ADVANCED PHARMACOLOGY NSG 533 MAIN
EXAMINATION SET QUESTIONS AND ANSWERS RATED A+
✔✔Can be used as monotherapy or as add-on therapy for T2DM .. Presenting A1C of 9
+ symptoms or failure to achieve goal A1C on adequate trial of 2-3 agents at maximally
tolerated doses - ✔✔Often starting with a long acting insulin
When glycemic goals aren't reached despite basal insulin (Good FBG and pre-prandial
BG, but elevated HbA1C), Consider prandial therapy with fast-acting insulin. Begin fast-
acting insulin before largest meal.Variation exists between ADA and ACCE in their
recommendations
If HbA1C still elevated, add fast-acting to another mealSulfonylurea can continue up
until the point where prandial (rapid) insulin is addedMetformin can / should continue !!
✔✔What agents are used to treat hypothyroid disease? What makes the medications
different and what do the guidelines recommend for use - ✔✔Recommendation 22.1:
Patients with hypothyroidism should be treated with Levothyroxine monotherapy. Grade
Aother forms of thyroid replacement may be associated with necessary cost, lack of
therapeutic rationale, increase adverse effects and allergenicity (animal based products)
Starting therapyNormal adult dose: 1.6 mcg/kg/day (~100-125 mcg/day) based on IBW
(LBW)Titration by 25-50 mcg every 4-6 weeks until TSH normalizesEXCEPTIONS
include elderly, chronically ill patients or history of cardiovascular disease . Initially 12.5-
25 mcg/day, then titrate to maintenance dose until TSH normalizesExpect higher
requirements during pregnancyThyroid hormone demandIncreases in TBGDestruction
of T4 by placental deiodinases
✔✔How is treatment monitored and how should results be interpreted as far as therapy
changes (the relationship between TSH and T3-4) - ✔✔Monitoring should be every 6-8
weeks after starting or dose/product change. If TSH is not in target range (0.5-2.5
mIU/L) alter dose in 10% to 20% increments. ..
levothyroxine has a T 1/2 of 6-10 days (and NTI .. see below). How does this relate to
the fact that after initiating or changing a does or changing a product (IE brand to
generic, generic to brand or one generic brand to another), TSH should be checked in
about 6 weeks?
✔✔Why are thyroid replacement drugs considered to have a narrow therapeutic index (
NTI )and what does that mean clinically? - ✔✔The therapeutic index (TI) is the range of
doses at which a medication is effective without unacceptable adverse events. Drugs
with a narrow TI (NTIs) have a narrow window between their effective doses and those
at which they produce adverse toxic effects. Oral Bioavailability: (erratic) 40-80%brand
vs generic Highly protein bound (99%)Half-lifeEuthyroid = 6-7 daysHypothyroid = 9-10
daysSteady State: @ 6 weeks or 4-5 t1/2 's ... this is the bases for monitoring @ six
weeks from start or changes!
Consider changes such as brand to generic, different generics manufactures, different
pharmacies, etcAny such change will require repeat lab monitoring @ ~ 6 weeks to
confirm the same clinical response
,✔✔What are some drug-drug, drug-food interactions associated with thyroid
replacement - ✔✔drug binding interactions, di-valent cations, amiodarone, certain
antibiotics
✔✔RECOMMENDATION 13 Methimazole should be used in virtually every patient who
chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy
when propylthiouracil is preferred, in the treatment of thyroid storm (inhibition of
peripheral conversion), and in patients with minor reactions to methimazole who refuse
radioactive iodine therapy or surgeryDelayed onset - ✔✔
✔✔Beta-blockers role in therapy? - ✔✔So .. beta blockers are used for Symptomatic
relief of hyperthyroidism until more definative therapy is instituted and thyroid levels
retun to normal or near normal..
Reduction of peripheral manifestations
Tachycardia, sweating, severe tremor, nervousness
Inhibition of peripheral conversion of thyroid hormones at higher doses (propranolol
ONLY)
Small therapeutic effect in magnitude
thyrotoxicosis
✔✔Why does amiodarone pose a unique concern to thyroid disorders -
✔✔"Amiodarone-normal thyroid autoregulation is lost because of the relatively high
iodine content" .. this fact can lead to a situation where amiodarone can cauase BOTH
hyper- and hypo- thyroidism, depending on the patient, through several process
blocking thyroid peroxidase
blocking proteolysis of Tg and thyroid hormone
altering organification, etc
✔✔What would you recommend if a patient is taking Nexium and Plavix together? -
✔✔As we have seen through our discussions, there is a lot of information (including an
FDA issued statement in the package insert) describing the drug interaction and
reduced efficacy of clopidogrel if used with a PPI (primarily omeprazole) (or in patients
who are genetically slow CYP2C19 metabolizers); however there is also evidence
based information indicating the interaction is not as significant as originally thought.
Bottom line: Despite pharmacokinetic evidence that omeprazole interferes with
clopidogrel metabolism, COGENT trial found addition of omeprazole to clopidogrel
reduced gastrointestinal events without increasing cardiovascular events.
✔✔Note there is no significant difference in efficacy among the H2RAs when given at
equipotent dosesCimetidine is associated with numerous clinically significant DIs
Dose reduction in renal and hepatic insufficiency and in the elderly
Duration of suppression ranges from 6-10 hours and varies with dose
, Note there is no significant difference in efficacy among the PPIs when given at
equipotent doses
Food may affect absorption. Given 30-60' before a meal. More flexibility in term of
dosing with newer agents (eg. dexlansoprazole)Delayed onset: 3-4 days for full
inhibition
Duration of action up to 24 hours due to covalent, irreversible inhibition of proton pump -
✔✔
✔✔Patients with known osteoporosis can remain on PPI therapy. Concern for hip
fractures and osteoporosis should not affect the decision to use PPI long-term except in
patients with other risk factors for hip fracture - ✔✔
✔✔Final thoughts on GERD: - ✔✔◦Therapy for GERD other than acid suppression,
including prokinetic therapy and/or baclofen, should not be used in GERD patients
without diagnostic evaluation.
◦For patients with partial response to once daily therapy with a PPI, tailored therapy with
adjustment of dose timing and/or twice daily dosing should be considered in patients
with night-time symptoms, variable schedules, and/or sleep
◦In patients with partial response to PPI therapy, increasing the dose to twice daily
therapy or switching to a different PPI may provide additional symptom relief.
◦ Maintenance PPI therapy should be administered for GERD patients who continue to
have symptoms after the PPI is discontinued, and in patients with complications
including erosive esophagitis and Barrett's esophagus
◦Histamine-receptor antagonists (H2RA) therapy can be used as a maintenance option
in patients without erosive disease if patients experience heartburn relief. Bedtime
H2RA therapy can be added to daytime PPI therapy in selected patients with objective
evidence of night-time reflux if needed, but may be associated with the development of
tachyphylaxis after several weeks of usage
✔✔Peptic ulcers (gastric and duodenal) are defects in the GI mucosa that extend
through the muscularis mucosa. Causal relationships associate with H. Pylori infection,
NSAIDs and SRMD. - ✔✔Therapy includes non-pharmacological interventions (similar
to GERD) and pharmacological with acid suppression (antacids, H2RAs, PPIs) and/or
mucosal protection (sucralfate, colloidal bismuth, misoprostol), and if present, H Pylori
eradication
Acid suppression - see treatment modalities under GERD (Duration / dosages may be
different based on indication)
Mucosal protectionSucralfate - In acid environment it turns into a viscous, sticky
polymer that binds selectively to ulcers and erosions creating a protective layerEfficacy
comparable to H2RAsChemically, contains Al(OH)3, thus behaves as Aluminum as far
as ADRs (eg constipation), DIs (eg chelation)Bismuth - MOA unclearBismuth coats
ulcers and erosions, creating a protective layer against acid and pepsinIt may stimulate
PG and mucus secretionIt binds bacterial endotoxins and has direct antimicrobial
activity against pylori
EXAMINATION SET QUESTIONS AND ANSWERS RATED A+
✔✔Can be used as monotherapy or as add-on therapy for T2DM .. Presenting A1C of 9
+ symptoms or failure to achieve goal A1C on adequate trial of 2-3 agents at maximally
tolerated doses - ✔✔Often starting with a long acting insulin
When glycemic goals aren't reached despite basal insulin (Good FBG and pre-prandial
BG, but elevated HbA1C), Consider prandial therapy with fast-acting insulin. Begin fast-
acting insulin before largest meal.Variation exists between ADA and ACCE in their
recommendations
If HbA1C still elevated, add fast-acting to another mealSulfonylurea can continue up
until the point where prandial (rapid) insulin is addedMetformin can / should continue !!
✔✔What agents are used to treat hypothyroid disease? What makes the medications
different and what do the guidelines recommend for use - ✔✔Recommendation 22.1:
Patients with hypothyroidism should be treated with Levothyroxine monotherapy. Grade
Aother forms of thyroid replacement may be associated with necessary cost, lack of
therapeutic rationale, increase adverse effects and allergenicity (animal based products)
Starting therapyNormal adult dose: 1.6 mcg/kg/day (~100-125 mcg/day) based on IBW
(LBW)Titration by 25-50 mcg every 4-6 weeks until TSH normalizesEXCEPTIONS
include elderly, chronically ill patients or history of cardiovascular disease . Initially 12.5-
25 mcg/day, then titrate to maintenance dose until TSH normalizesExpect higher
requirements during pregnancyThyroid hormone demandIncreases in TBGDestruction
of T4 by placental deiodinases
✔✔How is treatment monitored and how should results be interpreted as far as therapy
changes (the relationship between TSH and T3-4) - ✔✔Monitoring should be every 6-8
weeks after starting or dose/product change. If TSH is not in target range (0.5-2.5
mIU/L) alter dose in 10% to 20% increments. ..
levothyroxine has a T 1/2 of 6-10 days (and NTI .. see below). How does this relate to
the fact that after initiating or changing a does or changing a product (IE brand to
generic, generic to brand or one generic brand to another), TSH should be checked in
about 6 weeks?
✔✔Why are thyroid replacement drugs considered to have a narrow therapeutic index (
NTI )and what does that mean clinically? - ✔✔The therapeutic index (TI) is the range of
doses at which a medication is effective without unacceptable adverse events. Drugs
with a narrow TI (NTIs) have a narrow window between their effective doses and those
at which they produce adverse toxic effects. Oral Bioavailability: (erratic) 40-80%brand
vs generic Highly protein bound (99%)Half-lifeEuthyroid = 6-7 daysHypothyroid = 9-10
daysSteady State: @ 6 weeks or 4-5 t1/2 's ... this is the bases for monitoring @ six
weeks from start or changes!
Consider changes such as brand to generic, different generics manufactures, different
pharmacies, etcAny such change will require repeat lab monitoring @ ~ 6 weeks to
confirm the same clinical response
,✔✔What are some drug-drug, drug-food interactions associated with thyroid
replacement - ✔✔drug binding interactions, di-valent cations, amiodarone, certain
antibiotics
✔✔RECOMMENDATION 13 Methimazole should be used in virtually every patient who
chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy
when propylthiouracil is preferred, in the treatment of thyroid storm (inhibition of
peripheral conversion), and in patients with minor reactions to methimazole who refuse
radioactive iodine therapy or surgeryDelayed onset - ✔✔
✔✔Beta-blockers role in therapy? - ✔✔So .. beta blockers are used for Symptomatic
relief of hyperthyroidism until more definative therapy is instituted and thyroid levels
retun to normal or near normal..
Reduction of peripheral manifestations
Tachycardia, sweating, severe tremor, nervousness
Inhibition of peripheral conversion of thyroid hormones at higher doses (propranolol
ONLY)
Small therapeutic effect in magnitude
thyrotoxicosis
✔✔Why does amiodarone pose a unique concern to thyroid disorders -
✔✔"Amiodarone-normal thyroid autoregulation is lost because of the relatively high
iodine content" .. this fact can lead to a situation where amiodarone can cauase BOTH
hyper- and hypo- thyroidism, depending on the patient, through several process
blocking thyroid peroxidase
blocking proteolysis of Tg and thyroid hormone
altering organification, etc
✔✔What would you recommend if a patient is taking Nexium and Plavix together? -
✔✔As we have seen through our discussions, there is a lot of information (including an
FDA issued statement in the package insert) describing the drug interaction and
reduced efficacy of clopidogrel if used with a PPI (primarily omeprazole) (or in patients
who are genetically slow CYP2C19 metabolizers); however there is also evidence
based information indicating the interaction is not as significant as originally thought.
Bottom line: Despite pharmacokinetic evidence that omeprazole interferes with
clopidogrel metabolism, COGENT trial found addition of omeprazole to clopidogrel
reduced gastrointestinal events without increasing cardiovascular events.
✔✔Note there is no significant difference in efficacy among the H2RAs when given at
equipotent dosesCimetidine is associated with numerous clinically significant DIs
Dose reduction in renal and hepatic insufficiency and in the elderly
Duration of suppression ranges from 6-10 hours and varies with dose
, Note there is no significant difference in efficacy among the PPIs when given at
equipotent doses
Food may affect absorption. Given 30-60' before a meal. More flexibility in term of
dosing with newer agents (eg. dexlansoprazole)Delayed onset: 3-4 days for full
inhibition
Duration of action up to 24 hours due to covalent, irreversible inhibition of proton pump -
✔✔
✔✔Patients with known osteoporosis can remain on PPI therapy. Concern for hip
fractures and osteoporosis should not affect the decision to use PPI long-term except in
patients with other risk factors for hip fracture - ✔✔
✔✔Final thoughts on GERD: - ✔✔◦Therapy for GERD other than acid suppression,
including prokinetic therapy and/or baclofen, should not be used in GERD patients
without diagnostic evaluation.
◦For patients with partial response to once daily therapy with a PPI, tailored therapy with
adjustment of dose timing and/or twice daily dosing should be considered in patients
with night-time symptoms, variable schedules, and/or sleep
◦In patients with partial response to PPI therapy, increasing the dose to twice daily
therapy or switching to a different PPI may provide additional symptom relief.
◦ Maintenance PPI therapy should be administered for GERD patients who continue to
have symptoms after the PPI is discontinued, and in patients with complications
including erosive esophagitis and Barrett's esophagus
◦Histamine-receptor antagonists (H2RA) therapy can be used as a maintenance option
in patients without erosive disease if patients experience heartburn relief. Bedtime
H2RA therapy can be added to daytime PPI therapy in selected patients with objective
evidence of night-time reflux if needed, but may be associated with the development of
tachyphylaxis after several weeks of usage
✔✔Peptic ulcers (gastric and duodenal) are defects in the GI mucosa that extend
through the muscularis mucosa. Causal relationships associate with H. Pylori infection,
NSAIDs and SRMD. - ✔✔Therapy includes non-pharmacological interventions (similar
to GERD) and pharmacological with acid suppression (antacids, H2RAs, PPIs) and/or
mucosal protection (sucralfate, colloidal bismuth, misoprostol), and if present, H Pylori
eradication
Acid suppression - see treatment modalities under GERD (Duration / dosages may be
different based on indication)
Mucosal protectionSucralfate - In acid environment it turns into a viscous, sticky
polymer that binds selectively to ulcers and erosions creating a protective layerEfficacy
comparable to H2RAsChemically, contains Al(OH)3, thus behaves as Aluminum as far
as ADRs (eg constipation), DIs (eg chelation)Bismuth - MOA unclearBismuth coats
ulcers and erosions, creating a protective layer against acid and pepsinIt may stimulate
PG and mucus secretionIt binds bacterial endotoxins and has direct antimicrobial
activity against pylori
