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Pharmacology II > Uterine, Thyroid, & Osteoporosis Drugs > Flashcards

Uterine, Thyroid, & Osteoporosis Drugs Flashcards

1
Q

Oxytocin (Pitocin®, Syntocin®) - Indications/Therapeutics

A

• DOC to induce labor at term if indicated
– Augment labor in selected patients with uterine dysfunctional inertia
– Causes timed contractions (on then off)
– IV infusion is preferred for these
• For prevention of hemorrhage
– IM route is preferred for this
• For stimulation of milk let-down reflex
– Nasal application method (Cotton pledget)

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2
Q

Oxytocin (Pitocin®, Syntocin®) - Adverse Effects

A

• Water intoxication with convulsions
– Because of ADH like effect of oxytocin
– Serious complication that may occur
– If doses are large and infused for a prolonged period
• Uterine rupture with large dose
• Allergy
• Anaphylaxis
• Sinus bradycardiaof the fetus
– Premature ventricular contractions and other
arrhythmias of the fetus and fetal death due to
extreme uterine contractions, etc.

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3
Q

Oxytocin (Pitocin®, Syntocin®) - Pharmacokinetics

A
  • Very short half-life: 1-6 minutes

* Inactivated by liver and kidneys

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4
Q

Oxytocin (Pitocin®, Syntocin®) - Contrindications/Precautions

A
  • Malpresentation
  • Cephalopelvic disproportion
  • Complete placenta previa
  • Uterine scar from previous cesarean section
  • Unengaged head
  • Cervical scarring
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5
Q

Ergonovine maleate (Ergotrate®) - MoA

A

• Contraction of uterine smooth muscle through

activation of serotonin and a-adrenergic receptors

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6
Q

Ergonovine maleate (Ergotrate®) - Indications/Therapeutics

A

• After completion of labor and the delivery of the
placenta to produce firm uterine contractions and to
decrease uterine bleeding
– 2nd line after massage and oxytocin have failed
• For the same reasons following suction abortion

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7
Q

Ergonovine maleate (Ergotrate®) - Pharmacokinetics

A

• Rapid action
– 30-40 seconds after IV
– 10 minutes after oral use
• Action lasts several hours

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8
Q

Ergonovine maleate (Ergotrate®) - Adverse Effects

A
  • Transient hypertension – Contracts all smooth muscle

* Angina, MI

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9
Q

Ergonovine maleate (Ergotrate®) - Contraindications/Precautions

A

• C/I: Should never be used to induce labor.
– The contractions are strong, non-physiological,
continuous and will cause fetal hypoxia.
• Peripheral vascular or coronary artery disease

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10
Q

Prostaglandins

A

Dinoprostone (ProstinE2®)
Carboprost tromethamine (Prostin/M15®, Hemabate®)
Misoprostol (Cytotec®)

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11
Q

Prostaglandins - Indications/Therapeutics

A

• Expulsion of uterine contents (all):
– Intrauterine fetal death
– Missed abortion (miscarriage)
– Elective abortion
• Cervical ripening prior to delivery at term
(dinoprostone only)
• Postpartum bleeding due to uterine atony
– 3rd line, after massage, oxytocin, and ergots

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12
Q

Prostaglandins - Pharmacokinetics

A
  • For abortion & PPH: vaginal or rectal suppositories/pill
  • For cervical ripening: apply gel to cervix
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13
Q

Prostaglandins - Adverse Effects

A
  • G.I. disturbances, vomiting, diarrhea -Black Box
  • 30-70% experience fever, chills, headache
  • Many common but not serious (use correct dose)
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14
Q

Prostaglandins - Contraindications/Precautions

A

• For cervical ripening, problems with mother or fetus:
– Fetal distress, etc.
– History of difficult deliveries or caesarean section
• For abortions, should not be used in patients with:
– Acute pelvic inflammation
– C/I: Acute cardiac, pulmonary, renal, or hepatic
diseases
– Asthma, hypertension, anemia, jaundice or epilepsy

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15
Q

Tranexamic acid (Cyklokapron®) - Indications/Therapeutics

A

• Reduced death due to bleeding in women with
postpartum hemorrhage by 20-30% in trial
• Uterine bleeding (fibroids, other causes), when
hormonal therapy not wanted or C/I

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16
Q

Tranexamic acid (Cyklokapron®) - Pharmacokinetics

A

•Given IV
– Along with standard uterotonic therapy (should not
be regarded as an alternative therapy)

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17
Q

Tranexamic acid (Cyklokapron®) - Adverse Effects

A

• Can cause intravascular thrombosis

– Not seen in trial

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18
Q

Magnesium Sulfate (MgSO4) - MoA

A

• Relaxes the uterus probably by a direct effect

– Mechanism unknown

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19
Q

Magnesium Sulfate (MgSO4) - Indications/Therapeutics

A

• Considered 1st line drug
• Can prevent convulsions in pre-eclampsia and treat
eclampsia (FDA approved)

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20
Q

Magnesium Sulfate (MgSO4) - Pharmacokinetics

A

• IV, administered slowly (significant hypotension or

asystole if too fast)

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21
Q

Magnesium Sulfate (MgSO4) - Adverse Effects

A

• Flushing, diaphoresis, hypotension
• Depressed deep tendon reflexes, muscle paralysis,
weakness, lethargy, hypothermia
• Circulatory collapse, and cardiac, CNS, or respiratory
depression

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22
Q

Nifedipine (Procardia®)

A

• L-type calcium channel blocker

Mechanism of Action:
• Inhibits Ca2+influx (smooth muscle contractions)

Indications/Therapeutic Effects:
• Becoming 1st line agent (considering b2-agonists
problem)

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23
Q

Indomethacin (Indocin®) - MoA

A

• Inhibits COX enzyme: Reduction of prostaglandin

synthesis

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24
Q

Indomethacin (Indocin®) - Adverse Effects

A

• Maternal GI irritation, peptic ulceration,
thrombocytopenia, allergic reactions, headaches and
dizziness
• There are reports about partial closure of the fetal
ductus arteriosus, impaired fetal renal function,
bronchopulmonary dysplasia and persistent pulmonary
hypertension in the neonatal period

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25
Q

Progesterone - Indications/Therapeutics

A

• More effective than placebo in maintaining the length
of pregnancy when given prophylactically from the 16th
- 37th week of pregnancy or until delivery
– Not effective for acute treatment
• Recommended for high risk women with a history of
preterm birth
• Approved for use in ART to maintain the luteal phase
following IVF or ICSI.

26
Q

Levothyroxine sodium (Synthroid®)

A

• T4, produces normal levels of T3 and T4
• Drug of choice for hypothyroidism
• Drug levels must be carefully titrated to the individual
– TSH levels & Patient Sx
• T4 levels change slowly (t½= 7 days), ~5 weeks for
steady state

27
Q

Liothyronine sodium (Cytomel®)

A

• T3; t½= 24 hrs, shorter duration of action than T4
• Used for initial therapy (quicker steady state), not
maintenance

28
Q

Dessicated Thyroid (Armour Thyroid®)

A

• Mix of T4 and T3 hormones from pigs -> natural
hormones
• Batch potency can vary
• Pts w/ deficiency in the peripheral deiodinase enzyme
may respond better to this drug.

29
Q

Thioamides

A

Propylthiouracil (PTU) and Methimazole (Tapazole®)

30
Q

Thioamides - MoA

A 
• Inhibits the synthesis T4
 – Methimazole more potent
• PTU -> blocks conversion of T4 to T3
• Effects are gradual (use b-blockers)
 – Circulating T3/T4 lasts a week or so
31
Q

Thioamides - Indications/Precautions

A

• First line of treatment for Graves’
– Medical management
• Used with other treatments -> ↓thyroid storm risk

32
Q

Thioamides - Adverse Effects

A

• Black Box Warning for PTU
– Severe liver injury, acute liver failure
– Methimazole DOC in most cases
• Methimazole allergies and pregnancy -> PTU
• Itching and skin rash –most common
• Granulocytopenia and agranulocytosis
– Reversible
– Watch for sore throat, do blood test
• Headaches, nausea, jaundice, myalgia, arthralgia,
lymphadenopathy, psychosis, lupus-like syndrome • Goiter - may need to add T4 to reduce TSH levels
• Keep dose low in pregnancy
- Prevent cretinism and goiter in fetus

33
Q

Iodide - MoA

A

• Iodide rapidly decreases synthesis and release of
T4/T3
• Short-term effect (2-8 weeks)

34
Q

Iodide - Indications/Therapeutics

A

• Decreases vascularity and thyroid content of gland
• Used for 7-10 days before surgery
– Can decrease likelihood of thyroid storm
• Can use in radioactive emergencies

35
Q

Radioactive Iodine – 131 I - MoA

A

• 131I taken into the gland specifically
– Small amounts μCi = diagnostic
– Large amounts mCi = destroys gland

36
Q

Radioactive Iodine – 131 I - Indications/Therapeutics

A

• Used in elderly patients and those with heart disease
– Definitive treatment for Graves’, but thioamides
preferred
• Preferred treatment for toxic nodular goiter -> specific
destruction -> euthyroid

37
Q

Radioactive Iodine – 131 I - Adverse Effects

A

• Usually causes hypothyroidism over time
• Thyroid storm risk
– Decrease risk by use of thioamide (not iodide!) prior
to treatment

38
Q

Radioactive Iodine – 131 I - Contraindications

A

• Pregnancy, nursing, or mothers who lack childcare

39
Q

Beta-Blockers - MoA

A

• Non-specific β-blocker
• Propranolol specifically inhibits the peripheral
conversion of T4 to T3

40
Q

Beta-Blockers - Indications/Therapeutics

A

• ↓many of the Sx of hyperthyroidism
• Used to prepare for surgery and while waiting for
thioamides or 131I to take effect

41
Q

Beta-Blockers - Contraindications

A

• C/I: Asthma – use CCBs instead

42
Q

Calcitonin (Miacalcin®) - MoA

A
  • ↓ Bone resorption of Ca2+
  • Antagonizes parathyroid hormone
  • ↓ Bone pain and loss
  • ↑ Bone density
  • ↓ Osteoporotic fractures
43
Q

Calcitonin (Miacalcin®) - Pharmacokinetics

A
  • Nasal spray

* Injection

44
Q

Calcitonin (Miacalcin®) - Indications

A
  • Osteoporosis – (not 1st line)

* Paget’s disease

45
Q

Calcitonin (Miacalcin®) - Adverse Effects

A
  • May cause allergic reactions
  • Nasal rhinitis/ sinusitis -> nasal spray
  • Nausea and vomiting -> injection
46
Q

Parathyroid Hormone Drugs

A

Teriparatide (Forteo®)
Abaloparatide (TYMLOS®)
rhPTH(1-84) (NATPARA®)

47
Q

Parathyroid Hormone Drugs - MoA

A

• PTH and PTHrP both bind to the PTH Receptor type 1
(PTHR1) on the osteoblast and activate it.
• There are two conformations of PTHR1, RG and R0,
which are pro-osteoblast or pro-osteoclast,
respectively.

Teriparatide -or- Abaloparatide: More osteoblast activity -> Osteoporosis

rhPTH(1-84): More osteoclast activity -> Hypoparathyroidism

48
Q

Teriparatide & Abaloparatide - Pharmacokinetics

A

• Subcutaneous injection
– Teriparatide: peaks in 30 min, gone in 3 hours
-> Intermittent

49
Q

Teriparatide & Abaloparatide - Adverse Effects

A
  • Hypercalcemia and hypercalciuria
  • Injection site reactions
  • Dizziness, leg cramps
  • Abaloparatide: hyperuricemia
50
Q

Teriparatide & Abaloparatide - Contraindications

A

• Osteosarcoma (Black Label Warning)
– ↑ in rats, but not in humans yet
– Be careful in patients susceptible to any
osteosarcoma (Paget’s disease, radiation therapy,
open epiphyses, history)

51
Q

Denosumab (Prolia®) - MoA

A

• Antibody against receptor activator of nuclear factor
kappa-beta ligand (RANKL)
• Inhibits bone resorption
• Antibody to RANK-Ligand -> inhibits RANKL
– Factor made by osteoblasts that is necessary for the
formation of mature osteoclasts

52
Q

Denosumab (Prolia®) - Indications/Therapeutics

A

• Osteoporosis in men and postmenopausal women at
high risk for fractures
• ↑ Bone mass and strength in both cortical and
trabecular bone

53
Q

Denosumab (Prolia®) - Pharmacokinetics

A

• S.C. injection, once/6 months

54
Q

Denosumab (Prolia®) - Adverse Effects

A
  • Hypocalcemia(2%)

* Osteonecrosis of the jaw in cancer studies

55
Q

Denosumab (Prolia®) - Contraindications/Precautions

A 
•Absolute C/I:
 – Hypocalcemia, fix first
 – Pregnancy 
 – Cat X
• Relative
 – Chronic Kidney Disease
 – Patients at risk for serious infections (RANK-RANKL 
    signaling in lymphocytes
56
Q

Bisphosphonates

A

Alendronate (Fosamax) - Oral
Risedronate (Actonel) - Oral
Ibandronate (Boniva) - Oral, I.V.
Zoledronic Acid (Zometa) - I.V.

57
Q

Bisphosphonates - MoA

A 
• P-C-P bond analogs of pyrophosphate
• Substitutes for PO4 in Ca2+ binding 
 – Incorporates into bone
• Inhibits osteoclast activity and bone resorption 
 – Mechanism still not clear
58
Q

Bisphosphonates - Indications/Therapeutics

A 
• First line of treatment (DOC) for post-menopausal 
   osteoporosis
• Paget’s Disease
• Osteopenia -> may not be needed
• Reduce the incidence of fractures
• Improve the quality of life
59
Q

Bisphosphonates - Pharmacokinetics

A

• ORAL preparations: absorption is very poor
– Must be taken on an empty stomach!
– 1/2 glass of water
– Stay upright for 30 min after taking it to decrease
esophageal irritation
• Others are IV injection only
• Given anywhere from once/day to once/year

60
Q

Bisphosphonates - Adverse Effects

A

• Oral -> abdominal pain, upper GI irritation, esophageal ulceration, constipation, diarrhea, and flatulence
• I.V. -> renal toxicity if given too fast
• Nausea, vomiting
• May cause a mild hypocalcemia
• Possible atrial fibrillation
• ↑ Incidence of osteonecrosis of the jaw after major
dental work
• 2010 FDA safety communication: atypical bone fractures of the femur with long-term bisphosphonate therapy

61
Q

Bisphosphonates - Contraindications/Precautions

A

• Oral: inability to stand/sit upright or esophageal
disease
• IV: renal disease

Pharmacology II (4 decks)

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