Quiz One Flashcards
What are species differences that can effect drug response?
Different GI tracts (monogastric vs. ruminant)
Vomiting species vs. non-vomiting species
Drug metabolizing enzymes
Plasma protein binding
Effects of morphine in different species
What are some breed specific examples of how drugs can have different actions in the same species?
Collies are sensitive to Ivermectin
Boxers are sensitive to Phenothiazines
Australian Terriers are tolerant to Droperidol-fentanyl combo but are sensitive to its toxic effects
Why can drugs have different effects on individuals belonging to the same species and breed?
Individual genetics
How does body weight and composition affect drug dosage?
Dosages are calculated to the average adult individual; therefore obese, lean, or severely dehydrated patients require dosage modification
Compare and contrast pediatric vs. geriatric pharmacology
Pediatric: Decreased drug metabolism, drug excretion, BBB, increased total body H2O, decreased plasma protein binding, susceptible to adverse effects (yellow discoloration of teeth by tetracyclines, cartilage damage by fluoroquinolones, growth inhibition by glucocorticoids), antihistamines and barbiturates may cause hyperactivity, chronic phenobarbital therapy may effect learning and behavior
Geriatric: Decreased metabolism (P450 enzymes), decreased cardiac output, renal function, hepatic blood flow. Chronic diseases may be present, and changes in body composition may have occurred (increased amount of fat, decreased lean muscle mass, reduction of total body water, reduction of plasma albumin)
How does individual sex effect drug action and dosage?
Mature female animals generally have more fat than males
The repro cycle of male vs. female
Pregnancy/lactation
Differences in drug biotransformation
How can animal temperament affect drug efficacy?
Calm animals may need lower doses of CNS depressants than aggressive animals
What are idiosyncratic individual sensitivities?
Genetically determined unpredictable abnormal reactions
Less common than pharmacological adverse reactions
Can be very serious
Not dose dependent, drug withdrawal is therefore required
Common CS: fever, urticaria, anaphylaxis, organ toxicities
Mostly caused by reactive drug metabolites (RDMs) and the immune system
Give some examples of idiosyncratic individual sensitivities:
Enrofloxacin may cause retinal damage in some cats
Griseofulvin may cause liver damage in some cats
Captopril may cause renal disease in some dogs
What are drug allergies (hypersensitivities)?
Some drugs act as antigens
Prior exposure is necessary
Antigen-antibody reactions can cause allergy or anaphylaxis
Some drugs can act as haptens and cause hypersensitivity (penicillins, sulfonamides, aspirin, morphine, tubocurarine)
How can disease affect the efficacy of drugs?
Severe liver disease decreases drug metabolism
Severe kidney disease decreases renal excretion
Congestive heart failure decreases organ blood flow and renal excretion
What is drug tolerance?
An unusual resistance to the ordinary dose of a drug
Can be natural (ruminants to barbiturates), aquired (enzyme induction, increased excretion, down regulation of receptors), cross tolerance (thiopental in an animal under phenobarbital treatment), tachyphylaxis (acute acquired tolerance)
Compare and contrast IV vs. oral administration of a drug:
IV is faster with a short duration of action
Oral has a slower onset with a longer duration of action
Give some examples of how the route of administration can modify the effect of a drug:
Magnesium sulfate orally has a cathartic effect, intravenously it causes cardiac depression and muscle relaxation
Lidocaine locally is a local anesthetic, IV it is an antiarrhythmic
Give some examples of how the timing of administration can affect drug response:
When giving drugs orally, absorption is faster before meals than after
CNS stimulants may be more effective during the day
CNS depressants may be more effective at night
What is culmination?
When the rate of elimination is slower than the rate of absorption
Give an example of a desirable drug-drug interaction
Combined antihypertensive therapy (ACE inhibitor-thiazide diuretic)
Combined antimicrobial therapy (penicillin G-streptomycin)
Give an example of an undesirable drug-drug interaction:
Aminoglycoside antibiotic-aminoglycoside antibiotic
Undesirable drug-drug interactions are important in drugs that have narrow safety margins
What are the types of drug-drug interactions?
Summation (1+1=2) (ex. Two anticholinergics)
Potentiation (1+1>2) (ex. Epinephrine-procaine) (combined effect is greater than the sum of the two drugs acting independently)
Synergism (1+1>2) (ex. Neuroleptic-inhalation anesthetic) (the exaggeration of a drug by giving another drug with the same action)
Antagonism (administration of two drugs decreases the pharmacological response of the drugs)
What are the types of drug-drug antagonism?
Physical antagonism (activated charcoal)
Chemical antagonism (EDTA and lead)
Physiological antagonism (epinephrine and histamine)
Pharmacological antagonism
Competitive (atropine and acetylcholine)
Non-competitive (phenoxybenzamine and epinephrine)
What is the difference between pharmacodynamic and pharmacokinetic interactions?
Pharmacodynamic: two drugs act on the same receptors
Pharmacokinetic: alteration of absorption (calcium orally inhibits tetracyclines/fluoroquinolones), distribution, biotransformation (enzyme inducers such as phenobarbital can reduce the effect of other drugs, enzyme inhibitors such as chloramphenicol may increase the effect of other drugs), excretion (urinary alkalinizers enhance renal excretion of weak acidic drugs, urinary acidifiers can enhance excretion of weak basic drugs)
Give some examples of drug incompatibility:
Vitamin B complex with many antibiotics
Xylazine with thiopental
Tetracyclines with calcium
Sodium bicarbonate with epinephrine
What is drug disposition?
The study of the movement of drugs across body membranes from the time of absorption until elimination
What are the stages of drug disposition?
Absorption, distribution, biotransformation, excretion
Describe biological cell membranes
Composed of a lipid belayer, membranes have membrane carbohydrates and proteins, aqueous pores/junctions between cells
Describe passive diffusion and list the factors affecting it
Transmembrane and paracellular movement, simple diffusion
No energy required
Concentration gradient, degree of ionization (only non-ionized form can be lipid soluble), and lipid solubility affect it
What is the pKa of a drug?
The ph at which a weak electrolyte is 50% ionized and 50% non-ionized
True or false: a drug is more ionized in an opposite pH compared to it
True (ex. A weak acid is more ionized in an alkaline environment)
What is facilitated diffusion?
Carrier mediated transport that does not require energy
What is active transport?
When a substance moves against the concentration gradient
Requires energy
Carrier mediated transport
What is Pinocytosis?
A specific type of endocytosis where the cell engulfs the drug molecules dissolved in H2O
Is there absorption occurring when a drug is given IV?
No, it is already in the bloodstream.
Absorption is the transfer of the drug from the site of administration to the circulation.
What factors related to the drug affect absorption?
Molecular size (smaller=faster)
Lipid solubility (more lipid soluble=the greater the absorption)
Degree of ionization (the higher the ratio between N/I, the greater the absorption)
Dissolution of the drug in water (oral absorption of liquid drugs is faster than solids)
Small tablets are absorbed faster than big tablets
Route of administration (inhalation/sublingual>intramuscular>subcutaneous>oral)
What factors related to the animal affect drug absorption?
Blood flow (increased blood flow= greater absorption)
Heat or massage of IM injection increases blood flow and therefore absorption
Sympathetic stimulation increases blood flow to skeletal muscles but reduces it to the GIT/skin
Shock and edema decrease blood flow
Where is the main site of absorption for all drugs given orally?
Upper part of the SI (extensive surface area and rich blood supply)
Dependent on the rate of gastric emptying (faster=faster absorption)
What occurs during distribution of drugs?
The transport of drugs from the plasma to the tissues
Describe some examples of plasma protein binding
Acidic drugs bind mainly to albumin
Basic drugs bind mainly to acid alpha-1 glycoproteins and lipoproteins
Some drugs bind to globulin (ex. Steroids)
Generally reversible, prolongs the half-life of the drug, bound form is inactive, rate of bringing depends on the drug
List highly, moderately, and poorly perfused tissues
High: brain, liver, kidneys, endocrine glands
Moderate: muscle, skin
Poor: bone, adipose tissue
List some of the tissue barriers in the body
Brain (most effective) Eye Testicles Mammary gland Placenta (least effective)
What is biotransformation?
Chemical alteration of a drug molecule to prepare for excretion
Makes the molecule more water soluble, polar, and ionized, bioinactivation/detoxification
Occurs in the liver sER, liver hepatocyte cytoplasm/mitochondria, other tissues, and plasma
Explain phase I and phase II reactions of biotransformation:
Oxidation (most common phase I reaction)
Reduction
Hydrolysis
Conjugation (phase II)
What are some species differences that affect drug biotransformation?
Cats are deficient in glucuronyl transferases, hydroxylation, and dealkylation
Dogs lack acetylizing enzymes
Ruminants have less plasma pseudocholinesterase than horses, dogs, and cats
Ruminants and horses have high levels of oxidative enzymes
Equines are deficient in methylases
Pigs are deficient in sulfate conjugating enzymes
Birds lack oxidative enzymes
Fish have low levels of drug metabolizing enzymes
