Basic Principles Flashcards by Marlon Turaja

Arranged according to decreasing order of strength:

Covalent bonds, Electrostatic bonds, Hydrophobic bonding

Covalent bonds-not reversible

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Actions of a drug on the body

Pharmacodynamics

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It is the most important limiting factor for permeation.

Important for the diffusion of weak acid and weak base

Lipid diffusion - concentration only not charged

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Heparin activates anti-thrombin III, monitor: aPTT - cannot cross the placenta. Antidote?

Protamine sulfate

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Aqueous solubility is ___ proportional to electrostatic charge - ionization, polarity

Directly proportional - increased aqueous solubility = increased clearance

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Aqueous diffusion-passive movement of non-protein bound drugs through small water-filled pores. Affected by what?

Drug concentration and charge

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Law that predicts the rate of movement of molecules across the barrier. Absorption is faster in organs with larger SA and with thinner membranes

Fick’s law of Diffusion

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Weak acid: what form is more water soluble and undergoes better clearance?

Unprotonated (A-) form - while protonated (HA) form is more lipid soluble and more likely to cross membrane

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Excretion of weak acid maybe accelerated by alkalinizing the urine using what?

Bicarbonate

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pH determines the fraction of drug molecules charged versus uncharged predicted using what equation?

Henderson - Hasselbach equation

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Actions of the body on the drug - concerned absorption, distribution, metabolism and elimination

Pharmacokinetics

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Substance that brings a change in biologic function through its chemical action

Drugs

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Transfer of a drug from site of administration to the bloodstream

Absorption

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Three factors affecting the drug absorption

Route of administration
Blood flow
Concentration

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Most common route of drug administration.

Oral route - absorption is slow and less complete

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drug administration bypasses the first-pass effect, except? Intravenous, Subcutaneous, buccal or rectal

Rectal /suppository route - partial avoidance not complete

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Slowest route of drug administration

Topical route - for local effect , absorption varies with the area of application and drug formulation

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Drug distribution depends on major factors

Size of organ
Blood flow
Solubility
Binding

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True/False: bound drugs can cross membranes and exert their effect.

False - bound drugs CANNOT cross membrane

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Movement of drug molecules into and within biologic environment

Permeation

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Refers to chemical alteration of the drug

Drug metabolism

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Weak base: what form is more lipid soluble and more likely to cross biological membranes?

Unprotonated (B) form

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For acute inflammation what type of topical agents were used?

Drying agents - tinctures, wet dressing and lotions

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Acidic drugs are bound to albumin while basic drugs are bound to ____

Orosomucoid

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Three metabolic fates that a drug may undergo:

1. Temination of drug action 2. Drug activation 3. Elimination without metabolism

Refers to termination if drug action

Drug elimination

Determines the duration of drug action

1. Dose administered | 2. Rate of elimination following the last dose

Refers to characteristic half-life of elimination, most common type of elimination

First-Order Elimination - rate if elimination is proportionate to the concentration, decreases exponentially over time

Refers to constant rate of elimination regardless of concentration

Zero - Order Elimination - concentration decreases linearly over time

Drugs that display zero order kinetics

Warfarin, heparin, aspirin, tolbutamide, phenytoin, ethanol, theophylline - WHAT PET

Specific molecules with which drugs interact to produce changes in the function of the system, most are proteins

Receptors

Causes downward shift of the DRC, not overcome by adding more agonist

Non-competitive or Irreversible antagonists

Drug reversibly leaves the bloodstream and enters the target organ

Distribution

Sigmoid curve, response of a particular receptor-effector system measured against increasing drug concentrations

Graded Dose-Response curve

Do not provoke a biological response by themselves, blocks drug response in the presence of an agonist

Antagonist

____ and ____ are derived from dose-response curve

Efficacy (Emax) and potency (EC50)

Interact directly with the drug being antagonized to remove it or prevent it from reaching its target

Chemical antagonists

Refers to concentration required to bind 50% of the receptors

Kd - the smaller the Kd, the greater the affinity of a drug for its receptor

Concentration of a drug wherein half of the maximal effect is achieved

EC50 - potency

Not governed by Fick's law of Diffusion and is capacity-limited

Transport by special carriers - availability of carriers

Capable of fully activating the effector system when it binds to the receptor

Full agonists - sufficiently high concentrations result in all the receptors achieving the activated state

Binds to a different receptor, producing an effect opposite to that produced by the drug it is antagonizing

Physiologic antagonist

It shifts DRCs to the right (increased ED50) but same maximal effect is reached

Competitive/Reversible antagonist - effects overcome by adding more agonist

Refers to rapidly diminishing responsiveness after administration of a drug

Tachyphylaxis

Drugs that display tachyphylaxis

Metoclopromide, ephedrine, dobutamine, LSD, calcitonin, nitroglycerin, nicotine, hydralazine, desmopressin

Refers continuous activation may lead to depletion of essential substrates

Tolerance

One that is infrequently observed in most patients, not predictable

Idiosyncratic drug response

Concentration of a drug at the receptor site

Effective drug concentration

Purely pharmacokinetic parameter with no direct physical equivalent

Volume of distribution - can be altered by liver and kidney disease

If low Vd = distribute in blood, then medium Vd means?

Distribute in extracellular space or body of water | While high Vd - distribute in tissues

Most important pharmacokinetic parameter to be considered in defining a rational steady state during dosage regimen

Clearance - depends on the drug and the condition of the organ of elimination

Condition in which average total amount of drug in the body does not change over multiple dosing intervals

Steady state - input rate=elimination rate

Constant for drugs following first-order kinetics

Half-life

Fraction of the administered dose that reaches the systemic circulation

Bioavailability

Plan for drug administration over a time period

Dosage regimen

Equal to rate of elimination at steady state, important to maintain concentration above minimum therapeutic level

Maintenance dose - Vd is not involved in calculating MD

Large Vd for a therapeutic concentration be achieved rapidly

Loading dose

Refers to the safe range between minimum therapeutic conc and the minimum toxic concentration of a drug

Therapeutic window

Equation to calculate for patient's creatinine clearance

Cockroft-Gault equation Clearance = [(140-age)xweight(kg)]/[72xserum creatinine(mg/dL)] Multiplied by 0.85 in females

Metabolism: what phase converts the parent drug to more polar or more reactive product by unmasking or inserting a polar functional group

Phase I reactions - example: oxidation, reduction, deamination, hydrolysis

Mixed-function oxidases, high conc in smooth endoplasmic reticulum of liver

CYP450

Metabolism: at what phase involve conjugation of subgroups to -OH, -NH2 and -SH functions on the drug molecule

Phase 2 reaction - glucuronate, acetate

Most important organ for drug metabolism

Liver

CYP450 inducers

Ethanol, barbiturates, phenytoin, rifampicin, griseofulvin, carbamazepine, st. Johns wort and smoking

CYP450 inhibitors

Isoniazid, sulfonamides, cimetidine, ketoconazole, erythromycin, grapefruit juice, ritonavir, amiodarone, quinidine and valproic acid

Administration of single doses of the agent up to the lethal level in at least 2species

Acute toxicity

Required for most agents, esp intended for chronic use

Subacute/Chronic toxicity

FDA drug category: safe for both pregnant human and animal studies

Class A

FDA drug category: positive evidence of human fetal risk, but benefit from use in pregnant women maybe acceptable despite the risk

Class D

Teratogen: Fetal renal damage

ACE inhibitors

SE: antiepileptic drugs

Neural tube defect

Causes fetal hydantoin syndrome

Phenytoin

Cause neonatal hypoglycemia

Oral hypoglycemic agents

Teratogen causes vaginal clear cell adenoCA

Diethylstilbestrol / DES

Teratogenic effect of alcohol

Fetal alcohol syndrome

Teratogen causes Ebstein's anomaly

Lithium

Teratogen causes craniofacial malformation

Isotretinoin

Teratogen causes congenital hypothyroidism

Iodide

Teratogen causes Mobius sequence

Misoprostol

Preclinical data collected up to the time of submission and detailed proposal for clinical trials

Investigational new drug (IND)

Produces less than the full effect, act as inhibitor in the presence of an agonist

Partial agonist

Teratogen causes tooth discoloration

Tetracycline

Teratogenic effect of Sulfonamides

Kernicterus

Penicillamine teratogenic effect

Cutis laxa

Topical preparation used for chronic inflammation

Lubricating agents - creams, ointments

Thalidomide teratogenic effect

Phocomelia

Teratogenic effect of warfarin at 1st tri

Chondrodysplasia

Refer to drug for a rare disease

Orphan drug

Standard in vitro test for mutagenicity, loss of this dependence signals mutation

Ames test - uses Salmonella

Teratogenic effect of Streptomycin

Ototoxicity

Teratogenic effect of smoking

IUGR

Phase: careful evaluation of dose-response relationship and pharmacokinetics among normal human (25-50)

Phase 1 trial

Postmarketing surveillance phase

Phase 4 trial

Teratogenic effect of warfarin at 2nd trimester

CNS malformations

Teratogenic effect of warfarin 3rd trimester

Bleeding diathesis

Refer to two related drugs showing comparable bioavailability and similar times to achieve peak blood concentrations

Bioequivalence

Phase: explore further the spectrum of beneficial actions of the new drug. Large design involving many patients (1000-5000)

Phase 3 trial

Request for approval of general marketing of new agent for prescription uses

New drug application (NDA)

Evaluation of drug to moderate number of patients (100-300)

Phase 2 trial

Warfarin inhibits vitamin K dependent factors synthesis, antidote would be Vitamin K, FFP. What will you monitor in the patient?

PT/INR - can cross the placenta

Maximal effect achievable with increasing concentration of a drug

Emax or efficacy

Excretion of weak base maybe accelerated by acidifying the urine using what?

Ammonium chloride

Preferred route for drugs that has unpleasant taste and for patients who are vomiting

Rectal or suppository route

Basic Principles Flashcards

(103 cards)