4
lOMoAR
54 cPSD|
5 28505380
NR565 Pharmacology Fundamentals Study Guide
Be45familiar45with45the45interactive45activities45throughout45course45modules.4 5 You45could45s
ee45variations45of45those45same45questions45on45your45exams.
Week455
• Thyroid
o Thyrotropin-releasing45hormone45(TRH)45from45the45hypothalamus45stimulates
o release45of45thyroid-stimulating45hormone45(TSH)45from45the45pituitary.
o TSH45stimulates45all45aspects45of45thyroid45function,
▪ including45the45release45of45triiodothyronine45(T3)45and45thyroxine45(T4).
▪ T345and45T445act45on45the45pituitary45to45suppress45further45TSH45release.
o Diagnosis45&45Evaluation
▪ What45labs45are45used45to45diagnose?
▪ Serum45TSH45determinations45are45used45primarily45for45screening45
and45diagnosis45of45hypothyroidism45and45for45monitoring45replaceme
nt45therapy45in
hypothyroid45patients.
▪ Serum45TSH45determinations45can45also45distinguish45primary45hypothy
roidism45from45secondary45hypothyroidism.45In45primary45(thyroidal)45
hypothyroidism,45TSH45levels45are45high.45However,45in45secondary45
hypothyroidism
(hypothyroidism45resulting45from45anterior45pituitary45dysfunction),45TSH45
levels45are45low,45normal,45or45even45slightly45elevated—
despite45low45T345and45T4.
▪ Serum45Thyroxine45Test
• Testing45can45measure45either45total45T445(bound45plus45free)45
or45free45T4.45Measurement45of45free45T445is45preferred.45The4
5T445test45can45monitor
thyroid45hormone45replacement45therapy45and45screen45for45thyroid4
5dysfunction.45However,45in45both45cases,45the45size45of45TSH45is45ch
osen.
▪ Serum45Triiodothyronine45Test
• As45with45T4,45we45can45measure45either45total45or45free45T3.45M
easurement45of45free45T345is45preferred.45This45test45helps45dia
gnose45hyperthyroidism.
In45this45disorder,45levels45of45T345often45rise45sooner45and45to45
a45greater45extent45than45do45levels45of45T4.45T345determinations
45can45also45be45used45to45monitor45thyroid45hormone45replacem
ent45therapy45(all45thyroid45preparations45should45increase45level
s45of45T3).
, 4
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Thyroid45Test SERUM45VALUES
Normal Hypothyroid Hyperthyroid
Total45T445(µg/dL) 4.5–12.5 Under454.5 Over4512.5
Free45T445(ng/dL) 0.9–2 Under450.9 Over452
Total45T345(ng/dL) 80–220 Under4580 Over45220
Free45T345(pg/dL) 230–620 Under45230 Over45620
TSH45(miu/L) 0.3–6 Over456 Under450.3
Laboratory45studies45have45different45reference45ranges.45These45are45relative45ranges45and45a
re45not45absolute.
▪ Timeframe45for45re-check45of45labs45after45starting45levothyroxine
• 6-845weeks
▪ Signs45and45symptoms45of45hypo45and45hyperthyroidism
▪ Hyperthyroidism
• Tachycardia
• dysrhythmias45and45angina
• nervousness
• insomnia
• rapid45thought45flow
• rapid45speech
• Skeletal45muscles45may45weaken45and45atrophy.
• Metabolic45rate45is45raised
• increased45heat45production
• increased45body45temperature
• intolerance45to45heat
• skin45that45is45warm45and45moist
• Appetite45is45increased.
• weight45loss45occurs
• In45addition45to45thyrotoxicosis,45patients45with45Graves45disea
se45often45present45with45exophthalmos.45The45underlying45cau
se45is45an45immune-
mediated45infiltration45of45the45extraocular45muscles45and45orbital45fat4
5by45lymphocytes,45macrophages,45plasma45cells,45mast45cells,45and
45mucopolysaccharides.
, 4
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54 cPSD|
5 28505380
▪ Hypothyroidism
• Signs45and45symptoms45of45hypothyroidism45depend45on45
disease45severity.
• With45mild45hypothyroidism,45symptoms45are45subtle45and4
5may45go45unrecognized45for45what45they45are.
• In45contrast,45characteristic45signs45and45symptoms45emer
ge45with45moderate45to45severe45disease.
• The45face45is45pale,45puffy,45and45expressionless.
• The45skin45is45cold45and45dry.
• The45hair45is45brittle,45and45hair45loss45occurs.
• Heart45rate45and45temperature45are45lowered.
• The45patient45may45complain45of45lethargy,45fatigue,45and45intol
erance45to45cold.
• Mentation45may45be45impaired.
• Thyroid45enlargement45may45occur45if45reduced45T345and45T445pr
omote45the45excessive45release45of45TSH.
o Treatment
▪ Treatment45of45thyroid45storm
• thyrotoxic45crisis45can45be45life-
threatening45and45requires45immediate45treatment.45High45do
ses45of45potassium45iodide45or45strong45iodine
solution45are45given45to45suppress45thyroid45hormone45release
.45Methimazole45is45shown45to45suppress45thyroid45hormone45s
ynthesis.45A45β-
blocker45is45provided45to45reduce45heart45rate.45Additional45mea
sures45include45sedation,45cooling,45glucocorticoids,45and45intr
avenous45(IV)45fluids.
▪ Result45of45not45treating45hypothyroidism45during45pregnancy
• Maternal45hypothyroidism45can45result45in45perm
anent45neuropsychological45deficits45in45the45ch
ild
▪ Medication45to45treat45symptoms45of45hyperthyroidism45(notice45this45i
s45treating45symptoms45and45not45the45hyperthyroidism45itself)
• Methimazole
• Methimazole45(Tapazole)45is45the45first-
line45drug45for45hyperthyroidism.45Benefits45derive45from45inhibi
ting45thyroid45hormone45synthesis.
Methimazole45is45safer45and45more45convenient45than45PTU45and45he
nce45is45preferred45for45most45patients—
except45women45who45are45pregnant45or45breastfeeding45and45perha
ps45patients45who45are45in45thyrotoxic45crisis.
• 131I45is45indicated45for45adults45with45hyperthyroidism45and45pati
ents45who45have45not45responded45adequately45to45antithyroid4
5drugs45or45subtotal
thyroidectomy.
• Methimazole45can45cause45neonatal45hypothyroidism,45goiter,45an
d45even45congenital45hypothyroidism.45Accordingly,45the45drug45
should45be45avoided45during45the45first45trimester.45Use45in45the4
5second45and45third
trimesters45is45considered45safe.45Compared45with45methimazole,
45PTU45crosses45the45placenta45poorly,45hence45low45risk45to45th
e45fetus.
Accordingly,45if45a45thionamide45is45needed45during45the45first45trimest
er45of45pregnancy,45PTU45is45the45preferred45drug.
, 4
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5 28505380
▪ Drug/Food/Supplement45interactions45 with45levothyroxine45for45hypothyroidis
m
• The45following45drugs45can45reduce45the45absorption45of45levothyroxin
e:
•
• •45Histamine45245(H2)45receptor45blockers45(e.g.,45cimetidine45[Tagame
t])
• •45Proton45pump45inhibitors45(e.g.,45lansoprazole45[Prevacid])
• •45Sucralfate45(Carafate)
• •45Cholestyramine45(Questran)
• •45Colestipol45(Colestid)
• •45Aluminum-containing45antacids45(e.g.,45Maalox,45Mylanta)
• •45Calcium45supplements45(e.g.,45Tums,45Os-Cal)
• •45Iron45supplements45(e.g.,45ferrous45sulfate)
• •45Magnesium45salts
• •45Orlistat45(Xenical)
▪ Drugs45that45accelerate45levothyroxine45metabolism.
▪ Several45drugs45can45accelerate45the45metabolism45of45levothyroxine.
45Among45these45are45phenytoin45(Dilantin),45carbamazepine45(Tegr
etol,45Carbatrol),
rifampin45(Rifadin),45sertraline45(Zoloft),45and45phenobarbital.45Accor
dingly,45patients45taking45these45drugs45may45need45to45increase45t
heir45levothyroxine45dosage45to45maintain45adequate45levels.
▪
▪ Warfarin.
▪ Levothyroxine45accelerates45the45degradation45of45vitamin45K–
dependent45clotting45factors.45As45a45result,45the45effects45of45wa
rfarin45are45enhanced.
Therefore,45if45thyroid45hormone45replacement45therapy45is45started45in45
a45patient45taking45warfarin,45the45dosage45may45need45to45be45reduced
.
▪
▪ Catecholamines.
▪ Thyroid45hormones45increase45cardiac45responsiveness45to45catechola
mines,45thereby45increasing45the45risk45for45catecholamine-
induced45dysrhythmias.
Therefore,45caution45must45be45exercised45when45administering45catechol
amines45to45patients45receiving45levothyroxine45and45other45thyroid45pre
parations.
▪
▪ Other45interactions.
▪ Levothyroxine45can45increase45requirements45for45insulin45and45digoxi
n.45When45converting45patients45from45a45hypothyroid45to45a45euthyro
id45state,45insulin
dosages45and45digoxin45may45need45to45be45improved.
• Diabetes
o How45to45confirm45a45diagnosis45before45beginning45treatment
▪ Tests45Based45on45Blood45Levels45of45Glucose
• Excessive45plasma45glucose45is45diagnostic45of45diabetes
• Several45tests45may45be45used
o fasting45plasma45glucose45(FPG)45test4512645or45greater
o casual45plasma45glucose45test4520045greater
o oral45glucose45tolerance45test45(OGTT)4520045greater
• To45make45a45definitive45diagnosis,45the45patient45must45be45test
lOMoAR
54 cPSD|
5 28505380
NR565 Pharmacology Fundamentals Study Guide
Be45familiar45with45the45interactive45activities45throughout45course45modules.4 5 You45could45s
ee45variations45of45those45same45questions45on45your45exams.
Week455
• Thyroid
o Thyrotropin-releasing45hormone45(TRH)45from45the45hypothalamus45stimulates
o release45of45thyroid-stimulating45hormone45(TSH)45from45the45pituitary.
o TSH45stimulates45all45aspects45of45thyroid45function,
▪ including45the45release45of45triiodothyronine45(T3)45and45thyroxine45(T4).
▪ T345and45T445act45on45the45pituitary45to45suppress45further45TSH45release.
o Diagnosis45&45Evaluation
▪ What45labs45are45used45to45diagnose?
▪ Serum45TSH45determinations45are45used45primarily45for45screening45
and45diagnosis45of45hypothyroidism45and45for45monitoring45replaceme
nt45therapy45in
hypothyroid45patients.
▪ Serum45TSH45determinations45can45also45distinguish45primary45hypothy
roidism45from45secondary45hypothyroidism.45In45primary45(thyroidal)45
hypothyroidism,45TSH45levels45are45high.45However,45in45secondary45
hypothyroidism
(hypothyroidism45resulting45from45anterior45pituitary45dysfunction),45TSH45
levels45are45low,45normal,45or45even45slightly45elevated—
despite45low45T345and45T4.
▪ Serum45Thyroxine45Test
• Testing45can45measure45either45total45T445(bound45plus45free)45
or45free45T4.45Measurement45of45free45T445is45preferred.45The4
5T445test45can45monitor
thyroid45hormone45replacement45therapy45and45screen45for45thyroid4
5dysfunction.45However,45in45both45cases,45the45size45of45TSH45is45ch
osen.
▪ Serum45Triiodothyronine45Test
• As45with45T4,45we45can45measure45either45total45or45free45T3.45M
easurement45of45free45T345is45preferred.45This45test45helps45dia
gnose45hyperthyroidism.
In45this45disorder,45levels45of45T345often45rise45sooner45and45to45
a45greater45extent45than45do45levels45of45T4.45T345determinations
45can45also45be45used45to45monitor45thyroid45hormone45replacem
ent45therapy45(all45thyroid45preparations45should45increase45level
s45of45T3).
, 4
lOMoAR
54 cPSD|
5 28505380
Thyroid45Test SERUM45VALUES
Normal Hypothyroid Hyperthyroid
Total45T445(µg/dL) 4.5–12.5 Under454.5 Over4512.5
Free45T445(ng/dL) 0.9–2 Under450.9 Over452
Total45T345(ng/dL) 80–220 Under4580 Over45220
Free45T345(pg/dL) 230–620 Under45230 Over45620
TSH45(miu/L) 0.3–6 Over456 Under450.3
Laboratory45studies45have45different45reference45ranges.45These45are45relative45ranges45and45a
re45not45absolute.
▪ Timeframe45for45re-check45of45labs45after45starting45levothyroxine
• 6-845weeks
▪ Signs45and45symptoms45of45hypo45and45hyperthyroidism
▪ Hyperthyroidism
• Tachycardia
• dysrhythmias45and45angina
• nervousness
• insomnia
• rapid45thought45flow
• rapid45speech
• Skeletal45muscles45may45weaken45and45atrophy.
• Metabolic45rate45is45raised
• increased45heat45production
• increased45body45temperature
• intolerance45to45heat
• skin45that45is45warm45and45moist
• Appetite45is45increased.
• weight45loss45occurs
• In45addition45to45thyrotoxicosis,45patients45with45Graves45disea
se45often45present45with45exophthalmos.45The45underlying45cau
se45is45an45immune-
mediated45infiltration45of45the45extraocular45muscles45and45orbital45fat4
5by45lymphocytes,45macrophages,45plasma45cells,45mast45cells,45and
45mucopolysaccharides.
, 4
lOMoAR
54 cPSD|
5 28505380
▪ Hypothyroidism
• Signs45and45symptoms45of45hypothyroidism45depend45on45
disease45severity.
• With45mild45hypothyroidism,45symptoms45are45subtle45and4
5may45go45unrecognized45for45what45they45are.
• In45contrast,45characteristic45signs45and45symptoms45emer
ge45with45moderate45to45severe45disease.
• The45face45is45pale,45puffy,45and45expressionless.
• The45skin45is45cold45and45dry.
• The45hair45is45brittle,45and45hair45loss45occurs.
• Heart45rate45and45temperature45are45lowered.
• The45patient45may45complain45of45lethargy,45fatigue,45and45intol
erance45to45cold.
• Mentation45may45be45impaired.
• Thyroid45enlargement45may45occur45if45reduced45T345and45T445pr
omote45the45excessive45release45of45TSH.
o Treatment
▪ Treatment45of45thyroid45storm
• thyrotoxic45crisis45can45be45life-
threatening45and45requires45immediate45treatment.45High45do
ses45of45potassium45iodide45or45strong45iodine
solution45are45given45to45suppress45thyroid45hormone45release
.45Methimazole45is45shown45to45suppress45thyroid45hormone45s
ynthesis.45A45β-
blocker45is45provided45to45reduce45heart45rate.45Additional45mea
sures45include45sedation,45cooling,45glucocorticoids,45and45intr
avenous45(IV)45fluids.
▪ Result45of45not45treating45hypothyroidism45during45pregnancy
• Maternal45hypothyroidism45can45result45in45perm
anent45neuropsychological45deficits45in45the45ch
ild
▪ Medication45to45treat45symptoms45of45hyperthyroidism45(notice45this45i
s45treating45symptoms45and45not45the45hyperthyroidism45itself)
• Methimazole
• Methimazole45(Tapazole)45is45the45first-
line45drug45for45hyperthyroidism.45Benefits45derive45from45inhibi
ting45thyroid45hormone45synthesis.
Methimazole45is45safer45and45more45convenient45than45PTU45and45he
nce45is45preferred45for45most45patients—
except45women45who45are45pregnant45or45breastfeeding45and45perha
ps45patients45who45are45in45thyrotoxic45crisis.
• 131I45is45indicated45for45adults45with45hyperthyroidism45and45pati
ents45who45have45not45responded45adequately45to45antithyroid4
5drugs45or45subtotal
thyroidectomy.
• Methimazole45can45cause45neonatal45hypothyroidism,45goiter,45an
d45even45congenital45hypothyroidism.45Accordingly,45the45drug45
should45be45avoided45during45the45first45trimester.45Use45in45the4
5second45and45third
trimesters45is45considered45safe.45Compared45with45methimazole,
45PTU45crosses45the45placenta45poorly,45hence45low45risk45to45th
e45fetus.
Accordingly,45if45a45thionamide45is45needed45during45the45first45trimest
er45of45pregnancy,45PTU45is45the45preferred45drug.
, 4
lOMoAR
54 cPSD|
5 28505380
▪ Drug/Food/Supplement45interactions45 with45levothyroxine45for45hypothyroidis
m
• The45following45drugs45can45reduce45the45absorption45of45levothyroxin
e:
•
• •45Histamine45245(H2)45receptor45blockers45(e.g.,45cimetidine45[Tagame
t])
• •45Proton45pump45inhibitors45(e.g.,45lansoprazole45[Prevacid])
• •45Sucralfate45(Carafate)
• •45Cholestyramine45(Questran)
• •45Colestipol45(Colestid)
• •45Aluminum-containing45antacids45(e.g.,45Maalox,45Mylanta)
• •45Calcium45supplements45(e.g.,45Tums,45Os-Cal)
• •45Iron45supplements45(e.g.,45ferrous45sulfate)
• •45Magnesium45salts
• •45Orlistat45(Xenical)
▪ Drugs45that45accelerate45levothyroxine45metabolism.
▪ Several45drugs45can45accelerate45the45metabolism45of45levothyroxine.
45Among45these45are45phenytoin45(Dilantin),45carbamazepine45(Tegr
etol,45Carbatrol),
rifampin45(Rifadin),45sertraline45(Zoloft),45and45phenobarbital.45Accor
dingly,45patients45taking45these45drugs45may45need45to45increase45t
heir45levothyroxine45dosage45to45maintain45adequate45levels.
▪
▪ Warfarin.
▪ Levothyroxine45accelerates45the45degradation45of45vitamin45K–
dependent45clotting45factors.45As45a45result,45the45effects45of45wa
rfarin45are45enhanced.
Therefore,45if45thyroid45hormone45replacement45therapy45is45started45in45
a45patient45taking45warfarin,45the45dosage45may45need45to45be45reduced
.
▪
▪ Catecholamines.
▪ Thyroid45hormones45increase45cardiac45responsiveness45to45catechola
mines,45thereby45increasing45the45risk45for45catecholamine-
induced45dysrhythmias.
Therefore,45caution45must45be45exercised45when45administering45catechol
amines45to45patients45receiving45levothyroxine45and45other45thyroid45pre
parations.
▪
▪ Other45interactions.
▪ Levothyroxine45can45increase45requirements45for45insulin45and45digoxi
n.45When45converting45patients45from45a45hypothyroid45to45a45euthyro
id45state,45insulin
dosages45and45digoxin45may45need45to45be45improved.
• Diabetes
o How45to45confirm45a45diagnosis45before45beginning45treatment
▪ Tests45Based45on45Blood45Levels45of45Glucose
• Excessive45plasma45glucose45is45diagnostic45of45diabetes
• Several45tests45may45be45used
o fasting45plasma45glucose45(FPG)45test4512645or45greater
o casual45plasma45glucose45test4520045greater
o oral45glucose45tolerance45test45(OGTT)4520045greater
• To45make45a45definitive45diagnosis,45the45patient45must45be45test
