Pharm 2 Flashcards
Factors Modifying Drug Dosage and Response
Animal - Species Examples x6
The digestive tract in ruminants and nonruminants.
Vomiting in vomiting species.
Urine pH in different species.
Drug-metabolizing enzymes.
Plasma protein binding.
Effects of morphine in different species
Factors Modifying Drug Dosage and Response
Animal - Breed Examples x3
Collies are sensitive to ivermectin
Boxers are sensitive to phenothiazines
Australian terriers are tolerant to droperidol-fentanyl combination but sensitive to its toxic effects
Factors Modifying Drug Dosage and Response
Animal - Individual
Genetic differences
Factors Modifying Drug Dosage and Response
Animal - Body Weight
Dosages are usually calculated to the average adult individual
Obese, lean, or severely dehydrated required dosage modification
Factors Modifying Drug Dosage and Response
Animal - Age - Pediatric pharmacology
Newborn - decreased drug metabolism, drug excretion, blood-brain barrier, plasma protein binding. - increased total body water.
- Susceptibility to certain adverse effects: Yellow discoloration of teeth by tetracyclines. Cartilage damage by fluoroquinolones. Growth inhibition by glucocorticoids.
- pharmacodynamic differences: antihistamines and barbiturates may cause hyperactivity in children. Chronic phenobarbital therapy can affect learning and behavior.
Factors Modifying Drug Dosage and Response
Animal - Age - Geriatric pharmacology
Decreased metabolism (P450 enzymes), cardiac output, renal function.
Reduced hepatic blood flow.
Chronic diseases.
Changes in body composition (increase distribution)
Reduction in lean body mass, total body water, plasma albumin.
Increased amount of body fat.
Factors Modifying Drug Dosage and Response
Animal - Sex
Generally mature females have more fat than males.
The reproductive cycle (eg. pregnancy, lactation) may modify drug response.
Differences in drug Biotransformation.
Factors Modifying Drug Dosage and Response
Animal - Tempermant
Calm animals may need lower doses of CNS depressants than aggressive animals.
Factors Modifying Drug Dosage and Response
Animal - Idiosyncrasy (individual sensitivity)
Idiosyncratic drug reactions are genetically determined unpredictable abnormal actions.
Are less common than pharmacological adverse reactions but they can be very serious.
Are not dose-dependent and require drug withdrawal.
Commonly seen as fever, urticaria, anaphylaxis, and hematological and organ toxicities.
Most are caused by reactive drug metabolites (RDMs) which bind to cellular macromolecules resulting in cellular damage and usually involve the immune system
Factors Modifying Drug Dosage and Response
Animal - Idiosyncrasy (individual sensitivity) Examples x3
Enroflaxacin may cause retinal damage in some cats
Griseofulvin may cause liver damage in some cats
Captopril may cause renal damage in some dogs
Factors Modifying Drug Dosage and Response
Animal - Hypersensitivity (drug allergy)
Some drugs act as antigens (eg. blood, plasma, protein hormones)
Prior exposure is necessary
Antigen-antibody reactions can cause allergy or anaphylaxis
Some drugs act as haptens and cause hypersensitivity reactions by interaction with the immune system (eg. penicillins, sulfonamides, aspirin, morphing, tubocurarine)
Factors Modifying Drug Dosage and Response
Animal - Disease Examples x3
Severe liver disease decreases drug metabolism.
Severe kidney disease and Congestive heart failure decrease renal excretion.
Factors Modifying Drug Dosage and Response
Animal - Tolerance x4
Can be defined as unusual resistance to the ordinary dose of the drug
Natural tolerance: eg. Ruminants to barbiturates
Acquired tolerance: enzyme induction (from repeated use). Increased excretion. Down-regulation of receptors (#/sensitivity of receptors decreases).
Cross-tolerance: eg. Thiopental in an animal under phenobarbital treatment.
Tachyphylaxis: acute acquired tolerance, eg. ephedrine
Factors Modifying Drug Dosage and Response
Animal - Species
Species differences
Anatomical. Physiological. Biochemical.
Factors Modifying Drug Dosage and Response
Drug - Route of Administration
Can modify the ONSET and DURATION of action
Ex. IV has RAPID onset and SHORT duration of action. Oral has SLOWER onset and LONGER duration of action.
Can modify the ACTION of the drug
Ex. Magnesium sulfate orally has a cathartic effect, and IV it causes cardiac depression and muscle relaxation.
Factors Modifying Drug Dosage and Response
Drug - Timing of Administration
For oral administration, absorption is faster before THAN after meals.
CNS stimulants may be more effective during the day and CNS depressants may be effective at night.
Factors Modifying Drug Dosage and Response
Drug - Cumulation
Occurs when the rate of elimination is SLOWER than the rate of absorption
Eg. Digitalis
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Is the administration of drugs concurrently or sequentially.
Can have beneficial drug interactions or undesirable drug interactions.
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Examples of Beneficial Drug Interactions
Combined anti hypertensive therapy:
- ACE inhibitor AND thiazide diuretic
Combined anti microbial therapy:
- Trimethoprim AND sulfonamides.
- Penicillin G AND Streptomycin.
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Examples of Undesirable Drug Interactions
Undesirable drug interactions are especially important in using drugs that have a narrow safety margin.
Eg. Oral anticoagulants, antiarrhythmics, cardiac glycosides, anti cancer drugs.
- Amino glycoside antibiotic AND amino glycoside antibiotic
- Amino glycoside antibiotic AND muscle relaxant
- Chloramphenicol AND phenobarbital
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions x4
Summation
Potentiation
Synergism
Antagonism
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Summation
Addition
The sum of the effects of the drugs (1+1=2)
- Two anticholinergics
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Potentiation
Intensification
The combined effect is greater than the sum of the two drugs acting independently (1+1>2)
- Probenicid AND Penicillin G
- Epinephrine AND procain
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Synergism
The exaggeration of the effect of a drug by giving another drug that has the SAME action (1+1>2)
- Neuroleptic AND inhalation anesthetic.
- Trimethoprim AND sulfonamide
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Antagonism
Administration of a drug results in decrease in the pharmacological response of another drug.
Types - Physical. Chemical. Physiological. Pharmacological.
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Antagonism
Physical
Based on physical property of drugs
Eg. Activated charcoal (absorbs alkaloids) in alkaloid all poisoning
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Antagonism
Chemical
The drug counters the effect of another by chemical reaction/neutralization (not binding toe the receptor)
Eg. - Antacids (Mg, Al, Ca)
- Chelatic agents in heavy metal poisoning
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Antagonism
Physiological/ Functional
Opposite effect of two drugs on same function
Ex. Two drugs act on two different receptors that have opposite actions
Eg. Epinephrine AND histamine.
- Glucagon AND insulin on blood sugar
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Antagonism
Pharmacological
Opposite effect of two drugs binding to same receptors that are COMPETITIVE or NON-COMPETITIVE.
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Antagonism
Pharmacological - Competitive
Equilibrium/REVERSIBLE: Competition between agonist and antagonist for SAME specific site or receptor with WEAK BONDS
The effect of antagonist can be overcome by increasing concentration of agonist.
Eg. Atropine AND acetylcholine
IRREVERSIBLE: Have affinity for same receptor sites and bind with irreversible COVALENT BONDS.
Effects cannot be overcome by increasing concentration of agonist.
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Types of Drug-Drug Interactions - Antagonism
Pharmacological - Non-Competitive
Binds to a site other than the agonist site.
Prevents the receptor activation by the agonist.
Eg. Phenoxybenzamine AND epinephrine
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Mechanisms of Drug-Drug Interactions
Pharmacodynamic
Pharmacokinetic
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Mechanisms of Drug-Drug Interactions - Pharmacodynamic
Two drugs act on the same receptors
Eg. Acetylcholine AND atropine on muscarinic receptors
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Mechanisms of Drug-Drug Interactions - Pharmacokinetic
Alteration of Absorption.
Alteration of Distribution.
Alteration of Biotransformation.
Alteration of Excretion.
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Mechanisms of Drug-Drug Interactions - Pharmacokinetic
Alteration of Absorption
Drugs may inhibit or enhance absorption of other drugs.
- Calcium given orally inhibits absorption of tetracyclines.
- Epinephrine subcutaneously inhibits systemic absorption of local anesthetics
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Mechanisms of Drug-Drug Interactions - Pharmacokinetic
Alteration of Distribution
STRONGLY bound drugs to plasma proteins (Eg. Phenylbutazone, aspirin) DISPLACE weakly bound drugs (Eg. Warfarin) INCREASING their effects
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Mechanisms of Drug-Drug Interactions - Pharmacokinetic
Alteration of Biotransformation
- Enzyme INDUCERS such as phenobarbital may DECREASE the effects of other drugs
- Enzyme INHIBITORS such as chloramphenicol maybe INCREASE the effects of other drugs
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Mechanisms of Drug-Drug Interactions - Pharmacokinetic
Alteration of Excretion
- Urinary ALKALINIZERS, such as sodium biocarbonate, enhance renal excretion of weak ACIDIC drugs (Eg. Phenobarbital, phenylbutazone or aspirin).
- Urinary ACIDIFIERS, such as ammonium chloride, enhance renal excretion of weak BASIC drugs (Eg. Strychnine, procaine or amphetamine)
- Probenicid inhibits tubular secretion of penicillin G by competing on the carrier molecule
Factors Modifying Drug Dosage and Response
Drug - Drug-Drug Interactions
Drug Incompatibility
Physical or Chemical interactions
Ex. Vitamin B complex with many solutions of antibiotics.
- Xylazine with thiopental
- Tetracyclines with calcium
- Sodium bicarbonate with epinephrine
Factors Modifying Drug Dosage and Response
Environment
Ambient temperature
Humidity
Oxygen
