Pharmacology Exam 1

• Addition of hydrogen or removal of oxygen
• R-NO₂ => R-NH₂
• Enzyme is ____ reductase

• Breakdown of molecule to basic components with the addition of water
• Ester = body breaks down into acid and alcohol
• R-CO-O-C₂H₅ => R-CO-OH + HO-C₂H₅
• Enzyme is Esterase

• Removal of halogen groups
• R-C-CCL₃ => HCL +R-C-CCL₂
• Dehalogenase

• Opposite of reduction
• removal of hydrogen or addition of oxygen

catalyzed by enzymes in the ER/microsome

• Cytochrome p450
• Mixed Function Oxidase
• Monooxygenase

• many members of this family
• CYP-#ABC
• Enzyme containes heme
• Iron is present in oxidized (Fe3+) or reduced form (Fe 2+)
• Reduced form has affinity for carbon monoxide
• absorbs light maximally at 450 nm (p=peak light absorption)

• require O2 to work
• require reducing agent, NADPH

use 1 oxygen atom

R-CH₂-CH₂-CH₂-CH₃ => RCH₂-CH₂-CHOH-CH₃

OH added onto aromatic ring

• Ring-O-R => Ring-O-H + R-OH
• Oxidation of an alkyl group

• Ring-N-R => Ring-NH₂ + R-OH
• Oxidation of R (Alkyl group)

• Ring-S-R => Ring-SH + R-OH
• Oxidation of R (Alkyl Group)

• Ring with S in the ring. S becomes double bonded to O.
• _O
• ||
• _/^S_\ => _/^S_\

Alicyclic compound to aromatic by aromatase in the mitochondria.

• Alcohol dehydrogenase
• R-OH => Aldehyde => Acid
• Aldehyde dehydrogenase
• Located in cytosol and mitochondria
• Cytosolic enzymes are more efficient than mito

pyrazoles

disulfiram

• monoamine oxidase and diamine oxidase
• present in the mitochondria
• Mono = 1 amino group
• Di = 2 amino groups

• chemical structure is the nucleus in caffeine, theophyline or hypoxanthine
• converts to uric acid
• metabolized by xanthine oxidase

• catalyzes oxidation of purines
• present in the cytosol

allopurinol

soluble fraction

• Glucuronidation
• Sulfation
• Acetylation/acylation
• Glutathione conjugation reactions/mercapturic acid formation

• addition of glucuronic acid to the drug
• uses glycuronyl transferases
• high capacity, low affinity

uridinediphosphoglucuronic acid

• moves glucuronic acid from UDPGA to the drug
• enhances water solubility of drug
• also present in microsomes

• addition of sulfate group to the drug molecule
• active sulfate compound required

phosphoadenosinephosphosulfate

• trasfer sulfur from PAPS to drug in sulfation reaction
• present in cytosol
• high affinity, low capacity
• low amounts of PAPS limit the reaction

• two carbon compound added to the drug by acetyltransferase
• present in cytosol

• more than two carbons added to drug by acyltransferase
• present in cytosol

involve the tri-peptide glutathione

• tri-peptide
• cysteine - glutamate - glycine

• CYS - SH or G-SH
• Interacts with drugs enzymatically or non-enzymatically

• cross link between two glutathione molecules by S=S
• GSSG

• found in the cytosol
• forms a glutathione adduct on the drug to be excreted

• Depends on the drug attached to glutathione
• drug is attached to glutathione
• body removes glycine and glutamate then reacts with cysteine via acetylation.
• Drug-S-CYS-NH-O-CO-CH3

• Diet effects proteins
• May change enzymes
• High protein, low carb may increase metabolism
• High carb, low protein my decrease drug metabolism

May induce metabolism of certain drugs by enducing specific enzymes

• drug metabolism decreases
• decline in microsomal enzymes is more than in non-microsomal.

• Temperature
• Stress
• Smoking, first or second hand
• Genetics
• Disease states (liver = decrease metabolism)

Termination of the drug by inactivation or redistribution

• Renal
• Biliary (through the liver)
• Lungs (excretion of volatile molecules)

• Sweat
• Tears
• Saliva
• Milk

• Filtration from blood to glomerulus
• Secretion from blood to glomerulus
• Reabsorption from urine to blood

• drug must be small
• must be free drug
• blood pressure pushes molecules out of blood vessel and into the nephron
• drug moves from high concentration to low concentration

• Active transport process
• Carrier mediated process
• Involves saturability, specificity, energy
• moves from low to high concentration
• useful for drugs that cannot cross lipid membranes due to size or charge

• from urine to blood
• drugs that are able to cross lipid membranes of the nephron
• Must be unionized to cross membrane

• Drug must be kept in the ionized form in the urine
• keep pH low in the urine

increase the pH of the blood to make a basic drug move (unionized form) move into the urine

• Ionize the drug in the urine
• drink a lot of fluids
• Ingest NH₄CL (ammonium chloride) which acidifies urine

• Keep drug unionized
• Remove H+ from the urine (increase pH)
• Alkalinize the urine with sodium bicarb

• Alkalinize urine
• results in A- and H+

• Carrier mediated
• could administer a drug that has a higher affinity for a carrier for the drug you want to stay, to keep a drug in the system.

meat and fish

dairy

lithium

• Diminished blood supply to kidney and liver
• Proteins of transport mechanisms decreased
• Energy diminished