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Disease and Defense Unit 1 > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is pharmacology?

A

Study of the interactions of drugs (chemical substances) with biological systems.

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2
Q

What are the therapeutic effects of drugs?

A

Prevention, diagnosis, treatment, or cure of a particular disease.

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3
Q

What is the pharmacotherapeutic triumvirate?

A

Right drug, right dose, right target.

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4
Q

What is Cp?

A

The plasma concentration (mg/L) of a particular drug, a function of dose, absorption, metabolism, excretion

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5
Q

Drug effects (therapeutic or toxic) are correlated to:

A

drug plasma concentration, Cp

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6
Q

MEC?

A

Minimum Effective Concentration (for both desired response and adverse response)

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7
Q

What is the therapeutic window?

A

Range of plasma concentration of a drug above MEC for response and below MEC for toxicity.

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8
Q

What is the lag period of a drug?

A

Time between administration of a dose of medicine and time when Cp reaches MEC.

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9
Q

What is the onset of effect?

A

Time to reach MEC

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10
Q

What is the Duration of action?

A

Time above MEC

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11
Q

What is steady state for pharmacotherapy?

A

Rate of drug administration [RATE IN] = rate of drug elimination [RATE OUT].
Multiple doses administered to reach and maintain Cp in therapeutic window.

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12
Q

What is the time to steady state?

A

4-5 half-lives when maintenance doses are administered at constant interval

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13
Q

What is steady state concentration?

A

Average Cp after steady state achieved

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14
Q

What is a dosage regimen?

A

Key element in pharmacotherapeutics, designed to ensure that the desired steady state drug level is maintained in the therapeutic window. Balances rate of drug elimination with prescribed rate of drug administration.

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15
Q

What are the five elements of a prescription?

A 
Drug
Dose
Route
Frequency
Duration
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16
Q

What are the four broad categories of critical knowledge about any drug?

A

Pharmacodynamics/Mechanism of Action
Pharmacokinetics
Therapeutic Uses
Adverse Drug Reactions/Side Effects/Drug-Drug Interactions

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17
Q

What are pharmacodynamics?

A

Most important basic science characteristic of a drug, its Mechanism of Action

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18
Q

Why is Mechanism of Action important?

A

Enables identification of a drug target in the body (site of action) and the identification of the therapeutic category of a specific drug.

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19
Q

What is a drug target?

A

Commonly a membrane or intracellular receptor, an enzyme in a critical biosynthetic pathway, or a membrane transport protein.

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20
Q

What can drugs do and not do?

A

Drugs either enhance or block a normal physiological pathway. Drugs do not have unique actions

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21
Q

Why learn physiology?

A

Aids in identifying potential drug targets for drug action, as well as how the target should be manipulated (enhanced or blocked) to treat a given disease.

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22
Q

What are pharmacokinetics?

A

The processes of drug absorption, distribution, and elimination - very important (but apparently under-appreciated) for designing dosage regimens.

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23
Q

What is bioavailability, F?

A

How much of a dose of drug reaches its target.

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24
Q

What is time to peak effect?

A

How fast a drug reaches its target to achieve Tmax or Cmax.

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25
Q

What is the Volume of Distribution Vd?

A

Volume of body compartment (L) (i.e., plasma, interstitial space, cellular space, combination) into which an administered drug is expected to dilute. Dose (mg) administered to obtain desired concentration (mg/L).

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26
Q

What is drug absorption?

A

Passage of drug from site of drug administration into blood.

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27
Q

What is drug distribution?

A

Movement of drug from bloodstream to tissues, where it can access targets for both therapeutic and side effects of the drug.

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28
Q

What are some considerations of drug distribution?

A

Drug-protein binding, passage across blood brain barrier or placenta, selective accumulation affecting drug efficacy or toxicity (lungs, bone, ear, kidney/urine, saliva, breast milk).

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29
Q

What is Route of Administration?

A

Site of application of a drug into or on the patient. Drugs are administered to obtain either systemic or topical (local) action.

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30
Q

What is drug elimination?

A

Refers to the elimination of drug activity following drug administration by the combined processes of metabolism and excretion.

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31
Q

What is clearance, CL?

A

Combined effects of drug metabolism and excretion.

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32
Q

Where are drugs metabolized?

A

Liver

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33
Q

Where are drugs excreted

A

Kidneys, in urine

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34
Q

What is a side effect?

A

Drug effect on a non-target system at therapeutic doses.

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35
Q

What are extension effects?

A

Drug effect on target at higher-than-therapeutic doses (dose-dependent and predictable).

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36
Q

What are idiosyncratic reactions?

A

Not predictable, varies person-to-person, can be immunologic (allergic rxn) or metabolic (hepatotoxicity).

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37
Q

Which side effects of a drug should you know?

A

Most common, most severe.

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38
Q

Federal government and drugs

A

1) Controls what drugs may be prescribed or sold directly to the public (FDA)
2) Evaluation process for safety and efficacy
3) Equivalency of brand name versus generic
4) Placement of drugs into prescription or non-prescription categories

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39
Q

State government and drugs

A

Controls who may prescribe drugs (licensing), except controlled substances requires registration with DEA

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40
Q

Local government and drugs

A

may pass laws, such as with medical marijuana in colorado

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41
Q

In case of conflict, which laws (federal, state, local) govern?

A

Strictest laws apply

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42
Q

What are the four basic drug categories?

A

Prescription
Controlled Substances
OTC
Dietary Supplements

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43
Q

What separates controlled substances from prescription drugs?

A

Higher potential for abuse.

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44
Q

What separates dietary supplements from OTC drugs?

A

Dietary supplements undergo no evaluation for safety or efficacy, make no health claims, all statements “not evaluated by the FDA”.

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45
Q

What happened to drugs in 1938?

A

The Food, Drug, and Cosmetic Act of 1938 (and Kefauver Amendments of 1962) requires that new drugs released since 1938 be evaluated for proof of efficacy and safety before marketing to public is allowed.

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46
Q

What is a drug?

A

A known molecular entity intended as a therapeutic agent to diagnose, treat, cure, or prevent disease.

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47
Q

What is a dietary supplement?

A

Defined as a product intended to supplement the diet that contains a vitamin, mineral, amino acid, or herb/botanical and is not represented as food.

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48
Q

Describe the Dietary Supplement Health and Education Act of 1994

A

Allows for dietary supplements to be sold to the public without prior evidence of safety and efficacy, though a reasonable expectation of safety under directed use is expected.

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49
Q

Why do drugs need a prescription?

A

Habit-forming or not safe to use without strict guidance from licensed practitioner due to toxicities, methods of use, etc.

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50
Q

Why might a drug be OTC rather than prescription?

A 
self-diagnosable/treatable
high safety profile
directions understood by ordinary (non-clinical) person
method of use not difficult
benefits outweigh risks
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51
Q

What act controls the manufacture and distribution of depressant and stimulant drugs?

A

Controlled Substances Act of 1970

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52
Q

What defines a Schedule I drug?

A

High abuse potential, no currently accepted medical use (opiates, heroin, hallucinogenic substances, some depressants and stimulants)

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53
Q

What defines a Schedule II drug?

A

High abuse potential, but accepted medical use (opioid analgesics, hydrocodone +non-opioids, some stimulants (methamphetamine and cocaine!), some barbiturates (pentobarbital))

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54
Q

What defines a Schedule III drug?

A

Moderate abuse potential, accepted medical use. Abuse may lead to moderate or low physical dependence or high psychological dependence (codeine + non-opioids, some stimulants, some depressants, anabolic steroids)

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55
Q

What defines a Schedule IV drug?

A

Low potential for abuse, accepted medical use. Abuse may lead to limited physical or psychological dependence (some depressants, some stimulants, benzodiazepines, nonbenzodiazepine hypnotic agents)

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56
Q

What defines a Schedule V drug?

A

Little potential for abuse (less than Schedule IV), accepted medical use. Can be obtained without a prescription in some states, treated like Schedule III-IV in Colorado

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57
Q

How do you prescribe Schedule I drugs?

A

You can’t (legally).

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58
Q

How do you prescribe Schedule II drugs?

A

Must be in ink in prescriber’s handwriting, cannot be telephoned to pharmacist and cannot be refilled (emergency provisions exist)

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59
Q

What about decimal points in dosage amounts?

A

Always lead, never trail with a zero, i.e.,
2 not 2.0
0.2 not .2

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60
Q

How many grains in a gram?

A

15.43

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61
Q

How many grams in an ounce?

A

28.35 (30)

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62
Q

How many mL per drop?

A

0.05

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63
Q

What determines therapeutic or toxic drug affect?

A

Cp

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64
Q

What is pharmacokinetics concerned with?

A

Absorption, distribution, and elimination (metabolism and excretion) of drugs.

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65
Q

What is an LD?

A

Loading Dose, a single dose designed to reach a specified Cp

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66
Q

What is MD

A

Maintenance Doses, multiple doses designed to maintain a specified average plasma level at steady state

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67
Q

What is drug absorption?

A

Movement of a drug compound from the site of administration into the plasma compartment.

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68
Q

What is F?

A

Bioavailability, the extent of absorption from non-intravenous site of administration.

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69
Q

What is bioavailability used for?

A

Convert oral doses to intravenous doses and vice-versa

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70
Q

What is drug distribution?

A

Movement of drug from the plasma compartment to site of action, or target

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71
Q

What is Vd?

A

Volume of distribution, describes extent of movement of drug throughout various body compartments, used to convert a drug dose to a concentration (dilution factor)

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72
Q

What is drug elimination?

A

Metabolism and excretion of parent drug or drug activity from the plasma compartment

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73
Q

What is CL?

A

Clearance, measure of ability of body to remove drug from plasma compartment, related to elimination rate constant ke

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74
Q

What is Clearance used for?

A

Determine interval between doses necessary to maintain

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75
Q

What is the time to reach Cpss

A

4-5 half-lives

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76
Q

What is the time to eliminate a drug from plasma

A

4-5 half-lives

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77
Q

How are drugs metabolized?

A

Mostly by post-administration enzyme-catalyzed chemical structure transformation.

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78
Q

What is biotransformation?

A

Drug metabolism

79
Q

How long would drugs take to be excreted through renal function only?

A

Days to weeks, as urine formation is ~1mL/min

80
Q

What is the normal rate of urine formation?

A

About 1 mL per minute

81
Q

What is the primary organ of drug metabolism?

A

Liver

82
Q

What tissues other than the liver participate in drug metabolism?

A

Lung (30%), kidney (8%), Intestine (6%), placenta (5%), skin (1%), and gut bacteria

83
Q

What is the most frequent pathway of drug metabolism?

A

Oxidation

84
Q

Where exactly is drug metabolism frequently catalyzed?

A

Membrane-bound enzymes of the smooth endoplasmic reticulum, sometimes soluble enzymes in cytosol.

85
Q

Which type of enzymes often catalyze drug metabolism?

A

CYP450 enzymes

86
Q

What happens to lipid-soluble drugs during metabolism?

A

Generally converted to more water-soluble (polar) compounds for easier excretion.

87
Q

Describe Phase I and Phase II biotransformations

A

Phase I - Oxidation, reduction, or hydrolysis. Insert or unmask a functional group (-OH, -NH2, -SH) that renders the molecule more water soluble and prepare for Phase II reaction

Phase II - Endogenous substrate combines with pre-existing or metabolically inserted functional group (from Phase I rxn) to form a highly polar (water-soluble) conjugate that is readily excreted in the urine.

88
Q

What is the order of Phase I and Phase II biotransformations?

A

Phase II rxns can sometimes precede Phase I rxns. Phase II rxns can sometimes be sufficient to excrete a drug.
Some drugs bypass Phase I and Phase II completely, perhaps because they are already sufficiently water-soluble to be excreted.

89
Q

What other molecules “help” CYP450 in drug oxidation?

A

cofactor NADPH
flavoprotein NADPH-cytochrome P450 reductase
molecular oxygen

90
Q

What type of process is drug metabolization, overall?

A

Detoxifying, i.e., forming readily excretable, pharmacologically inactive metabolites

91
Q

Beyond metabolizing drugs to a less active or inactive form, what other metabolic outcomes exist?

A

Metabolize an active drug to a more active drug:
(codeine -> morphine, hydrocodone -> hydromorphone)
Metabolize a prodrug to an active drug:
(Omeprazole -> a Sulfenamide, Enalapril -> Enalaprilat, Valacyclovir -> Acyclovir)
Metabolize to a toxic metabolite (rare):
(Acetaminophen -> N-Acetyl-benzoquinoneimine (hepatotoxic))
Any combination of the above!

92
Q

What factors influence drug metabolism?

A 
Diet/nutritional factors
sex differences
Age
Genetics
Disease states
93
Q

How do diet and nutritional factors affect drug metabolism?

A

Not well known in humans:
High protein : carbohydrate diet stimulates oxidase (CYP)
Malnutrition has complex influence (generally decrease)
Inducers present in charbroiled food

94
Q

How does sex influence drug metabolism?

A

Not well studied, significant differences possible

95
Q

How does age influence drug metabolism?

A

Perinatal - some enzyme systems not well-developed at birth, deficient glucuronidation -> gray baby syndrome after chloramphenicol administration

Neonatal - most metabolic pathways open, but lower rates than adults. Glucoronidation still deficient -> gray baby syndrome. After 2 weeks of life, both phase I and phase II enzymes begin to mature

Old age - Not well-studied, but decrease drug metabolism (CYP) due to decreased liver mass and decreased blood flow to liver

96
Q

Describe gray baby syndrome

A

Side effect in newborn infants of IV chloramphenicol administration. This condition is due to a lack of glucuronidation reactions occurring in the baby, thus leading to an accumulation of toxic chloramphenicol metabolites.

97
Q

What is chloramphenicol?

A

Broad spectrum antibiotic (gram negative and positive, anaerobic bacteria) used widely in developing world

98
Q

How do genetic factors influence drug metabolism?

A

Under/over-expression of metabolic enzymes, such as with CYP2D6, CYP2C9, etc

99
Q

Discuss CYP2D6

A

Key enzyme converting codeine to morphine in vivo. Under- or overexpression of CYP2D6 leads to variable analgesic effect of codeine

100
Q

Discuss CYP2C9

A

Key enzyme in Warfarin pathway (Vitamin K agonist), bleeding problems

101
Q

How do disease states influence drug metabolism?

A

May require dosage adjustment or avoidance
Hepatic diseases - reduced metabolism
Non-hepatic diseases - reduction in drug metabolism with some disorders (hyperthyroidism, pituitary insufficiency, tumors, diabetes, id, inflammation)

102
Q

How does alcohol consumption influence drug metabolism?

A

Complex:
Acute alcohol exposure -> competitive inhibition
Chronic exposure w/o hepatocellular damage ->induction of some microsomal biotransformations (CYP2E1)
Alcoholic cirrhosis -> decrease in metabolism

103
Q

Discuss P-Glycoproteins in Drug Elimination

A

“Permeability” glycoproteins, located on membranes of intestinal, renal, and hepatic epithelial cells. Transporters that are members of the ABC (ATP Binding Casette) family. In the gut (entry site), they decrease absorption by returning molecules to the gut. In the kidney and liver (exit sites), they enhance elimination.

104
Q

Discuss P-glycoprotein inhibitors and inducers vis a vis Cp

A

Inhibitors => increase Cp

Inducer => decrease Cp

105
Q

Discuss P-glycoprotein and drug/drug interaction

A

If one drug is an inhibitor or inducer of p-glycoprotein, then it will modify the absorption/excretion of another drug. Much cross-over from CYP450 proteins.

106
Q

Which organ is most important for drug excretion?

A

Kidneys, especially for water-soluble and non-volatile compounds

107
Q

Discuss glomerular filtration and drug excretion

A

Clearance by filtration at rate of 120 mL/minute (yes, one-hundred twenty mils per minute)
Drugs smaller than albumin (69,000 daltons) will be filtered
Only free drug is filtered, NOT protein-bound drug

108
Q

What is the half-life of drugs cleared by glomerular filtration

A

One to four hours, slower if protein bound

109
Q

Discuss active tubular secretion and drug excretion

A

Direct transport from blood to urine, cleared at a rate of 120-600 mL/min
Occurs in the proximal tubule with drugs that are stronger acids and bases via fixed capacity (saturable) mechanisms
Plasma protein binding does not affect rate of secretion
Poorly developed process in neonates

110
Q

What is the half-life of drugs excreted via active tubular secretion?

A

1-2 hours, longer in neonates

111
Q

Give examples of drugs cleared via active tubular secretion

A

Acids: Penicillins, salicylate, diuretics
Bases: Morphine, catecholamines, histamine, hexamethonium, tolazoline

112
Q

Discuss tubular reabsorption and drug excretion

A

Water-soluble drugs less likely to be reabsorbed (across lipid membrane). Lipid-soluble, uncharged molecules are easily reabsorbed, passive diffusion occurs in the proximal and distal tubules. Diffusion of weak acids and bases is dependent upon urine pH (non-ionized form of molecule will cross membrane). Active reasbsorption important for endogenous compounds such as glucose and amino acids. Most drugs reduce active transport, rather than enhancing it.

113
Q

How are high molecular weight drugs excreted?

A

Often exreted into bile, but reabsorbed from the small intestine before elimination in urine (not feces)

114
Q

Discuss enterohepatic cycling

A

Drugs and drug metabolites are excreted by liver in bile, stored in gall bladder, subsequently released to small intestine. Possible bacterial enzyme activity, then reabsorption of drug back across gut lining, return to liver via superior mesenteric and portal veins.

115
Q

How does enterohepatic cycling affect drug half-life

A

Increases it

116
Q

What do antibiotics do to enterohepatic cycling

A

Antibiotics that reduce gut flora can decrease enterohepatic recycling, leading to decreased Cp. Potential drug-drug interaction issues

117
Q

Discuss drugs and breast milk

A

Most drugs do cross into breast milk, but at low levels (morphine conversion

118
Q

How to handle maternal drugs and breast feeding?

A

Decynchronization. Breast feed at end of dosing, or administer drug immediately after nursing. Administer a dose prior to infant’s longest sleep time. Short nursing periods -> increased fat milk content during feeding

119
Q

Drug considerations for breast feeding mothers

A

Select drugs that don’t pass into breast milk, drugs with rapid clearance (>0.3 L/hr/kg), drugs with high protein binding.
Avoid drugs that are lipid soluble, drugs contraindicated by AAP, drugs affecting synthesis.
Because milk is more acidic than plasma (pH 6.5 v 7.4), it accumulates basic compounds (opiate analgesics) via ion trapping.

120
Q

Discuss pulmonary excretion of drugs

A

Gases, alcohols, and volatile substances. Occurs via simple diffusion across lung epithelia, no specialized system. Clearance rate depends on respiratory rate.

121
Q

Discuss other drug excretion pathways

A

Sweat - skin reactions to ingested drugs
Saliva - drug “taste” after IV administration. Note that such drugs are then swallowed as an oral administration
Hair - excretion into hair responsible for cancer chemotherapy-induced hair loss

122
Q

What order of kinetics governs virtually all drug elimination?

A

First order kinetics - rate of elimination is proportional to Cp

123
Q

Why does drug elimination follow first order kinetics?

A

The major biological processes responsible for drug elimination in the liver and kidney are first order processes

124
Q

Recall the calculus of first order elimination

A

dC/dt = -kCp

Rearrange and integrate –> ln (Cp/Cp0) = -kt

125
Q

What does the slope of the plot of ln Cp vs time give?

A

Elimination rate constant, k (or ke)

126
Q

Formula to estimate remaining amount of drug as function of time and initial concentration?

A

C2 = C1 * exp(-kt)

127
Q

Formula to calculate drug half-life from ke?

A

t1/2 = ln(1/2)/ke or

t1/2 = 0.693/ke

128
Q

What does the elimination constant ke represent?

A

Fraction of drug leaving body per unit time vial all elimination processes.

129
Q

What is the formal definition of clearance?

A

Volume of plasma (Vd) which is comletely cleared of drug in a given period of time by the combined processes of excretion.

130
Q

What is the formula for calculating clearance?

A

CL = Vd * ke

131
Q

What is tau?

A

Dosage interval

132
Q

What is the relationship between maintenance dose, tau, clearance, and steady-state Cp?

A

MD/tau = CL * Cpss

133
Q

Discuss hepatic clearance

A

Varies with blood flow to liver, protein-drug binding, and intrinsic hepatic metabolic activity (remember co-administration of inducers and inhibitors)
If hepatic clearance is efficient, then blood flow to liver will influence clearance rate

134
Q

Discuss renal clearance

A

Varies with kidney function. Changes in renal function necessitate changes in dosage to prevent drug accumulation/depletion

135
Q

How can you calculate a loading dose (LD)?

A

LD = Cp0 * Vd

Loading dose in mg = desired Cp * volume of distribution

136
Q

Why not use a loading dose?

A

Transiently high Cp can be toxic during alpha phase, before drug distributes out of the plasma compartment

137
Q

Why is therapeutic window important for MD?

A

Narrow therapeutic window requires more frequent, smaller maintenance doses or even continuous IV loading. Wide therapeutic window allows for less frequent, larger MD.

138
Q

How should tau and t1/2 be related?

A

tau <= t1/2, i.e., time interval less than or equal to one half-life.

139
Q

For tau <= t1/2, how much will Cp fluctuate?

A

fluctuate less than 50% during interval, most common dosing regime

140
Q

How can plasma level fluctuations be modified?

A

slow down absorption via controlled or extended release preparations

141
Q

Zero order kinetics and drug elimination?

A

Rate of elimination is independent of Cp, indicates saturation of hepatic metabolic enzyme systems.

142
Q

Give some examples of drugs with zero order elimination kinetics.

A

At therapeutic doses: aspirin, phenytoin, ethanol

At toxic doses: many hepatically eliminated drugs

143
Q

Describe generalized scheme of drug action

A

Binding of Drug to Receptor -> Signal Transduction -> Amplification -> Physiological Response

144
Q

What type of transduction and amplification mechanisms exist?

A

Ligand-gated ion channels (fast, msec) - affect ion channels and change membrane potential

G-protein-coupled receptors (fast, sec) - produce 2nd messenters such as cAMP, cGMO, IP3

Kinase-linked receptors or hormone (nuclear receptors) (slow, hours) - change gene transcription and protein synthesis

145
Q

Describe the types of drug receptor molecules

A

Proteins > nucleic acids > membrane lipids

146
Q

Discuss proteins as drug binding sites

A

Majority of binding sites. Secondary and tertiary structures allow for greatest specificity of fit, as in hormone and neurotransmitter receptors, receptor of voltage-gated ion channels, enzymes, transport proteins, and structural proteins

147
Q

Name a transport protein target molecule

A

the Na+/K+/2Cl- cotransporter in the kidney

148
Q

Name a structural protein target molecule

A

tubulin

149
Q

Name an ion channel target molecule

A

nicotinic cholinergic, 5HT3 serotoninergic

150
Q

How is drug action selected?

A

Specificity of receptor, as determined by size, shape, electrical charge, binding affinity, etc.

151
Q

Discuss dobutamine

A

Interacts with Beta-1-adrenergic receptors on the heart, but has no effect on acetylcholine or adenosine receptors at normal therapeutic doses
Acts to increase heart rate in the same manner as endogenous ligand norepinephrine

152
Q

Pharmacologic agonists and antagonists?

A

Agonist drugs trigger a response in the absence, or in augmentation, of endogenous signalling compounds. Antagonists block endogenous signals by binding receptor without signal throughput or by binding endogenous molecule.
Antagonist drug has no effect if no endogenous molecule is present to block

153
Q

Metoprolol

A

Not an agonist, but lowers heart rate by blocking endogenous norepinephrine at Beta-1 adrenergic receptors

154
Q

What is the shape of a dose-response curve, and why?

A

Hyperbolic, response reaches saturation, levels out. Plot against log of dose gives sigmoidal curve. Read ED50 from dose-response curve, or read EC50 from concentration-response curve.

155
Q

What can be interpreted from the nearly linear portion of a dose-response curve plotted as function of log of dose?

A

Therapeutic range

156
Q

What is drug potency?

A

Refers to the concentration (EC50) or dose (ED50) required to produce 50% of that drug’s individual maximal effect

157
Q

Drug potency is a function of?

A

Affinity (Kd) to receptors and efficiency of this drug-receptor complex to generate a response

158
Q

What is the intrinsic efficacy of a drug?

A

Efficiency of a drug-receptor complex in generating or stifling a signalling response

159
Q

What is the most important determinant of a drug’s clinical utility?

A

Drug efficacy

160
Q

How are drug potencies compared?

A

Look at EC50 (ED50). Lower number implies higher potency, as half-max effect is achieved at lower Cp

161
Q

In choosing between 2 drugs, do you look at efficacy or potency?

A

Efficacy. Potency is more important for determining dose.

162
Q

For therapeutic purposes, how is potency expressed?

A

In terms of a particular therapeutic endpoint, as in, 20mg of lisinopril to lower BP by 10-15 mm Hg

163
Q

Two categories of antagonist drugs?

A

Receptor and non-receptor

164
Q

Where do nonreceptor antagonist drugs bind?

A

A different receptor than the receptor responsible for the effect we would like to block

165
Q

Where do chemical antagonist drugs bind?

A

Bind the agonist molecule directly, prevent endogenous binding

166
Q

Give some examples of chemical antagonist drugs

A

EDTA (chelating agent) binds lead ions
Antacid bases neutralizing excessive stomach acid
Osmotic diuretics
Protamine (positively charged molecule) countering the effects of heparin (negatively charged molecule)

167
Q

What is a quantal dose-response curve?

A

Used in evaluating risk vs benefit in a population. Give the population a dose of drug, measure the per cent of population demonstrating therapeutic effect. Increase dose, get a sigmoidal curve, read ED50. Also get LD 50 in non-human subject studies.

168
Q

How do you calculate the therapeutic index?

A

Therapeutic Index = LD50/ED50

169
Q

Distinguish quantal dose-response curve from graded dose-response curve.

A

quantal dose-response curve is the all-or-nothing action vs dose in a population, as opposed to amount of response in an individual with varying dose

170
Q

What is TD50?

A

Toxic Dose in 50% of population

171
Q

How does therapeutic index reflect drug safety?

A

Higher therapeutic index means much harder to go from therapeutic dose to lethal dose. Higher number is safer in clinical use.

172
Q

What is a standard therapeutic index?

A

Most drugs have TI greater than 10-20

173
Q

What is the standard safety margin?

A

Percent by which a dose that is effective in 99% of the population must be increased to cause death in 1% of the population.

174
Q

How do you calculate SSM

A

Standard safety margin = [(LD1/ED99) - 1] * 100

175
Q

How is SSM different from TI

A

Much more conservative, takes into account extremes of population response, rather than just midrange.

Also, if LD and ED curves overlap, TI will not show you the possible fatal consequences of a prescription.

176
Q

How are values for Cp MEC and Cp toxic selected?

A

Arbitrary, but most commonly ED99 and LD1, respectively

177
Q

Describe two extension effects

A

Insulin - lowers blood glucose for therapeutic effect, but causes hypoglycemia at toxic effect
Heparin - treat thromboembolic disorders at therapeutic effect, cause bleeding at toxic effect

178
Q

What is a side effect?

A

For a Cp within therapeutic window, a non-target response triggered by the same drug-receptor interaction responsible for therapeutic effect at target.

179
Q

Give and example of a side effect

A

Beta-adrenergic receptor antagonists lower blood pressure by action on the heart, but cause bronchospasm in the lungs.

180
Q

What is an idiosyncratic reaction to a drug?

A

Genetically determined abnormal response (unpredictable)

181
Q

Give an example of an idiosyncratic drug response

A

Prolonged muscle paralysis due to impaired metabolism of succinylcholine

182
Q

What is a drug allergy?

A

Adverse response of immunologic origin, unpredictable, severity is dose INDEPENDENT

183
Q

Example of drug allergy?

A

Penicillin-induced anaphylactic shock

184
Q

Describe drug categories for pregnancy

A

5 categories
A => safe
B/C/D => confusing, includes most drugs
X => proven teratogenic (i.e., thalidomide)

185
Q

Which patients are at high risk for drug-drug interactions?

A

Elderly
High-risk clinical situations
Patients with renal/hepatic disease
Patients with multiple prescribing physicians

186
Q

How can drugs interact?

A

Pharmacokinetically (i.e., enhanced/reduced absorption and excretion)
Pharmacodynamically (at the receptor level to change drug action)

187
Q

Give two examples of pharmaceutical interactions

A

Occurs when 2 (or more) drugs are mixed in the same IV fluids
Chemical inactivation or precipitation via pH changes or alteration of vehicle

188
Q

What is the most important determinant of poisoning outcomes?

A

Good supportive care. Optimal supportive care is essential until the toxin is eliminated.

189
Q

What is good supportive care?

A

Cardiopulmonary support and protection of airway
Assess electrolytes, acid-base balance, fluids
CNS precautions (seizures from hypoxia)
Renal function support

190
Q

Describe pharmacokinetic strategies for dealing with drug toxicity

A

Prevent or decrease absorption (decrease RATE IN)
Inhibit toxication
Enhance metabolism (detoxication)
Increase elimination of toxin (increase RATE OUT)

191
Q

Describe pharmacodynamic strategies for dealing with drug toxicity

A

“Antidotes”

192
Q

How to reduce absorption?

A

Emesis
Gastric Lavage
Chemical adsorption
Osmotic cathartics

193
Q

Discuss acetaminophen toxicity

A

Initially nausea, vomiting, diaphoresis, abdominal pain

24-48 hours -> hepatic damage

194
Q

Treatment for acetaminophen toxicity?

A

Activated charcoal initially pre-absorption

N-acetylcystein (Mucomyst) within 36 hours (10 hours most effective)

Disease and Defense Unit 1 (1 decks)

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