Pharm Exam 1

Front 1

What is pharmacodynamics?

Back 1

the study of the biochemical and physiologic effects of drugs and their mechanisms of action

Front 2

What is pharmacokinetics?

Back 2

the way the body handles drug absorption, distribution, biotransformation, and excretion

Front 3

What are the 4 stages which all drugs go through when introduced into the body?

Back 3

absorption, distribution, metabolism, and excretion

Front 4

What is methenamine used to treat?

Back 4

UTIs, releases formaldehyde and acts through simple chemical interactions

Front 5

What is an electrostatic interaction?

Back 5

attraction between functional groups having opposite charges

Front 6

What is hydrogen bonding?

Back 6

hydrogen covalently bonded to an electronegative atom is attracted to another electronegative atom

Front 7

What molecules affect gene expression?

Back 7

corticosteroids, mineralocorticoids, sex steroids, Vitamin D, thyroid hormone, and P450 inducers

Front 8

What are the 2 major consequences of drugs which act through affecting the gene transcription of cells?

Back 8

1)the effects occur after a lag period of 30 minutes to several hours b/c of the time required for the synthesis of new proteins
2)effects persist for hours or days even after the hormone concentration has been reduced to 0 b/c new proteins that have been synthesized last until they are degraded

Front 9

What molecules act through protein tyrosine kinase signaling?

Back 9

insulin, epidermal growth factor, and platelet derived growth factor

Front 10

What is imatinib (gleevec)?

Back 10

a BCR-ABL tyrosine kinase inhibitor
-it is a type of signal transduction inhibitor
-sorafenib and sunitinib also inhibit several protein tyrosine kinases
-used to decreased the response to some of the growth factors which may be overstimulated in some cancers

Front 11

What molecules/drugs act through ligand gated channels?

Back 11

-nicotinic/ACh-->sodium channel
-GABA-->chloride channel
-benzodiazepines (eg diazepam)-->chloride
-barbiturates-->chloride

Front 12

What 2 compounds enhance the effects of GABA on it's receptor?

Back 12

benzodiazepines
phenobarbital

Front 13

What are the drugs and receptors that increase cAMP formation (Gs)?

Back 13

epinephrine (B1 and B2), norepinephrine (B1 and B2), isoproterenol (B1 and B2), dopamine (D1), dobutamine (B1), histamine (H2), FSH, glucagon, ACTH

Front 14

What 2 substances inhibit phosphodiesterase and subsequently increase cAMP levels?

Back 14

caffeine and theophylline

Front 15

What are some drugs and receptors that inhibit cAMP formation (Gi)?

Back 15

norepinephrine (alpha2), dopamine (D2), clonidine (alpha 2), ACh (M2), morphine, serotonin

Front 16

What are some Gq coupled receptors which act through IP3/DAG?

Back 16

-M1 and M3 muscarinic receptors (ACh)
-Alpha 1 receptors (NE, and phenylephrine)
-serotonin receptors

Front 17

Where does NO production occur and in response to what?

Back 17

in endothelial cells in response to activation of histamine or muscarinic receptors

Front 18

What does sildenafil (viagra) do?

Back 18

it inhibits the enzyme PDE V (which inactivates cGMP normally) which will increase its concentration and lead to increased vasodilation

Front 19

Name an alpha 1 antagonist?

Back 19

phentolamine

Front 20

Name a Beta 1 and 2 antagonist?

Back 20

propanolol

Front 21

What is the EC50 of a drug?

Back 21

the drug concentration at which the effect is 50% or half the maximal effect

Front 22

What is Kd?

Back 22

the drug concentration at which the receptor occupancy is half the maximal (or 50%)

Front 23

What is drug affinity?

Back 23

a measure of the propensity of a drug to BIND with a given receptor

-a drug with an affinity of 10^-7 has a greater affinity for a receptor than a drug with a Kd or 10^-6 M

Front 24

What is drug potency?

Back 24

a comparative expression relating to the dose required to produce a particular EFFECT of given intensity relative to a standard reference

-a drug that exerts 50% of its effect at lower concentrations (ED50) is more potent than one that exerts the same effect at higher concentrations

Front 25

What is drug efficacy?

Back 25

a biologic response resulting from the binding of a drug to its receptor
-a receptor antagonist has no efficacy b/c it does not directly provoke a biologic response, it does have potency tho (the smaller the dose needed to block a specific response the more potent the antagonist)
-this concept is synonymous with intrinsic activity of a drug

Front 26

What effect do competitive inhibitors have on Vmax and Km?

Back 26

-they decrease affinity (increase Km) and Vmax is unchanged

Front 27

What is threshold dose?

Back 27

a dose below which no response is observed

Front 28

What is the therapeutic ratio for humans?

Back 28

TR=TD50/ED50

where TD50 is the dose that is toxic to 50% of the population (humans)

Front 29

What is pharmacokinetic tolerance?

Back 29

the response to the drug is lessened b/c the drug induces enzymes responsible for its own metabolism
-AKA metabolic tolerance
ex: pentobarbital sleeping time is reduced in subjects pretreated with barbiturates for several days
-also, the dose of warfarin must be increased in pts. taking barbiturates or phenytoin b/c they induce enzymes that metabolize warfarin

Front 30

What is pharmacodynamic tolerance?

Back 30

tolerance develops at the cellular level
-may be due to changes in receptor number or function
-ex: continuous exposure to B-adrenergic agonists results in receptor downregulation and decreased responsiveness to the drug
-also, the dose of opioids (morphine) must be increased over time to obtain sufficient relief of pain

Front 31

What is tachyphylaxis?

Back 31

when there is a very rapid development of tolerance
-occurs with indirectly acting amines such as tyramine and amphetamine which exert their effects by releasing monoamines from the mobile pool
-if several doses are given over a short time, the monoamine pool is depleted reducing the response in successive doses

Front 32

What is desensitization?

Back 32

-it is a mechanism of drug tolerance
-refers to a process that occurs rapidly such as when exposure to an agonist results in the conversion of a channel to an altered state that remains closed (ex: succinylcholine)
-another type is when a receptor coupling element is phos. to an inactive form

Front 33

What is down-regulation?

Back 33

-a mechanism of drug tolerance
-refers to the process of ligand-induced endcytosis and degradation of receptors which decreases receptor number b/c the rate of degradation is enhanced w/o an increase in receptor synthesis
-in general, agonists cause a down-reg if admin. at high doses for prolonged periods

Front 34

What is physiologic tolerance?

Back 34

occurs when 2 agents that yield opposing physiologic effects are administered
-ex: histamine admin. w/NE they counteract each others effects

Front 35

What is competitive tolerance?

Back 35

occurs when a receptor antagonist is admin. w/an agonist
-ex: yohimbine (natural tx for impotence) may block the hypotensive effect of clonidine or methyldopa

Front 36

What is chemically induced increased drug activity?

Back 36

-admin. of a certain chemical can serve as an antagonist to a specific receptor target and this tends to cause an increase in the number of receptors (up-regulation)
-ex:admin. of general anesthetic halothane causes increase in catecholamine sensitivity
-ex: catecholamine sens. also enhanced in pts. admin. a B-adrenergic receptor antagonist

Front 37

What is surgically induced increased drug activity?

Back 37

a supersensitivity of postsynaptic receptors to agonists develops when the presynaptic nerve has been surgically destroyed or lesioned, resulting in a decrease in the amount of endogenous agonists and an increase in receptor # (denervation supersens)

Front 38

How does a deficiency in degrading enzymes lead to increased drug activity?

Back 38

-these deficiencies are typically generic in nature
-ex: there is an increased sensitivity to succinylcholine (sk. mm. relaxant) in pts. with abnormal serum cholinesterase
-ex: primaquine (anti-malarial drug) induces acute hemolytic anemia in pts. with G6PD deficiency

Front 39

How does competition for binding sites lead to increased drug activity?

Back 39

-drugs may displace one another from plasma albumin binding sites, enhancing the response to one agent
-ex: the dose of warfarin must be decreased in pts. taking phenytoin (anticonvulsant) which will displace warfarin from plasma albumin

Front 40

What is drug synergism?

Back 40

when the effect of the combination is larger than the sum of the two individual effects (ex: antihypertensive agents)

Front 41

What is drug potentiation?

Back 41

when one drug that does not have a specific effect increases the effect of another drug

Front 42

What does an "overextension" of the therapeutic effect of a drug refer to?

Back 42

we call is an overextension of the drug is a toxic rxn is mediated by the same "receptor-effector" mechanism
ex: excessive fall in BP by an antihypertensive drug

Front 43

What types of drugs have a higher likelihood of producing Hypersensitivity rxns?

Back 43

highly charged molecules (penicillin, heparin) and compounds with a long half-life (isoniazid, etc)

Front 44

Describe a Type I HS rxn.

Back 44

includes anaphylaxis, urticaria, and angiodema
-rxn is mediated by the synthesis of an Ab directed toward the allergen
-IgE molecules bind to blood basophils and tissue mast cells via Fc receptors for the Ab
-when the drug is introduced into the body it binds to IgE bound to the sensitized cells which causes release of inflamm. mediators (LTs, PGEs, histamine)

Front 45

How is a type I HS rxn treated?

Back 45

-immediate tx consists of an injection of epinephrine (0.5 mL of 1:1000 solution or 0.5 mg IV or IM)
-corticosteroids sometimes used
-EX: penicillin induced anaphylaxis

Front 46

Describe a type II HS rxn.

Back 46

-some AI syndromes can be induced by drugs
-damage usually mediated by IgM or IgG binding to cells or tissue which activates complement (these rxns usually subside w/in months after drug withdrawal)
-immunosuppressive therapy required only in unusually severe cases

Front 47

Describe a type III HS rxn.

Back 47

-mediated by immune complexes, also called serum sickness
-reactions usually last 6-12 days and subside once the agent is removed
-corticosteroids useful in treating severe cases
-several drugs including sulfonamides, penicillins, thiouracil, anticonvulsants, and iodides can induce immune vasculitis
-stevens-johnson syndrome is a more severe form of vasculitis caused by sulfonamides

Front 48

Describe type IV HS rxn.

Back 48

-cell-mediated or delayed HS often occurs when drugs are applied topically
-mediated by sensitized T-cells
-ex:poison ivy

Front 49

What is a drug idiosyncrasy?

Back 49

an abnormal response to a drug that is not immunologically mediated
-likely that these defects are all genetically determined abnormalities of enzymes and receptors
-often referred to as "pharmacogenetic disorder"

Front 50

Describe the examples of drug idiosyncrasies.

Back 50

1)Apnea caused by succinylcholine in pts. with abnormal serum cholinesterase (succinylcholine depolarizes motor end plate which causes paralysis and relax. of voluntary mm.), pts. with abnormal serum cholinesterase cannot destroy the drug and remain paralyzed for 4-8 hours instead of 30 mins.
2)fast and slow acetylation of isoniazid, slow have low hepatic-N-acetyltransferase and are more prone to isoniazid induced B6 defic. (anemia), fast more prone to hepatotox.
3)hemolytic anemia elicited by primaquine in pts. whose RBCs are deficient in G6PD, RBCs without this enzyme cannot regen. NADPH b/c they don't have G6PD which is a major regulatory site of the pentose phosphate pathway
4)Barbiturate induced porphyria in pts. with abnormal heme synthesis-barbituric acid mimics part of the heme structure thereby occupying a portion of the heme site on the protein that regulates production of ALA synthase (heme normally inhibits prod. of ALA synth), barbituric acid is a less effective repressor -->more poryphyrins produced

Front 51

What is the dibucaine number?

Back 51

a measure of the ability of a pt. to metabolize succinylcholine and can be used to identify at-risk pts.
-under standard test conditions, dibucaine inhibits the normal enzymes by 80% and the abnormal by only 20%
-this is not a routine clinical procedure however

Front 52

What is the incidence of a placebo response in most clinical trials?

Back 52

fairly constant between 20-40%
-this can complicate the evaluation of efficacy and toxicity in clinical trial

Front 53

What is a single-blind design study?

Back 53

-it involves the use of a placebo administered to the same subjects in a crossover design if possible or to a separate control group
-does not protect against observer bias b/c the clinical scientist knows which pts. are receiving test agent and which get the placebo

Front 54

What is a double-blind design study?

Back 54

neither the pt. nor the clinical scientist knows who is receiving the test agent
-protects against investigator and subject bias in the collection and eval. of data

Front 55

In what manner is L-DOPA transported into the CNS?

Back 55

via facilitated diffusion
-does not require energy, slower than active transport, and goes with the concentration gradient

Front 56

What form will predominate of an acidic drug in a weakly acidic medium?

Back 56

the less ionized form which means that it will be more lipid soluble and rapidly absorbed

Front 57

What will happen if a weakly basic drug diffuses into an acidic medium?

Back 57

it will become ionized and will accumulate in that environment (known as ion trapping)

Front 58

What 2 compounds will make the urine pH more alkaline?

Back 58

sodium bicarbonate
acetazolamide

Front 59

How can we acidify the urine?

Back 59

give ammonium chloride

Front 60

In what form are strong acids and strong bases in the body?

Back 60

they are ALWAYS IONIZED
-they are never lipid soluble and can not penetrate lipid membranes by passive diffusion

Front 61

What is bioavailability of a drug?

Back 61

the amount of active drug available in the bloodstream
-bioavailability is 100% for IV drugs
-calculated by dividing the AUC produced with any non-IV admin. by the AUC produced with IV admin.

Front 62

What is "first pass effect"?

Back 62

the initial metabolism of a drug while passing through the wall of the gut and liver
Example: Morphine by the oral route is absorbed completely but its bioavail. is only 33%. About 67% of morphine is extracted in the liver thus we say it has a significant first pass-effect or high extraction ratio
-this first pass effect can be eliminated to some extent by using routes other than oral

Front 63

How does gastric emptying time affect drug absorption?

Back 63

the longer the gastric emptying time, the more delayed absorption is b/c the drug resides for a longer time in the poor absorptive environment of the stomach before it reaches the intestine

Front 64

Describe subcutaneous absorption of drugs.

Back 64

usually occurs more slowly
-large volumes should not be admin. this way unless they contain hyaluronidase (an enzyme that facilitates their spread through the tissues)

Front 65

Describe absorption via intraperitoneal injection.

Back 65

-the peritoneal cavity has a large absorbing surface but drugs must first pass into the portal vein and therefore first pass metabolism is possible
-these are seldom used

Front 66

How is the volume (apparent) of distribution calculated?

Back 66

total amount of drug in the body/concentration in plasma
=Div/Co
Co=concentration of drug in plasma at time zero
Div=intravenous dose

Front 67

Describe the significance of Vd (volume of distribution).

Back 67

-the values for most drugs do not represent their actual distribution in the body fluid
-it is a conceptual figure
-drugs that distribute extensively or that bind extensively to peripheral tissues always show large Vd and vice versa
-low Vd would indicate that the drug is mostly present in the plasma
-drugs with very high plasma protein binding have low Vd

Front 68

Describe how fat can act as a reservoir for drugs.

Back 68

lipid soluble drugs will accumulate in the fat
-ex: obese individuals are harder to anesthetize b/c you must first saturate their fat store before circulating levels of the drug become significant

Front 69

What are the sites of drug exclusion?

Back 69

CSF, ocular fluid, endolymph fluid, fetal fluid, pleural fluid

Front 70

What kinds of drugs will accumulate in breast milk?

Back 70

-basic drugs b/c the milk is more acidic than plasma
-fat soluble drugs b/c of high lipid content of milk
-tetracyclines which chelate Ca will accumulate

Front 71

Describe the concept of redistribution.

Back 71

-several forms may occur but the most clinically relevant is observed with highly lipid-soluble agents
example: when thiopental is admin. IV, it is initially distributed to areas of highest blood flow such as brain, liver, and kidneys, after this the drug is redist. to and stored in mm. and fat which decreases plasma concentrations
-as the plasma level falls, the drug then diffuses out of the sites of initial accumulation decreasing the brain levels and terminating the clinical effect
-thiopental is a rapidly onset, short acting general anesthetic

Front 72

What are the 2 ways in which drug elimination from the body occurs?

Back 72

1)first order kinetics
2)zero order kinetics

Front 73

What is clearance of a drug?

Back 73

a measure of the capacity of the body to remove a drug
-systemic clearance is the sum of all clearances (renal+hepatic+lung+others)
-for most drugs the clearance is constant over the usual plasma concentration range (first order elim)

Front 74

How many half-lives does it take to reach a steady state condition and concentration (first order elim only)?

Back 74

about 5 half lives

Front 75

What percent of the steady-state drug concentration is achieved in 3.3 half-lives?

Back 75

90%

Front 76

Describe the plateau state of a steady state concentration for first order elimination drugs.

Back 76

-attained after 4-5 half lives
-time to plateau is independent of dose
-level of plateau is proportional to dose

Front 77

What will shortening the dosing interval do to the steady state concentration of a drug?

Back 77

it will increase it

Front 78

What is maintenance dose?

Back 78

the quantity of drug to be administered at selected intervals, or by continuous infusion, to produce steady state plasma levels
-alternate name for this concept is target concentration (TC)

Front 79

How is dosing rate calculated?

Back 79

it is equal to the elimination rate
CL*TC/F
F=bioavailability

Front 80

How is maintenance dose calculated?

Back 80

it is the dosing rate multiplied by the dosing interval
(CL*TC/F) X dosing interval

Front 81

How is loading dose calculated?

Back 81

Vd X TC
-used to achieve immediate therapeutic concentration

Front 82

Describe generic drugs.

Back 82

they contain the same active ingredients, different formulation, similar dissolution, similar AUC, and do have FDA approval, cost less

Front 83

What are the properties of most pharmacologically active drugs?

Back 83

-lipid soluble (can diffuse across lipid membranes)
-unionized or partially ionized at phys. pH
-strongly bound to plasma proteins and other tissues
-not readily excreted by the kidney
-tend to remain in the body for a long time unless liver metabolizes them and kidney excretes them

Front 84

Where is the most important biotransformation site?

Back 84

the liver
-but drugs can also be metabolized in the GI tract, intestinal wall, skin, lung, kidney, etc..

Front 85

What are the 2 classes of rxns in which all drug biotransformations are divided?

Back 85

1)Phase I reactions (modification of the molecule)
2)Phase II reactions (conjugation)

Front 86

Describe Phase I reactions.

Back 86

-they usually convert lipid-soluble parent compounds to more polar metabolites (that are less lipid soluble)
-these metabolites are often inactive and readily excreted
-these rxns usually introduce or unmask certain functional groups (OH, SH, etc), the metabolic products formed are generally inactive, but sometimes can be more active than parent compound
-these rxns are not compound specific (no specific enzymes), the enzymes attack specific groups or bonds of many different molecules
-

Front 87

Describe Phase II reactions.

Back 87

-the resulting products of these rxns will be of larger molecular wt., increased polarity (less lipid soluble), and decreased biological activity
-some of these rxns produce free radicals which then must be reduced by Glutathione
-the groups most often involved in conjugate formation are glucuronyl, sulfate, methyl, acetyl, glycyl, and glutathione

Front 88

Describe the size of molecules able to pass through the kidney.

Back 88

MW<350=excreted by kidney (lost in urine)

MW>350=excreted into GI tract and bile
-in the GI tract digestive or bacterial enzymes may free the conjugated drug which can then be reabsorbed into the bloodstream

Front 89

What drug is administered in a conjugated form and why?

Back 89

estrogen
-the conjugates are metabolized in the GI tract and some of the drug will get absorbed

Front 90

What are 3 notable drugs which increase the activity of the microsomal oxidase and conjugating systems when administered repeatedly?

Back 90

rifampin
ethanol
carbamazepine

Front 91

Describe how the toxicity of acetaminophen is altered with induction of the p450 system.

Back 91

it's toxicity is increased b/c the phase I metabolites are mainly responsible for the toxicity seen with acetaminophen use

Front 92

What is the only phase II enzyme that is microsomal and, therefore, inducible?

Back 92

glucoronyl transferase

Front 93

Give some examples of phase I reactions (oxidative) that are not catalyzed via the p450 system.

Back 93

1)ethanol also metabolized by cytoplasmic enzyme, alcohol dehydrogenase (not inducible) in addition to CYP2E1

2)xanthine oxidase inactivates 6-mercaptopurine
3)MAO inactivates many biologically active amines (NE, tyramine)

Front 94

What are some important reductive rxns that take place as phase I rxns?

Back 94

-warfarin is inactivated by conversion of a ketone to a hydroxyl group by CYP2A6

Front 95

What types of bonds are susceptible to hydrolysis (phase I rxn)?

Back 95

ester (more) and amide (less)

Front 96

In the elderly what usually occurs first: liver or kidney decline in function?

Back 96

kidney before liver
-capacity for renal excretion decreases and then the capacity for Phase I metabolism becomes reduced
-the capacity for conjugation is maintained for the longest time

Front 97

What is the relationship between penicillin and probenecid?

Back 97

they share the same transport system in the kidney for excretion
-when admin. together, competition occurs for excretion and probenecid prolongs the action of penicillin by retarding its excretion

Front 98

Describe the excretion of digoxin and aminoglycosides.

Back 98

they are highly polar drugs which means they have low tubular permeabillity (cannot freely diffuse across the lipid membrane)
-the filtered drug remains in the tubule and its concentration rises until it is about 100 times as high in the urine as in the plasma (very easily excreted this way)

Front 99

What significance does the ion-trapping effect have on drug excretion?

Back 99

it basically means that a basic drug is more rapidly excreted in acidic urine b/c the low pH within the tubule favors ionization and thus inhibits reabsorption
ex: urinary alkalinization is used to accelerate the excretion of aspirin and phenobarbitol in treating suspected cases of overdose

Front 100

What is subacute toxicity?

Back 100

occurs from repeated exposures of an agent over a period of no longer than 3 months

Front 101

What is chronic toxicity?

Back 101

occurs from repeated exposures over a period >3 months

Front 102

What are the primary determinants of toxicity?

Back 102

-dose and dose rate
-duration of exposure
-route of exposure (IV>inhalation>SC>oral>topical)

Front 103

After what time point is gastric lavage not recommended?

Back 103

after 4 hours

Front 104

What are the contraindications for gastric lavage?

Back 104

-more than 30 mins have elapsed since ingestion of a corrosive material
-hydrocarbon solvents have been ingested
-coma, stupor, delirium or convulsions are present or imminent

Front 105

What are the drugs that reduce absorption/enhance elimination?

Back 105

activated charcoal: adsorb chemicals
ipecac syrup:oral emetic
Ammonium chloride: acidify urine
sodium bicarbonate:alkalinize the urine
magnesium sulfate:cathartic
mannitol:osmotic diuretic

Front 106

What are some drugs that chelate metals??

Back 106

-deferoxamine mesylate:used for iron poisoning
-dimercaprol:arsenic, gold, mercury, and acute lead poisoning
-edetate, Ca disodium:used for lead poisoning
-penicillamine:used for Wilson's disease, cystinuria, and resistant cases of rheumatoid arthritis, chelates copper (also used for lead)

Front 107

What are some drugs that inactivate toxins?

Back 107

-acetylcysteine:used in acetaminophen poisoning
-digoxin-specific FAB abs:used for cardiac glycoside tox.

Front 108

WHat is flumazenil?

Back 108

used for benzo overdoses

Front 109

What can be used to treat cholinesterase inhibitor protein overdose/toxicity?

Back 109

atropine

Front 110

Describe Botulinus toxin poisoning. (including sx, tx, and cause)

Back 110

food borne toxin which is an exotoxin produced by an anaerobic microbe clostridium botulinum, can be destroyed easily by boiling
-causes paralysis of mm. by preventing release of Ach
-sx are vomiting, double vision, and muscular paralysis (flaccid)
-tx: emesis, lavage, or cathartic depending on time elapsed since ingestion, support vital signs and draw blood for toxin determination in blood, give type ABE botulinus antitoxin

Front 111

Describe bacterial food poisoning. (acute gastroenteritis)

Back 111

caused by toxins elaborated during the growth of salmonella
-sx appear 2-4 hrs after eating and include severe GI inflammation, mild fever, dehydration, occasionally shock
-tx is anti emetic to control severe vomiting, maintain fluid intake, and supportive care

Front 112

Decribe toxicity by bleach.

Back 112

-bleaches are normally 3-6% solutions of sodium hypochlorite in water
-sx: severe irritation, hypotension, delirium, coma
-tx: remove from skin by flooding with water, DO NOT use emesis, lavage, or acid antidotes, but DO give milk, melted ice cream or beaten eggs, antacids can be helpful

Front 113

Describe toxicity by organophosphates.

Back 113

-an agricultural poison that is an irreversible cholinesterase inhibitor
-sx:cholinomimetic symptoms of the SLUD (salivation, lacrimation, urination, and defecation
-milk intox. causes anorexia, headache, dizziness, weakness, anxiety, tremors of the tongue and eyelids, miosis and impairment of visual acuity
-moderate tox. results in nausea, salivation, tearing, abdominal cramps, vomiting, sweating, slow pulse, etc.
-severe tox. results in diarrhea, pin point and NR pupils, resp. difficulty, pulmonary edema, cyanosis, coma and heart block
-tx: remove contaminated clothing wash skin thoroughly, cautiously give a small dose of atropine to block cholinergic effects, then increase dose as needed
-2PAM may also be given to reactivate the Achase enzyme
-gastric lavage or emesis if ingestion was recent, support vital signs

Front 114

Describe toxicity by carbamates.

Back 114

-an agricultural toxin that is a reversible cholinesterase inhibitor
-sx and tx similar to organophosphates but 2PAM is CONTRAINDICATED!!

Front 115

Describe toxicity by strychnine.

Back 115

-was widely used as a rodenticide but is rarely used today b/c rats quickly become bait shy
-a competitive agonist of glycine, glycine is an important inhibitory transmitter to motorneurons and interneurons in the SC, strychnine blocks this and causes convulsions and rigidity of skeletal mm.
-sx: convulsions, death results from resp. paralysis and failure
tx: IV diazepam or succinylcholine to control convulsions, after convulsions and hyperactivity are controlled prevent further absorption of strychnine using charcoal

Front 116

Describe toxicity via chlorophenoxy compounds.

Back 116

-an herbicide that produces signs of neuromuscular involvement in high doses
-these agents are usually contaminated with TCDD which is extremely toxic in some spp but not as much so in humans (this compound may have reproductive and carcinogenic affects in large amounts for long periods)
-

Front 117

Describe toxicity by dinitrophenols.

Back 117

an herbicide that uncouples ox. phos. thus increasing metabolic rate and temperature

Front 118

Describe toxicity by paraquat.

Back 118

undergoes redox cycling and causes free radical-mediated injury to lungs

Front 119

Describe toxicity by halogenated hydrocarbons.

Back 119

an occupational hazard (ex. carbon tetrachloride, chloroform, methylene chloride, etc)
-mechanism of liver toxicity for CCl4 results from metabolism by cytochrome P450 to the trichlormethyl free radical (CCl3), free radical induced lipid peroxidation causes an increase in intracell. Ca leading to cell death
-sx: CNS depressants, may cause cardiac arrhythmias at high doses by sensitizing the myocardium to catecholamine stimulation, liver and kidney damage
-tx: remove contaminated clothing to stop further absorption, treat sx and support vitals

Front 120

Describe poisoning by methanol.

Back 120

-the acute tox. results from its rapid metabolic conversion to formaldehyde and formic acid
-sx: visual disturbances, metabolic acidosis, death is usually due to acidosis and resp. failure
-tx: emesis or gastric lavage, antidot is 50% ethanol IV (since they compete for same enzyme alcohol dehydrogenase)
-alternatively, fomepizole, a synthetic alc. dehydrogenase inhibitor is used
-treat acidosis with sodium bicarb.

Front 121

Describe toxicity by ethanol.

Back 121

sx: CNS effects include stim. due to inhibition of inhibitory pathways (GABA), followed by anaesthetic like CNS depression at higher doses, visual impairment, musc. incoordination, slowing of reaction time, euphoria, resp. depression and coma
-effects on kidney include diuresis by ADH inhibition and temp. positive fluid balance
-increased salivation and gastric secretion stimulates the appetite
-peripheral vasodilation causes warm, flushed skin, inferfering with normal homeostatic mechanisms
-tx: with acute poisoning support vital signs, avoid depressant drugs, hemodialysis if blood levels are greater than 500 mg %
-in chronic poisoning treat seizures associated with alcohol withdraw with IV diazepam, addiction and family counseling

Front 122

What is disulfiram?

Back 122

it is given to discourage alchohol use
-it inhibits acetaldehyde dehydrogenase causing an accumulation of acetaldehyde in the blood resulting in nausea and vomiting

Front 123

Describe toxicity by isopropyl (rubbing) alcoho.

Back 123

sx: CNS depression (like other alcohols), renal damage
-tx: gastric lavage,

Front 124

Describe toxicity by ethylene glycol and diethylene glycol.

Back 124

sx: similar to ethanol, CNS depression, kidney damage due to calcium oxalate crystals
-tx: gastric lavage, give ethanol IV as an antidote since it prevents the conversion of glycols to oxalic acid by competing for the dehydrogenase
-give fomepizole a synthetic alcohol dehydrogenase inhibitor

Front 125

Describe toxicity by petroleum distillates.

Back 125

-a hydrocarbon, mixtures of aliphatic hydrocarbons like kerosene, diesel fuel, and gasoline, white spirit, polishes and other household products
-sx:pulmonary irritation by high concentration of vapor, CNS depression by ingestion or inhalation, severe pneumonitis after aspiration
-tx: emesis and gastric lavage w/o tracheal intubation are CONTRAINDICATED

Front 126

Describe toxicity by aromatic hydrocarbons.

Back 126

examples are benzene, toluene, xylene
-sx: CNS stimulation at low doses or early in high doses followed by CNS depression , kidney and liver damage, cardiac arrhythmias caused by catecholamine release can be enhanced by high exposure, long term exposure to benzene can cause aplastic anemia and leukemia
-tx: remove ingested hydrocarbon by gastric lavage only if aspiration can be prevented, DO NOT INDUCE EMESIS, control convulsions with IV diazepam

Front 127

Describe toxicity by oxalic acid and oxalates.

Back 127

-they are corrosives
-sx: local irritation and corrosion of the GI tract, mm weakness, convulsions and ollapse due to Ca chelation, renal tubular damage due to Ca oxalate ppt
-tx: ppt oxalate in the GI tract by giving Ca in any form (milk, antacids, etc)
-monitor renal function and force fluids to prevent oxalate crystals from depositing in the kidney tubules, specific antidote is Ca gluconate IV
-DO NOT USE GASTRIC LAVAGE OR EMETICS

Front 128

Describe toxicity by mineral acids.

Back 128

-examples are hydrochloric, sulfuric, acetic, perchloric
-sx: irritation, inflammation, and or necrosis in all parts of the GI tract exposed to the corrosive substance
-death usually due to unresolved hypovolemic shock after massive hemorrhage
-tx: do not use gastric lavage or emesis, dilute the acid with water, give analgesics to reduce pain, a non specific antidote is milk of magnesia

Front 129

Describe toxicity by strong alkali.

Back 129

-corrosive, hydroxides in soaps, cleansers, drain cleaners
-sx: irritation, inflammation and tissue damage, more penetrating than strong acids, death usually due to hypovolemic shock
-tx: DO NOT USE GASTRIC LAVAGE OR EMESIS
-dilute with water and treat sx, support vitals

Front 130

Describe toxicity by arsenic and arsine.

Back 130

-occur in many chemical forms and cause toxicity by binding to sulfhydryl groups on enzymes and interfering with cell. metabolism
-sx: acute causes GI disturbances, CNS effects where convulsions and coma are the terminal signs, ventricular arrhythmias, kidney tubular damage
-chronic causes polyneuritis, nephritis, dermatitis, cardiac failure, cirrhosis, personality changes
-tx: remove ingested arsenic by lavage or emesis, dimercaprol or penicillamine can be used to chelate

Front 131

Describe toxicity by lead.

Back 131

-one of most toxic metals b/c it accumulates in the body, usually occurs in kids, primarily stored in bones but sx are due to lead in soft tissues
-sx:acute inorganic lead tox. leads to GI irritation and kidney damage
-chronic inorganic lead tox. lines the gums, basophilic erythrocyte stippling (characteristic of immature RBCs due to RNA in the cells), accumulation of aminolevulinic acid (hgb precursor) due to inhibition of heme synthesis by lead
-GI effects, constipation, pain
-CNS effects in lead-poisoned kids (BBB more permeable)
-hyperirritability loss of recently developed skills, finally coma and intractable convulsions, wrist drop, ankle drop, paralysis, weakness, incoordination, etc
-acute organic lead by organo-lead cmpds are much more likely to get into CNS and can even cause sx in adults
-tx: remove unabsorbed lead, chelation forms the organic form of lead which is more likely to cross the BBB but in cases of severe CNS tox it must be used

Front 132

Describe toxicity by iron.

Back 132

-sx: severe GI irritation, inflammation, necrosis and hemorrhage resulting in hypotension, metabolic acidosis and shock
-tx: lavage only within the 1st hr after ingestion
-admin deferoxamine orally and parenterally

Front 133

Describe toxicity by mercury.

Back 133

all inorganic mercury salts are toxic, many effects of acute poisoning are related to GI tract damage
-sx:
acute:irritation and superficial corrosion, abdominal pain, vomiting
secondary effects: diarrhea, shock, acute renal tubular necrosis
delayed effects: severe kidney damage leading to anuria, severe GI damage and hemorrhage
chronic effects: early: salivation, stomatitis (swollen, bleeding gums)
late: erethism (emotional instability, tremor, more severe stomatitis, coarse jerky movements, depression, loss of memory, hallucinations, mania
-organic mercury has predominately CNS effects: paresthesia, mm. twitching, ataxia, gross constriction of visual fields
-tx: lavage or induce emesis, give milk, raw eggs, or charcoal, give dimercaprol parenterally for inorganic mercury but not orally since the chelated form is more readily absorbed from GI tract

Front 134

What is dimercaprol (BAL)?

Back 134

used to chelate arsenic, lead, gold, and inorganic mercury
-can have toxic effects such as CNS disturbance, CV disturbance, BAL-iron complex is toxic so avoid medicinal iron during therapy
-usual course for metal poisoning is 7-14 days by deep IM injection
-can be used with virtually complete renal shutdown

Front 135

What is calcium disodium edetate?

Back 135

used to chelate lead, zinc, alternate choice for other metals
-can cause renal damage, EKG abnormalities, toxic effects can be avoided using less than 50mg/kg/day
-during use urine flow must be maintained, therapy should not exceed 5-7 days, do not use NaEDTA b/c it will bind Ca and cause hypocalcemia

Front 136

What is penicillamine?

Back 136

used to chelate copper (Wilson's disease), alternate antidote for other metals
-can have toxic effects such as nephrotic syndrome, pyridoxine deficiency, transient eosinophilia, contraindicated in kids w/chronic renal insufficiency

Front 137

What is succimer?

Back 137

a lead chelator similar to dimercaprol but can be given orally, GI disturbances most common side effect

Front 138

What is deferoxamine?

Back 138

used to chelate specifically iron
-toxic effects include rapid infusion may induce shock, long term therapy may cause ocular damage
-oral dose is effective in binding iron in the GI tract

Front 139

What are methemoglobin inducing agents?

Back 139

-agents which oxidize hemoglobin to methemoglobin (Fe3+, ferric form) which is incapable of carrying O2
-direct acting agents are nitrites
-indirect are converted to metabolites which oxidize hgb to methgb

Front 140

What are the ramifications of nitrite toxicity?

Back 140

-sx:chocolate colored blood, hypotension, hypoxia and cyanosis, convulsions, coma, resp. failure
-tx: only necessary when 35% or more of hgb is in the oxidized form
-methylene blue
-in severe cases O2 admin. and exchange transfusions are helpful

Front 141

Describe toxicity by carbon monoxide.

Back 141

-odorless, colorless, one of most common causes of lethal poisonings in US
-CO has a greater affinity than O2 for Hgb and carboxyhemoglobin cannot transport O2, also impairs the ability of oxyhgb to give up its O2 to peripheral tissues
-sx:headache, dizziness, stupor, carboxyhemoglobin is cherry red so victims may have bright red healthy looking mucus membranes
-tx:terminate exposure immediately, admin. O2 by best means possible, do not give methylene blue

Front 142

Describe toxicity by cyanide.

Back 142

colorless gas with an odor of almonds
-cyanide complexes with ferric iron of cytochrome oxidase and produces cell. anoxia by inhibiting O2 use in the mito., one of most rapid acting poisons
-sx: dizziness, headache, convulsions, hypotension, resp. failure,
-tx: tx must be rapid to be of any benefit, form methemoglobin by admin. of Na nitrite or amyl nitrite, the methemoglobin competes with cytochrome oxidase for the cyanide ion
-rhodanese is the normal enzyme which leads to excretion of cyanide in the body (binds cyanide with thiosulfate to be excreted), sulfur is the limiting cofactor so sodium thiosulfate is given directly after nitrite admin (to make methgb)
-give 100% O2

Front 143

Describe toxicity by free crystalline silica.

Back 143

only very small particles of free crystalline forms of silica appear to cause silicosis
-sx:first stage:dyspnea and SOB,
second stage:weakness, resp problems
third stage:total disability, expirations are prolonged and difficult, induces a predisposition to TB, pt. usually dies of right heart failure
-tx:only symptomatic and supportive
-also seems to lead to cancer

Front 144

Describe toxicity by asbestos.

Back 144

can lead to linear fibrosis of the lungs, pleural adhesions and calcifications and tumors after moderate exposures
-cig smoking multiplies the risk of lung cancer
-sx: dyspnea, resp impairment and disability, pleural mesothelioma, brochogenic carcinoma
-tx: only sx and supportive

Front 145

Describe radon toxicity.

Back 145

naturally occurring radioactive gas which can't be seen or smelled
-increased risk of lung cancer, multiplied by smoking
-

Front 146

Who is often considered to be the father of pharmacology?

Back 146

Paracelsus

Front 147

What entity regulates drugs?

Back 147

the FDA

Front 148

What information must a prescription note contain?

Back 148

-the prescriber's information (name, degree, address, phone #),
-patient's name, date and address
-drug name
-strength of the drug
-quantity to be dispensed
-directions for taking the rx (how many times/day)
-refill information
-waiver of childproof containers, additional information, such as warnings regarding use
-prescriber's signature
-DEA number for scheduled drugs only
-state license #

Front 149

Describe the properties for a rx of non-scheduled drugs.

Back 149

-rx valid for one year from date of issue
-may be refilled multiple times
-may be faxed or phoned into a pharmacy
-may be preprinted

Front 150

Describe schedule 1 drugs.

Back 150

high abuse potential, with no recognized medical use (heroid, LSD, PCP,e tc)
-cannot be prescribed legally and are only used for research

Front 151

Describe schedule 2 drugs.

Back 151

-high abuse potential
-DEA number needed
-only a 30 day supply can be prescribed
-best to write out the number being prescribed in brackets following the number
-NO REFILLS
-cannot be filled more than 90 days following issuance of the rx
-no phone orders except in Emergency with written script within 7 days indicating it was recently placed by phone
-no pre-printed rx
-the rx should contain only ONE DRUG PER RX (unless in a hospital)

Front 152

Describe schedule 3, 4, and 5 drugs.

Back 152

-lower abuse potential than schedule 2
-DEA number required
-may be refilled 5 times
-rx must be rewritten after 6 mos.
-no pre printed rx

Front 153

What are some examples of non-microsomal (and therefore non-inducible) metabolism?

Back 153

-esterases and amidases
-MAO
-alchohol and aldehyde dehydrogenases

Front 154

What are some of the major types of conjugation reactions?

Back 154

glucoronidation, acetylation, glutathione conjugation, glycine conjugation, sulfate conj, methylation, water conj.

Front 155

Where does blood flow/venous drainage from the buccal mucosa go?

Back 155

into systemic veins, not portal circulation

Front 156

How much ethanol is eliminated per hour in humans?

Back 156

10 grams/hr

Front 157

How is half life calculated?

Back 157

0.7 * Vd/CL
or
0.693/Kel
Kel=elimination constant

Front 158

What is the therapeutic index?

Back 158

LD50/ED50

Front 159

What is the margin of safety?

Back 159

LD1/ED99

Front 160

How is clearance calculated?

Back 160

Vd*(Keq)
Keq=elimination rate

Front 161

What are inducers of many of the P450 enzymes including 3A4?

Back 161

rifampin, barbiturates, phenytoin, carbamazepine, glucocorticoids, St. John's wort

Front 162

What are the inducers for CYP1A2 P450 enzyme?

Back 162

smoking
charcoal broiled foods
cruciferous veggies
dioxin

Front 163

What are the inhibitors for many P450 enzymes?

Back 163

cimetidine, amiodarone, paroxetine, fluoxetine

Front 164

What are the CYP3A4 inhibitors?

Back 164

ketoconazole, itraconazole, HIV protease inhibitors, erythromycin, clarithromycin, diltiazem, nicardipine, verapamil, grapefruit juice

Front 165

What are the CYP2D6 inhibitors?

Back 165

quinidine
SSRIs

Front 166

What are the inducers for CYP2D6?

Back 166

there are none!