Pharmacology Flashcards
What is calcineurin?
Calcium/calmodulin dependent PHOSPHATASE
Which proteins/immunoglobulins (when bound to their drug) will inhibit calcineurin?
Cyclophilin (Cyclosporin)
FK Binding Protein (Tacrolimus)
Macrophilin (Pimecrolimus)
Actions of cyclosporine
- Prevents early T cell activation
- Prevents synthesis of cytokines (esp. IL-2)
- Stimulates secretion of TGF-B
What are unique toxicities of cyclosporine?
- Hirsutism
2. Gingival hyperplasia
Azathioprine affects which phase of the cell cycle?
S phase
Azathioprine mechanism
Purine Analog (A, G)
- Metabolized to ribonucleotide monophosphates (and some di or tri phosphates) → feedback inhibition of enzymes required for purine nucleotides
- Triphosphates become incorporated into DNA and cause RNA miscoding and faulty transcription
Azathioprine has a greater affect on (humoral/cell mediated) immunity
Cell mediated
Side effects of azathioprine?
- BM suppression
- Acute pancreatitis
- Hepatotoxicity
Mycophenolate blocks which phase of the cell cycle?
S phase
*Non-myelotoxic
Mycophenolate MOA
Inhibits monophosphate dehydrogenase → responsible for purine synthesis
- Inhibits lymphocyte proliferation
- Reduces IFN-y production and auto-antibody products
Mycophenolate adverse effects
- GI Hemorrhage
- Anorexia
- Diarrhea
Leflunomide blocks which phase of the cell cycle?
S phase
Leflunomide MOA
- Inhibits dihydroorotate dehydrogenase → blocks pyrimidine synthesis
- Inhibits T and B lymphocytes
- Anti-proliferative effect on smooth muscle cells and fibroblasts - Inhibits tyrosine kinase
What is the metabolite of leflunomide?
TMFA
- GI effects in humans
- Renal effects in dogs
What is the formula for carbonic anhydrase activity?
H + HCO3 -> H2CO3 -> H2O + CO2
What is essential for carbonic anhydrase activity?
Zinc
What are the clinical uses for carbonic anhydrase inhibitors?
- Antiglaucoma agents
- Diuretics (weak diuretic)
- Decrease CSF production
What is an important adverse event for tacrolimus?
Severe vasculitis
*Others include hepatic failure and intussusception
Cyclosporine formulations: Which is better?
Neoral vs Sandimmune?
Neoral is better
*Sandimmune requires emulsification by bile salts
What toxicities are associated with digoxin?
- CNS: Depression
- GI: Anorexia, vomiting
- Myocardium: Prolongation of PR interval and AV block, severe myocardial toxicity
- Renal failure
- Electrolyte abnormalities: Hyperkalemia, Hyponatremia
*Things that will exacerbate the toxicity: Hypokalemia, Hypercalcemia, Hypothyroidism, and Renal Disease
What is a contraindication of digoxin use?
Ventricular arrhythmias
Demeclocycline
- Class
- Uses
- AE
- Tetracycline
- ADH inhibitor, Used for treatment of SIADH
- Nephrotoxic
Macrocyclic lactones
1. MOA
Irreversible opening of glutamate gated chloride channels leading to neuronal depolarization - parasitic paralysis
Class?
1. Ivermectin, mibemycin, selamectin, moxidectan
- Macrocyclic lactones
TMS
- Class
- Bacteriostatic/Bacteriocidal
- Time/Concentration Dependent
- MOA
- Targets
- AE
- Resistance
- BBB?
- Sulfa
- Bacteriostatic
- Time dependent
- Inhibition of DNA/RNA synthesis → folic acid inhibitor, purine synthesis inhibitor
- Gram + and Gram -, minimal effect on anaerobes
- Allergic reactions to sulfonamide component
- Resistance due to altered DHFR or DHFR overproduction
- Lipid soluble → penetration of BBB
Rifampin
- MOA
- Targets
- AE
- Resistance
- Inhibits bacterial RNA polymerase → no mRNA production
- Intracellular bacteria (mycobacterium, brucella, bartonella)
- Hepatotoxicity → one of the most powerful microsomal hepatic enzyme inducers, Induces p450
- Resistance via RNA polymerase point mutation → resistance arises quickly when used with other drugs
