Week 4 - Endocrine Drugs Flashcards
Primary tx for hypothyroidism is
hormone replacement
In primary hypothyroidism what is used to monitor tx
TSH concentration
in hypothyroidism, Free T4 is what type of indicator??
what do we expect it to be normal or abnormal?
normal range when TSH is inhibited
Measurement of free T4 is warranted in
secondary hypothyroidism when TSH release is impaired
TSH release is impaired in
secondary hypothyroidism
T4 is the prohormone to?
T3
Goal of therapy for hypothyroidism: (4)
- Correction of hypothyroidism to euthyroid
- Reduction of symptoms
- Reduction in goiter size
- Prevention of cancer recurrence
when you see goiters, what are some of our concerns?
- difficult airway
- pressure on airway
- tracheal displacement/deviation
In PRIMARY hypothyroidism what do we see/find?
- Increase [plasma] of TSH
- Primary defect is OF thyroid
- Ant. Pituitary attempts to stimulate hormonal output by releasing TSH (hence the elevated TSH level)
In SECONDARY hypothyroidism what do we see/find?
Defect is at:
- hypothalamus OR the
- Ant. Pituitary
–> Low concentrations of both TSH and thyroid hormones circulating in plasma
Tx of choice for primary hypothyroidism:
T4: Levothyroxine (synthetic)
T4 half life is
7-10days
**allows for missing a dose for several days w/o adverse consequences.
IV(parenteral) T4 can be administered at what percent of patients oral dose?
80%
example: take 100mcg/day == 80mcg/day IV
An isomer of T3; supplemental T3 is:
Liothyronine
Liothyronine is ___ to ___ times as potent as levothyroxine.
- 5 to 3 times as potent
- rapid onset; short DOA
Is T3/Liothyronine used for long term replacement?
no - b/c of short doa and rapid onset
How do we tx HYPERthyroidism?
- Anti-thyroid meds
- radioiodine
- and/or surgery
***TSH levels useful for determining diagnosis of hyperthyroidism but not for
degree of severity
Measuring free T3 and T4 is necessary to assess
in hyperthyroidism
the efficacy of treatment
Once steady state achieved, what level can be used to assess the efficacy of therapy
TSH
Compounds that interfere with synthesis of thyroid hormones or reduce amount of thyroid tissue:
- Thionamides
- Inhibitors of iodide transport mechanism
- Iodide
- Radioactive iodine
‘TIIR
examples of Thionamides:
Methinmazole
Propylthiouracil
Carbimazole
(MOA) Thionamides: exert immunosuppressive effect via a reduction in concentrations of
anti-thyrotropin-receptor antibodies
In addition to blocking hormone synthesis, Propylthiouracil also inhibits
the peripheral deiodination (removal of iodine) of T4 and T3.
anti-thyroid drugs are useful in tx before
elective surgery
**don’t want to have a T.Storm during surgery
thionamides levels peak:
1-2 hrs after ingestion
are thionamides available in parenteral form?
no
Methimazole half life is:
4-6 hrs and dosed every day
Half life of propylthiouracil is:
75 mins!!!
dosed several times a day
*poor compliance
Minor side effects of thionamide therapy are observed in ~ 5% of pts:
- Urticarial
- Macular skin rash
- Arthralgias
- GI discomfort
- **Granulocytopenia and agranulocytosis are serious but rare; most likely to occur in first 3 months of anti-thyroid drug therapy
**Granulocytopenia and agranulocytosis are serious but rare. if to occur, when would they?
most likely to occur in first 3 months of anti-thyroid drug therapy
** what may be the earliest sign of development of agranulocytosis?
Pharyngitis or fever may be
Recovery is likely if the anti-thyroid drug is d/c’ed at the first signs.
propylthiouracil has reported toxicity of what?
hepatic
**which anti-thyroid crosses the placenta AND appears in breast milk?
methimazole
**Which anti-thyroid has limited placental crossing and is the preferred drug for use in pregnancy?
Propylthiouracil
the oldest available therapy for hyperthyroidism is:
iodide
*** Most important clinical effect of high doses of iodide is:
is inhibition of release of thyroid hormone.
….May reflect ability of iodide to antagonize the ability of TSH and cyclic adenosine monophosphate to stimulate hormone release
Iodide useful in tx before elective
thyroidectomy.
Combination of oral potassium iodide and propranolol is a recommended approach.
Combination of oral potassium iodide and propranolol is a recommended approach for :
tx before elective thyroidectomy.
Allergic reactions to iodide:
- angioedema and
- laryngeal edema:
- life threatening.
therapy of choice for Grave’s hyperthyroidism
Radioiodine
** Radioactive iodide is administered after ….
euthyroidism is achieved via thionamides
____ (form of radioactive iodide) is most administered and is rapidly and efficiently trapped by thyroid gland cells and the subsequent emission of destructive Beta rays act almost exclusively on these cells with little of no surround damage
131-I
131-I can destroy thyroid gland in how many weeks?
6-18 weeks
***Iatrogenic hypothyroidism must be considered preop in any pt who has
previously been treated with 131-I
– b/c 10% of tx pts become hypothyroid in first yr after 131-I tx and risk increases 2-3% annually thereafter.
1/2 to 2/3 pts are cured by how many doses of 131-I?
a single dose
- remainder require 1-2 more doses
contraindication of 131-I?
pregnancy (fetal thyroid will concentrate the isotope)
Except for this cancer, most cancers accumulate little radioactivity thus 131-I is not an effective tx for ca
follicular cancer
analogue of cortisol:
prednisolone
mg prednisolone anti-inflammatory effect is equivalent to how many mg of cortisol?
5mg Prednisolone = 20 mg Cortisol
Suitable for sole replacement of therapy in adrenocortical insufficiency b/c of the presence of glucocorticoid and mineralocorticoid effects
PrednisoLone
Flood pg 763-prednisone and prednisolone *
analogue of cortisone:
Prednisone
Prednisone is converted to
PrednisoLone after absorption in GIT
similar to prednisolone in anti-inflammatory effects
Methyl derivative of prednisolone:
Methylprednisolone
How many mg of Methylprednisolone = 20 mg of cortisol?
4 mg is equivalent to 20 mg of cortisol.
Used IV for glucocorticoid effect
Methylprednisolone
Fluorinated derivative of prednisolone.
Betamethasone:
how many mg of Betamethasone = 20 mg of cortisol?
0.75mg is equivalent to 20 mg of cortisol. PO and IV available.
Betamethason has No mineralocorticoid properties and cannot be a replacement for…
adrenocortical insufficiency
Fluorinated derivative of prednisolone and isomer of betamethasone:
Dexamethasone:
how many mg of Dexamethasone = 20 mg of cortisol?
0.75 mg is equivalent to 20 mg of cortisol.
dexamethasone Can be used to treat certain types of
cerebral edema
Triamcinolone:
fluorinated derivative of prednisolone:
how many mg of Triamcinolone is = to 20 mg of cortisol?
4 mg is equivalent to 20 mg of cortisol.
what drug is used often in epidural injection for tx of lumbar disc disease ?
why?
Triamcinolone
The hexacetonide preparation injected intra-articularly may provide therapeutic effects 3 months or longer
**SE of Triamcinolone:
- mild dieresis w/ Na loss
- Edema (in decreased GFR)
- *skeletal muscle weakness
- *anorexia (vs appetite stimulation)
- sedation (vs. euphoria)
Unusual side effect of this drug is an increase incidence of skeletal muscle weakness; anorexia rather than appetite stimulation and sedation rather euphoria.
Triamcinolone
Side Effects of Chronic Corticosteroid Therapy:
- Suppression of HPA axis
- Electrolyte and metabolic changes
- Osteoporosis
- PUD
- Skeletal muscle myopathy
- CNS dysfunctions
- Peripheral blood changes
- Inhibition of normal growth
**HPA axis is responsible for
modulating inflammatory reactions throughout the body;
working with
- hypothalamus,
- pituitary gland, and
- adrenals
Increased susceptibility______ or
______ accompanies tx with corticosteroids
to bacterial or fungal infection
corticosteroids are associated with decreasing the effectiveness of…
of anticoagulants
Systemic use of corticosteroids for < 7 days even at high doses are unlikely to cause
adverse side effects.
Inhaled corticosteroids are unlikely to evoke adverse
systemic effects
Forms/causes of Parathyroid dependent or non-parathyroid dependent
Parathyroid: (3)
- Primary and Tertiary hyperparathyroidism
- Familial hypocalciuric hypercalcemia
- Lithium induced hypercalcemia
Lithium may induce
hypercalcemia —> parathyroid
Hypercalcemia of malignancy is usually associated with destructive bone lesions or
secretion of a PTH-like tumor peptide
Hypercalcemia from parathyroid disease is associated with (
bone loss and osteoporosis
management of hypercalcemia (parathyroid)
Management: IVF Bisphosphonates Calcitonin Glucocorticoids
Bisphosphonates:
Pyrophosphate analogues that lower calcium levels by inhibiting osteoclastic medicated bone
reabsorption
Bisphosphonates Treat hypercalcemia in:
- malignancy,
- primary hyperparathyroidism,
- vitamin A intoxication,
- granulomatous disease, and
- Paget’s disease
***Renal injury and jaw osteonecrosis reported with
bisphosphonates
***Renal injury and jaw osteonecrosis reported with bisphosphonates impacts anesthesia … how?
renal clearance
jaw mobility, mouth opening
Bisphosphonates should be used early in course b/c may take …..
2 days to see significant results
Glucocorticoids decrease synthesis of
1,25-dihydroxyvitaminD
decreased synthesis of 1,25-dihydroxyvitaminD does what 2 things:
- ) decrease intestinal absorption of calcium and
2. )increase renal excretion of calcium
High risk of hypocalcemia:
Rhabdomyolysis Pancreatitis Sepsis, fat embolism Burns, massive transfusions Hypoalbuminema Hypomagnesemia Renal insufficiency
if calcium and magnesium are low… what else may be low?
K+
Most common setting for symptomatic hypocalcemia is within
12-24 hours after surgery,
surgeries particularly associated with hypocalemia:
- total or subtotal thyroidectomy or
- 4 gland parathyroid exploration or removal
**Long-standing hypocalcemia with hyperphosphatemia and PTH deficiency is associated with :
- calcification of the basal ganglia
- with extrapyramidal signs
Hypocalcemia can cause:
Neuromuscular irritability
Arrhythmias
CHF (decreased contractility)
Hypotension
***Acute severe hypocalcemia (with normal albumin) is a medical emergency with death from laryngeal spasm or grand mal seizures. What is the critical value?
Ca+ < 7.5 mg/dL
This is indicated for acute symptomatic hypocalcemia
IV calcium
10% calcium gluconate contains less elemental calcium than calcium chloride
but is less likely to cause
tissue necrosis during an extravasation
1 Cause of DI
inadequate secretion of vasopressin by the posterior pituitary
2
In DI- Hyper or Hypo natremia?
in DI - you see excessive water loss and HYPERnatremia via polyuria.
3 Name 5 things that can cause DI
- Neurotrauma
- surgery of the pituitary and hypothalamus
- Cerebral ischemia
- Cerebral malignancy
- nephrogenic DI
4
What is nephrogenic DI
results from an inability of the renal tubules to respond to adequate amts of centrally produced AVP does not respond to exogenous admin of the hormone either.
5
What role does Vasopressin have in evaluating DI
- Evaluation; administration results in a brief effect b/c of rapid enzymatic breakdown of peptides in teh tissues, especially the kidneys.
6 What is the role of DDAVP in DI
administration of synthetic selective V2-R agonist, DDAVP (desmopressin), treats central DI.
DDAVP has an intense antidiuretic effect (V2) and decreased vasopressor (V1) effect.
7
Elimination ½ life of DDAVP and side effects of DDAVP
1/2 time = 2.5-4.4 hours
SE (less than vasopressin): although Nausea and increases in SBP can be seen
8
What are the routes of DDAVP
PO (0.3 to 0.6 mg/day)
IV (1-4 mcg/day)
Nasally (5-40 mcg/day)
9 Why is DDAVP the drug of choice
d/t inadequate production of AVP by the posterior pituitary.
10 What can DDAVP treat? What can it not treat?
Not effective in the tx of nephrogenic DI
- effective in increasing vWb factor, minimize intraoperative blood loss in cardiac surgery
- may decrease SVR leading to hypotension
11 How does DDAVP and Von Willebrand relate
DDAVP causes endothelial cells to release von Willebrand factor, tissue-type plasminogen activator , and prostaglandins
12 When does DDAVP not decrease bleeding
-does not decrease bleeding following cardiopulm bypass in pts who were maintained on aspirin therapy until day of surgery.
13 Explain briefly ACE-I and perioperative hypotension
inhibits the renin-angiotensin system and can cause refractory hypotension after administration of anesthesia.
- in these cases, catecholamine admin may be unsuccessful
- vasopressin may be effective to tx hypotension from anaphylaxis and severe catecholamine deficiency after resection of a pheochromocytoma
14 Describe Vasopressin’s role in the Refractory Cardiac Arrest
40U IV - was similar to epi 1 mg IV for mgmt of Vfib and PEA.
- Vasopressin was more effective than epi for mgmt of asystole and tx of refractory cardiac arrest
- AHA recs a single dose of 40Units considered instead of epi q 3-5mins for pts being tx for cardiac arrest.
- vasopressin functions as a vasoconstrictor when it is administered in supraphysiologic doses which serve to displace peripheral blood vol to the central circulation w/o some of the AE’s produced by epi
15 Describe Vasopressin’s role in esophageal varices
Vasopressin may serve as an adjunct in the control of bleeding E. Varices and during abd surgery in pts w/cirrhosis and portal HTN.
- infusion of 20U over 5” results in marked decreases in hepatic BF lasting about 30mins.
- only a moderate increase in systemic BP occurs. This effect on the portal circulation is attributable to marked splanchnic vasoconstriction. An alternative to systemic administration is the infusion of vasopressin directly into the superior mesenteric artery.
it has not been established whether selective arterial administration is after than systemic administration w/respect to cardiac and vascular side effects
16 List 7 side effects of Vasopressin that the CRNA needs to be aware of
- vasoconstriction
- increased SBP
- increased Pulmonary artery pressures
- vasoconstriction of Coronary arteries/ decrease in coronary BF ==> angina
- stimulate gi smooth muscle
- Decrease in PLT count
- Allergic rxns from urticaria to prophylaxis
- prolonged use may result in antibody formation and a shortened DOA.
