Week 4: Endocrine System Flashcards
1
Q
Physiological response to high plasma glucose
A
- Inhbt. alpha cells of the pancreas
- Stim. beta cells of the pancreas = inc. insulin
- Liver: Inc. glycolysis, inc. glycogenesis, inc. lipogenesis
- Cells: Inc. GLUT-4 receptors = inc. glucose transport into cell
2
Q
Type 1 diabetes
A
Autoimmune attack of beta cells, little to no insulin synthesis/release
3
Q
Type 2 diabetes
A
Dec. sensitivity to insulin, dec. beta cell function over time
4
Q
Gestational diabetes
A
From inc. cortisol and placental production of insulin-antagonizing hormones
5
Q
Diabetic ketoacidosis: Cause, presentation, treatment
A
Cause: High plasma glucose w/ no insulin
Presentation:
- Glucose excreted in urine (glycosuria)
- Water follows glucose out (dehydration, cerebral dehydration, shock)
- Ketoacidosis
Treatment:
- Dec. plasma glucose
- Treat dehydration
- Treat acidosis
6
Q
Hyperosmolar hyperglycemic state: Cause, presentation, treatment
A
Cause: Gradual rise in plasma glucose
Presentation:
- Glucose excreted in urine (glycosuria)
- Water follows glucose out (dehydration, cerebral dehydration, shock)
Treatment:
- Dec. plasma glucose
- Treat dehydration
7
Q
Complications of tight glucose control
A
Inc. risk of hypoglycemic episodes
8
Q
The main difference between types of insulin is (PK/PD)
A
PK
9
Q
Actions of insulin
A
- Glycogenesis
- Cellular uptake of glucose
- Protein synthesis
- Triglyceride synthesis
10
Q
NPH
A
- Intermediate-acting insulin
- Can be combined with short-acting insulin
11
Q
Detemir
A
- Long-acting insulin
- Usually wears off during sleep
12
Q
Glargine
A
- Longest-acting insulin
- No peak time of activity
13
Q
Aspart
A
Short-acting insulin
14
Q
Lispro
A
Short-acting insulin
15
Q
Glulisine
A
Short-acting insulin
16
Q
Blood glucose effectors (5)
A
- Stress (inc.)
- Ingestion (inc.)
- Exercise (dec.)
- Alcohol (dec.)
- Illness (inc.)
17
Q
Hypoglycemia: Possible causes
A
Insulin OD, dec. PO intake, nausea/vomiting/diarrhea, excessive alcohol consumption, exercise
18
Q
Hypoglycemia: Presentations
A
Glucose <70, high HR, sweating, nervousness, severe = confusion, coma, death, hypokalemia
19
Q
Biguanides: Names, actions, AE
A
Metformin
Actions:
- Inhibits liver glucose production
- Sensitizes insulin receptors
- Reduces gut glucose absorption
AE:
- Dec. B12 and folate absorption
- Lactic acidosis w/ toxicity
- GI upset upon initiation
Drug of choice for initial therapy in type 2
20
Q
Sulfonylureas: Names, actions, AE
A
Glipizide, Glyburide
Actions: Promotes insulin release
AE:
- Hypoglycemia
- Weight gain
- Disulfiram reaction with alcohol
21
Q
Meglitinides: Names, actions, AE
A
Nateglinide, Repaglinide
Actions: Promotes insulin release
AE:
- Hypoglycemia
- Weight gain
Shorter acting than Sulfonylureas
22
Q
Thiazolidinediones: Names, actions, AE
A
Rosiglitazone, Pioglitazone
Actions: Inc. insulin response from cell
AE:
- HF due to fluid retention
- Upper respiratory infections, headaches, sinusitis, myalgia
- Bladder carcinoma from long-term/high dose therapy
23
Q
Alpha-glucosidase inhibitors: Names, actions, AE
A
Acarbose, Miglitol
Actions: Inhibit brush border enzymes -> delayed carb absorption
AE:
- GI discomfort
- Dec. iron absorption -> anemia risk
- Long term -> liver dysfunction
24
Q
Dipeptidyl-peptidase-4 inhibitors (DDP-4): Actions, AE
A
Actions: Inc. incretin = inc. insulin secretion response
AE:
- Hypersensitivity reactions
- Rare: Pancreatitis
25
Sodium-glucose-2 transporter inhibitors (SGLT-2): Actions, AE
Actions: Block renal reabsorption of glucose -> glucose excreted in urine
AE:
- Female UTI
- Inc. urination -> dehydration, hypotension
26
Why do some oral antidiabetics carry a hypoglycemia risk and some don’t?
Those that do promote insulin release
Those that do not work via other mechanisms (decreased insulin resistance, decreased glucose absorption or glucose excretion)
27
When should metformin be held?
Hypoperfusion states such as sepsis, cardiac failure, renal failure, etc.
28
Why do thiazolidinediones not work for type 1 diabetics?
Insulin must be present since the drug works by increasing insulin sensitivity
29
Lugol solution: Class, uses, actions, AE
Class: Non-radioactive iodine
Uses: Hyperthyroidism
Actions: Inhibits T4/T3 synthesis and systemic release
AE: High doses can cause paradoxical response → hyperthyroid symptoms
30
Somatropin: Uses, ROA, adverse effects
Uses: Pediatric or adult GH deficiency
ROA: IM or subQ
Adverse effects: Hyperglycemia
31
Cabergoline, Bromocriptine: Uses and effects
Uses: Prolactin excess
Effects: Bind dopamine receptors in pituitary directly
32
Non-reproductive effects of estrogen (5 ish)
1. Bone: Maintain bone density and mass
2. CV: Vasodilation, dec. LDL, inc. HDL
3. Blood: Inc. coagulation and fibrin breakdown
4. CNS protection
5. Glucose homeostasis
33
Exogenous estrogen: AE (4)
- Endometrial hyperplasia -> CA
- Breast CA
- CV thromboembolic events
- Gallbladder disease, jaundice
34
Exogenous estrogen: Uses (6)
1. Menopausal hormone therapy
2. Female hypogonadism
3. Acne
4. Cancer palliation
5. Gender affirmation therapy
6. Contraceptives
35
Non-reproductive effects of progesterone (3)
- Suppression of GI smooth muscle -> constipation
- Suppression of maternal immune system
- Growth/proliferation of breast ducts
36
Exogenous progesterone: AE (3)
- Breast tenderness
- Headache
- Abdominal discomfort
37
Exogenous progesterone: Uses (6)
1. Menopausal hormone therapy
2. Dysfunctional uterine bleeding or amenorrhea
3. Infertility
4. Premature delivery prevention
5. Endometrial hyperplasia and carcinoma
6. Contraceptives
38
Naturally, what hormone peaks significantly at ovulation?
LH
39
Naturally, what hormone is inc. during the proliferative phase of the menstrual cycle?
Estrogen
40
Menopause: Cause, presentation
Cause: Gradual dec. in ovarian estrogens
Presentation:
- Vasomotor symptoms (night sweats, hot flashes)
- Sleep disturbances
- Urogenital atrophy
- Altered lipid metabolism
- Changes in cognition and sexual response
41
Why is hormone therapy for menopause controversial?
Risk of increased thromboembolic events (CV events like blood clots, MI, CVA, etc.)
42
Hormone therapy: Indications
- Mod-severe vasomotor symptoms
- Mod-severe vulvar and vaginal atrophy
- Prevention of osteoporosis
43
Hormone therapy: ABSOLUTE contraindications (6)
1.Pregnancy
2. Breast, endometrial CA
3. Acute liver disease
4. Uncontrolled HTN
5. Thrombosis: DVT, MI, CVA
6. Undiagnosed vaginal bleeding
44
Hormone therapy: RELATIVE contraindications (7)
1. History of benign breast disease or uterine fibroid
2. Strong family history of breast CA
3. Chronic liver disease
4. Heavy tobacco use
5. CVD/CAD
6. DM
7. Migraine
45
Why is progesterone added to HT and oral birth control?
To prevent endometrial CA
(estrogen only = unopposed proliferation of the endometrium!)
**no uterus, no need to add progesterone!
46
What does SERM stand for and what does it mean?
Selective estrogen receptor modulator
Agonize some estrogen receptors, antagonize others - attempts to provide benefits w/out risks
47
Tamoxifen: Class, actions, AE, uses
Class: SERMs
Actions:
- Inhbts. cell growth in breast tissue
- Protects against osteoporosis
- Improves lipid profile
AE:
- Inc. endometrial cancer risk
- Inc. hot flashes
- Inc. thromboembolism risk
Uses: Breast cancer prevention and treatment
48
Raloxifene: Class, actions, AE, uses
Class: SERMs
Actions:
- Inhbts. cell growth in breast tissue
- Protects against osteoporosis
- Improves lipid profile
AE:
- Inc. hot flashes
- Inc. thromboembolism risk
Uses:
- Osteo prevention
- Breast cancer prevention in high-risk patients
49
Raloxifene: What's unique?
No risk of endometrial cancer
50
Which hormones are in oral contraceptives?
Estrogen and progesterone
or
just progesterone
51
Combination oral contraceptives: Mechanism of action
Suppression of ovulation: high estrogen provides negative feedback to suppress FSH (follicle cannot mature, no ovulation occurs)
Also alters cervical mucus & endometrium
52
Progestin-only "minipills": Mechanism of action
Cervical secretion changes
53
Progestin-only "minipills": What's unique?
- Avoids estrogen risks
- MUCH less effective
54
Combination oral contraceptives: AE
- Excess estrogen: Nausea, breast tenderness, edema
- Excess progestin: Inc. appetite, fatigue, depression
55
Depot medroxyprogesterone acetate (injection) : Actions, AE
Actions: Inhibition of FSH/LH secretion
AE: Bone loss risk
56
Copper IUD: Actions, AE
Actions: Local foreign body reaction and chemical changes that are toxic to sperm
AE: Pelvic inflammatory disease if STI is present
57
Levonorgestrel IUD: Actions, AE
Actions: Thickens cervical mucus, inhibits ovulation, alters endometrium
AE: Pelvic inflammatory disease if STI is present
58
Mifepristone: Class, uses, actions, contraindications/AE
Class: Antiprogestin
Uses: Medical abortion
Actions: Blocks progesterone receptors → de-implantation; cervical softening and dilation
AE:
- Abdominal pain
- Vaginal bleeding
- Bacterial infection (give antibiotic)
Contraindications: Ectopic pregnancy, hemorrhagic disorders, anticoagulant use
59
Misoprostol: Class, uses, actions, contraindications/AE
Class: Prostaglandin
Uses: Medical abortion
Actions: Directly stimulates uterine contractions
AE:
- Abdominal pain
- Vaginal bleeding
- Bacterial infection (give antibiotic)
Contraindications: Ectopic pregnancy, hemorrhagic disorders, anticoagulant use
60
Clomiphene: Uses, actions, AE
Uses: Follicular maturation
Actions: Blocks estrogen receptors in the hypothalamus/pituitary
- Causes inc. in LH/FSH
- Blocks negative feedback so that follicular maturation and ovulation can occur
AE:
- Hot flashes
- Bloating
- Breast engorgement
- Ovarian hyperstimulation
61
Menotropin: Uses, actions, AE
Uses: Follicular maturation
Actions: 50:50 mix of LH:FSH, direct action on ovary to induce follicular maturation
- If ovaries can respond to LH/FSH, ovulation is ~100%
AE: Ovarian hyperstimulation
62
Follitropin: Uses, actions, AE
Uses: Follicular maturation
Actions: FSH that acts on ovary, stimulating follicles
AE: Ovarian hyperstimulation
63
Ovarian hyperstimulation syndrome (OHSS): Cause, presentation, prevention
Cause: Exogenous hormone administration for infertility leads to exaggerated response -> ovaries swell, leak fluid, and are painful
Presentation:
- Abdominal pain
- Severe: Fluid accumulation in abdomen/chest, electrolyte disturbances, blood clots, renal failure
Prevention: Ultrasound monitoring
64
hCG and choriogonadotropin alpha (recombinant hCG): Uses, actions, AE
Uses: Ovulation
Actions: Acts on ovary to induce ovulation by stimulating LH surge
- IM
- Administered AFTER clomiphene or menotropin/follitropins
AE: Ovarian hyperstimulation or rupture of ovarian cysts
65
Cabergoline, Bromocriptine: Class, uses, actions, AE
Class: Ergot alkaloid derivatives
- Dopamine agonists
Uses: Corrects amenorrhea and infertility
Actions: Activates dopamine receptors in anterior pituitary
- Inhibits prolactin secretion
AE: Headache, nausea, dizziness
66
Cabergoline: What's unique?
Preferred, better tolerated, easier dosing
67
What do tocolytics do?
Suppress uterine contractions
68
4 classes of tocolytics
1. Beta 2 agonists
2. Ca2+ channel blockers
3. COX inhibitors
4. Oxytocin receptor blockers
69
Terbutaline: Class, actions, AE
Class: B2 agonist
Actions: Agonizes B2 on uterine smooth muscle, dec. contractions
AE:
- Pulmonary edema
- HypoTN
- Hyperglycemia
- Tachycardia
70
Nifedipine: Class, actions, AE
Class: Ca2+ channel blocker
Actions: Blocks Ca2+ from sarcoplasmic reticulum, dec. contractions
AE:
- Tachycardia
- Facial flushing
- Headache
- Dizziness
- Nausea
71
Indomethacin: Class, actions, AE
Class: COX inhibitor
Actions: Inhibits PG synthesis, dec. contractions and cervical ripening
AE:
- Nausea
- Gastric irritation
- Inc. postpartum bleeding
72
Oxytocin receptor blockers: Actions
Block uterine contractions by preventing initiation
73
Magnesium sulfate: Class, uses, actions, AE
Class: ACh inhibitor
Uses: NOT A TOCOLYTIC
- Neuroprotective effects to fetus
Actions: Inhibits ACh at NMJ
AE:
- Adverse: HypoTN, flushing, headache, dizziness
- Severe: Hypothermia, paralytic ileus, pulmonary edema
74
Hydroxyprogesterase caproate: Uses, AE
Uses: Prevention of preterm labor for singleton pregnancy/history of preterm labor
AE:
- Injection site reactivity
- Hives
- Nausea/diarrhea
75
Magnesium sulfate: Fetal effects
Hypotonia
Sleepiness
Associated with inc. infant mortality
76
Contraindications of induction of labor (5)
1. Umbilical cord prolapse
2. Transverse fetal position
3. Active genital herpes
4. History of c-section or myomectomy
5. Placenta previa
77
Indications for induction of labor
- Post-term(>40 weeks)
- Placental abruption
- Premature
78
Dinoprostone: Class, actions, AE, ROA
Class: Prostaglandin (PGE2)
Actions: Cervical ripening via breakdown of collagenase
AE:
- Fetal distress
- Tachysystole
- Systemic absorption -> nausea/vomiting, diarrhea, fever
ROA: Vaginal gel or pouches
79
Clinical considerations when administering prostaglandin for induction of labor
Monitor fetal heart rate & contractions
fetal distress can occur, tachysystole (rapid contractions) can occur
80
Misoprostol: Class, uses, AE
Class: Prostaglandin (PGE2)
Uses: Cervical ripening
AE: Higher tachysystole
81
Misoprostol: What's unique?
Not technically approved for cervical ripening, but more effective and cheaper
82
Clinical considerations when using oxytocin/Pitocin to stimulate uterine contractions
Only use if fetal lungs are mature and cervix is ripe
83
Pitocin: Effects, AE
Effects:
- Uterine stimulation: Inc. force, frequency and duration of contractions -> number of receptors inc. as labor progresses
- Milk ejection
- Water retention
AE:
- Shivering
- Temp elevation
84
Pitocin: What's unique?
Drug of choice for postpartum hemorrhage due to uterine atony
85
Most common cause for postpartum hemorrhage
Uterine atony (80%)
Uterine muscles don’t contract enough to clamp the placental blood vessels shut after childbirth.
86
Misoprostol (Cytotec): Class, uses, actions, AE
Class: Prostaglandin
Uses: Postpartum hemorrhage
Actions: Stimulates uterine contractions
AE:
- Nausea/vomiting, diarrhea (rare)
- Shivering
- Temp elevation
87
Caboprost tromethamine (Hemabate): Class, uses, actions, contraindications/AE
Class: Prostaglandin
Uses: Postpartum hemorrhage
Actions: Stimulates uterine contractions and INTENSE vasoconstriction
Contraindications:
- Pelvic inflammatory disease
- Cardiac/pulmonary/renal disease
- Caution in asthma, HTN, diabetes
AE:
- GI issues
- HTN
- Bronchoconstriction
88
Methylergonovine (Methergine): Uses, actions, contraindications/AE
Uses: Postpartum hemorrhage
- Only in emergencies
Actions: Stimulates uterine contractions and arteriole/venous constriction
Contraindications/AE:
- HTN
- Nausea, vomiting
- Headache
89
Tranexamic acid (TXA): Class, uses, actions, contraindications/AE
Class: Fibrinolysis inhibitor
Uses: Menorrhagia
Actions: Inhibits plasmin
- Dec. fibrin mesh dissolving
- Keeps clots in the body
Contraindications/AE:
- History of thrombosis
90
Thyroid-stimulating hormone (TSH): Function, stimulation, inhibition
Function: Stimulates synthesis and release of T3/T4
Stimulation: TRH from hypothalamus
Inhibition: T3 + T4
91
Differences between T3 and T4
T3: More potent, shorter half-life, less made
T4: Acts as a supply of T3, longer half-life, more made
92
Actions of thyroid hormone (3)
1. Inc. metabolic rate -> inc. O2 consumption and heat production
2. Inc. HR and contractility -> inc. CO and myocardial O2 demand
3. Promotion of growth and development
93
Adult hypothyroidism: Causes, presentation (6), treatment
Causes:
- Thyroid gland malfunction, often chronic autoimmune thyroiditis (Hashimoto's)
- Iodine insufficiency
- Surgical resection or destruction due to radioactive iodine
Presentation:
- Pale/puffy/expressionless face
- Cold/dry skin
- Brittle hair w/ hair loss
- Dec. HR and temp
- Lethargy/fatigue
- +/- goiter
Treatment: T4 replacement therapy
94
Congenital hypothyroidism: Causes, presentation (4), treatment
Causes:
- Failure in thyroid development
- Autoimmune disease
- Iodine or TSH deficiency
- Exposure to radioactive iodine in utero
Presentation:
- Large, protruding tounge
- Potbelly
- Dwarfish stature
- Impaired development of nervous system, bones, teeth, muscle
Treatment: T4 replacement therapy ASAP
95
Levothyroxine: Class, uses, contraindications/AE (7), ROA
Class: T4 replacement
Uses: Hypothyroidism
- Takes 1 month to take full effect
Contraindications/AE:
- Hyperthyroidism
~Affected by~
- Food (dec. absorption)
- CYP450 inducers induce metabolism
- Dec. T4 -> T3 metabolism
- Inc. thyroglobulin binding (binds T3 and T4 together)
- Warfarin: Inc. blood-thinning effects
- Catecholamines: Inc. sensitization of heart
ROA: PO (on empty stomach) and IV
96
Liothyronine: Class, uses
Class: T3 replacement
Uses: Hypothyroidism
- Only when T4 can't convert to T3 or myxedema coma
97
Graves disease: Cause, presentation (5), treatment
Cause: Autoimmune disease. Overproduction of thyroid-simulating immunoglobulins (TSIs), antibodies that stimulate TSH receptors on thyroid gland
Presentation:
- CV: Tachycardia, dysrhythmias, angina
- CNS: Anxiety, insomnia
- High metabolic rate -> inc. heat production
- Weight loss despite appetite
- Exophthalmos
Treatment: Dec. thyroid hormone production
- Thyroid resection
- Radiation
- Suppression of synthesis with antithyroid drug
- Supportive care: Beta blockers
98
Toxic nodular goiter: Cause, presentation (4), treatment
Cause: Thyroid adenoma
Presentation:
- CV: Tachycardia, dysrhythmias, angina
- CNS: Anxiety, insomnia
- High metabolic rate -> inc. heat production
- Weight loss despite appetite
Treatment: Dec. thyroid hormone production
- Thyroid resection
- Radiation
- Suppression of synthesis with antithyroid drug
- Supportive care: Beta blockers
99
Thyrotoxic crisis (thyroid storm): Cause, presentation, treatment (6)
Cause: Can occur in those with severe
hyperthyroidism under severe stress
- Major surgery
- Severe illness
Presentation:
- Profound hyperthermia
- Tachycardia,
- Restlessness
- Agitation
- Tremor
- If severe: Unconsciousness, coma,
hypotension, HF
Treatment: Immediate treatment is required
1. Suppress T4/T3 synthesis
2. Suppress T4/T3 release
3. Beta blockers (tachycardia)
4. Sedation
5. Cooling
6. IV fluids
100
3 types of drugs for hyperthyroidism
Antithyroid drugs, radioactive iodine, and nonradioactive iodine
101
Methimazole: Class, uses, actions, AE
Class: Thionamides
Uses: Hyperthyroidism
Actions: Inhibits peroxidase to inhibit T4/T3 synthesis
AE:
- Cannot be used in 1st trimester pregnancy, crosses too much into placenta
- Rare: agranulocytosis, hepatotoxicity, vasculitis
- Overdose: hypothyroidism
- Goiter bc no negative feedback to TSH → release more so enlarge gland
102
Methimazole: What's unique?
- Longer half-life
- More potent
- Less serious adverse effects
103
Propylthiouracil (PTU): Class, uses, actions, AE
Class: Thionamides
Uses: Hyperthyroidism and thyrotoxic crisis
Actions: Inhibits peroxidase to inhibit T4/T3 synthesis peripherally
AE:
- Rare: agranulocytosis, hepatotoxicity, vasculitis
- Overdose: hypothyroidism
- Goiter bc no negative feedback to TSH → release more so enlarge gland
104
Propylthiouracil (PTU): What's unique?
- Shorter half-life
- Can be used in 1st trimester
105
Adrenocorticotropic-stimulating hormone (ACTH): Function, stimulation, inhibition
Function: Stimulates synthesis & release of glucocorticoids & androgens from adrenal cortex
Stimulation: Corticotropin-releasing hormone (CRH) which is released following circadian rhythm and in times of stress
Inhibition: CORT from cortisol negative feedback
106
Cortisol deficiency: Presentation
Hypotension, hypoglycemia, cachexia,
depression/lethargy
107
Cortisol excess: Presentation (8)
HPA axis suppression, HTN, hyperglycemia,
fat redistribution, CNS excitation, osteoporosis, menstrual irregularities, infection risk
108
Aldosterone deficiency: Presentation
Hyponatremia (hypoNa+), hyperkalemia (hyperK+), acidosis, cellular dehydration
Late and untreated: Dec. plasma volume -> renal failure, CV collapse, death
109
Aldosterone excess: Presentation (8)
myocardial/vascular remodeling &
fibrosis, SNS activation, baroreceptor reflex
disruption -> decreased contractility, dysrhythmias,
HTN -> HF, MI
110
Androstenedione excess: Presentation
In females = virilization
111
Androstenedione deficiency: Presentation
Failure to develop secondary sexual characteristics in males and females of pubescent age
112
Primary endogenous androgen
Androstenedione
113
Primary endogenous glucocorticoid
Cortisol
114
Primary endogenous mineralcorticoid
Aldosterone
115
Cushing syndrome: Definition, possible causes, presentation
Definition: High glucocorticoid levels
Possible causes:
- ACTH hypersecretion (usually pituitary adenoma)
- Glucocorticoid hypersecretion (usually adrenal adenomas/carcinomas)
- High doses of exogenous glucocorticoids
Presentation:
- Hyperglycemia with glucosuria
- HTN & fluid/electrolyte disturbances
- Osteoporosis, muscle wasting, fat redistribution
- Menstrual irregularities
- Infection risk
116
Describe the approach to treatment for Cushing syndrome
Drugs are only used as adjuncts or if surgery isn't appropriate/successful
117
Spironolactone: Class, actions, AE
Class:
- K+ sparing diuretic
- Aldosterone antagonist
Actions:
- Corrects HTN -> allows Na and water excretion
- Conserves K+ because hyper-aldosterone caused hypokalemia
AE:
- Hyperkalemia
- Gynecomastia
- Menstrual irregularities
118
What time of day should adrenal hormone replacement therapy be administered?
Morning
(mimics endogenous secretion)
119
Primary adrenocortical insufficiency (Addison Disease): Possible causes, presentation, treatments
Possible causes:
- Autoimmune (most)
- TB/other infections
- Adrenal hemorrhage
- Cardiac arrest
- Medications
Presentation: Anorexia, nausea, weight loss, low BP, hyperK+, hypoNa+
- Severe = hypotensive crisis
Treatments: Replacement therapy
- Glucocorticoid
- Mineralcorticoid
120
Secondary and tertiary adrenocortical insufficiency: Possible causes, presentation, treatments
Possible causes:
- Secondary = dec. ACTH
- Tertiary = dec. CRH
Presentation: Hypoglycemia, malaise, loss of appetite, reduced stress response
Treatments: Glucocorticoid replacement therapy
121
Acute adrenal insufficiency (Adrenal crisis): Possible causes, presentation, treatments
Possible causes:
- Adrenal or pituitary failure
- Insufficient glucocorticoid replacement, especially after abrupt discontinuation of chronic therapy
Presentation: Hypotension, dehydration, weakness, lethargy
- Severe = shock, death
Treatments: Replacement therapy
- Glucocorticoid
- Supportive treatment (fluids, sodium, +/- glucose)
122
Congenital adrenal hyperplasia: Possible causes, presentation, treatments
Possible causes: Enzyme deficiency that's needed for glucocorticoid synthesis
Presentation:
- Increased height but premature epiphyseal closure = short adult stature
- Masculinization of external
genitalia in girls
- Penile enlargement in boys
Treatments: Lifelong glucocorticoid
123
Hydrocortisone: Class, uses, actions, AE, ROA
Identical to cortisol
Class: Glucocorticoid drug
Uses: Primary adrenal insufficiency (Addison's disease)
Actions: Glucocorticoid and mineralcorticoid actions
AE: None at physiologic dose
ROA: PO, IV for stress dose
124
Dexmethasone: Class, uses, actions
Class: Glucocorticoid drug
Uses: Secondary and tertiary adrenal insufficiency
Actions:
- High glucocorticoid activity
- Very little mineralocorticoid actions
125
Oxytocin: Function, stimulation, inhibition
Function:
Stimulation:
Inhibition:
126
Antidiuretic hormone (ADH): Function, stimulation, inhibition
Function: Acts on collecting ducts of kidney -> inc. H2O permeability -> concentrates urine
Stimulation: High blood osmolality
Inhibition: Low blood osmolality
127
Diabetes insipidus: Definition, causes, presentation
Definition: Complete or partial deficiency in ADH
Causes: Inherited, TBI, neurosurgery, other various causes
Presentation: Excessive thirst and excessive dilute urine
128
Vasopressin: Uses, effects, AE
Uses: Diabetes insipidus and post-op abdominal distension
Effects: Vasoconstriction, identical to ADH
AE: All due to water intoxication/dec. osmolality
- Early signs: Drowsiness, confusion, headache
- Late signs: Seizures, coma
- High vasopressin doses -> hypertension, angina, MI
129
Desmopressin (DDAVP): Uses, effects, AE, ROA
Uses: Diabetes insipidus
Effects: Structurally analogous to ADH
AE: All due to water intoxication/dec. osmolality
- Early signs: Drowsiness, confusion, headache
- Late signs: Seizures, coma
ROA: PO, intranasal
- No vasoconstriciton
- Long duration
130
Is the dose of gluco/mineralocorticoid HIGHER for replacement therapy or for anti-inflammation?
Anti-inflammation
for replacement therapy, we just give the dose that results in the patient having normal hormone levels (not suppressing inflammation). Only higher doses (i.e. putting the patient in “excess”) result in decreased inflammation & infection risk
131
Prednisone: Class, uses, actions
Class: Glucocorticoid drug
Uses: General adrenocortical insufficiency
Actions:
- Glucocorticoid activity
- Less mineralocorticoid activity
- Longest acting (more potent)
132
Lugol solution: What's unique?
Immediate effect but temporary
133
Male hypogonadism: Definition and drug options
Definition: Testes fail to produce adequate testosterone
Drug options:
- Testosterone enanthate
- Testosterone cypionate
134
Testosterone preparations: PO
- Erratic effects.
- Both options are 17-alpha-alkylated androgens = hepatoxicity (thus not preferred)
135
Testosterone preparations: Transdermal
- Patches, gels, liquids.
- Can be transferred w/ skin-skin contact.
- More consistent
testosterone levels than PO
136
Testosterone preparations: Nasal gel
May interact w/ other nasal sprays
137
Testosterone preparations: Implantable pellets
- 3-6 months.
- For hypogonadism or delayed puberty (long acting)
138
Testosterone preparations: Buccal tablets
- Have to stay in place until removed (can still eat/brush teeth/etc).
- May transfer drug
through saliva with kissing
139
Testosterone preparations: IM
- T cypionate & T enanthate: long acting.
- High [T] with initial injection, decreases over time
140
Testosterone therapy: AE
- Virilization (most common) – in females,
fetuses & boys
- Premature epiphyseal closure
- Hepatotoxicity
- Increased LDL/decreased HDL: atherosclerosis risk
- Edema: due androgen-induced Na+/H2O
retention
- Abuse potential
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Adverse effects of androgen abuse
- Na+/H2O retention = HTN
- High doses suppress LH & FSH = testicular shrinkage, sterility, gynecomastia
- CAD/MI risk
- Hepatotoxicity
- Psychologic effects: depression, mania, aggressiveness
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Oral phosphodiesterase (PDE5) inhibitors: Uses, actions, contraindications/AE
Uses: Erectile dysfunction
Actions: Inhibits PDE5 so that cGMP accumulates -> erection
Contraindications:
- MI
- Angina
- HypoTN
- HF
- Can't be taken with alpha blockers or nitroglycerin
AE:
- HypoTN
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What are 4 types of oral phosphodiesterase (PDE5) inhibitors and what is unique about each of them?
Sildenafil: preferred
Vardenafil: prolonged QT
Tadalafil: long-acting
Avanafil: short-acting, fastest onset
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How do the injectable ED (erectile dysfunction) drugs work?
Vasodilation that allows rapid inflow of arterial blood
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List two main pharmacologic interventions for premature ejaculation
Selective serotonin reuptake inhibitors (SSRIs)
Local anesthetics
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Benign prostatic hyperplasia: Presentation
- Urinary hesitancy, frequency, urgency
- Nocturia
- Straining to void
- Long term, can lead to obstructive nephropathy, bladder stones, recurrent UTIs
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Finasteride, Dutasteride: Class, actions, AE
Class: 5 alpha reductase inhibitors
Actions: Inhibits T → DHT conversion, promotes regression of tissue
AE:
- Decreased libido
- Gynecomastia
- Decreases PSA → evaluate for prostate cancer
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