Drugs Flashcards
Amytal (Amobarbital)
- Reversible Inhibitor of Complex I (NADH Dehydrogenase)
- Blockade of ETC with Amytal has been shown to protect cardiac muscle during ischemia-reperfusion by limiting ROS production
○ Protective against ROS accumulation - Still will make some ATP via Complex II and BYPASS REACTIONS (via Succinate DH –> FADH2)
- Blockade of ETC with Amytal has been shown to protect cardiac muscle during ischemia-reperfusion by limiting ROS production
Rotenone
- Inhibits Complex I (NADH Dehydrogenase)
- Naturally occurring pesticide
- Fish poison
Antimycin
- Inhibits Complex III
○ Binds to cytochrome b in the reduced state –> stops ETC
○ Inhibits BOTH BYPASS AND NON-BYPASS REACTIONS (because it’s beyond complex II)
§ Complexes I, CoQ, + Complex II: fully reduced
§ Complexes III, Cytochrome C, + Complex IV: fully oxidized because no electron transport can occur here and beyond- Antifungal: agricultural use
Cyanide
- Inhibits Complex IV
○ CN binds to oxidized form of Heme Iron (Ferric: Fe 3+) –> prevents Complex IV from being reduced!- Treatment for Cyanide Poisoning:
○ Nitrite (NO2-) followed by Thiosulfate (S2O3)
§ Nitrate: Hemoglobin + Nitrite –> Met-Hb (Fe3+) –> Met-Hb competes for binding of CN to Complex IV–> CN-Met-Hb (Fe3+)
§ Thiosulfate: Thiosulfate –> reacts with CN – SCN (Thiocyanate) + SO3 –> excreted urine
□ Thiocyanate is less toxic and more hydrophilic –> excreted in urine
○ Thiosulfate can also work on its own
§ Thiosulfate + CN –> via Rhodanese enzyme (endogenous) –> SCN (Thiocyanate) + SO3 –> Urine
- Treatment for Cyanide Poisoning:
Oligomycin
- Inhibits Fo portion of ATP Synthase:
- Blocks proton flow through Fo –> prevents reentry of protons into mitochondrial matrix
- NO ATP MADE
- Proton gradient builds up
- Electron transport will soon stop because of the difficulty of pumping protons against a VERY steep proton gradient –> inhibition of ATP formation by Oligomycin also prevents oxidation reduction reactions
- Used in the lab
AraC
cancer treatment
- Damage the inner mitochondrial membrane: dissipates proton flow so it goes back into matrix
AZT
used as HIV treatment
- Damage the inner mitochondrial membrane: dissipates proton flow so it goes back into matrix
Aspirin
- Kidnaps protons within intermembrane space –> cross inner membrane –> into matrix
○ Able to do this because it is very LIPID SOLUBLE and weak base
DNP (Dinitrophenol) high dose
- Kidnaps protons within intermembrane space –> cross inner membrane –> into matrix
○ Able to do this because it is very LIPID SOLUBLE and weak base
Atratyloside
- Inhibits ADP/ATP Antiporter (ATP/ADP Translocase)
- Prevents transport and availability of ADP in the matrix for ATP synthesis –> stops ATP synthesis
- Atractyloside Poisoning occurs in Mediterranean area and Northern Africa:
○ Atractylis gummifera L:
§ Easily confused with wild artichoke
§ Children eat because sweet tasting and roots like chewing gum
Disulfarim
- Inhibits Acetaldehyde Dehydrogenase activity
- Causes unpleasant effects when even small amounts of alcohol are consumed
○ Unpleasant effects due to ↑acetaldehyde - Discourages drinking but not a cure for alcoholism
- Causes unpleasant effects when even small amounts of alcohol are consumed
NAPQI (N-Acetylbenzoquinonemine)
- metabolite of Tylenol (Acetaminophen) by MEOS system
- chronic heavy drinks who are sober: CYP activity is enhanced. as a result, the metabolism of Tylenol is enhanced –> increase in NAPQI –> LIVER DAMAGE
Phenytoin
- Inhibits Folate Conjugase (Expressed on jejunum epithelium)
- prevents conversion of polyglutamate folate –> monoglutamate folate
Methotrexate
- COMPETITIVE INHIBITOR of DHFR
- prevents conversion of Folate –> DHF –> THF
- chemotherapeutic
Aminopterin
- Inhibits DHFR
- prevents conversion of Folate –> DHF –> THF
- chemotherapeutic*
Leucovorin (Folinic Acid)
- Bypasses the metabolic block of Methotrexate
- Bypasses DHFR block of Methotrexate
- Effective at combating the neurotoxicity, GI toxicity, and myelosuppression effects of Methotrexate
○ Folinic Acid is the ACTIVATED form of Folate
Sulfonamides
- Inhibits DHPS (Dihydropteroate Synthetase) in bacteria
- this enzyme is unique to bacteria
- prevents Folic Acid synthesis in bacteria
Trimethoprim
- PREFERENTIALLY inhibits bacteria DHFR (Dihydrofolate Reductase) over human DHFR
- Prevents THF formation
Azaserine
Potent inhibitors of purine nucleotide synthesis by irreversibly inhibiting PRPP-amido-transferase
- glutamine analog
DON
Potent inhibitors of purine nucleotide synthesis by irreversibly inhibiting PRPP-amido-transferase
- glutamine analog
Ribavirin
- Inhibits IMP Dehydrogenase
- Depletes intracellular pools of GUANINE nucleotides
- antiviral used to treat Hepatitis C
Mycophenolic Acid
- Inhibits IMP Dehydrogenase
- Depletes intracellular pools of GUANINE nucleotides
- used as immunosuppressant to prevent graft rejction (renal transplants)
Allopurinol
Xanthine Oxidase Inhibitor; 3-fold mechanism
1. Allopurinol --> COMPETITIVELY inhibits Xanthine Oxidase 2. Allopurinol is converted to Alloxanthine by Xanthine Oxidase i. Alloxanthine is a potent IRREVERSIBLE inhibitor of Xanthine Oxidase - Xanthine and hypoxanthine are more soluble than uric acid and can be excreted in the urine easily*** 3. Allopurinol --> ↓Xanthine Oxidase --> ↑Hypoxanthine --> salvaged to produce IMP i. IMP is an INHIBITOR of PRPP-Amido-Transferase --> ↓purine synthesis and thus ↓purine degradation
- used for GOUT treatment
- hypoxanthine analog
Hydroxyurea
Inhibitor of Ribonucleotide Reductase
- used as a cancer treatment
5-Fluorouracil
- Gets converted to 5-FdUMP by Thymidine Kinase
- 5-FdUMP covalently inhibits Thymidylate Synthase
- Leads to THYMINELESS CELL DEATH
- used an cancer treatment
Acyclovir
- used to treat Herpes Simplex Virus
- phosphorylated by viral Thymidine Kinase
- (P)-Acyclovir then acts as a DNA chain terminator
- Guanosine Analog
Sovaldi
- used to treat Hepatitis C
- Uridine analog
- obligate chain terminator
Bactrim
mix of Sulfonamide + Trimethoprim
- inhibits THF production in bacteria
Abarcose
Inhibits alpha-glucosidases:
- Slows absorption of carbohydrates in the small intestine - ↓postprandial elevations in blood glucose - used for DM 2 - also used to LOWER CHOLESTEROL
Sulfonyureas (Gilburide)
Inhibits ATP-sensitive K+ channel in B-cells
- ↑K+ intracellular concentration - Causes longer depolarization of the B-cell membrane - Longer triggering and opening of voltage-gated Ca channels - Elicits a RISE in intracellular Ca2+
- ↑insulin secretion from B-cell
- ↓serum glucagon levels
- used for DM 2
Metformin (Biguanides)
INHIBITS GNG STIMULATES GLYCOLYSIS
- Inhibits complex I of ETC –> ↓ATP production –> ↑AMP –> ↑AMPK
- ↑AMP –> inhibit AC –> ↓cAMP –> ↓PKA –> ↓GNG + ↑Glycolysis
- ↑AMPK –> IMPROVES INSULIN SENSITIVITY:
○ ↑AMPK –> ↑insulin receptor function
○ ↑AMPK –> ↑glucose transport
○ ↑AMPK –> ↓FA synthesis
- Improves insulin sensitivity: • ↑insulin receptor function • ↑glucose transport • ↓FA synthesis • ↑Glycolysis • ↓GNG - used for DM 2
DPP-4 Inhibitor (Januvia)
Inhibits DPP-4 (hydrolase) –> ↑active incretins
- Enhances insulin secretion due to ↑incretins
- used for DM 2
SGLT2 Inhibitor
Block the reabsorption of glucose in the kidney
- ↑glucose secretion in urine
- ↓blood glucose
- But MAY lead to UTI (urinary tract infections)
○ Glucose in the urine may facilitate bacterial overgrowth
- ↓blood glucose
- used for DM 2
Thiazolidinedione (Avandia)
Activates PPARy transcription factor
- ↑insulin sensitivity of adipose tissue - ↑glucose uptake into adipose tissue and muscle - Leads to WEIGHT GAIN - ↑insulin sensitivity of adipose tissue - ↓blood glucose - used for DM 2
Statins
- Inhibits HMGCoA Reductase
- increases # of LDL receptors on liver
- decreases LDL
- lowers cholesterol
Ezetimibe
- inhibits absorption of cholesterol at the brush border membrane in the intestinal membrane
- increases # of LDL receptors on the liver
- LDL decreases
- LOWERS CHOLESTEROL
Nicotinic Acid (Niacin)
- inhibits mobilization of FFA from peripheral adipose tissue to the liver
- LDL decreases
- LOWERS CHOLESTEROL
Bile Acid Sequestrants (BAS)
- depletes bile acid pool and disrupts enterohepatic circulation of bile acids, thus increasing bile acid synthesis from cholesterol
- LDL decreases
- LOWERS CHOLESTEROL
Fibrates
- decreases VLDL
- increases HDL
- LOWERS CHOLESTEROL
