhibits the biological function of the receptor, irreversible |
| Dose-response drug relationships? | -low dose-no response
-increase dose, increase response
-maximum response, when adding more dose has no effect
ED50-when drug produces 50% of its maximum effect
LD50-lethal dose that kills 50% population in a set time of exposure |
| Therapeutic Index? | -ratio between a dosage being lethal to being therapeutic
=TD50/ED50
-measures drug safety
-high ED, more safe |
| Variability in drug response? | 1. biological system (age, status, gender, weight etc.
2. drug & admin (route, dose, formulation, repeated-allergy,resistence)
3. drug interactions (chemical or physical, during metabolism, receptor level, excretion level, protein binding level) |
| Drug Classification? | -structure
-system it effects
-physiological effect
-pathological effect
-their use
-legislation |
