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310 Cards in this Set
- Front
- Back
chemistry and pharmokinetics of NSAIDs
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-weak organic acids
-well absorbed -metabolized by CYP3A or CYP2C of P450 enzyme -elimination: renal and biliary excretion / reabsorption -protein bound 98% -found in synovial fluid |
|
Properties of the NSAIDs
|
Anti-inflammatory property of NSAIDs
-reversible or irreversible inhibition of COX -Inhibition of prostaglandin synthesis -Inhibition of chemotaxis -down-regulation of IL-1 production -Inhibition of free radical production -Interference with CA++ mediated intracellular events |
|
Pharmacodynamics of NSAIDs
|
analgesia, anti-inflammatory, and antipyrexia
also inhibit platelet aggregation, except COX-2 selective agents and non-acetylated salicylates |
|
Toxicity of NSAIDs
|
-Gastric irritant-- gastric ulcers & bleeds
-Nephrotoxicity--d/t intereference with autoregulation of renal flow -hepatotoxicity |
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Adverse effects of NSAIDs
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-CNS: headache, tinnitus, dizziness
-CV: fluid retention, hypertension, edema, congestive heart failure -GI: abdominal pain, nausea, vomiting, ulcers and bleeding -Hematologic: thrombocytopenia, neutropenia, anemia -Hepatic: abnormal liver function, liver failure -Pulmonary: asthma -rashes: all types and pruritus -Renal: renal insufficiency, renal failure, hyperkalemia, proteinuria |
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Aspirin
Pharmacokinetics |
-rapidly absorbed from the stomach and upper intestine
-peak plasma concentration in 1-2 hours -serum half life 15 min -hydrolyze to acetic acid -salisylate is bound to albumin -urine alkalization increases rate of excretion of salisylate |
|
Aspirin
MOA |
IRREVERSIBLE inhibition of COX
COX is an enzyme that converts arachidonic acid into prostaglandins and related compounds (prostacyclin, thromboxane A2). |
|
Aspirin
Clinical Uses |
decrease incidents of TIA, thromboses and MI
long-term use decreases incidences of colon cancer |
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Aspirin
Adverse Effects |
gastric intolerance, gastric ulcers, hepatotoxicity, asthma, rashes, GI bleeding, occasional renal toxicity
|
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Nonacetylated Salisylates
|
(magnesium choline salicylate, sodium salicylate, salicyl salicylate)
-effective anti-inflammatory drugs -ineffective analgesics -DO NOT inhibit platelet aggregation -DO NO inhibit COX -preferable drug for pts with asthma, bleeding tendencies, and renal dysfunction. |
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COX-2 Selective Inhibitors
|
-inhibit COX-2
-analgesia, anti-pyretic, and anti-inflammatory effects -DOES NOT inhibit platelet aggregation -Celecoxib: fewer GI ulcers, may cause rashes, does not affect platelet aggregation, interacts with warfarin b/c they are metabolized by CYP2C9 -Meloxican: fewer GI symptoms, inhibits thromboxane A2 synthesis |
|
Nonselective COX inhibitor
Diclofenac |
-GI ulcers and bleeding are less frequent
-renal adverse effects common (impaired renal blood flow and decreased GFR) -recommended for post op analgesia |
|
Nonselective COX inhibitor
Diflunisal |
-undergoes enterohepatic cycle with reabsorption
-long half life--13 hours -used in rheumatoid arthritis, cancer, dentistry -limit in pts with renal impairment |
|
Nonselective COX inhibitor
Flurbiprofen |
-inhibits COX, TNF-a, NOS
-effective in perioperative anaglesia in minor surgeries -adverse effects similar to NSAIDs with additional neuro symptoms-- cogwheel rigidity, ataxia, tremor, myoclonus |
|
Nonselective COX inhibitor
Ibuprofen |
-800mg TID has anti-inflammatory effect
-lower doses for analgesia -adverse effects: fluid retention ****COMBINATION WITH ASA DECREASES ANTI-INFLAMMATORY AND CARDIOPROTECTIVE FEATURES OF ASA |
|
Nonselective COX inhibitor
Indomethacin |
-MOA: inhibit COX, phospholipase A and C, decrease neutrophil migration, decrease T cell and B cell proliferation
-Use: analgesia -S/E: common to other NSAIDs, GI complications can progress to pancreatitis, CNS--h/a, dizziness, confusion, depression, psychosis, hallucinations, Hematology--thrombocytopenia and aplastic anemia, Renal papillary necrosis ** Probenecid prolongs half-life d/t inhibiting renal and biliary clearance |
|
Nonselective COX inhibitor
Nabumetone (nonacid NSAID) |
-half life 24 hours, requires 1 daily dose
-S/E: similar to other NSAIDs, less damaging to GI, but very expensive, can cause pseudoporphyria, photosensitivity |
|
Nonselective COX inhibitor
Piroxicam |
-inhibit polymorphonuclear leukocyte migration
-decreases oxygen radical production -inhibits leukocyte function -long half life permits once daily use -used in rheumatic diseases -s/e: peptic ulcer and bleeding at doses >20mg/d, headaches, rashes, photosensitivity |
|
Important interactions of NSAIDs with other drugs
|
-ASA displaces anticoagulants from their binding site on albumin
-ASA displaces tolbutamide (hypoglycemic drug) and phenytoin (antiepileptic drug) from their binding site on albumin -Analgesic doses of ASA (<2gm/day) decreases renal excretion of sodium urate and antagonized uricosuric effect of sulfinpyrazone and probenecid (NO ASA to gout pts) -Absorption of ASA altered by antacids -ASA competes for tubular reabsorption with PCN G, which prolongs its half life. -Corticosteroids increase renal clearance of salicylates -alcohol may increase GI bleeding if taking ASA |
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Disease-Modifying Antirheumatic Drugs (DMARDs)
|
-T cell modulators
-B-cell cytotoxic agents -TNF-a blocking agents -DMARDs act to slow down destructive processes |
|
Abatacept
MOA half life indications effect adverse effects |
-MOA: inhibit activation of T cell
-Half life: 13-16 days -Indications: mod to severe RA -Effect: reduces s/s and progression RA -Adverse effects: increased risk of resp infections, rare anaphylaxis, anti-abatacept antibody formation, malignancies (lymphoma) |
|
Azathioprine
MOA Indications Adverse effects |
-MOA: suppresses inosinic acid synthesis, B cell and T cell function, IG production and IL-2 secretion
-Indications: RA, 2mg/kg, also for psoriatic arthritis, reactive arthritis, polymyocytis, systemic lupus erythematosus, behcet's disease -adverse effects: bone marrow suppression, GI disturbances, increased risk of infection, lymphoma, fever, rash, hepatotoxicity and allergies rare |
|
Chloroquine & Hydroxychloroquine
MOA Pharmacokinetics Indications Adverse Effects |
-MOA: unclear, but possible suppression of T lymphocytes, decrease leukocyte chemotaxis, trapping of free radicals, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis
-Pharmacokinetics: rapidly absorbed, 50% protein bound, deaminated in liver, half life 45 days -Indications: malaria and rheumatic diseases, SLE, sjogren's syndrome -Adverse effects: ocular toxicity, dyspepsia, n/v, abd pain, night mares, safe in pregnancy |
|
Cyclosporine
MOA Pharmacokinetics Indications Adverse effects |
-MOA: through regulation of gene transcription inhibits IL-1 and IL-2 receptor production, T cell and B cell function
-Pharmacokinetics: 30% bioavailability, metabolized by CYP3A -Indications: RA, at 3-5mg/kg/d 2 doses -Adverse effects: nephrotoxicity d/t interactions with dilitazem, K sparing drugs and other CYP3A drugs, hypertension, hyperkalemia, hepatotoxicity, gingival hyperplasia, hirsutism |
|
Methotrexate
MOA Pharmacokinetics Indications Adverse Effects |
-MOA: inhibition of AICAR transformylase and thymidylate synthase, directly inhibits proliferation, stimulates apoptosis in immune-inflammatory cells
-Pharmacokinetics: absorbed 70%, half life 9-24 hours, excreted in urine and bile -Indications: RA 25-35mg weekly, also used in juvenile chronic arthritis, ankylosing spondylitis, polymyositis, dermatomyositis -adverse effects: nausea and mucosal ulcers, hepatotoxicity, hypersensitivity-type resp reaction, GI and liver toxicity can be reduced by leucovorin 24 hours before administration of methotrexate or by use of daily folic acid. -Contraindicated in pregnancy -Methotrexate conc increases in the presence of cloroquine |
|
Rituximab
MOA Pharmacokinetics Indications Adverse effects |
-MOA: targets CD20 B-lymphocytes which reduces presentation of antigens to T-lymphocytes and reduced proinflammatory cytokines
-Pharmacokinetics: given as two 1000mg IV injections biweekly, pretreated with IV methyprednisolone 30 min prior to rituximab to reduce severity of reaction -Indications: mod to severe RA in combination with methotrexate -adverse effects: rashes, possible anaphylaxis |
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Sulfalazine
MOA Pharmacokinetics Indications Adverse effects |
-MOA: decreases IgA and IgM, suppresses T-cells and B-cells, and release of inflammatory cytokines
-Pharmacokinetics: only 10-20% is absorbed, undergoes enterohepatic circulation, reduced to sulfapyridine in the intestine. Sulfapyridine is excreted after hepatic acetylation and hydroxylation. Half life 6-17h -Indications: RA, juvenile chronic arthritis, ankylosing spondylitis -Adverse effects: n/v, headache, rash are common. Hemolytic anemia, methemoglobinemia, neutropenia, thrombocytopenia are rare. *Reversible infertility occurs in men. |
|
TNA-a blocking agent
Adalimumab MOA Pharmacokinetics Indications Advserse effects |
-MOA: human IgG, anti-TNF-a, prevents interaction of TNF-a with p55 and p75 cell surface receptors, and results in down-regulation of T-cell function
-Pharmacokinetics: given SQ, half life 10-20 days, methotrexate decreases clearance by 40%, 40mg for RA -Indications: RA, ankylosing spondylitis, psoriatic arthritis, juvenile idiopathic arthritis, chron's disease -Adverse effects: risk of bacterial infections and macrophage dependent infections |
|
Glucocorticoid Drugs
indications |
-used in 70% of RA patients b/c of the ability to slow new bone erosions
-also used in vasculitis, SLE, Wegener's granulomatosis, psoriatic arthritis -for long term therapy the dose should not exceed 7.5mg daily -should be used with caution due to toxicity |
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Acetaminophen
Use |
-mild to moderate pain
-NO anti-inflammatory effect -alleviates headache, myalgia fever at doses up 500mg QID -pain reduction is equivalent to ASA |
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Acetaminophen
Pharmacokinetics |
-administered orally, peak concentration in the blood at 30-60 min
-metabolized by hepatic enzymes -half life 2-3 hours, -high dose have renal and hepatic toxicity effects |
|
Acetaminophen
Adverse effects |
-increase in hepatic enzymes, dizziness and disorientation occurs with large doses
-ingestion of a 15g dose is lethal; caution is necessary in patients with liver diseases |
|
Aspirin and Gout
|
ASA can not be used in patients with gout because it inhibits the secretory transporter of urate, and causes its accumulation in the body.
|
|
drugs used for Gout
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colchicine
allopurinol uricosuric agents glucocorticoids NSAIDs |
|
Colchicine
MOA Indications Adverse Effects |
-MOA: anti-inflammatory effect is produced by binding to the intracellular protein-tubulin, and preventing it's polymerization into microtubules; inhibition of leukotriene B4
-Indications: gouty arthritis, mediterranean fever, sarcoid arthritis, hepatic cirrhosis -Adverse effects: diarrhea, n/v, abd pain, possible hepatic necrosis, acute renal failure, DIC, seizures, overdose is presented by burning throat pain, bloody diarrhea, shock, hematuria, and oliguria |
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Uricosuric Agents
MOA Adverse effects |
-MOA: probenecid and sulfinpyrazone decrease the body pool of urate in patients with gout; affect active transport sites of urate in the kidney and reduce reabsorption in the PCT
-adverse effects: GI irritation, rash, nephrotic syndrome, aplastic anemia -caution: maintain large urine volume to prevent urate stone formation |
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Allopurinol
MOA Adverse effects Cautions |
MOA: Allopurinol is an isomer of hypoxanthine; allopurinol is converted to alloxanthine whihc inhibits xanthine oxidase and reduces urate production
-Adverse effects: GI intolerance, n/v/d, peripheral neuritis, necrotizing vasculitis -Cautions; interactions with mercaptopurines, cyclophosphamide, probenecid, and oral anticoags |
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recommended daily intake of iodide
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150mcg
(200 mcg during pregnancy) |
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In patients with hyperthyroid, T3/T4 clearance is _____ and 1/2 life is _____
a. increased b. decreased |
In patients with hyperthyroid, T3/T4 clearance is increased and 1/2 life is decreased
|
|
In patients with hypothyroid, T3/T4 clearance is _____ and 1/2 life is ______.
a. increased b. decreased |
In patients with hypothyroid, T3/T4 clearance is decreased and 1/2 life is increased.
|
|
name drugs that induce hepatic microzomal enzymes, which will increase the metabolism of T3 and T4
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rifampin, phenobarbital, phenytoin, imatininb, protease inhibitors
|
|
why is synthetic T4 the DOC for thyroid hormone replacement?
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cheap, stable, uniform, non-allergenic, long 1/2 life (7 days), easily measured in lab, long shelf life,
-T4 allows body to convert to T3 |
|
why is Synthetic T3 not routinely used for thyroid hormone replacement?
|
shorter 1/2 life (24 h), higher cost, monitoring issues, increased potency,
greater risk for cardiotoxicity, should be avoided in pts with cardiac disease |
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Antithyroid Agents
|
thioamides
anion inhibitors iodides radioactive iodine adrenoceptor-blocking agents |
|
Thioamides
(Methimazole and Prophythiouracil) |
METHIMAZOLE (MTZ)
-10x more potent -completely absorbed, rate variable -1/2 life 6 hours -QD dosing -renal excretion 48 hours (only 65-75% recovered) PROPHYLTHIOURACIL (PTU) -rapidly absorbed but only 50-80% bioavailable -1/2 life 1.5 hours -Q6 h dosing -renal excretion 24 hours |
|
Thioamides and pregnancy
|
Caution must be employed!
MTZ and PTU both cross placenta--> concentrate in fetal thyroid--> risk for hypothyroidism -Category D -PTU preferred b/c it is more strongly protein bound and therefore crosses to placenta less readily -MTZ associated with malformations (rare) -Lactation is considered safe |
|
MOA of thioamides
|
-inhibit peroxidase-catalyzed reactions-- blocking organification and iodotyrosine coupling
-inhibit peripheral deiodination of T3/T4 (less potent at the tissue level) -BUT DO NOT block iodide uptake |
|
Adverse reactions to Thioamides
|
-50% cross sensitivity between PTU and MTZ
-if severe reaction, switching drugs not recommended -rash (4-6%), occas fever, nausea/vomiting -altered taste (with MTZ) -Fatal agranuloctyosis (0.1-0.5%)-- occurs in elderly or high doses, rapidly reversible, dc drug and cover pt with abx and consider colony stimulating factors -Hepatitis (PTU) -Cholestatic jaundice (MTZ) -Rare: uritcarial rash, vasculitis lupus-like reaction, lymphadenopathy, hypoprothromboinemia, exfoliative dermatitis, polyserositis, acute arthralgia |
|
Anion Inhibitors
(Perchlorate, pertechnetate, thiocyanate) |
MOA: block uptake of iodide by thyroid gland by competitive inhibition of iodide transport
-can be overcome by large doses of iodides -Major clinical use: block reuptake of iodide in pts with iatrogenic hyperthyroidism (eg amiodarone-induced) *Perchlorate rarely used (associated with aplastic anemia) |
|
Iodides
|
-used only in severe hyperthyroidism or thyroid storm
-MOA: inhibition of organification (thyroglobulin proteolysis), inhibit hormone release temporarily (2-8 wks then gland escapes block)--> severe thyrotoxicosis -decreases gland size and vascularity, useful pre-op |
|
disadvantages/toxicity of iodides
|
-adds to overall iodine stores
-delays thioamide and RIA therapy -start thioamides 1st, avoid if considering RIA -avoid in pregnancy (fetal goiter) -adverse rx: acneiform rash, swollen salivary glands, mucous membrane ulcerations, conjunctivitis, rhinorrhea, drug fever, metallic taste, bleeding disorders, and anaphylaxis |
|
RIA
|
-only isotope used to treat thyrotoxicosis
-oral solution, rapidly absorbed, concentrated in thyroid, incorporated into follicles -destruction within a few weeks -1/2 life 5 days, effect depends on B rays emission rate |
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Manifestations of destruction of gland by RIA
|
epithelial swelling/necrosis, follicular disruption, edema, leukocyte infiltration
|
|
Advantages and Contraindications of RIA
|
Advantages
-easy to use, effective, cheap, painless, no evidence of long term radiation injury Contraindications -not in pregnancy or lactation (Category X)-- will destroy fetal thyroid gland |
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Adrenoceptor-Blocking agents
|
non-sympathomimetic beta blockers
(metoprolol, propranolol, atenolol) don't treat the gland: adjunctive therapy -sx's of thyrotoxicosis mimic sympathetic stimulation -high levels (propranolol >160mg/d) may reduce T3 by 20% by inhibiting peripheral conversion of T4 to T3 |
|
management of thyroid storm
|
-Beta blocker: control symptoms
-MTZ or PTU: block hormone synthesis -RIA: inhibit peripheral conversion of T4 to T3 -Iodide: block thyroid hormone release -Glucocorticoids: reduce T4/T3 conversion, possibly treat autoimmune process in grave's disease |
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causes of Hypothyroidism (undersecretion of T4)
|
-autoimmune disease (hashimoto's)
-iatrogenic: destruction of gland (RIA or surgery), antithyroid medications -Drug induced- amiodarone (but also causes hyperthyroidism), Lithium (TSH stimulation 50% goiter, but also inhibits hormone synthesis/secretion, onset 6 mo to 2 yrs) |
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Management of hypothyroidism
|
-daily synthetic T4, allows conversion at receptor level
-absorption/effectiveness varies by individual -must be taken on empty stomach (food, coffee & drugs will decrease absorption) -7 day 1/2 life--> QD dosing -takes 6-8 weeks to see change in TSH |
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Monitoring during Thyroid replacement
|
-Peds: watch G&D
-Monitor TSH and T4 regularly -TSH normal range 0.5-2.5 -elderly esp w/ cardiac disease-- start slow, go slow, watch for angina or arrhythmia |
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Toxicity s/s of thyroid drugs
|
related to serum hormone levels
Children: restless, insomnia, accelerated bone maturation Adults: nervous, heat intolerance, palpitations, tachycardia, weight loss Elderly: osteoporosis, atrial fibrillation |
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Dosing for Thyroid drugs
|
Adults
1.6ug/kg/ideal weight initially 75-100ug/day for women 100-150ug/day for men Elderly (lower dose initially) 1.5ug/kg/day/ideal body weight 25-50ug/day x5 weeks final dose: 70% of adult dose |
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Special problems in management of hypothyroidism
|
-Myxedema and coronary artery disease
-Myxedema Coma -Hypothyroidism and pregnancy -sublinical hypothyroidism -drug induced hypothyroidism |
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Grave's disease
|
-an autoimmune disease
-antibody (TSH-R Ab) attacks TSH receptor in follicular cell membrane--> stimulates growth/activity of cell -spontaneous remission possible (not common) -diagnosis: TSH is low and T3/T4, FT3/FT4 is high, antibodies present |
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management of grave's disease
|
-antithyroid drug therapy is useful for young patients, mild disease, and small glands
-MTZ and PTU is administered until the disease undergoes spontaneous remission -long therapy 12-18 mo, but 50-70% recurrence -MTZ generally preferred (unless pregnant) -PTU decrease peripheral conversion so "activated" thyroid level decreases more quickly than MTZ |
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Management--thyroidectomy
|
-large and/or multinodular glands
-pre-surgery: antithyroid meds--10-14 days; potassium iodide decreases vascularity -80-90% of pts need replacement after near total thyroidectomy |
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Management- RIA
|
-preferred if >age 21
-no CV disease--> full dose (no pre-treatment) -severe thyrotoxicosis, CV disease, elderly--> pre-treat with antithyroid drug (MTZ preferred) unti euthyroid -stop antithyroid 5-7 d; avoid iodides (decreases uptake) -gland shrinks 6-12 weeks (2nd treatment ocassionally) -hypothyroidism occurs 80% following RIA |
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Adjuncts to Antithyroid therapy
|
-B blocker (propranolol)-- controls tachycardia, HTN, a fib, monitor serum T4, and gradually wean
-Diltiazem TID--used in pts who can't take B blockers (asthma) -nutrition, vitamin supplements -Barbiturates-- accelerate T4 breakdown (induces hepatic enzymes), sedative effect helpful -bile acid sequestrants-- increase fecal excretion of T4 |
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Toxic Multi-Nodular Goiter
|
-usually seen in postmenopausal women with a long history of goiter
-hypersecrete T3 usually -single nodule--> surgery or RIA -multiple nodules--> MTZ or PTU + surgery |
|
Subacute thyroiditis
|
-viral infection destroys parenchyma
-transient flood of hormone into circulation -may occurs with hashimoto's -supportive therapy (B blockers, ASA or NSAIDs, steroids for inflammation) -Most pt will recover but some pts with underlying thyroid disease don't recover---> replacement |
|
Special Problems of hyperthyroidism
|
-thyroid storm
-exopthalmos (non-reversible) -myxedema (nonpitting, rx steroids -nenoatal graves -subclinical hyperthyroidism -amiodarone-induced |
|
Non-toxic goiter
|
-syndrome of thyroid enlargement without excessive thyroid hormone production
-excessive TSH stimulation--> gland grows -causes: iodine deficiency, hashimoto's thyroiditis, germline mutations, ingestion of goitrogens, thyroid cancer |
|
Thyroid cancer
|
surgery--> RIA---> replacement for life
-monitor for recurrence by withdrawing thyroxine replacement for 4-6 wks to see if hypothyroid sx occur. -tumor recurrence likely if rise in T4 levels or I scan positive |
|
Describe blood flow in pre-term infants that affect drug absorption.
|
Preterms
-low muscle mass -diminished perfusion -absorption irregular and unpredictable -drug might remain in muscle longer -blood flow might suddenly improve (unexpected surge in drug, can be toxic and deadly) |
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Describe GI Function (gastric acids) in pre-term and full-term infants that affect drug absorption
|
Full-term
-gastric acid secretion begins after birth, increases over several hours Pre-term -occurs more slowly -highest conc day 4 of life *consider this in drugs affected by ph |
|
Describe GI function (Gastric emptying) in infants that affect drug absorption
|
Gastric emptying is prolonged by 6-8 hours 1st day of life
-Drugs that are absorbed in stomach are absorbed more completely than anticipated -Drugs that are absorbed in small intestine will have a delayed therapeutic effect |
|
Describe peristalsis in infants that affect drug absorption
|
Peristalsis is irregular and slow
When there is diarrhea, drug time with intestine is shorter--> causing a decreased extent of absorption |
|
Describe GI enzyme activity in infants that affect drug absorption
|
lower in newborn
lower duodenal levels of amylase and other pancreatic enzymes low concentrations of bile acids and lipase---> affects absorption of lipid-soluble drugs |
|
Drug Distribution differences in infants compared to adults
|
-- preemies have less fat than full-term (1% vs. 15%)--> lipid soluble drugs will not accumulate appropriately
--drug/protein binding is reduced in neonates--> increased amount of unbound drug--> causing free drugs to cause greater drug effect or toxicity |
|
what are potential problems with the fact that some drugs compete with serum bilirubin for binding to albumin?
|
-drugs given to jaundiced neonates can displace bilirubin from albumin--> leading to hyperbil--> kernicterus
conversely, As serum bilirubin rises, bili will displace the drug from albumin---> increased risk of free drug--> causing a greater drug effect or toxicity |
|
difference of metabolism in neonates and adults
|
metabolism of most drugs are in liver
-neonates have 50-70% metabolizing activity than adults -lower cytochrome p450 dependent mixed function -decreased ability to metabolize drugs -slow clearance -prolong elimination of half-life |
|
metabolism in toddlers
|
drugs are metabolized faster and require a higher dose/kg..
|
|
Drug excretion differences in children and adults.
|
GFR is lower in newborns than children and adults--> 30-40% the adult value, but even lower in preemies
by 12 months, reaches adult values |
|
difference between elixir-alcohol solution vs. suspensions
|
Elixir-alcohol solution
-molecules are dissolved and evenly distributed -no shaking necessary -first dose should have same drug content as last dose Suspensions -undissolved particles of drug "suspended" in solution -MUST be shaken thoroughly -if not, each dose will be slightly different -lower peak concentration or toxicity |
|
True or False
Formula feeding is associated with more morbidity and mortality than use of medications in breast-feeding mothers |
true
|
|
education on safe administration of drugs in lactation..
|
In relatively safe drugs,
-take 30-60 minutes after nursing -and 3-4 hours before the next feeding -results in lower concentrations in breast milk Drug with NO safety data, -should be avoided -or pump and dump for duration -and for 1-2 half-lives after completion of drug regimen -have mom have a store of milk before starting drug regimen-- or must use formula -stay away from drugs with long-half lives (12 hours) |
|
Antibiotics and lactation
|
-can be detected in breast milk
-tetracycline in breast milk 70% of maternal serum -tetracycline is never given to infants and small children --> cause teeth staining, and affects growth of bones/teeth -INH--> equal does in breast milk and maternal blood--> cause b12 deficiency in infants |
|
sedatives and lactation
|
produce phamacologic effects-- sedation
barbs chloral hydrate diazepam |
|
Opioids and lactation
|
--heroin, methadone, morphine--> can cause dependence, observe for withdrawal during taper period
--Codeine is generally safe, but use with caution -documented deaths from opioid toxicity in b.f. infants |
|
Anesthetics and lactation
|
Versed
-not detected in breast milk after 7 hours -hold bf for 4-5 hours after administration Propofol -small amt detected in breast milk at 24h+ |
|
Lithium and lactation
|
breast conc equal to maternal blood
-very large dose to infant even if low therapeutic dose in mom |
|
Drug of choice of anti-depressants postpartum
|
Zoloft (sertraline)
-excreted in breast milk in low doses -on low doses, no detectable drug found in serum of bf infants |
|
Meds to AVOID in lactation
|
radiation, radioactive iodine, chemotherapy, cytotoxics, immunomodulating drugs
-increased risk of cancer, thyroid drugs |
|
Alcohol and nicotine during lactation
|
alcohol
-minimal use (<1/day) no reported harm -excessive amts (2+/day) produces effects Nicotine -conc in breast milk is low -doesn't produce effects in infants -can be absorbed other ways-- 2nd/3rd smoke |
|
Caffeine during lactation
|
-small amt excreted in milk
-10mg caffeine will have sx |
|
Calculating ped doses
|
age (young's rule)
dose= adult dose x (age in yrs/age+12) weight (clark's rule) dose= adult dose x (weight in kg/70) body surface area is more accurate (impt for chemo drugs) |
|
what is a teratogen?
|
1) cause characteristic malformations
2) predictable effects at particular stages of development 3) dose dependent incidence |
|
Pregnancy Risk Categories
A B C D X |
A: no risk to fetus
B: no risk in animal fetus; info on humans not available C: Adverse effects in animal fetus; info on humans not available D: Evidence of human fetal risk; potential benefits may be acceptable despite risks X: NEVER! Fetal abnormalities reported with known evidence of fetal risk |
|
Fetal therapeutics
|
- involves drug administration to the pregnant woman with the fetus as the target of the drug
-corticosteroids stimulate fetal lung maturity -phenobarbital stimulates fetal hepatic metabolism--> reduces fetal jaundice, hyperbili -antiarrhytmic agents decreases fetal arrhythmia -AZT (zodivudien) decreases vertical HIV transmission |
|
Placental and fetal drug metabolism
|
Placental Barrier
-semipermeable barrier -some drugs metabolized as they cross (can be good or bad d/t toxic byproducts) -Drugs cross placenta enter fetal circulation via fetal vein -40-60% of umbilical venous blood flow enter fetal liver, and the remainder bypasses the liver and enters the fetal circulation -A large portion of drug may return to placental in artery and cycle back umbilical vein again |
|
Factors that affect drug passage to placenta
|
Drugs that are lipid soluble cross the placenta easily, whereas drugs that are ionized, highly polar, or protein bound cross with difficulty.
|
|
several dietary supplements or herbal medications affect antiplatelet/anticoagulant therapy. Of the ones listed in the text, which herbals do not affect therapy?
|
only echinacea, milk thistle, saw palmetto, and melatonin do not affect therapy.
|
|
Ephedra, Ma-huang
|
Use: diet aid, stimulant, bronchodilator
Toxic effects: CNS and cardiac toxicity -avoid in pts at risk for stroke, MI, uncontrolled BP, seizures, anxiety |
|
Enchinacea
|
-enhance immune function, for colds, URI; anti-inflammatory properties
-Adverse Effects: IV- flu sx; oral- unpleasant taste, GI upset, rash -Avoid in pts with immune deficiency d.o. (AIDS, cancer), autoimmune d.o., and Tuberculosis -Avoid in pts taking immunosupressant meds |
|
Garlic
|
-lipid lowering potential
-variable results in lowering BP -fibrinolytic therapy Adverse effects: nausea, hypotension, allergy, and bleeding(rare) -use in caution with anit-clotting meds (ibuprophen, aspirin, warfarin) b/d garlic's antiplatelet effect |
|
Ginkgo
|
-CV: increased blood flow, reduce blood viscosity, promote vasodilation, improve tissue perfusion
-metabolic: antioxidant radical-scavenging properties -CNS: unpredictable results for txt of cognitive impairment and dementia -Adverse effects: nausea, h/a/, GI upset, diarrhea, allergy, anxiety, and insomnia |
|
Ginseng
|
-improve stress response
-Adverse effects: vaginal bleeding, mastalgia, insomnia, nervousness, HTN, -irritability, sleeplessness, and manic behavior reported in psych pts using ginseng and other meds (psych, estrogenic, hypoglycemic) -avoid in combination w/ warfarin -caution in pts who are immunocompromised, taking immune stimulants, and who have autoimmune d.o. |
|
Milk Thistle
|
insufficient evidence to support claims of limiting liver damage, anti-inflammatory properties, or chemotherapeutic properties
-Adverse effects: GI upset, derm, h/a |
|
Saw Palmetto
|
-inconsistent results for txt of BPH
-Adverse effects: 1-3% GI upset, HTN, decreased libido, abd pian, impotence, back pain, urinary retention, h/a |
|
St. John's Wort
|
antidepressant effects
Adverse effects: photosensitization, hypomania, mania, and autonomic arousal caution or avoid in pts taking antidepressants/stimulants-- potential serotonin syndrome or MAO crisis -this herb induces hepatic enzymes -subtherapuetic levels of digoxin, birth control, cyclosporine, HIV drugs, warfarin, irinotecan, theophylline, anticonvulsants |
|
Coenzyme Q10
|
Use: HTN, heart failure, ischemic heart disease, prevention of statin-induced myopathy
Adverse effects: 1% GI upset Drug interactions: decrease effects of warfarin |
|
Glucosamine
|
Use: osteoarthritic knee pain, results are variable
Adverse effects: milk diarrhea, nausea Drug interactions: Increase INR in pts taking warfarin --> bleed, bruise |
|
Melatonin
|
Use: jet lag, insomnia
-melatonin should not be used by females and males attempting to conceive or females breastfeeding Adverse effects: next day drowsiness, fatigue, h/a, irritability, variable BP- Increase or decrease, |
|
Risk factors to Dietary supplements and herbal medications
|
--often perceived as more beneficial b/c of "natural" connoation-- but does not guarantee safety
--under- reported adverse events -chemical analysis is rarely performed on the products -lack of adequate testing for drug interactions |
|
Sources of OTC medication reference
|
1) Handbook of Nonprescription Drugs
2) Nonprescription Drug Therapy-- online reference 3) Physician's Desk Reference for Nonprescription Drugs, Dietary Supplements and Herbs |
|
Overuse of some OTC-- problems
|
- decongestant nasal sprays (afrin)>3 days cause rebound congestion
-antacids--- long term use cause constipation, hypophosphatemia -Laxative abuse-- abd cramping, fluid and electrolyte disturbance -OTC sympathomimetic/caffeine drugs-- insomnia, nervousness, restlessness -ASA, acetaminophen, ibuprophen, naproxen may increased hepatotoxicity GI hemorrhage in pts who drink excessive amt of alcohol -Antihistamines--- sedation, drowsiness |
|
Analgesics and allergy, cough, and cold preparations, contain sympathomimetics. Who should avoid or use these meds with caution?
|
type 1 diabetics, pts with hypertension, angina, or hyperthyroidism
|
|
How or why a med is classified as OTC ?
|
these meds were judged by the review panel to be generally safe and effective for consumer use without medical supervision.
|
|
Reasons why it is essential for clinicians to be familiar with the OTC class of products
|
1) Many OTC meds are effective in treating common ailment, and it is important to be able to help the pt select a safe, effective product
2) many active ingredients contained in OTC drugs may worsen existing medical conditions or interact with prescription drugs 3) misuse or abuse of OTC products may produce significant medical complications |
|
Carbon Monoxide (CO)
|
-competes with oxygen for binding sites of Hgb
-affinity is about 220x higher than oxygen -form carboxyhemoglobin-- cannot transport oxygen to tissues - hypoxia -treatment: hyperbatic oxygen |
|
Lead Pharmacokinetics
|
-Absorption: respiratory and GI tract
-Distribution: soft tissue, brain, bone marrow, brain, kidney, liver, muscle, gonads, the later to bone matrix -Elimination: 70% kidney -half life blood/soft tissues 1-2 mo -half life bone years to decades |
|
Lead Pharmacodynmics
|
CNS
- deficits in neurocognitive function in children -h/a, fatigue, visual-motor impairment Blood-anemia -interfere with heme synthesis -increase erythrocyte membrane fragibility and decrease its survival time -Kidney: renal dysfunction -Gi tract-- severe abd pain -CV- increased BP -Reproductive- stillbirth/ SAB |
|
Aresenic Pharmacokinetics
|
-Absorption: respiratory and GI tract
-Distribution: soft tissue, liver, kidney, nails, hair, skin -Metabolism: liver -Elimination: Kidney, prolong half life |
|
Arsenic Phamacodynamics
|
-GI tract: Gastroenteritis, hypotension d/t fluid loss
-Blood: panycytopenia, develop in 1 wk -Cardio-pulm: congestive cardiomyopathy, pulm edema -CNS: delirium, encephalopathy, coma, delayed onset of peripheral neuropathy |
|
Mercury Phamacokinetics
|
-Absorption: respiratory and GI tract
-Distribution: soft tissue, kidney, CNS -Elimination: urine, feces, week to months -may retain in kidney and brain for years |
|
Mercury Intoxication
|
-acute: pneumonitis, noncardiogenic pulm edema
-chronic: tremor, neruopsychiatric disturbance, gingivostomatitis |
|
Chelators
|
Purpose: prevent or reverse the toxic effects of heavy metal on cellular target
MOA: form covalent bond with heavy metal; enhance excretion of complex; redistribution to other organ |
|
Dimercaptrol (BAL)-- chelator
|
Indication:
-acute posion of arsenic and inorganic mercury -severe lead poison in conjunction with Ca EDTA -IM injection (10% peanut oil) -Adverse effect: high incident of HTN, tachycardia, N/V, fever, thrombocytopenia, increase PT -precaution: redistribution of arsenic and mercury to CNS |
|
Succimer-- chelator
|
Indication: treatment of lead conc >45mcg/dl for children, also used of arsenic and inorganic mercury
PO only Adverse effect: well tolerated, but GI disturbances, rash, and reversible increase of liver enzymes Precaution: redistribution, short half life 2-4 hours |
|
Ca EDTA--chelator
|
Indication: high lead concentration, also for poison of zine, manganese
Parental formulation-- ca sodium salt Elimination: urine short half life 1 hr Adverse effect-- nephrotoxicity-- hydration |
|
Deferoxamine-- chelator
|
-Indication: iron poisoning
-Parental formulation (IM or IV) -elimination: urine-- orange red color -adverse effect: hypotension |
|
Management of poisoned pt
|
A, B, C
Dextrose-- for altered status, unless rapid bedside glucose test demonstrates that pt is not hypoglycemic Alcoholics-- give B1 thiamine 100mg first to prevent Wernicke's syndrome--- sx: confusion, ataxia, vision changes, nystagmus, diplopia, ptosis |
|
Treatments of poisoned pt
|
-decrease absorption- decontamination
-skin-- remove clothes -GI tract: emesis, gastric lavage, activated characoal, cathartics -Increase excretion: hemodialysis, change urine ph -reduce amt of toxin at cellular target- antidotes |
|
Acetaminophen antidote
|
Acetylcysteine
-acts as glutathione and binds the toxic metabolite |
|
Methanol & ethylene glycol antidote
|
fomepizole & ethanol
-competitive inhibitor of alcohol dehydrogenase |
|
Beta blockers antidote
|
Glucagon
raise intracellular cAMP independent to B receptor |
|
Cyanide antidote
|
coventional kit (amyl nitrite, Na nitrite, and Na thiosulfate
Hydroxocobalamin |
|
Benzodiazepines antidote
|
flumazenil
-may precipitate seizures |
|
Opioids- antidote
|
naloxone
short 1/2 half 1-1.5 hr, must repeat dose |
|
Pharmacologic change associated with aging
|
Decreased renal function
|
|
Pharmacokinetic Change in Elderly
Absorption |
-changes not specifically related to aging
-conditions that may alter absorption: -altered nutritional habits -greater consumption of nonprescription drugs (OTC-laxatives, antacids) -changes in gastric emptying (esp older diabetic) |
|
Pharmacokinetic Change in Elderly
Distribution |
-reduced lean mass
-reduced body water -increased fat (as percentage of body mass) -decrease in serum albumin -ratio of drug bound to albumin is altered |
|
Pharmacokinetic Change in Elderly
Metabolism |
-Certain drugs metabolized more slowly
-change in phase I reactions -changed caused by decreased liver flow, slower recovery from liver injury, malnutrition, diseases affecting heart failure |
|
Pharmacokinetic Change in Elderly
Elimination |
-major organ: kidney
-2/3 of elderly have abnl renal function/decreased creatinine clearance -half lives of drugs increased--> toxicity -don't depend on Serum creatinine clearance alone-- use cockcroft-gault formula |
|
Cockcroft-Gault formula
|
Creatinine clearance (ml/min)=
(140-age) x (weight/kg)/72 x serum clearance in mg/dl * doses for drugs should be based on creatinine clearance (make adjustments) * 12 or 24 hour creatinine clearance is more precise |
|
Pharmacodynamic changes in elderly
drugs that elderly pts are more sensitive and less sensitive |
-increased sensitivity to some sedative-hypnotics and analgesics
-decreased responsiveness to beta-adrenoceptor agonists |
|
CNS drugs: Sedative- Hypnotics and Elderly
|
-Benzodiazepines and barbiturates have longer half-lives
-decline in renal function and liver disease can impair elimination -may have increased volume of distribution -Monitor closely for motor impairment-- ataxia |
|
Analgesics and Elderly
|
-Often more sensitive to respiratory changes
-Use with caution -Also be cautious of underutilization in chronic severe pain patients |
|
Antipsychotics and Antidepressants Drugs
|
-Sedative effects of these drugs may be the actual cause of the apparent improvement.
-Adjust dosage because of increased responsiveness in elderly -Adjust lithium based on renal function and use of thiazides -Careful dosing as well with antidepressants |
|
Alzheimer's Disease and Elderly
|
-Chronic progressive neurodegenerative disorder with global, nonreversible impairment in cerebral functioning.
-Cholinesterase inhibitors primary drug of choice -Adjuncts may include antidepressants, antipsychotics, agents for insomnia management, and agents for management of behavioral and psychological symptoms |
|
Antihypertensives and Elderly
|
-Thiazides recommended as initial drug
-Calcium channel blockers -No beta blockers! unless heart failure is present d/t potential airway problems assoc w/ beta blockers -routinely monitor orthostatic hypotension |
|
Positive Ionotropic agents and Elderly
|
-1/2 lives of drugs are increased by 50%
-Cardiac glycosides frequently overused -“Dig toxicity” very common |
|
Antiarrhythmic agents and Elderly
|
-Quinidine and procainamide clearance decrease and half lives increase
-Avoid disopyramide (major toxicities) -Lidocaine clearance unchanged but half-life increased -Change in paradigm regarding treatment of atrial fibrillation |
|
Antimicrobial Drugs and Elderly
|
-May see changes in half-lives because of decreased renal function
-Gentamicin, kanamycin, and netilimicin more than double. -Tobramycin may not be as marked |
|
Anti-inflammatory drugs and elderly
|
-NSAIDS have toxicities elderly are very susceptible to bleeding, gastric ulcers
-Aspirin: GI irritation and bleeding -Newer NSAIDS: renal damage -No evidence COX-2 NSAIDS are safer -Corticosteroids useful if NSAIDS not indicated, S/E osteoporosis |
|
Opthalmic drugs and elderly
|
-Glaucoma:More common; Medications unchanged
-Macular degeneration: Antioxidants Antibodies against vascular endothelial growth factor (VEGF)-- Avastin, Lucentis, or Macugen |
|
Posterior Pituitary Hormone
Oxytocin Function? Dose effect- small? high? |
-peptide hormone similar to vasopressin (ADH)
-Function: contract smooth muscle--> uterine ctx, milk ejection -small dose: increased frequency and force -high dose: sustained ctx's (tetany) and antidiuretic and pressor effects |
|
Contraindications to Oxytocin
|
-high dose/prolonged--> fetal distress, placental abruption, uterine rupture
-oxytocin bolus--> hypotension -activation of ADH--> retain water, water intoxication (hyponatremia, heart failure, seizures, death) -DO NOT GIVE: fetal distress, prematurity, abnormal fetal lie, cephalopelvic disproportion, uterine surgery |
|
Oxytocin Antagonist
|
Atosiban for PTL supression
NOT FDA approved! |
|
Posterior Pituitary
Vasopressin (ADH) |
-peptide hormone (2 types-- vasopressin and desmopressin)
-desmopressin is 4000X more antidiuretic to pressor ratio -released in response to dropping BP or increasing plasma tonicity (antidiuretic and vasopressor properties) -Too little ADH= diabetes insipidus |
|
Kinetics and dynamics of Vasopressin/Desmopressin
|
Vasopressin: IV or IM
1/2 life 15 min renal/liver metabolism Desmospressin: IV, SQ, PO, or IN 1/2 life 1.5-2.5 h nasal bioavailability better than oral -activates 2 G protein subtypes -1) vascular smooth muscle -2) renal tubule cells |
|
Clinical uses of vasopressin/desmopressin
|
Pituitary Diabetes Insipidus
Esophageal variceal bleeding Diverticular bleeding Desmopressin: hemophilia A and Von Willebrands |
|
Vasopressin (ADH) Antagonists
|
Investigational: Conivaptan and Tolvapatan
-for hyponatremia and acute heart failure b/c often assoc with high vasopressin hormone Conivaptan: IV hyponatremia (NOT CHF) |
|
How are the anterior pituitary hormones G-protein group regulated?
|
-regulated by feedback from hormones produced by target organs
-TSH/TRH inhibited by T3 and T4 -GnRH inhibited by estrogen/progesterone/testosterone -ACTH inhibited by corisol |
|
How are the anterior pituitary hormones (GH and Prolactin) regulated?
|
GHRH--> stimulates GH release
Insulin-like Growth factor (IGF-1) inhibits GH SST (somatostatin) inhibits GH release Dopamine inhibits prolactin -hypothalamus doesn't produce anything stimulates prolactin -chronic inhibition |
|
Structure and kinetics of GH
|
-GH resembles prolactin
-Somatotropin (recombinant GH) -1/2 life 20-25 min, peak 2-4 h -hepatic clearance -dose 3-7x/wk |
|
Dynamics of GH
|
-increased IGF-1
-stimulate long bones until epiphysis close -increased muscle mass -decreased fat -GH: reduces insulin sensitivity -IGF-1: increases insulin sensitivity |
|
uses of GH
|
-correct GH deficiency
-treat short stature -severe wasting (AIDS) -short bowel syndrome/ after gastric bypass-- d/t nutritional deficiencies -anti aging -increase muscle mass |
|
S/E contraindications of GH
|
-peripheral edema, myalgia, arthralgia
-hypothyroidism -scoliosis -Intracranial HTN -turner syndrome---> otitis media -pancreatitis, gynecomastia, nevus growth -contraindicated if cancer |
|
A small number of children with growth failure have severe IGF-1 deficiency that is not responsive to exogenous GH.. what drugs is used for IGF-1 deficeincy?
|
Mescasermin
-complex containing IGF-1 and IGF-3 -IGF-1 does the work, IGF-3 increases the 1/2 life of IGF-1 -SQ BID -risk hypoglycemia (eat 20 before/after injection) |
|
excess GH production must be treated with:
|
GH antagonists
Somatostatin Analalogs (octreotide) Receptor agonists (dopamine) receptor antagonist (pegvisomant) |
|
Somatostatin analogs and GH receptor agonists..
action? |
reduce the production of GH
|
|
GH receptor antagonist (pegvisomant)
action? |
prevents GH from activating its receptor
|
|
Somatostatin Analogs
|
-found in hypothalamus, CNS, pancreas, and GI
-Inhibits GH, glucagon, insulin, and gastrin -rapidly cleared 1/2 life 1-3 min -metabolism/excretion: kidney - |
|
Ocreotide (Lanreotide)--- most widely used Somatostatin Analog
|
-1/2 life 80 min (30x longer)
- 45x more potent in inhibiting GH release -2x as potent in reducing insulin secretion (hyperglycemia rare) -SQ q 8 h -Adverse effects: GI- N/V/cramps, gall stones in 6 mo; Cardiac-- bradycardia, conduction disturbances; Vit b12 deficiency |
|
GH receptor Antagonist--- Pegvisomant
|
used to txt acromegaly
PEG derivative of mutant GH -blocks signal transduction -PEG increases potency by reducing clearance |
|
GnRH Analogs
|
Ascitate Salt: Gonadorelin
Synthetic: Goserelin, Histrelin, Leuporlide, Naferelin, Triptorelin |
|
Pulsatile administration of GnRH analogs
Continuous administration of GnRH analogs |
Pulsatile IV adminstration q 1-4 hours stimulates FSH and LH secretion
Continuous Administration: biphasic -1st 7-10 days agonist (increased concentration of gonadal hormones= "flare") -after 10 days= inhibition of GnRH GnRH analogs more commonly used to suppress GnRH, less commonly to stimulate |
|
GnRH Analogs for stimulation
uses? |
-female infertility
-male infertility -diagnosis of LH responsiveness (distinguish whether delayed puberty in a hypogonadotropic adolescent is d/t constitutional delay or to hypogoandotropic hypogonadism |
|
GnRH Analogs for supression
uses? |
-controlled ovarian hyperstimulation
-Endometriosis (x6 mo limit) -Uterine fibroids (3-6 mo) -Central precocious puberty (stop age 11/12) -prostate cancer -advanced breast/ovarian cancer -endometrial thinning (prior to endometrial ablation) -PCOS |
|
Toxicity s/e of GnRH anlogs
|
-CNS: h/a, light-headedness, nausea, flushing,
-local swelling at injection site, -hypersensitivity (after prolonged use)-- bronchospasm, anaphylaxis, -sudden pituitary apoplexy and blindness -menopausal sx -ovarian cysts -bone loss (osteoporosis) -men: decreased libido, decreased HCT |
|
GnRH antagonists
|
-inhibit secretion of FSH and LH
Syntehetic dicapeptides: -Genirelix and Cetrorelix (controlled ovarian hyperstimulation) -Abarelix and Degarelix (advanced prostate cancer) |
|
Kinetics of GnRH antagonists
|
-rapidly absorbed
-Ganirelix and Cetrorelix-- SQ delivery -0.25mg/day maintain GnRH suppression -single dose 0.3mg suppress LH x96h -Abarelix: IM -peak conc 3 days -1/2 life 13 days -dosing: day 1, 13, 28 then q 14d |
|
GnRH Antagonists
uses |
Supression
-Controlled ovarian hyperstimulation (prevent LH surge) -advanced prostate CA |
|
what are advantages of using GnRH antagonists over GnRH agonists for controlled ovarian hyperstimulation and advanced prostate cancer?
|
Controlled Ovarian Hyperstimulation
-advantages over GnRH agonists: -delay use until 6-8 of cycle (less drug) -less negative impact on ovary (less exposure to other ovarian stimulation drugs) -lower risk for ovarian hyperstimulation -adherence is critical Advanced prostate cancer -for men that cannot tolerate GnRH agonists -risk for severe tumor flare -for men who decline surgery |
|
Toxicity effects of GnRH antagonists
|
-generally well tolerated
-nausea, h/a most common -in pts with prostate cancer--- allergic responses seen--skin, hypotension, syncope, prolong QT -menopause like sx: hot flashes, h/a |
|
Dopamine Agonists
|
used for prolacin suppression
Ergot: Bromocriptine, Cabergoline Non-ergot (Europe): quinagolide |
|
Prolactin
|
-structurally similar to GH
-Normally suppressed except in lactation -a deficiency in prolactin= failure to lactate -d/o are usually pituitary, rarely hypothalamus -SX: amenorrhea, galactorrhea, infertility, loss of libido, CNS sx if large tumor-- visual changes, -no prolactin replacement -for pts with symptomatic hyperprolactinemia, inhibition of prolactin secretion can be achieved w/ dopamine agonists, which act in the pituitary to inhibit prolactin release |
|
Dopamine agonists
action |
-inhibits prolactin secretion by binding to Dopamine D2 receptor
-Effective in suppressing prolactin -GH release also reduced (Rx acromegaly) -used in parkinson's disease |
|
Kinetics of Dopamine agonists
|
oral and vaginal routes
1/2 life 7-65 hours (slower peak with transdermal route) |
|
Uses of dopamine agonists
|
-Hyperprolactinemia (shrink pit tumor, restore ovulation)
-Physiologic lactation (prevent engorgement when b.f not desire, though use is discouraged d/t toxicity) -Acromegaly (need high dose) |
|
Toxicity effects of Dopamine Agonists
|
-CNS- h/a, lightheadedness, fatigue, psychiatric, rarely stroke
-Other: nausea, ortho hypotension, erythromelalgia, vag irritation (vag route) -High doses: cold-induced peripheral digital vasospasm, pulmonary infiltrates -in early pregnancy: some women may need if adenoma is large, no assoc w/ SAB or malformations |
|
Gonadotropins
|
FSH, LH, HCG
|
|
Gonadotropins Chemistry and Kinetics
|
-FSH, LH, and HCG share identical alpha chains--- beta chain cofer specificity
-HCG and LH beta chains identical -SQ or IM -QD dosing -1/2 lives vary by route and preparation (oil based or non-oil based) |
|
FSH has 3 available forms
|
1) Urofollitropin -- post menopausual women's urine
2) Follitropin alpha 3) Follitropin beta -increased cost, shorter 1/2 life, stimulate E2 secretion more effeiciently |
|
LH form
|
Lutropin Alfa
-SQ -1/2 life 10h -only approved for: used with follitropin alpha and stimulating follicles in intfertile women with profound LH deficiency -NOT approved for use with other FSH preps or for stimulating endogenous LH surge! |
|
HCG has 2 forms
|
1) Human HCG from pregnant women's urine-- IM injection
2) Choriogonadotropin alpha (rhCG) recombinant form of hCG |
|
Gonadotropins
Uses |
ovulation induction
male infertility |
|
Gonadotropins
Ovulation induction |
-treat annovulation (Hypogonadotropic hypogonadism, PCOS, obesity)
-hyperstimulate ovaries (controlled) (protocols are in place to prevent multi-fetal pregancies and avoid ovarian hyperstim syndrome) -Expensive -Day 3-7 begin daily injection of FSH may combine with LH if HH -Monitor with serial u/s -add GnRH blocker to prevent premature LH surge-- this requires progesterone support for luteal phase- give progesterone supplements -when endometrium and follicles ready--- HCG IM-- induce follicular maturation -insemination or oocyte retrieval |
|
Gonadotropins
Male infertility |
-s/s treated with androgens
-Infertility tx--> LH and FSH -Traditional tx (4-6 mo): HCG several times a week x 8-12 weeks, then hMG for 3x/wk -more recently: urofollitropin, rFHS & rLH more protocols -ICSI: intracytoplasmic sperm injection-- 1 sperm injected directly into mature ooctye |
|
S/E of Gonadotropins
|
Ovarian hyperstimulation syndrome--> ovarian enlargement, ascites, hydrothorax, hypovolemia--> shock, hemoperitoneum, fever, and arterial thromboembolism
Multifetal pregnancy-- increased risk for poor outcomes-- GDM, preeclampisa, preterm delivery Less common: h/a, depression, edema, hCG antibodies, Males-- gynecomastia, females--- ovarian cancer |
|
Contraindications to Estrogens
|
--estrogen dependent neoplasms such as carcinoma of the endometrium or breast
--avoid in undiagnosed genital bleeding, liver disease, or hx of thromboembolic disorder, smokers |
|
Contraindications/Cautions/Adverse Effects to Progestins
|
-increases BP,
-reduce HDL levels -in postmenopause women--> increase breast cancer risk |
|
2 estrogen receptors
|
Estrogen-alpha: negative feedback
Estrogen-beta: positive estradiol - LH relationship |
|
Ovarian Hormones
|
-estrogen
-progestin -other (androgens, inhibin, activin, relaxin) |
|
3 natural human estrogens
|
1) estradiol- E2 Ovaries (potent form)
2) Estrone E1-- adrenal glands and fat 3) Estriol E3-- placenta |
|
Kinetics of Synthetic estrogen
|
-tightly bound to Sex hormone binding globulin (60-70% SHBG, 30% albumin, 1% free)
-PO--> exrected in bile--> reabsorbed intestine -high ratio hepatic/systemic effects causing increased clotting factors and plasma renin substrate -hepatic effects can be minimized by avoiding 1st pass liver exposure--> transdermal |
|
Synthetic estrogen
Mechanism |
-plasma estrogens in the blood are bound to SHBG, from which they dissociate to enter the cell and bind to Er alpha or beta receptor
|
|
Er alpha and beta receptors
|
Er alpha
-uterus, liver, kidney, and heart Er beta -ovary, prostate, lung, GI, bladder, hamatoopoietic, and CNS -co expressed: mammary gland, epidydymis, thyroid, adrenal, bone, and certain regions of the brain |
|
Estrogen effects
Female Maturation |
-vaginal epithelium maturation
-myometrial stimulation -endometrium maturation -fallopian tube motility -stromal and ductile breast development -cervical mucous (spinnbarkeit) -secondary sex characterisitics-axillary/pubic hair -epiphysis closing -Subq fat -Skin structure, function, pigmentation-- nipples, areola, genital |
|
Estrogen Effects
Metabolic |
-decreased bone resorption (decreased breakdown of bone and release of Ca to blood)
-Increased osteoclast apoptosis -antagonize osteoclastic effects of parathyroid and IL-6 -stimulate adipose production of leptin (a hormone for fat metabolism) -higher levels of protein (CBG, TBG, SHBG, transferrin, renin substrate, and fibrinogen)--- increased levels of bound hormone |
|
Estrogen Effects
Cardiovascular |
maintain structure/function vessels
alters plamsa lipids -increased HDL -decreased LDL (slightly) -decreased cholesterol -increased triglycerides |
|
Estrogen effects
coagulation |
net increased coagulability
Increase Factor II, VII, IX, X decreased antithrombin III Increased plasminogen decreased platelet adhesion |
|
Estrogen clinical uses
|
Primary Hypogonadism
post menopausal HRT |
|
Basic principles of HRT
|
-Begin close to onset of menopause
-stop as soon as reasonable no uterus--> E only If uterus present--> E and P bc unopposed E can lead to hyperplasia (cancer) |
|
Risks and benefits of Estrogen only HRT
|
Risks
-increased blood clots, in legs/lungs -increased stroke -increased coronary artery disease Benefits -Decrease hot flashes -decrease osteoporosis and fractures -decrease breast cancer |
|
risks and benefits of Estrogen and Progesterone combination HRT
|
Risks
-increased blood clots, in legs/lungs -increase stroke -increased coronary heart disease -increase breast cancer Benefits -Decrease hot flashes -decreased osteoporosis and fractures -decreased colorectal cancer |
|
other clinical uses of Estrogen
|
-hemorrhage
-dysmenorrhea -PCOS -breast cancer -prostate cancer -wound healing -inhibit growth in tall girls -bulimia nervosa -traumatic liver injury |
|
Progesterone
|
-"hormone of pregnancy"
-acts primarily during pregnancy and lactation -acts on Estrogen primed tissues |
|
Progestin kinetics
|
-rapidly absorbed (any route)
-1/2 life 5 min -need high dose for oral route d/t 1st pass -In liver, converted to prenendiol then conjugated w/glucuronic acid, excreted renally as prenanediol glucuronide |
|
Progestin effects
|
-stimulate lipase
-Increase insulin levels and insulin's response to glucose -promote glycogen storage -promote ketogenesis -competes with aldosterone for receptor -increase body temp -depressant and hypnotic effects -breast-- alveolobular development -decrease plasma amino acid levels -endometrium: maturation and secretion |
|
progesterone therapeutic uses
|
-hormone replacement
-contraception-- implanon, depo provera -pregnancy/infertility (won't prevent SAB, some use in PTL, support corpus luteum) |
|
Progesterone and Diagnosis
|
For dysfunctional uterine bleeding, progesterone can be used as a test of estrogen secretion.
-Differentiate between anovulatory cycle and Premature ovarian failure -in estrogen primed tissues, Pg will cause withdrawal bleed -but if no bleed, then there was no estrogen on board -DUB= anovulation (lots of E, no LH surge), adding Pg will cause withdrawal bleed -POF= no ovulation (lots of FSH, no estrogen, no LH surge)--> no withdrawal bleed |
|
Other ovarian hormones
Inhibin and Activin |
-Inhibin decreases FSH secretion
-Activin increases FSH secretion |
|
Other ovarian hormones
Relaxin |
-synthesized by luteinized granulosa cells (corpus luteum)
-found in ovary, placenta, uterus, and blood -insulin-like structure and function -increase glycogen synthesis, H20 uptake in myometrium -decrease uterine contractility -clinical trials: dysmenorrhea, Premature labor or delayed labor |
|
Hormonal Contraception
2 types |
combined E+P
Progestin |
|
MOA of Combined E+P and Progestin only
|
Combined E + P
-selective inhibition of pituitary -mimic pregnancy==> inhibit ovulation -alters cervical mucuous and tubal motility Progestin Only -alters cervical mucous -mimic pregnancy, may not inhibit ovulation |
|
Organ effects of Contraceptives
|
ovary- inhibition
vagina- low maturation index (Pg) uterus-- atrophic endometrium cervical mucous-- thick scanty breast- non-lactating (tenderness, enlargement); lactating (low dose has little impact on milk production) |
|
other effects of oral contraceptives
|
-Endocrine-- Increased binding globulins and circulating hormones
-coagulation -decreased bile flow (cholestasis) -Increased triglycerides and HDL -Decreased carbs absorbed from Gi tract; Pg increases insulin resistance -Increased bp, hr, increased co -less acne |
|
Adverse s/e of contraceptives
|
Mild-- nausea, breast pain, edema, break thru bleeding, h/a, worsening migraines, amenorrhea
Mod- BTB in pg methods, wt gain (depo), pigmentation chantes, bacturia (ureteral dilation) Severe- thromboembolism, jaundice, GB disease, depression, Increased ?breast and cervical cancer (but decreased ovarian and endometrial) |
|
Contraindications to contraceptives
|
Thrombophelibitis, coagulopathy
cardiovascular d.o. unexplained vag bleeding pregnancy cancer (e dpendent) avoid in liver disease, asthma, exczema, migraines, DM, HTN, optic neuritis, retrobulbar neuritis, seizure d.o. |
|
Estrogen and Progesterone Inhibitors/Antagonists
|
Tamoxifen, Raloxifene, Clomiphene, Mifepristone, Danazol, Aromatase inhibitors
|
|
Tamoxifen
|
SERM
for breast cancer adverse effects n/v |
|
Clomiphene (clomid)
|
-Partial estrogen agonist
-drug for infertility -inhibits negative feedback--> more FSH adverse effects: hot flashes, h/a, constipation, allergic rxn, increase growth of endometrial implant, n/v, depression, fatigue, breast tenderness, weight gain, multi-fetal gestation |
|
Mifepristone
|
binds to Pg receptor, inhibit P activity
-abortifacient adverse effects: v/d abdominal/pevlic pain, 5% heavy bleed |
|
Danazol
|
suppress ovarian function
-inhibit LH surge -inhibit gonadal function for endometriosis, breast pain, hemophila, ITP, angioneurotic edema adverse effects: wt gain, edema, decrease breast size, acne, increase hair growth, deep voice, h/a, hot flashes, libido changes, muscle cramps, adrenal suppression |
|
Aromatase inhibitors
|
inhibit estrogen synthesis
use breast cancer |
|
Androgen and Anabolic steroids
|
Testosterone
Dihydrotestosterone Androstenedione (DHEA) DHEAS Dehydroepiandrosterone |
|
Androgen effects
|
growth: ht, wt, lean body mass
genital penile and testicular gorwht prostate and seminal vesicles pubic, axillary, facial hair sebaceous glands thickening, darkening of skin larynx and vocal cords thickens sexual function |
|
Metabolic effects of androgens
|
decrease hormone binding
decrease carrier proteins Increase liver synthesis |
|
Effects of glucocorticoids on the body
|
see adrenocortical hormones lecture
ch 39 |
|
Dexamethasone Suppression Test
|
diagnostic test used to diagnose cushing's syndrome
if etoh abuse, depression, or anxiety present, then must used the "combined test" which includes dexamethasone then CRH bolus dexamethasone can also be used to dx tumor or ectopic ACTH syndrome (see lecture notes, pt 8) |
|
role of glucorcorticoids have on the genetics
|
10-20% of all genes expressed in a cell are influenced (regulated) by glucocorticoid
|
|
Agents that reduce intragastric acidity
|
antacids
H2 receptor antagonists proton pump inhibitors |
|
Mucosal protective agents
|
sulcralfate
prostaglandin analogs bismuth compounds |
|
Factors responsible for mucosal erosions or ulceration
|
acid
pepsin bile |
|
defensive factors of GI mucosa
|
-mucus secretion
-bicarbonate secretion -prostaglandins -blood fow -restitution and regeneration after cellular inury |
|
what do Antacids do?
|
-weak bases that react with HCL to form a salt and water
-partially neutralize gastric HCL acid -increase intragastric ph -inhibit pepsin |
|
what are some antacids?
|
-sodium bicarb (alka seltzer)
-Calcium carbonate (tums) -Aluminum hydroxide (amphojel) -Magnesium hydroxide (milk of magnesia) *useful for mild symptomatic reflux and dyspepsia |
|
Adverse effects of antacids
|
Hypercalcemia
Hypermagnesemia Diarrhea-- magnesium aluminum toxicity Constipation-- aluminum and calcium |
|
Drug interactions with Antacids
|
--antacids change gastric or urinary ph
--alter rates of drug absorption, bioavailability, renal elimination, and/or drug dissolution -reduce gastric hydrolysis of drugs *iron, fluroquinolones, etc will interact |
|
MOA of H2 Receptor antagonists
|
MOA reduce acid secretion
by blocking histamine from binding to the parietal cell H2 receptor -in the presence of H2 blockers, stimulation of parietal cell by gastrin or acetylcholine is diminished *prescription doses inhibit 60-70% of 24hr acid secretion -duration of action: 10hrs rx dose, 6 hrs otc dose |
|
Name some H2 receptor antagonists
|
-end with -tidine
-cimetidine, ranitidine, nizatidine, famotidine *note renal insufficiency requires a dose adjustment |
|
Clinical uses of H2 receptor antagonists
|
GERD
PUD stress-related gastritis |
|
Adverse effects of H2 antagonists
|
-GI discomfort (diarrhea, constipation)
-CNS effects (h/a, drowsiness, psychosis) -dermatologic (rash) -Hematologic (thrombocytopenia) |
|
MOA of Proton Pump inhibitors
|
-irreversibly bind to H/K ATPase (proton pump)--- acid inhibition lasts 24h
-inhibit both basal and meal stimulated gastric acid secretion, blocking the final outcome pathway in acid secretion -also blocks pepsin which is not inhibited by H2 blockers |
|
Absorption of Proton pump inhibitors
|
-absorbed in the small intestine, transported into the bloodstream to the acidic canaliculus of the parietal cell for protonation to the active form
-prodrugs require an acidic environment for conversion to the active form -this conversion requires an actively secreting proton pump -PPIs are more effective when taken 30-60 min prior to a meal on an empty stomach * superior to H2 blockers for acid reduction and mucosal healing *takes 3-4 days for the pump to be inhibited |
|
Name Proton Pump inhibitors
|
--ends with -prazole
-esomeprazole -lanzoprazole -rabeprazole -omeprazole -pantoprazole |
|
Clinical uses of PPIs
|
GERD
PUD H pylori associated ulcers NSAID associated ulcers |
|
Drug regimen treatment for H-pylori ulcers
|
Goal-- heal the ulcer and eradicate the organism
-most effective treatment-- triple therapy--> 2 abx and a PPI for 14 days, then PPI for 4-6 weeks -PPIs promote eradication by driect antimicrobial properties, and by raising the intragastric pH, lowering the MIC of the abx |
|
Adverse effects of PPIs
|
-GI discomfort (nausea, diarrhea, abd pain)
-CNS effects (headache, dizziness) -increased risk for infection (c-diff, pneumonia) -rare skin rash; increased liver enzymes |
|
other Clinical uses of PPIs
|
-Non-ulcer dyspepsia
-stress-related mucosal bleeding (omeprazole FDA approved) -Gastrinoma (omeprazole) |
|
Mucosal Protective agent
-sulcrafate (carafate) |
-forms a viscous, tenacious paste in water or acidic solutions that binds to ulcers or erosions for 6h
-possibly binds to positively charged proteins in the base of ulcers or erosions restricting further damage, and stimulating mucosal prostaglandin and bicarb secretion |
|
Mucosal Protective agents
Prostaglandin analog-- misoprostol (cytotec) |
-acid inhibitory and mucosal protective
-stimulates mucus and bicarb secretion and enhances mucosal blood flow -binds to prostaglandin receptor on parietal cell modestly reducing histamine stimulated cAMP production |
|
Mucosal protective agents
Bismuth compounds |
-coats ulcers and erosions, protecting against acid and pepsin
-may stimulate prostaglandin, mucus, and bicarb secretion -direct antimicrobial activity against H pylori used as 2nd line therapy in 4 drug regimen -Bismuth subsalicylate (pepto-bismol) -Bismuth sucitrate potassium (pylera) |
|
Drugs that stimulate GI motility
|
5-HT Serotonergic Agonist
Cholinomimetic agents Dopamine receptor antagonists Macrolides Laxatives |
|
Laxative types
|
bulk forming (metamucil, fibercon)
stool surfactant agents (softeners) Osmotic (MOM, mag citrate, miralax) Stimulant (senna, bisacodyl) Chloride Channel activator (amitiza) Opioid Receptor antagonists |
|
Antidiarrheal agents
|
-opioids agonists (immodium, lomotil)
-Kaolin & Pectin (kkaopectate) -Bile Salt-binding resins (cholestyramine, Questran) -Octreotide (somatostatin) |
|
Drugs for Irritable bowel syndrome
|
-Antispasmodics (anticholinergic)
-Serotonin Receptor antagonist--diarreha -Chloride channel activator-- for constipation |
|
Antiemetic agents
|
-Serotonin antagonists (zofran)
-Corticosteroids (dexamethasone) -Neurokinin Receptor Antagonist (emend) -Phenothiazines (compazine, phenergan) -Butyrophenones (inaspsine) -Substituted Benzamides (reglan) -H2 Antihistamines and Anticholinergic (benadryl, dramamine) -Benzodiazepines (ativan, valium) -Cannabinoids (marinol) |
|
Drugs to treat Inflammatory Bowel disease
|
-Aminosalicylates
-glucocorticoids -Purine analogs -methotrexate -anti tumor necrosis factor -anti-integrin therapy |
|
bile acid therapy for gallstones
|
Urosodiol
-gall stone dissolution |
|
Drugs used to treat variceal hemorrhage
|
-somatostatin and octreotide
-beta blockers |
|
Type 2 diabetes is the leading cause of
|
blindness in adults
kidney failure non-traumatic lower-limb amputations |
|
Therapies for Type 2 diabetes
|
INSULIN DEMAND
--GLUCOSE INFLUX (alpha glucosidase inhibitors) --INSULIN RESISTANCE (TZDs, Metformin, Dopamine agonists) --GLUCAGON SECRETION (GLP 1 Mimetic, Symlin, DPP4 Inhibitor) INSULIN SUPPLY --ACUTE B-CELL DYSFUNCTION (sulfonylureas and glinidies) --CHRONIC B-CELL DYSFUNCTION (insulin) |
|
Sulfonylurea (SFU)
|
-2nd Gen:
-Glimerpiride (most selective) -Glyburide (non-selective), least heart friendly and more likely to cause nocturnal hypoglycemia |
|
NON-SFU
Glinides |
Shorter DOA, dosed frequently throughout the day
|
|
MOA of SFU and NON-SFU
|
Bind to ATP-dependent K+ channel of B-cells
-increase insulin secretion |
|
SFU concerns
|
Increased Cardiac Mortality
arrhythmias, MI, CV death *1st gen most problematic, non-selective |
|
Biguanide (metformin) MOA
|
activates 5'Adenosine monophosphate- Activated protein kinase
-decrease gluconeogenesis, hepatic glucose production -increase skeletal glucose uptake |
|
Concerns of Biguanide (metformin)
|
-B12 deficiency: diabetic peripheral neuropathy; level should be at least >500
-Lactic acidosis -Contraindicated in pts with impaired renal function *GFR indicator of renal function <30 absolute contraindication |
|
Thiazolidinediones (TZDs) MOA
|
-selective agonists for the PPARy (gamma)
-increased GLUT-4 transporter production -insulin-mediated glucose disposal into the peripheral tissue -INSULIN MUST BE PRESENT -prolong onset of action 10-12 wk |
|
Black box warning TZDs
|
Actos: contraindicated in CHF
Avandia: risk of MI |
|
Alpha Glucosidase Inhibitors MOA
|
-inhibit pancreatic and intestinal enzymes found in the small intestine
-prevents the breakdown of complex startch and disaccharids into monosaccharides -defers digestion and absorption distally *GREAT FOR POST PRANDIAL HIGH B.S. |
|
Bad effects of Alpha Glucosidase Inhibitors
|
-contraindicated in pts with inflammatory bowel disease or cirrhosis
-hypoglycemia |
|
Incretins role in GI tract
|
--stimulate insulin secretion
|
|
GLP-1 analogs MOA
|
-glucagon suppression
-enhance insulin and amylin secretion -delay gastric emptying -enhance satiety -enhance insulin secretion ONLY in the presence of hyperglycemia -insulin secretion decreases as blood glucose levels decrease |
|
Cautions for GLP-1 Analogs
|
end stage renal disease
severe GI disease: gastroparesis (slow gastric emptying) -hemorrhaging or necrotizing pancreatitis |
|
Black box warning of Victoza (GLP-1 Analog)
|
risk of thyroid c-cell tumors
|
|
DPP-IV Inhibitors
use and cautions |
-glucagon suppression
Caution in severe renal impairment Concerns: hemorrhagic or necrotizing pancreatitis, cancer |
|
Amylin (symlin)
MOA Contraindications |
Peptide hormome co-secreted with insulin from pancreas in response to food
-inhibits glucagon secretion -delays gastric emptying -enhance satiety (similar to GLP-1 analog) Contraindications: gastroparesis Black box warning: hypoglycemia |
|
Dopamine agonists (cycloset)
MOA |
acts centrally to reduce resistance to insulin-mediated suppression of hepatic glucose output and tissue glucose disposal
Caution: liver impairment |
|
Rapid acting
-Humalog (lispro) -Novolog (aspart) -Apidra (glulisine) |
Onset 0.25 hr
peak 0.5-2 hr duration 3-5 hr |
|
Short Acting
-humulin R -novolin R |
onset 0.5-1 hr
peak 2-4 hr duration 5-8 |
|
Intermediate acting
-Novolin N -Humulin N |
onset 1-2 hr
Peak 4-12 hr duration 16-20 hr |
|
Long Acting
-Lantus (glargine) -Levemir (detemir) |
Onset 1-2
Peak none Duration 20-24hr |
|
Insulin concerns
|
hypoglycemia
--glucose --glucagon injection 1mg Hypertrophy of sq fat -rotate injection sites |
|
"Beta shift"
|
phenomenon--> increase of LDL in serum as hypertriglyceridemia subsides
|
|
Metabolic Syndrome
|
-Hypertriglyceridemia
-Low HDL -insulin resistance -hypertension -abdominal obestiy |
|
Treatment for metabolic syndrome
|
fibrates or niacin, metformin, TZDs
|
|
Statins
|
Inhibit HMG-COA Reductase
Increase HDL Decreased LDL small Decrease TG |
|
Who should not take statins?
|
pregnancy
planning pregnancy breastfeeding |
|
Toxicity of statins
|
-Hepatotoxic (increase serum aminotranferase)
-caution in hepatic dz, asians, elderly -Increased CK w/physical acivity -d/c for s/s of myopathy or rhabdo -monitor LFTs and CK |
|
Nicacin (Nicotinic Acid)
|
-decreased VLDL, LDL and Lp (a), HDL catabolism, Triglycerides
|
|
Toxicity of Niacin
|
-cutaneous vasodilation
-pruritus -rashes -acanthosis nigricans -nausea/abd discomfort *avoid in PUD -monitor hepatic, Increased aminotransferases, gout, atrial arrhythmia, amblyopia, potentiates antihypertensives |
|
Fibric Acid Derivatives
|
decreased VLDL and LDL
|
|
Toxicity of Fibric Acid Derivatives
|
Rash, GI upset, myopathy, arrhythmias, hypokalemia, increased aminotransferases or ALK phos, decreased WBC or HCT, rhabdomyolysis, increased gallstones
Potentiates coumadin |
|
Bile Acid-Binding Resins
|
isolated Increased VLDL
toxicity: malabsorption vit K and folic acid, increased gallstones |
|
Drug interactions with bile acid-binding resins
|
take all meds 1 hour before or 2 hours after other meds
|
|
reversal agent for heparin
|
protamine sulfate
|
|
reversal agent for warfarin (coumadin)
|
vit k
|