Pharm 2 Flashcards by Sarah Pratt

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

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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

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Factors Modifying Drug Dosage and Response

Animal - Individual

Genetic differences

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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

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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.

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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.

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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.

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Factors Modifying Drug Dosage and Response

Animal - Tempermant

Calm animals may need lower doses of CNS depressants than aggressive animals.

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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

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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

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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)

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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.

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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

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Factors Modifying Drug Dosage and Response

Animal - Species

Species differences

Anatomical. Physiological. Biochemical.

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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.

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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.

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Factors Modifying Drug Dosage and Response

Drug - Cumulation

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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

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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

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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

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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

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Summation

Potentiation

Synergism

Antagonism

Factors Modifying Drug Dosage and Response

Drug - Drug-Drug Interactions

Types of Drug-Drug Interactions - Summation

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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

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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

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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

Pharm 2 Flashcards

(40 cards)