Medicinal Organic Chem (Sir Jan's Notes 1st Part)

Functionalized metabolite

metabolite after phase 1

amine and nitrogen compound

Azido compounds (Azides) --> reduction

Functionalized metabolite

metabolite after phase 1

amine and nitrogen compound

Azido compounds (Azides) --> reduction

Glutathione conjugation

What type of conjugation for detoxifying chemically reactive electrophillic compounds

Cysteine
Glycine
glutamine

Components of glutathione

Acetylation (Acetyl Conjugation)

For termination of activity & detoxification (Conjugation)

Acetylation (Acetyl Conjugation)

Important route of primary amino groups

Acetylation (Acetyl Conjugation)

Acetyl group supplier: Acetyl-CoA

Acetylation (Acetyl Conjugation)

Undergone by sulfonamides

N-acetyltransferase

Transferase enzyme for acetylation

Hydralazine, Isoniazid, Anesthetics, Sulfonamides

Examples for acetylation

N-Acetylation

Sulfonamides are metabolized by

Hydrophobic

N-Acetylation increases ____ Character

Acetylation

reduces aqueous solubility

Acetylation polymorphism

variation in acetylating activity

Europeans, Caucasians, Egyptians, (low doses)

Slow acetylators

Eskimos & Asians (High Doses)

Fast acetylators

S-Adenosylmethionine (SAM)

Coenzyme of methyation

Methyl transferase

transferase enzyme for methylation

Methylation (Methyl conjugation)

Minor pathways that leads to non-poar & inactivated compounds

Methylation (Methyl conjugation)

Biosynthesis of epinephrine, melatonin

Methylation (Methyl cnjugation)

Inactivation of norepinephrine, dopamine, serotonin, histamine

Glucoronidation

Most Common
can cause Gray baby syndrome

UDP-glucuronosyl transferase
UDP-glucuronic acid acyl transferase

enzymes for glucoronidation

UDP- glucuronic acid

cofactor of glucorinidation

Sulfation

Phenolic group requirement
primary Conjugation of neonates

Sulfotransferase

Sulfation enzyme

PAPS
3-phosphadenosyl 5-phosphasulfate 3-phosphadenosine 5-phosphasulfonic acid

cofactor of sulfation

Glycine (most common), glutamine

cofactor of amino acid conjugation

Glutathione-S- transferase

enzyme of glutathione conjugation

Glutathione

glutathione conjugation cofactor

Acetyl conjugation

metabolism N-containing drugs & compounds

N-acetyltransferase

enzyme of acetyl conjugation

Acetyl-CoA

acetyl conjugation cofactor

Methyl conjugation

Minor; important in biosynthesis of epinephrine & melatonin and for the catabolism of catecholamine

Methyltransferase
COMT Catechol-O-MT
PENMT
Phenylethanolamine N-MT

Enzyme of methyl conjugation

SAM S-adenosyl methionine

Methyl conjugation cofactor

First-Pass Metabolism / Pre-systemic metabolism

When orally administered drugs are extensively
metabolized before reaching the systemic circulation

Isoproterenol
Meperidine
Propoxyphene
Lidocaine
Nitroglycerine
Propranolol
Morphine
Pentazocine
Salicylamide

Drugs with extensive first pass effect

Sodium valproate

Enzyme inhibitor

Isoniazid

Enzyme inhibitor

cimetidine

Enzyme inhibitor

ketoconazole

Enzyme inhibitor

fluconazole

Enzyme inhibitor

alcohol (acute)

Enzyme inhibitor

ciprofloxacin

Enzyme inhibitor

erythromycin

Enzyme inhibitor

sulfonamide

Enzyme inhibitor

omeprazole

Enzyme inhibitor

metronidazole

Enzyme inhibitor

grape fruit

Enzyme inhibitor

Phenobarbital (barbiturates)

Enzyme inducer

Phenytoin

Enzyme inducer

Phenylbutazone

Enzyme inducer

Rifampicin

Enzyme inducer

Sulfonylurea

Enzyme inducer

carbamazepine

Enzyme inducer

alcohol (chronic)

Enzyme inducer

meprobamate

Enzyme inducer

St. John's wort

Enzyme inducer

valencia oranges

Enzyme inducer

Enzyme inhibitor

low enzyme activity
low drug metabolism
high drug effect
increase the potential for toxicity

Enzyme inducers

high enzyme activity
high drug metabolism
low drug effect
subsequently decrease the therapeutic concentration

Antisepsis

application of agent to living tissue to prevent infection

Decontamination

destruction or reduction in the number of microorganisms

Disinfection

chemical or physical treatment on inanimate surfaces

Sanitization

reduction of microbial load on inanimate surface to a level acceptable for public health purposes

Sterilization

kill or remove all types of microorganisms

Pasteurization

kills nonsporulating microorganisms by hot water @ 65C-100C

Cidal

kill

static

prevent growth

High-level disinfection (HLD)

the destruction of all viruses, vegetative bacteria, fungi, mycobacterium, and some, but not all, bacterial spores

Intermediate-level disinfection

the destruction of all mycobacteria, vegetative bacteria, fungal spores, and some nonlipid viruses, but not bacterial spores

Low level disinfection

a process that can kill most bacteria (except mycobacteria or bacterial spores), most viruses (except some nonlipid viruses) and some fungi

Alcohols and related compounds
phenols and its derivatives
oxidizing agents
halogen containing compounds
cationic surfactants
preservatives
dye
mercury containing compound

Anti infective agents

Octanol only

increase in carbon number means increase in antibacterial activity up to _____

Non polar, decrease water solubility, decrease antibacterial activity

higer than 9 carbon means in SAR

branching

In SAR this decreases the antibacterial property

primary > Secondary > Tertiary

Isomeric alcohol potency decreases in the order

Protein denaturation/ precipitation

MOA of isopropyl alcohol

ethanol, grain alcohol, wine spirit, cologne spirit, spiritus vini rectificatus

Alcohol USP is also known

Ethanol

most wildly abused of all recreational drugs

95%

commercial ethanol at what concentration?

Fermentataion of grains and other CHOs
Hydration of ethene

Ethanol is manufactured by

Ethanol—> acetaldeehyde —> acetic acid

Metabolism of alcoho

Alcohol dehydrogenase

ethanol to acetaldehyde enzyme

Aldehyde dehydrogenase

Acetaldehyde to acetic acid enzyme

Fomepizole

Inhibits alcohol dehydrogenase
used as an antidote for methanol poisoning

Disulfiram

used as a deterrent for alcohol addiction
inhibits aldehyde dehydrogenase
for the accumulation of aldehyde

Absolute alcohol

95% alcohol

Dehydrated alcohol

99% alcohol, prepared by azeotropic Distillation

Diluted alcohol

49-50% alcohol

Denatured alcohol

EtOH rendered unfit for use in beverages by the addition of subs

Specially denatured alcohol

treated with subs. So that its use is permitted for specialized purpose ex. Iodine in alohol

2-propanol or 2-propanol-2-ol

Isopropyl alcohol IUPAC

Isopropyl alcohol

substitute for ethanol

Propylene

isopropyl OH is prepared by sulfuric acid catalyzed hydration of ____

C2H4O

Molecular formula of isopropyl alcohol

alkylation of bacterial protein by nucleophilic opening of oxide ring

MOA of isopropyl alcohol

Isopropyl alcohol

used to sterilize (gas sterilant) temperature sensitive pharmaceuticals and
equipment that can't be autoclaved

alkylation of bacterial protein by nucleophilic opening of oxide ring

MOA of ethylene oxide