Pharmacist Alerts

Enalapril for Enalaprilate (antihypertensive)

Prodrugs to improve membrane permeability (mask polar/ionizable carboxylic acids)

Increases lipophilicity

aspirin(masked) for salicylic acid

Prodrugs to mask toxicity and side effects

Chloramphenicol(antibiotic) for Palmitate ester

Prodrugs to lower water solubility (foul taste)

Chloramphenicol(antibiotic)  for Succinate ester

Prodrugs to increase water solubility (for i.v drugs)

(phase 2) UGT1A1 convets Active irinotecan(SN-38) into inactive form; to stop diarrhea

Potential toxicity of irinotecan is diarrhea

B-Glucuronidase into raloxifene to get reabsorbed

Enterohepatic recycling; reabsorption of drug after deconjugation

Sulfhdryl alkylation by acrolein and using Mesna to reduce toxicity

Cytoprotective Agents

Fluconazole(water soluble) for Tioconazole

Increase polarity from structural changes (add polar groups)

Bethanechol (selective) for Acetylcholine (non-selective)

Steric shields: adding methyl group

Irinotecan converted to SN38, PEGylated Liposomal irinotecan for SN38 for longer circulation time in plasma

Steric shields: Pegylation PEGylated Liposomal Irinotecan

Lidocaine for Procaine

Steric and Electronic effects (adds methyl and amide group)

Uracil Mustard(anticander drug) drug smuggled into cell by carrier proteins for (amino acids, nucleic acid bases)

Targeting drug: Linking a drug to a biosynthetic building block; increase selectively drugs to target, reduces toxicity

Kadcyla: antibody-drug conjugate

Selective drug targeting to cancer cells

Valacyclovir hydrochloride for Acyclovir

Prodrug: dosing advantage; metabolism: hydrolysis of ester

Carbidopa protects L-dopa

Drug added to protect another drug

inhibits the decarboxylase enzyme involved in decarbocaylation of L-Dopa.

DOXIL

Using NPs to improve solubility and stability of poorly water-soluble drugs for cancer cells

Marqibo (anti-cancer drug)

Loading and retention of Vincristine and slow drug release in the tumor environment

Onivyde

A PEGylated liposomal formulation of Irinotecan

Vyxeos (Cytarabine and Daunorubicin)

Multitherapy nanoparticles: 2/more therapeutics treatment of disease. Prolonged plasma life

Ciprofloxacin

Acid-Base properties of FGs in the drug

Abraxane

Nanoemulsion for encapsulated drugs

Effect of pH on absorption of basic drug

Acidic environment: conjugate acid (ionized) increases  decreases in drug absorption

 

Alkaline environment: base (unionized increases)  increases drug absorption

Effect of pH on absorption of acidic drug (Henderson-Hasselbach Equation)

Basic envr. Conj. Base (ionized) increases  decrease drug absorption

 

Acidic envr. Acid (unionized) increases  increase drug absorption

Trapping morphine in stomach

Morphine more ionized in acidic stomach and is it is trapped, cannot diffuse across stomach

Alkalinization of urine to eliminate drugs

Alkalinazation of urine: increase excretion of acetylsalicylic acid (aspirin), an acidic drug

Acid, Base, Absorption

Ecstasy gets into brain easily

Ecstasy (MDMA)(weak base) when accepting H+, makes difficult to cross biological membrane in stomach. Can diffuse in small intestine, gives up H+ becoming nonpolar to diffuse

One isomer may contribute to undesirable side effects and significant toxicity

Thalidomide: S isomer caused birth defect

Water solubility of dif salt forms of selective drugs

Atarax treating itching

Vistaril treating anxiety

Procain ease pain of IM injection

Reversible drug/ enzyme inhibitors

Sulfa drugs

Irreversible drug/ enzyme inhibitors

Orlistat

Anticancer Alkylating agents

Crosslinking: due to covalent bond/interactions of nucleophilic groups.  Alkylation of nucleic acid bases

Hydrogen Bondings important for biological activity, intra h-bond can mask binding of a group

Methyl-p-benzoate (para) more potent/active than methylsalycylate (ortho)

Serendipity (drug of chance)

Do not use with cheese, wine, beer, yeast

MAO (monoamine oxidase) inhibitor

(cheese effect)

Rational approach: histamine a natural substrate for H2 receptors H2R to treat heartburn

Cimetidine (Tagament)

Rational approach: natural substrate

Screening of modified lead compounds  Metiamide

Ranitidine (Zantac)

Selectivity of adrenergic agents

Vary Alkyl Substituents

Salbutamol (ventolin, agonist) and Propranolol (antagonist) for Adrenaline

Extension of extra FGs

ACE inhibitors (Enalaprilat)

Chain extension to increase interactions

N-Phenethylmorphine

Simplification: remove excess rings

Morphine and Cocaine

Action of amphotericin B (antifungal agent)

Agents interacting with cell membrane lipids: builds tunnels through membrane and drains cells

Nanoparticle characteristics

Smaller in size, solubility, dif physical and chemical properties

Mechanisms of Resistance to the Effects of Anti-Cancer Drugs

Upregulation of MDR efflux pumps

Decreased cellular uptake

Prodrugs to improve BBB membrane permeability

Trojan horse strategy: Levodopa for Dopamine

pH-partition theory weak acid is absorbed in stomach

Absorption (diffusion) of aspirin

pH-partition theory weak base is absorbed in small intestine

Absorption (diffusion) of Codeine

Imatinib (Gleevec)

Drug discovery inhibiting drug targets

Cancer chemotherapy

Atorvastatin

Drug discovery inhibiting drug targets

Cardiovascular Medications

Acyclovir

Drug discovery inhibiting drug targets Antiviral Drugs

Serotonin Reuptake Inhibitors (Fluxetine/Prozac)

Drug discovery inhibiting drug targets

Psychiatric Medications

Penicillin V is more orally active than G

Penicillin V is orally active as compared Penicillin G

Certain Foods affect the activity of P450 enzymes

Grapefruit juice inhibits activity

Brussel sprouts/Cigarette smoke enhance activity