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Pharmacology

Pharmacology for Vet Techs

QuestionAnswer
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
Created by: sherloki