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Toxicology > Test #1 > Flashcards

Test #1 Flashcards

1
Q

Any molecule used to alter body functions thereby preventing or treating disease

A

Drug

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2
Q

What are the 3 fundamental pathways of pharmacology?

A
  • Site of administration: Leads to entry of drug into plasma
  • Distribution of Drug: Plasma–>intracellular & interstitial fluids (tissues)
  • Elimination: Hepatic metabolism –> excretion via urine & feces (excretion or output)
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3
Q

The science of drug preparation & the medical use of drugs began to develop as the precursor to pharmacology

A

Materia medica

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4
Q

In the late 18th & early 19th centuries, what two dudes began to develop the methods of experimental animal physiology & pharmacology?

A

Francois Magendie

Claude Bernard

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5
Q

The study of the relation of the individual’s genetic makeup to his or her response to specific drugs

A

Pharmacogenomics

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6
Q

Type of knockout mice that will usually have complete suppression of that function

A

Homozygous

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7
Q

Type of knockout mice that will usually have partial suppression of a particular function

A

Heterozygous

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8
Q

What is the specific molecule in the biologic system that a drug molecule interacts with? It plays a regulatory role.

A

Receptor

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9
Q

What is the advantage of rectal administration of a drug?

A
  • Prevents destruction of the drug by intestinal enzymes or by low pH in the stomach
  • Useful if drug induces vomiting when given orally or if pt is already vomiting
  • Eliminates the issue of taste
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10
Q

M/C common route of drug administration. Also most complicated pathway to the tissues.

A

Oral

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11
Q

Drugs that administered orally are mostly absorbed where?

A

Duodenum

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12
Q

This type of drug administration allows the drug to diffuse into the capillary network & to enter the systemic circulation directly

A

Sublingual

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13
Q

What is the advantage of sublingual drug administration?

A

Drug bypasses the liver therefore it is not inactivated by the liver

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14
Q

This administration route is used for drugs that are poorly absorbed from the GI tract or for drugs that are unstable in the GI tract (insulin). Also used for unconscious pts. Provides rapid onset of action & most control over the actual dose delivered to body

A

Parenteral Route

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15
Q

What is the M/C type of parenteral route.

A

Intravenous

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16
Q

Type of parenteral route that is used for specialized depot preparations into nonaqueous vehicle such as ethylene glycol or peanut oil. As the vehicle diffuses out of the muscle, the drug precipitates at the site of injection then dissolves slowly, providing a sustained dose over an extended period of time

A

Intramuscular

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17
Q

What route of drug administration provides for the rapid delivery of a drug across the large surface area of the alveolar membrane. Can produce actions almost as rapidly as IV

A

Inhalation

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18
Q

What route of drug administration is used for local effects?

A

Topical

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19
Q

What route of drug administration achieves systemic effects by application of drugs to the skin usually via a transdermal patch. Used for sustained delivery of drugs such as anti-motion sickness agent (scopolamine) or the antianginal drug (nitroglycerin)

A

Transdermal

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20
Q

The transfer of a drug from its site of administration to the blood stream

A

Absorption

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21
Q

The rate & efficiency of absorption depends on what?

A

Route administration

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22
Q

What type of drug administration has complete absorption?

A

IV

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23
Q

What are characteristics of passive diffusion?

A

Doesn’t involve a carrier
Is not saturable
Shows a low structural specificity
Most drugs gain access to the body by this mechanism

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24
Q

A drug tends to pass through membranes if it’s what?

A

Uncharged

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25
Q

Uncharged drugs are more water or lipid soluble than charged drugs?

A

Lipid soluble

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26
Q

This mode of drug entry involves specific carrier proteins & shows saturation kinetics

A

Active transport

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27
Q

What are characteristics of active transport?

A

Energy dependent
Is driven by the hydrolysis of ATP
Capable of moving drugs against a concentration gradient

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28
Q

A cellular process of actively engulfing liquid. A phenomenon in which minute invaginations are formed in the surface of the cell membrane & close to form fluid filled vesicles

A

Pinocytosis

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29
Q

What the body does to the drug. The movement of drugs w/i the body from administration to elimination

A

Pharmacokinetics

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30
Q

Pharmacokinetics encompasses what 4 things?

A

Absorption
Distribution
Metabolism
Excretion of drugs

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31
Q

This refers to the action of the drug at the cellular level. What the drug does to the body. Encompasses the binding of a drug to its receptor or binding site.

A

Pharmacodynamics

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32
Q

“Drug absorption” is only applicable to drugs administered via what routes?

A

Enteral
Topical
(Injectable drugs are administered directly into the blood stream so they’re not absorbed)

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33
Q

This is a measure of how lipophilic a drug is

A

Partition coefficient (more lipophilic, higher partition coefficient)

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34
Q

Drugs w/ low partition coefficients are likely to distribute in the _______ & thus more likely to have _______ effects

A

plasma; peripheral

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35
Q

Drugs w/ low partition coefficients are likely be eliminated by what?

A

Renal filtration

36
Q

Drugs w/ high partition coefficients will distribute in ________ tissue & are more likely to cross the __________ & distribute into the CNS w/ CNS effects

A

adipose; blood-brain barrier

37
Q

Drugs w/ high partition coefficients are eliminated by what?

A

Undergo hepatic metabolism & eliminated in the bile

38
Q

By what 3 biochemical mechanisms are drugs absorbed into cells?

A

Passive diffusion
Transport by special carrier proteins
Active transport

39
Q

What does drug distribution depend upon?

A

Degree of ionization at physiological pH
On the partition coefficient
Binding to plasma proteins

40
Q

Which types of drugs extensively bind to plasma albumin?

A

Aspirin
Phenytoin
Prednisone

41
Q

The amount of space available in the body in which drugs may be stored. In theory, it refers to a homogenous distribution of drug

A

Volume of distribution (Vd)

42
Q

A large volume of distribution (Vd) signifies what?

A

In general, it means that a higher dose can be tolerated.

43
Q

How are drugs eliminated from the system?

A

Liver metabolism
Renal filtration
Redistribution

44
Q

The process by which the drugs that are concentrated will have activity in one particular tissue or organ may be eliminated by removal of drug from the target tissue to other storage sites in the body

A

Redistribution

45
Q

Drugs that are small in molecular size, & highly soluble in water, may be eliminated unchanged thru what method?

A

Renal filtration

46
Q

Drugs that are less soluble in water are first metabolized where?

A

Liver

47
Q

Phase I reactions of renal filtration convert lipophilic molecules into more polar molecules by doing what?

A

INtroducing or unmasking a polar functional group such as -OH or -NH2. (most of these reactions utilize the microsomal P450 enzymes)

48
Q

Phase II reactions of renal filtration are what type of reactions?

A

Conjugation reactions

49
Q

What converts the coagulation proteins from the inactive form to the active form?

A

Serine Proteases

50
Q

How does heparin work?

A

Binds tightly to antithrombin causing a conformational change leading to more rapid interactions w/ activated clotting factor proteases (IIa, IXa, & Xa)

51
Q

Where is heparin obtained from?

A

Porcine intestine or bovine lung tissue

52
Q

What are complications assoc. w/ heparin?

A

Reversible alopecia
Osteoporosis/spontaneous fx’s (long term)
Transient thrombocytopenia
Bleeding complications

53
Q

Shorter chain LMW fractions of heparin inhibit activated factor _____ but have less effect on ______

A

Factor X; Thrombin (IIa)

54
Q

What are examples of LMW heparins?

A

Enoxaparin
Dalteparin
Tinzaparin

55
Q

What are benefits of LMW Heparins?

A

Have good efficacy
Increased bioavailability from the subcutaneous site
Require less frequent dosing

56
Q

What is used to reverse heparin action?

A

Protamin

57
Q

These directly bind to the active site of thrombin II (w/o additional binding proteins) thereby inhibiting thrombin’s downstream effects

A

Direct Thrombin Inhibitors

58
Q

What are examples of Direct thrombin inhibitors?

A

Hirudin
Bivalirudin
Argatroban
Melagatran

59
Q

A specific, irreversible thrombin inhibitor obtained from the leech.

A

Hirudin (recombinant form known as Lepirudin)

60
Q

How does Hirudin work?

A

It can reach fibrin-bound thrombin in thrombi & inactivate it.

61
Q

This is used for tx of pts who have thrombosis & thrombocytopenia as a result of an antibody-mediated reaction to heparin. Used to prevent thrombosis in the fine vessels of reattached digits. No antidote available

A

Lepirudin

62
Q

IV admin w/ a rapid onset of action. Short half-life. Inhibits platelet aggregation
FDA approved for use in percutaneous angioplasty

A

Bivalirudin

63
Q

FDA approved for use in pts w/ heparin induced thrombocytopenia (HIT) w/ or w/o thrombosis. Also, for coronary angioplasty in pts w/ HIT.

A

Argatroban

64
Q

Argotroban’s clearance is not affected by renal disease but is dependent on what?

A

Liver function (requires a dose reduction in pts w/ liver ds)

65
Q

Used for tx of pts who need anticoagulation but are resistant to heparin b/c of genetic deficiency in antithrombin III & also in some cases of acquired antithrombin III deficiency

A

Antithrombin III

66
Q

Several protein coagulation factos require what nutrient for their activation before they can participate in the clotting process

A

Vit. K

67
Q

How long after administration of warfarin are the anticoagulant effects observed?

A

8-12 hours after administration

68
Q

How are long does it take to reverse the effects of warfarin w/ Vit. K?

A

24 hours

69
Q

Coagulation factors II, VII, & X require what on glutamic acid residues in order to bind calcium during coagulation reaction?

A

Gamma carboxylation (requires Vit. K

70
Q

Warfarin inhibits what involved in the recycling of Vit. K thus leading to a deficiency of procoagulant forms of factors II, VII, IX, & X

A

Reductase enzymes

71
Q

Na-salt of warfarin is rapidly & completely absorbed after what type of administration?

A

Oral

72
Q

Warfarin binds to what which prevents its diffusion into the CSF, urine, & breast milk?

A

Plasma albumin

73
Q

How to treat adverse effects of warfarin?

A 
Withdrawal of the drug
Administration of Vit. K, given by IV
Whole blood transfusion
Frozen plasma
Plasma concentrate of the blood factors
74
Q

What effects does warfarin have on a developing fetus?

A

Bone defects

Hemorrhage

75
Q

These drugs increase warfarin’s clearance & thereby reduce the anticoagulant effect of a given dose

A

Cytochrome P450 inducing drugs (barbiturates, carbamazepine, phenytoin)

76
Q

These drugs reduce warfarin’s clearance & increase the anticoagulant effect of a given dose

A

Cytochrome P450 inhibiting drugs (amiodarone, cimetidine, disulfiran)

77
Q

What is the difference b/w anticoagulant/anti-platelet drugs & thrombolytic drugs?

A

Anticoagulant/antiplatelet drugs are administered to prevent the formation of clots.
Thrombolytic drugs are used to lyse already formed clots

78
Q

How is fibrinolysis initiated?

A

By activation of plasminogen to plasmin (thrombolytic drugs are plasminogen activators). The plasmin then catalyzes the degradation of fibrin.

79
Q

What’s the difference b/w 1st generation of plasminogen activators & 2nd generation?

A 
1st generation (streptokinase & urokinase) convert all plasminogen to plasmin throughout the plasma
2nd generation (Altepase & Reteplase) tissue type plasminogen activator (t-PA) selectively activate plasminogen bound to fibrin
80
Q

Platelets are regulated by what 3 categories of substances?

A
  • Agents generated outside the platelets
  • Agents generated w/i the platelets that interact w/ platelet membrane receptors
  • Agents generated w/i the platelets that act w/i the platelets
81
Q

What chemical signals oppose platelet activation?

A 
Elevated prostacyclin (PG12) levels
Decreased plasma levels of thrombin & thromboxanes
82
Q

What are chemical signals that promote platelet aggregation?

A

Decreased prostacyclin levels (PG12)
Exposed collagen
Increased synthesis of thromboxanes (Txa2)

83
Q

Where is thromboxane (TXA2) generated?

A

Within the platelets

84
Q

Where is prostacyclins (PG12) generated?

A

By the endothelial cells of the blood vessels

85
Q

This drug can irreversibly inhibit TXA2 production in platelets

A

Aspirin

Toxicology (3 decks)

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