Test #1 Flashcards
Any molecule used to alter body functions thereby preventing or treating disease
Drug
What are the 3 fundamental pathways of pharmacology?
- 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)
The science of drug preparation & the medical use of drugs began to develop as the precursor to pharmacology
Materia medica
In the late 18th & early 19th centuries, what two dudes began to develop the methods of experimental animal physiology & pharmacology?
Francois Magendie
Claude Bernard
The study of the relation of the individual’s genetic makeup to his or her response to specific drugs
Pharmacogenomics
Type of knockout mice that will usually have complete suppression of that function
Homozygous
Type of knockout mice that will usually have partial suppression of a particular function
Heterozygous
What is the specific molecule in the biologic system that a drug molecule interacts with? It plays a regulatory role.
Receptor
What is the advantage of rectal administration of a drug?
- 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
M/C common route of drug administration. Also most complicated pathway to the tissues.
Oral
Drugs that administered orally are mostly absorbed where?
Duodenum
This type of drug administration allows the drug to diffuse into the capillary network & to enter the systemic circulation directly
Sublingual
What is the advantage of sublingual drug administration?
Drug bypasses the liver therefore it is not inactivated by the liver
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
Parenteral Route
What is the M/C type of parenteral route.
Intravenous
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
Intramuscular
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
Inhalation
What route of drug administration is used for local effects?
Topical
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)
Transdermal
The transfer of a drug from its site of administration to the blood stream
Absorption
The rate & efficiency of absorption depends on what?
Route administration
What type of drug administration has complete absorption?
IV
What are characteristics of passive diffusion?
Doesn’t involve a carrier
Is not saturable
Shows a low structural specificity
Most drugs gain access to the body by this mechanism
A drug tends to pass through membranes if it’s what?
Uncharged
Uncharged drugs are more water or lipid soluble than charged drugs?
Lipid soluble
This mode of drug entry involves specific carrier proteins & shows saturation kinetics
Active transport
What are characteristics of active transport?
Energy dependent
Is driven by the hydrolysis of ATP
Capable of moving drugs against a concentration gradient
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
Pinocytosis
What the body does to the drug. The movement of drugs w/i the body from administration to elimination
Pharmacokinetics
Pharmacokinetics encompasses what 4 things?
Absorption
Distribution
Metabolism
Excretion of drugs
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.
Pharmacodynamics
“Drug absorption” is only applicable to drugs administered via what routes?
Enteral
Topical
(Injectable drugs are administered directly into the blood stream so they’re not absorbed)
This is a measure of how lipophilic a drug is
Partition coefficient (more lipophilic, higher partition coefficient)
Drugs w/ low partition coefficients are likely to distribute in the _______ & thus more likely to have _______ effects
plasma; peripheral
Drugs w/ low partition coefficients are likely be eliminated by what?
Renal filtration
Drugs w/ high partition coefficients will distribute in ________ tissue & are more likely to cross the __________ & distribute into the CNS w/ CNS effects
adipose; blood-brain barrier
Drugs w/ high partition coefficients are eliminated by what?
Undergo hepatic metabolism & eliminated in the bile
By what 3 biochemical mechanisms are drugs absorbed into cells?
Passive diffusion
Transport by special carrier proteins
Active transport
What does drug distribution depend upon?
Degree of ionization at physiological pH
On the partition coefficient
Binding to plasma proteins
Which types of drugs extensively bind to plasma albumin?
Aspirin
Phenytoin
Prednisone
The amount of space available in the body in which drugs may be stored. In theory, it refers to a homogenous distribution of drug
Volume of distribution (Vd)
A large volume of distribution (Vd) signifies what?
In general, it means that a higher dose can be tolerated.
How are drugs eliminated from the system?
Liver metabolism
Renal filtration
Redistribution
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
Redistribution
Drugs that are small in molecular size, & highly soluble in water, may be eliminated unchanged thru what method?
Renal filtration
Drugs that are less soluble in water are first metabolized where?
Liver
Phase I reactions of renal filtration convert lipophilic molecules into more polar molecules by doing what?
INtroducing or unmasking a polar functional group such as -OH or -NH2. (most of these reactions utilize the microsomal P450 enzymes)
Phase II reactions of renal filtration are what type of reactions?
Conjugation reactions
What converts the coagulation proteins from the inactive form to the active form?
Serine Proteases
How does heparin work?
Binds tightly to antithrombin causing a conformational change leading to more rapid interactions w/ activated clotting factor proteases (IIa, IXa, & Xa)
Where is heparin obtained from?
Porcine intestine or bovine lung tissue
What are complications assoc. w/ heparin?
Reversible alopecia
Osteoporosis/spontaneous fx’s (long term)
Transient thrombocytopenia
Bleeding complications
Shorter chain LMW fractions of heparin inhibit activated factor _____ but have less effect on ______
Factor X; Thrombin (IIa)
What are examples of LMW heparins?
Enoxaparin
Dalteparin
Tinzaparin
What are benefits of LMW Heparins?
Have good efficacy
Increased bioavailability from the subcutaneous site
Require less frequent dosing
What is used to reverse heparin action?
Protamin
These directly bind to the active site of thrombin II (w/o additional binding proteins) thereby inhibiting thrombin’s downstream effects
Direct Thrombin Inhibitors
What are examples of Direct thrombin inhibitors?
Hirudin
Bivalirudin
Argatroban
Melagatran
A specific, irreversible thrombin inhibitor obtained from the leech.
Hirudin (recombinant form known as Lepirudin)
How does Hirudin work?
It can reach fibrin-bound thrombin in thrombi & inactivate it.
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
Lepirudin
IV admin w/ a rapid onset of action. Short half-life. Inhibits platelet aggregation
FDA approved for use in percutaneous angioplasty
Bivalirudin
FDA approved for use in pts w/ heparin induced thrombocytopenia (HIT) w/ or w/o thrombosis. Also, for coronary angioplasty in pts w/ HIT.
Argatroban
Argotroban’s clearance is not affected by renal disease but is dependent on what?
Liver function (requires a dose reduction in pts w/ liver ds)
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
Antithrombin III
Several protein coagulation factos require what nutrient for their activation before they can participate in the clotting process
Vit. K
How long after administration of warfarin are the anticoagulant effects observed?
8-12 hours after administration
How are long does it take to reverse the effects of warfarin w/ Vit. K?
24 hours
Coagulation factors II, VII, & X require what on glutamic acid residues in order to bind calcium during coagulation reaction?
Gamma carboxylation (requires Vit. K
Warfarin inhibits what involved in the recycling of Vit. K thus leading to a deficiency of procoagulant forms of factors II, VII, IX, & X
Reductase enzymes
Na-salt of warfarin is rapidly & completely absorbed after what type of administration?
Oral
Warfarin binds to what which prevents its diffusion into the CSF, urine, & breast milk?
Plasma albumin
How to treat adverse effects of warfarin?
Withdrawal of the drug Administration of Vit. K, given by IV Whole blood transfusion Frozen plasma Plasma concentrate of the blood factors
What effects does warfarin have on a developing fetus?
Bone defects
Hemorrhage
These drugs increase warfarin’s clearance & thereby reduce the anticoagulant effect of a given dose
Cytochrome P450 inducing drugs (barbiturates, carbamazepine, phenytoin)
These drugs reduce warfarin’s clearance & increase the anticoagulant effect of a given dose
Cytochrome P450 inhibiting drugs (amiodarone, cimetidine, disulfiran)
What is the difference b/w anticoagulant/anti-platelet drugs & thrombolytic drugs?
Anticoagulant/antiplatelet drugs are administered to prevent the formation of clots.
Thrombolytic drugs are used to lyse already formed clots
How is fibrinolysis initiated?
By activation of plasminogen to plasmin (thrombolytic drugs are plasminogen activators). The plasmin then catalyzes the degradation of fibrin.
What’s the difference b/w 1st generation of plasminogen activators & 2nd generation?
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
Platelets are regulated by what 3 categories of substances?
- 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
What chemical signals oppose platelet activation?
Elevated prostacyclin (PG12) levels Decreased plasma levels of thrombin & thromboxanes
What are chemical signals that promote platelet aggregation?
Decreased prostacyclin levels (PG12)
Exposed collagen
Increased synthesis of thromboxanes (Txa2)
Where is thromboxane (TXA2) generated?
Within the platelets
Where is prostacyclins (PG12) generated?
By the endothelial cells of the blood vessels
This drug can irreversibly inhibit TXA2 production in platelets
Aspirin
