Steroids MOA
Prevent T-cell activation by blocking cytokine production
Steroid Adverse Effects
Cushing's syndrome, osteoperosis, myopathy, cataracts, glucose intolerance, hypercholesterol
Azothioprine MOA
Disrupts purine incorporation into DNA, prevents proliferation of T-cells
Azothioprine Adverse Effects
Hematological effects, infections, pancreatitis, cholestatic jaundice, heoatitis, interstitial pneumonitis, increase levels with allopurinaol causing increasd neutropenia
Mycophenolate mofentil MOA
Inhibit inosine monophosphate dehydrogenase in guanine synthesis, inhibits DNA synthesis in T and B cells
Mycophenolate Mofentil Adverse Effects
N/V/D - direct GI toxicity, infections, sepsis, leukopenia, lymphoma
Alprostadil
PGE1 analog, erectile dysfunction, maintain ductus arteriosus
Misoprostol
PGE1 analog, GI cytoprotection, abortifacient
Carboprost
PGF2a analog, postpartum bleeding, abortifacient
Dinoprostone
PGE2, abortifacient, cervial preparation
Lubiprostone
PGE1 analog, activates Cl channels to increas fluid secretion into GI, treatment of chronic idiopathic constipation and IBS-constipation
Epoprostenol
PGI2 analog, dilates pulmonary arteries, pulmonary hypertension
Treprostinil
PGI2 analog, dilates pulmonary arteries in pulmonary hypertension
Bimatoprost, Latanoprost, Travoprost
PGF2a analog, increases aquesous humor outflow, open angle glaucoma
Montelukast
LTD4 leukotriene antagonist
Zarfirlukast
leukotriene antagonist, inhibits CYP2C19, 3A4
Zileuton
5-lipoxygenase inhibitor, flu-like syndrome, drowsiness, hepatic enzyme elevation, inhibits CYP1A2, 3A4
CD4+
T-helper cells
CD8+
Cytotoxic T cells
Innate or natural immunity
receptor mediated, no priming, low affinity
Adaptive or learned immunity
antigen specific, priming needed, very high affinity
B lymphocytes
Hummoral immunity, mature in lympohid tissue, slow, responsible for autoimmune, suppress bone marrow to decrease actions, activated by cytokines
T lymphocytes
cellular immunity, must pass through thymus, quick
Antigen presenting cells
dendritic cells, macrophages, B cells
MHC class 1
on all nucleated cells, CD8+ cells
MHC class 2
on B cells, APC, CD4+ cells
Hyperacute rejection
activationof complement, within minutes
Accelerated acute rejection
both cellular and humoral immunity, within 1-4 days
Acute rejection
90% T-cell mediated, 10% humoral mediated, symptoms due to cytokine release
Antiproliferative agents
Azathioprin, Mycophenolate mofetil
Immunoglobins
anti-lymphocyte antibodies
Calcineurin inhibitors
cyclosporin, tacrolimus
IL-2 receptor antagonists
Basiliximab, Daclizumab
mTOR (Target of Rapamycin) inhibitors
Sirolimus
ATGAM
horse, binds peripheral T-cells, rejection prophylaxis and early rejection
Thymoglobulin
Rabbit, depletes circulating T-cells, rejection prophylaxis and early rejection
Muromonab (OKT-3)
mouse, inhibits transduction of antigen recognition, causes internalization of T-cell receptors, acute rejection, first dose response
Basiliximab
mouse, antibody against IL-2 CD25 receptor, prevents activated T-cell killing, prophylaxis and acute rejection
Daclizumab
humanized, antibody against IL-2 CD25 receptor, prevents activated T-cell killing, prophylaxis and acute rejection
Cyclosporin
binds cyclophilin, inhibits calcineurin, prevents NF-AT from stimulating IL-2 transcription
Cyclosporin adverse effects
renal dysfunction, diabetogenic, hyperglycemia, hirsutism
Tacrolimus
Binds FKBP-12 to inhibit calcineurin, prevents NF-AT activating IL-2 transcription, maintenance and rescue
Tacrolimus Adverse Effects
hyperglycemia (more), nephrotoxicity, more disorientation, alopecia
Sirolimus
binds FKBP-12 and inhibits mTOR, acute rejection, prophylaxis, impaired wound healing
Everolimus
similar to sirolimus
Amnesia
hippocampus
Immobiliry
thalamus
Analgesia
pain pathways
Unconsciousness
RAS
Clonidine
decrease NE in the descending pathway - can lower doses of anesthetics
Neostigmine and atropine
used to reverse blockade after surgery
Nitrous Oxide
works on NMDA and K+ receptors, low MAC, fast equilibrium, causes sedation and analgesia, least incidence of malignant hyperthermia, interacts with Vit. B12
Halothane
low MAC, high blood:gas coefficient, CYP2E1 (alcoholics), used in children
Sevoflurane
Lower MAC than halothane, used in children, not irritating, bronchodilator
Enflurane
muscle relaxation, pungent odor, faster induction, little arrhythmias, high conc. causes CNS excitation and seizures
Isoflurane
unconsciousness and muscle relaxation, little effect on CO or arrhythmias, most widely used
Desflurane
Unconsciousness and some muscle relaxation, used for maintenance, 99% eliminated unchanged, irritating to respiratory tract
Xenon
no effect on BP, respiration, CO, no liver or renal toxicity
Dantrolene
blocks Ca release from RYR1 in malignant hyperthermia
Thiopental, Methohexital
used for induction, no analgesia, metabolized by liver, good for head injury, reduces BP and CO
Propofol
little accumulation, less bronchospasm, anti-emetic, hypotension, pain at injection site
Ketamine
not complete unconsciousness, analgesic, reduced senses, immobility, amnesia, increases BP and CBF, less respiratory depression, bronchodilation, unpleasant recovery
Etomidate
little effect on BP or CO, best for coronary disease, cardiomyopathy, CVD, N/V
benzodiazepines
anxiolysis, sedation, amnesia
Dexmetetomidine
analgesic, alpha-2 autoreceptor
pKa >> pH
mostly charge form
pKa < pH
mostly uncharge form (better loacl analgesia)
Cocaine
low potency, short duration of action
Procaine
low potency, short duration of action, not topically effective, dentistry
Benzocaine
too much can cause methemoglobinemea (dose not bind oxygen)
Lidocaine
CYP1A2,insensitivity in ADHD
Etidocaine
lasts longer than lidocaine, obstetrical procedures
Bupivavaine, merpivacine, ropivacane
obststrical procedures, more cardiac complications (depression)
Prilocaine
immediate potency, dentistry, low cardiac, used in intravenouse regional anestheasia, toxic metabolit - methemoglobinemia
Interferon
activates NK cells, upregulates Th1 cells and macrophages, flu-like syndrome
Interferon a-2-a
anticancer, hepatitis C, flu, depression, hpotension, arrhythmia
Interferon a2b
hepatitis B, flu, depression, hpotension, arrhythmia
Interferon b-1a, b-1-b
relaapsing MS, flu
Interferon gamma-1b
activates phagocytosis, increases oxygen radicals, flu, GI distress, weight loss, depression
Stem Cell Growth Factor (Stemgen)
stimulate blood progenitor cells for transplant, increases release from marrow
Sargramostim (CSF)
enhances maturation of neutrophils, platelets, macrophages, eosinophils, RBC, monocytes, stimulate bone marrow, neutropenia, aplastic anemia
Filgrastim (CSF)
glycoprotein, not glycosylated, stimulates proliferation, stimulate WBC, neutropenia and decrease infections after chemotherapy
Pegfilgrastim
Pegylated, increase duration of action
Interleukin-11
increase megakaryocyte maturation, chemotherapy induced thrombocytopenia
Thrombopoietin
increases megakaryocytes
Eltrombopag
non-peptide thrombopoietin agonist, increase platelets, hepatotoxic
Romiplostim
fusion protein linked to two IgI that acts as TPO agonist, bone marrow fibrosis
Plerixafor
CXCR4 receptor antagonist, increase CD34+ stem cell in blood, teratogenic
Erythropoietin
enhances survival, maturation, and proliferation of RBC, used in anemia, use lowest dose, increased cancer?