4
lOMoAR
94 cPSD|
9 28505380
NR565 Pharmacology Fundamentals Study Guide
Be49familiar49with49the49interactive49activities49throughout49course49modules.4 9 You49could49s
ee49variations49of49those49same49questions49on49your49exams.
Week495
• Thyroid
o Thyrotropin-releasing49hormone49(TRH)49from49the49hypothalamus49stimulates
o release49of49thyroid-stimulating49hormone49(TSH)49from49the49pituitary.
o TSH49stimulates49all49aspects49of49thyroid49function,
▪ including49the49release49of49triiodothyronine49(T3)49and49thyroxine49(T4).
▪ T349and49T449act49on49the49pituitary49to49suppress49further49TSH49release.
o Diagnosis49&49Evaluation
▪ What49labs49are49used49to49diagnose?
▪ Serum49TSH49determinations49are49used49primarily49for49screening49
and49diagnosis49of49hypothyroidism49and49for49monitoring49replaceme
nt49therapy49in
hypothyroid49patients.
▪ Serum49TSH49determinations49can49also49distinguish49primary49hypothy
roidism49from49secondary49hypothyroidism.49In49primary49(thyroidal)49
hypothyroidism,49TSH49levels49are49high.49However,49in49secondary49
hypothyroidism
(hypothyroidism49resulting49from49anterior49pituitary49dysfunction),49TSH49
levels49are49low,49normal,49or49even49slightly49elevated—
despite49low49T349and49T4.
▪ Serum49Thyroxine49Test
• Testing49can49measure49either49total49T449(bound49plus49free)49
or49free49T4.49Measurement49of49free49T449is49preferred.49The4
9T449test49can49monitor
thyroid49hormone49replacement49therapy49and49screen49for49thyroid4
9dysfunction.49However,49in49both49cases,49the49size49of49TSH49is49ch
osen.
▪ Serum49Triiodothyronine49Test
• As49with49T4,49we49can49measure49either49total49or49free49T3.49M
easurement49of49free49T349is49preferred.49This49test49helps49dia
gnose49hyperthyroidism.
In49this49disorder,49levels49of49T349often49rise49sooner49and49to49
a49greater49extent49than49do49levels49of49T4.49T349determinations
49can49also49be49used49to49monitor49thyroid49hormone49replacem
ent49therapy49(all49thyroid49preparations49should49increase49level
s49of49T3).
, 4
lOMoAR
94 cPSD|
9 28505380
Thyroid49Test SERUM49VALUES
Normal Hypothyroid Hyperthyroid
Total49T449(µg/dL) 4.5–12.5 Under494.5 Over4912.5
Free49T449(ng/dL) 0.9–2 Under490.9 Over492
Total49T349(ng/dL) 80–220 Under4980 Over49220
Free49T349(pg/dL) 230–620 Under49230 Over49620
TSH49(miu/L) 0.3–6 Over496 Under490.3
Laboratory49studies49have49different49reference49ranges.49These49are49relative49ranges49and49a
re49not49absolute.
▪ Timeframe49for49re-check49of49labs49after49starting49levothyroxine
• 6-849weeks
▪ Signs49and49symptoms49of49hypo49and49hyperthyroidism
▪ Hyperthyroidism
• Tachycardia
• dysrhythmias49and49angina
• nervousness
• insomnia
• rapid49thought49flow
• rapid49speech
• Skeletal49muscles49may49weaken49and49atrophy.
• Metabolic49rate49is49raised
• increased49heat49production
• increased49body49temperature
• intolerance49to49heat
• skin49that49is49warm49and49moist
• Appetite49is49increased.
• weight49loss49occurs
• In49addition49to49thyrotoxicosis,49patients49with49Graves49disea
se49often49present49with49exophthalmos.49The49underlying49cau
se49is49an49immune-
mediated49infiltration49of49the49extraocular49muscles49and49orbital49fat4
9by49lymphocytes,49macrophages,49plasma49cells,49mast49cells,49and
49mucopolysaccharides.
, 4
lOMoAR
94 cPSD|
9 28505380
▪ Hypothyroidism
• Signs49and49symptoms49of49hypothyroidism49depend49on49
disease49severity.
• With49mild49hypothyroidism,49symptoms49are49subtle49and4
9may49go49unrecognized49for49what49they49are.
• In49contrast,49characteristic49signs49and49symptoms49emer
ge49with49moderate49to49severe49disease.
• The49face49is49pale,49puffy,49and49expressionless.
• The49skin49is49cold49and49dry.
• The49hair49is49brittle,49and49hair49loss49occurs.
• Heart49rate49and49temperature49are49lowered.
• The49patient49may49complain49of49lethargy,49fatigue,49and49intol
erance49to49cold.
• Mentation49may49be49impaired.
• Thyroid49enlargement49may49occur49if49reduced49T349and49T449pr
omote49the49excessive49release49of49TSH.
o Treatment
▪ Treatment49of49thyroid49storm
• thyrotoxic49crisis49can49be49life-
threatening49and49requires49immediate49treatment.49High49do
ses49of49potassium49iodide49or49strong49iodine
solution49are49given49to49suppress49thyroid49hormone49release
.49Methimazole49is49shown49to49suppress49thyroid49hormone49s
ynthesis.49A49β-
blocker49is49provided49to49reduce49heart49rate.49Additional49mea
sures49include49sedation,49cooling,49glucocorticoids,49and49intr
avenous49(IV)49fluids.
▪ Result49of49not49treating49hypothyroidism49during49pregnancy
• Maternal49hypothyroidism49can49result49in49perm
anent49neuropsychological49deficits49in49the49ch
ild
▪ Medication49to49treat49symptoms49of49hyperthyroidism49(notice49this49i
s49treating49symptoms49and49not49the49hyperthyroidism49itself)
• Methimazole
• Methimazole49(Tapazole)49is49the49first-
line49drug49for49hyperthyroidism.49Benefits49derive49from49inhibi
ting49thyroid49hormone49synthesis.
Methimazole49is49safer49and49more49convenient49than49PTU49and49he
nce49is49preferred49for49most49patients—
except49women49who49are49pregnant49or49breastfeeding49and49perha
ps49patients49who49are49in49thyrotoxic49crisis.
• 131I49is49indicated49for49adults49with49hyperthyroidism49and49pati
ents49who49have49not49responded49adequately49to49antithyroid4
9drugs49or49subtotal
thyroidectomy.
• Methimazole49can49cause49neonatal49hypothyroidism,49goiter,49an
d49even49congenital49hypothyroidism.49Accordingly,49the49drug49
should49be49avoided49during49the49first49trimester.49Use49in49the4
9second49and49third
trimesters49is49considered49safe.49Compared49with49methimazole,
49PTU49crosses49the49placenta49poorly,49hence49low49risk49to49th
e49fetus.
Accordingly,49if49a49thionamide49is49needed49during49the49first49trimest
er49of49pregnancy,49PTU49is49the49preferred49drug.
, 4
lOMoAR
94 cPSD|
9 28505380
▪ Drug/Food/Supplement49interactions49 with49levothyroxine49for49hypothyroidis
m
• The49following49drugs49can49reduce49the49absorption49of49levothyroxin
e:
•
• •49Histamine49249(H2)49receptor49blockers49(e.g.,49cimetidine49[Tagame
t])
• •49Proton49pump49inhibitors49(e.g.,49lansoprazole49[Prevacid])
• •49Sucralfate49(Carafate)
• •49Cholestyramine49(Questran)
• •49Colestipol49(Colestid)
• •49Aluminum-containing49antacids49(e.g.,49Maalox,49Mylanta)
• •49Calcium49supplements49(e.g.,49Tums,49Os-Cal)
• •49Iron49supplements49(e.g.,49ferrous49sulfate)
• •49Magnesium49salts
• •49Orlistat49(Xenical)
▪ Drugs49that49accelerate49levothyroxine49metabolism.
▪ Several49drugs49can49accelerate49the49metabolism49of49levothyroxine.
49Among49these49are49phenytoin49(Dilantin),49carbamazepine49(Tegr
etol,49Carbatrol),
rifampin49(Rifadin),49sertraline49(Zoloft),49and49phenobarbital.49Accor
dingly,49patients49taking49these49drugs49may49need49to49increase49t
heir49levothyroxine49dosage49to49maintain49adequate49levels.
▪
▪ Warfarin.
▪ Levothyroxine49accelerates49the49degradation49of49vitamin49K–
dependent49clotting49factors.49As49a49result,49the49effects49of49wa
rfarin49are49enhanced.
Therefore,49if49thyroid49hormone49replacement49therapy49is49started49in49
a49patient49taking49warfarin,49the49dosage49may49need49to49be49reduced
.
▪
▪ Catecholamines.
▪ Thyroid49hormones49increase49cardiac49responsiveness49to49catechola
mines,49thereby49increasing49the49risk49for49catecholamine-
induced49dysrhythmias.
Therefore,49caution49must49be49exercised49when49administering49catechol
amines49to49patients49receiving49levothyroxine49and49other49thyroid49pre
parations.
▪
▪ Other49interactions.
▪ Levothyroxine49can49increase49requirements49for49insulin49and49digoxi
n.49When49converting49patients49from49a49hypothyroid49to49a49euthyro
id49state,49insulin
dosages49and49digoxin49may49need49to49be49improved.
• Diabetes
o How49to49confirm49a49diagnosis49before49beginning49treatment
▪ Tests49Based49on49Blood49Levels49of49Glucose
• Excessive49plasma49glucose49is49diagnostic49of49diabetes
• Several49tests49may49be49used
o fasting49plasma49glucose49(FPG)49test4912649or49greater
o casual49plasma49glucose49test4920049greater
o oral49glucose49tolerance49test49(OGTT)4920049greater
• To49make49a49definitive49diagnosis,49the49patient49must49be49test
lOMoAR
94 cPSD|
9 28505380
NR565 Pharmacology Fundamentals Study Guide
Be49familiar49with49the49interactive49activities49throughout49course49modules.4 9 You49could49s
ee49variations49of49those49same49questions49on49your49exams.
Week495
• Thyroid
o Thyrotropin-releasing49hormone49(TRH)49from49the49hypothalamus49stimulates
o release49of49thyroid-stimulating49hormone49(TSH)49from49the49pituitary.
o TSH49stimulates49all49aspects49of49thyroid49function,
▪ including49the49release49of49triiodothyronine49(T3)49and49thyroxine49(T4).
▪ T349and49T449act49on49the49pituitary49to49suppress49further49TSH49release.
o Diagnosis49&49Evaluation
▪ What49labs49are49used49to49diagnose?
▪ Serum49TSH49determinations49are49used49primarily49for49screening49
and49diagnosis49of49hypothyroidism49and49for49monitoring49replaceme
nt49therapy49in
hypothyroid49patients.
▪ Serum49TSH49determinations49can49also49distinguish49primary49hypothy
roidism49from49secondary49hypothyroidism.49In49primary49(thyroidal)49
hypothyroidism,49TSH49levels49are49high.49However,49in49secondary49
hypothyroidism
(hypothyroidism49resulting49from49anterior49pituitary49dysfunction),49TSH49
levels49are49low,49normal,49or49even49slightly49elevated—
despite49low49T349and49T4.
▪ Serum49Thyroxine49Test
• Testing49can49measure49either49total49T449(bound49plus49free)49
or49free49T4.49Measurement49of49free49T449is49preferred.49The4
9T449test49can49monitor
thyroid49hormone49replacement49therapy49and49screen49for49thyroid4
9dysfunction.49However,49in49both49cases,49the49size49of49TSH49is49ch
osen.
▪ Serum49Triiodothyronine49Test
• As49with49T4,49we49can49measure49either49total49or49free49T3.49M
easurement49of49free49T349is49preferred.49This49test49helps49dia
gnose49hyperthyroidism.
In49this49disorder,49levels49of49T349often49rise49sooner49and49to49
a49greater49extent49than49do49levels49of49T4.49T349determinations
49can49also49be49used49to49monitor49thyroid49hormone49replacem
ent49therapy49(all49thyroid49preparations49should49increase49level
s49of49T3).
, 4
lOMoAR
94 cPSD|
9 28505380
Thyroid49Test SERUM49VALUES
Normal Hypothyroid Hyperthyroid
Total49T449(µg/dL) 4.5–12.5 Under494.5 Over4912.5
Free49T449(ng/dL) 0.9–2 Under490.9 Over492
Total49T349(ng/dL) 80–220 Under4980 Over49220
Free49T349(pg/dL) 230–620 Under49230 Over49620
TSH49(miu/L) 0.3–6 Over496 Under490.3
Laboratory49studies49have49different49reference49ranges.49These49are49relative49ranges49and49a
re49not49absolute.
▪ Timeframe49for49re-check49of49labs49after49starting49levothyroxine
• 6-849weeks
▪ Signs49and49symptoms49of49hypo49and49hyperthyroidism
▪ Hyperthyroidism
• Tachycardia
• dysrhythmias49and49angina
• nervousness
• insomnia
• rapid49thought49flow
• rapid49speech
• Skeletal49muscles49may49weaken49and49atrophy.
• Metabolic49rate49is49raised
• increased49heat49production
• increased49body49temperature
• intolerance49to49heat
• skin49that49is49warm49and49moist
• Appetite49is49increased.
• weight49loss49occurs
• In49addition49to49thyrotoxicosis,49patients49with49Graves49disea
se49often49present49with49exophthalmos.49The49underlying49cau
se49is49an49immune-
mediated49infiltration49of49the49extraocular49muscles49and49orbital49fat4
9by49lymphocytes,49macrophages,49plasma49cells,49mast49cells,49and
49mucopolysaccharides.
, 4
lOMoAR
94 cPSD|
9 28505380
▪ Hypothyroidism
• Signs49and49symptoms49of49hypothyroidism49depend49on49
disease49severity.
• With49mild49hypothyroidism,49symptoms49are49subtle49and4
9may49go49unrecognized49for49what49they49are.
• In49contrast,49characteristic49signs49and49symptoms49emer
ge49with49moderate49to49severe49disease.
• The49face49is49pale,49puffy,49and49expressionless.
• The49skin49is49cold49and49dry.
• The49hair49is49brittle,49and49hair49loss49occurs.
• Heart49rate49and49temperature49are49lowered.
• The49patient49may49complain49of49lethargy,49fatigue,49and49intol
erance49to49cold.
• Mentation49may49be49impaired.
• Thyroid49enlargement49may49occur49if49reduced49T349and49T449pr
omote49the49excessive49release49of49TSH.
o Treatment
▪ Treatment49of49thyroid49storm
• thyrotoxic49crisis49can49be49life-
threatening49and49requires49immediate49treatment.49High49do
ses49of49potassium49iodide49or49strong49iodine
solution49are49given49to49suppress49thyroid49hormone49release
.49Methimazole49is49shown49to49suppress49thyroid49hormone49s
ynthesis.49A49β-
blocker49is49provided49to49reduce49heart49rate.49Additional49mea
sures49include49sedation,49cooling,49glucocorticoids,49and49intr
avenous49(IV)49fluids.
▪ Result49of49not49treating49hypothyroidism49during49pregnancy
• Maternal49hypothyroidism49can49result49in49perm
anent49neuropsychological49deficits49in49the49ch
ild
▪ Medication49to49treat49symptoms49of49hyperthyroidism49(notice49this49i
s49treating49symptoms49and49not49the49hyperthyroidism49itself)
• Methimazole
• Methimazole49(Tapazole)49is49the49first-
line49drug49for49hyperthyroidism.49Benefits49derive49from49inhibi
ting49thyroid49hormone49synthesis.
Methimazole49is49safer49and49more49convenient49than49PTU49and49he
nce49is49preferred49for49most49patients—
except49women49who49are49pregnant49or49breastfeeding49and49perha
ps49patients49who49are49in49thyrotoxic49crisis.
• 131I49is49indicated49for49adults49with49hyperthyroidism49and49pati
ents49who49have49not49responded49adequately49to49antithyroid4
9drugs49or49subtotal
thyroidectomy.
• Methimazole49can49cause49neonatal49hypothyroidism,49goiter,49an
d49even49congenital49hypothyroidism.49Accordingly,49the49drug49
should49be49avoided49during49the49first49trimester.49Use49in49the4
9second49and49third
trimesters49is49considered49safe.49Compared49with49methimazole,
49PTU49crosses49the49placenta49poorly,49hence49low49risk49to49th
e49fetus.
Accordingly,49if49a49thionamide49is49needed49during49the49first49trimest
er49of49pregnancy,49PTU49is49the49preferred49drug.
, 4
lOMoAR
94 cPSD|
9 28505380
▪ Drug/Food/Supplement49interactions49 with49levothyroxine49for49hypothyroidis
m
• The49following49drugs49can49reduce49the49absorption49of49levothyroxin
e:
•
• •49Histamine49249(H2)49receptor49blockers49(e.g.,49cimetidine49[Tagame
t])
• •49Proton49pump49inhibitors49(e.g.,49lansoprazole49[Prevacid])
• •49Sucralfate49(Carafate)
• •49Cholestyramine49(Questran)
• •49Colestipol49(Colestid)
• •49Aluminum-containing49antacids49(e.g.,49Maalox,49Mylanta)
• •49Calcium49supplements49(e.g.,49Tums,49Os-Cal)
• •49Iron49supplements49(e.g.,49ferrous49sulfate)
• •49Magnesium49salts
• •49Orlistat49(Xenical)
▪ Drugs49that49accelerate49levothyroxine49metabolism.
▪ Several49drugs49can49accelerate49the49metabolism49of49levothyroxine.
49Among49these49are49phenytoin49(Dilantin),49carbamazepine49(Tegr
etol,49Carbatrol),
rifampin49(Rifadin),49sertraline49(Zoloft),49and49phenobarbital.49Accor
dingly,49patients49taking49these49drugs49may49need49to49increase49t
heir49levothyroxine49dosage49to49maintain49adequate49levels.
▪
▪ Warfarin.
▪ Levothyroxine49accelerates49the49degradation49of49vitamin49K–
dependent49clotting49factors.49As49a49result,49the49effects49of49wa
rfarin49are49enhanced.
Therefore,49if49thyroid49hormone49replacement49therapy49is49started49in49
a49patient49taking49warfarin,49the49dosage49may49need49to49be49reduced
.
▪
▪ Catecholamines.
▪ Thyroid49hormones49increase49cardiac49responsiveness49to49catechola
mines,49thereby49increasing49the49risk49for49catecholamine-
induced49dysrhythmias.
Therefore,49caution49must49be49exercised49when49administering49catechol
amines49to49patients49receiving49levothyroxine49and49other49thyroid49pre
parations.
▪
▪ Other49interactions.
▪ Levothyroxine49can49increase49requirements49for49insulin49and49digoxi
n.49When49converting49patients49from49a49hypothyroid49to49a49euthyro
id49state,49insulin
dosages49and49digoxin49may49need49to49be49improved.
• Diabetes
o How49to49confirm49a49diagnosis49before49beginning49treatment
▪ Tests49Based49on49Blood49Levels49of49Glucose
• Excessive49plasma49glucose49is49diagnostic49of49diabetes
• Several49tests49may49be49used
o fasting49plasma49glucose49(FPG)49test4912649or49greater
o casual49plasma49glucose49test4920049greater
o oral49glucose49tolerance49test49(OGTT)4920049greater
• To49make49a49definitive49diagnosis,49the49patient49must49be49test
