Glucocorticoids:

Use?

first line therapy for transplant recipients, ITP, RA, allergies, asthma,  chemo, GVHD

Use: ALL organ transplants, more potent than Cyclosporine A

Mechanism: IL-2 inhibitor…binds to FKBP to prevent calcineurin activation…very similar to CSA

Use: prophylaxis in organ transplants..USE IN PATIENTS WITH HIGH RISK FOR NEPRHOTOXICITY

Mechanism: Binds to circulating FK506-binding protein 12…. Blocks IL-2 receptor…Block mTOR signaling (not involved in calcineurin!)

Contra/Interactions: grapefruit juice….DO NOT GIVE WITH CYCLOSPORINE!! AGGRAVATES RENAL DYSFUNCTION

Adverse effects: dose related myelosuppresion, thrombocytopenia, anemia, decreased wound healing, increased LFTs, HTN, rash, acne, diarrhea

Use:kidney, liver, and heart transplants…USE WITH GLUCOCORTIOIDS, BUT NOT AZATHIOPRINE

Mechanism: IMP DEHYDROGENASE inhibitor (this is the rate limiting step in guanosine synthesis)

Use:anticancer, RA, GVHD

Mechanism: folate analog, cytotoxic and anti-inflammatory

Use: solid-organ transplant rejection…PREVENT ACUTE RENAL REJECTION

Mechanism: binds to lymphocytes and mediates Complement mediated lysis!  (Antibodies to CDs..depletes circulating lymphocytes

Interactions/Contraindications:DON'T ADMINISTER WITHIN 2 MONTHS OF LIVE VACCINE

Adverse Effects:myleosuppresion (dose limiting), anaphylaxis, hypo/hypertension, utricaria and rash (nephrotoxicity with serum sickness), thrombosis and phlebitis assoc with infusion

Use:PLAQUE PSORIASIS

Mechanism:inhibits t cell activation by binding to CD2, reduces T cells!

Use:prophylactic for renal transplant

Mechanism:Binds to IL-2 Receptor (CD25) on T cells

Note: Basiliximab has a higher affinity!!

Use:organ transplants

Mechanism:AB against CD3, depletes T cells Adverse Effects:CYTOKINE RELEASE SYNDROME, INFECTION, potentially fatal pulmonary edema!! CV collapse

Use:HSV-1, 2 (DNA virus)….(VZV and EBV to some extent)

Mechanism: activated by viral TK (A-P)…then host kinases phosphorylate…A-PPP… causes DNA chain termination during replication

Interactions:NEPHROTOXIC DRUGS can cause renal damage…ZIDOVUDINE (AZT) can cause lethargy

Adverse Effects:NEPHROTOXICITY (with high IV dosing)….some neurotoxicity

Use: CMV, CMV RETINITIS

Mechanism: Cytosine nucleoside analogue… CAN BECOME ACTIVATED IN UNINFECTED CELLS…. HIGHER AFFINITY FOR CMV DNA POLYMERASE

Use: CMV RETINITIS (good to use for resistant strains)

Mechanism: NON-NUCLEOSIDE INHIBITOR (doesn't need to be activated by TK kinase)…IT'S AN INORGANIC PYROPHOSPHATE ANALOGUE…inhibits viral DNA pol

Interactions/Contraindications: Nephrotoxic drugs, additive effects…PENTAMIDE INCREASES HYPOCALCEMIA RISK

Adverse Effects: NEPHROTOXICITY, HYPOCALCEMIA (CNS effects (HA and anxiety)

Use: CMV retinitis who are intolerant to other therapies!!

Mechanism: 21 BASE PAIR OLIGONUCLEOTIDE COMPLEMENTARY TO viral mRNA (antisense)

iritis......  intravitreal injection

Note:  Iritis is NOT a song by The Goo Goo Dolls

Use: INFLUENZA A PROPHYLAXIS AND TREATMENT

Mechanism: targets viral M2 proton channel, INHIBITS UNCOATING FROM ENDOSOME

Interactions: antihistamines, anticholinergics, alcohol (increase CNS effects)

Adverse effects: CNS effects (ataxia, insomnia, confusion, seizures)

Use: influenza A and B (treat within 48 hours of onset)

Mechanism: INHIBIT VIRAL NEURAMINIDASE (THEY ARE SIALIC ACID ANALOGUES)…can't BUD AND RELEASE!

Effects: transient (GI distress)…behavioral problems?

ORAL, RAPID

Effects: BRONCHOSPASM!  DON'T GIVE TO PATIENTS WITH ASTHMA

It's inhaled

Use: CHRONIC HEPATITS C and RSV in children (overall, a wide range of RNA and DNA viruses)

Mechanism: IMP dehydrogenase inhibitor?, interferes with viral mRNA capping and viral RNA pol

PREVENTS ACTIVATION OF ZIDOVUDINE!

Can cause hemolytic anemia

Elimination:Kidney

Resistance: mutations in DNA pol, RNA pol, HIV RT

Use: IFN-a for Chronic Hep B/C, Kaposi's Sarcoma

Mechanism: boots host immune response, stop viral protein synthesis

Adverse Effects: DOSE-LIMITING, MYELOSUPPRESION, NEUTROPENIA

injected, subQ (PEGYLATED), slows absorption, decreased clearance

Use:HIV

Mechanism: BLOCK FUSION TO CD4 T CELLS…BINDS VIRAL GP41

Use: HIV

Mechanism: CCR5 antagonist

Use: HIV, reduce risk of maternal fetal transmission

Mechanism: Zido-P by host cells, competes for RT!!! "NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR"…chain terminatory, block viral replication

Use: HIV

Mechanism: non-competitive inhibitors of HIV RT

Interactions: METABOLISM OF PROTEASE INHIBITORS INCREASED BY NNRTI'S…monitor or adjust dose of protease inhibitor

Side Effects: RASH, GRANULOCYTOPENIA, GI problems….. Efavirenz also has drowsiness, dizziness, altered dreams, HA

Use: HIV

Mechanism:protease inhibitors!!.. HIV mRNA can't be cleaved into proper fragments?

Interactions: other drugs metabolized by CYP3A4….NNRTI'S MAY INCREASE METABOLISM OF PROTEASE INHIBITORS!

Adverse Effects: GI PROBLEMS, BUFFALO HUMP, HYPERGLYCEMIA, NEPHROLITHIASIS

Use: HIV

Mechanism: Integrase inhibitor

Treatment for TB...use for up to 24 months...

Rifampin Isoniazid Pyrazinamide Ethambutol Streptomycin

Use: alone for prophylaxis…or combo for TB!

Mechanism: inhibibts Mycolic Acid…bacteriostatic for growing forms, bacteriostatic for resting forms

Use:TBL and Leprosy…inhibit G+ and G- bacteria

Mechanism: inhibit DNA dep RNA polymerase…binds to bacterial form with higher affinity

Use: for LEPROSY

Mechanism: ANTIFOLATE, SIMILAR TO SULFONAMIDES….PABA ANALOGUES THAT INHIBIT DIHYDROPTEROATE SYNTHASE…

Use: invasive candidiasis….aspergillosis

Mechanism: cell wall synthesis destruction by inhibiting 1,3-beta glucan synthase

Interactions: immunosuppressants (Cyclosporine)…CAN CAUSE HEPATOTOXICITY

Adverse Effects:some phlebitis, GI, hypersensitivity

Use: CANDIDIASIS

Mechanism: binds ergosterol in fungal umembranes

Used for: DERMATOPHYTES…NAIL FUNGUS (ONYCHOMYCOSIS, JOCK ITCH (T. CRURIS, ATHLETE'S FOOT (T. PEDIS)…ringworm (Tinea Capitis)

Mech: INHIBITS SQUALENE EPOXIDASE…. (INTERFERES WITH ERGOSTEROL SYNTHESIS)… leads to accumulation of sterol squalene in fungi, toxic

Use: superificial and systemic fungal infections…NOT ASPERGILLOSIS

Mechanism: interfere with Lanosterol-14a demethylase (CYTOCHROME P450 ENZYME)….ergosterol synthesis

Broad spectrum (REALLY ASPERGILLOSIS)

INTERFERE WITH LANOSTEROL 14A DEMETHYLASE, ...THIS LEADS TO IMPAIRED ERGOSTEROL SYNTHESIS

Use: SYSTEMIC INFECTIONS…(ESP CANDIDA AND CRYPTOCOCCUS)….USED WITH AMPHOTERICIN B FOR CRYPTOCOCCAL MENINGITIS

Mech: INHIBIT DNA/RAN SYNTHESIS…CYTOSINE NUCLEOSIDE ANALOGUE… CONVERT DRUG TO 5-FLUORURACIL BY CYTOSINE DEAMINASE (NOT PRESENT IN MAMMALS)

Use: DERMATOPHYTES (SKIN, HAIR, NAIL)…RINGWORM CAUSED BY MICROSPORUM, EPIDERMOPHYTON, OR TRICHOPHYTON

Mechanism: BINDS MICROTUBULES…MITOSIS INHIBITOR (CAUSES MULTINUCLEATED CELLS)

TERATOGENIC AT HIGH DOSES

get blood counts 1/wk for first month…HA, rash, photosensitivity

Use: PCP (fungus) 

Mechanism: Sufla inhibits DHPS                          Trimethoprim inhibits DHFR……

DHPS is not present in mammals… DHFR is present in mammals, but different

Use- PCP, Leishmaniasis, African Trypanosomniasis

No known mechanism (orphan drug)

avoid other nephrotoxic drugs

nephrotoxicity, cardiovascular, hypoglycemia!.....  

Use: Anaerobeic Protozoa + Heliobacter, Clostridium

Mechanism: anaerobic ET generates damaging free radicals

Caution for: PATIENTS WITH ACTIVE DISEASE OF CNS…

Adverse effects:  mild, generally safe

Infection with P. Falciparum... progression can be rapid and severe

IV for aggressive malaria!

Severe malaria = parasitemia > 5% (24-48 hours to live)

Pregnancy--> 3x more likely to develop severe malaria

Quinine + Doxycycline

Atovaquone/Proguanil

Mefloquine

Quinine + Doxycycline

Mefloquine

Use: plasmodium/malaria…prophylaxis and treatment

Mechanism: parasitized RBCs take up 100x more chloroquine than uninfected.  Radiolabled chloroquine binds to toxic heme in the parasite food vacuole, heme can't polymerize, parasite dies in own waste

Resistance--> extensive, most mutations in food vacuole transporter "crt" mutation

Use: effective against erythrocytic forms of Plasmodium….USE AGAINST CHLOROQUINE RESISTANT STRAINS!

Mechanism: inhibition of heme polymerization

NOT FOR PATIENTS WITH EPILEPSY OR MYASTHENIA GRAVIS, OR PSORIASIS…hemolysis in patients with G6PD…also, DON'T GIVE TO PATIENTS WITH TINNITUS OR OPTIC NEURITIS more toxic…

cinchonism (flushed sweaty skin), hypoglycemia, hypotension

mutations in multidrug resistance transporter, mdr1

Use for: chloroquine resistant strains of malaria

Mechanism: inhibition of heme polymerization

do not give to patients with seizures

well tolerated, avoid in pregnant women

 slowly eliminated (delay pregnancy for 3 months after drug) mdr1 mutations

mdr1 mutations

Use: malaria prophylaxis...also Toxoplasmosis and PCP

Mechanism: selective mitochondrial inhibitor (parasite cytochrome bc1 complex)…structural analogue of ubiquinone, respiratory chian electron carrier

Use: malaria prophylaxis, also toxoplasmosis and PCP

Mechanism: enhances collapse of mitochondrial membrane potential and its metabolite is a DHFR inhibitor

SEVERE MALARIA...IV 24 HOURS

CAN BE CARDIOTOXIC WITH LOW BP, LOW BLOOD SUGAR AND PROLONGED QTc interval

Artemisin based combination therapy (ACT).... use and mechanism?

administered?

Use: Malaria

Mechanism:

Heme iron reacts with drug to form damaging free radicals...inhibits SERCA PUMP

Rectal administration, don't use for prophylaxis

USE: TOXOPLASMOSIS AND ANTIMALARIAL AND ANTIBACTERIAL

mechanism: DHPS AND DHFR INHIBITORS RESPECTIVELY

CLINDAMYCIN...

IT INHIBITS PROTEIN SYNTHESIS IN A UNIQUE PLASTID LIKE ORGANELLE IN TOXOPLASMOSIS

leishmaniasis....can have pain at injection site (IV or IM)

most excreted in urine

Use: Chagas disease and 2nd stage of African Sleeping Sickness

Mechanism: free radical formation

Use: AfricanSleeping Sickness

Use: Hemolymphatic stage of African sleeping sickness

(also PCP, leishmaniasis)

Use: african sleeping sickness (t. brucei)

mechanism: orinithine decarboxylase inhibitor (prevents synthesis of polyamines)

Use: chronic stage of T. Brucei

(african sleeping sickness)

results in death

Melarsoprol is given IV

use: nematodes/roundworms

mechanism: inhibits microtubule polymerization/mitotic spindle poison, bind worm tubulin with higher affinity than mammalian orthologue

orally  

these are generally absorbed poorly...great for killing worms in the gut!

use: nematodes/roundworms 

especially Ascaris, Hookworm, Pinworm

Mechanism: depolarizing neuromuscular blocking agents, results in spastic paralysis

Use: ascaris

Mechanism: GABA receptor agonist, hyperpolarization, reduced excitability...FLACCID PARALYSIS

Use: broad spectrum antiparasitic….NEMATODEs, FOR FILARIAE CAUSING RIVER BLINDNESS (ONCHOCERCIASIS)

Mech: kills larvae in host…LARVAE…not adult!....INDUCES PARALYSIS VIA GLUTAMATE GATED CL- CHANNELS

contradindicated when BBB is impaired..can afect GABA receptors!!

UseL flatworms, cestodes (schistosome, tapeworms)

mechanism: spastic paralysis and tegument damage

this is a tapeworm in the eye...can damage host's eye!!

other info:

(given orally, extensive first pass metabolism, inducers of CYP reduce the amount of praziquantel..excreted as metabolites in urine 24 hours later)