Drugs Flashcards
(169 cards)
1
Q
How does the body prevent cortisol from activating the MR receptor?
A
11BHSD converts cortisol to cortisone, which will not bind
2
Q
What is cross-coupling?
A
Hormone A makes the cell sensitive to hormone B.
3
Q
Target tissue specificity depends on ___
A
The type and number or receptors in tissues
4
Q
Hormone receptor specificity refers to
A
ability of a hormone to interact with its receptor but not others
5
Q
What is spillover?
A
High concentrations of a promiscuous hormone activate another receptor and non-physiologic effects are seen
6
Q
These hormones are made as preprohormones
A
Peptide class
7
Q
These hormones circulate free (not bound to plasma proteins)
A
Peptide
8
Q
These hormones cannot cross the plasma membrane
A
Peptide
9
Q
These hormones are mainly degraded int he kidney (some liver and lung)
A
Peptide
10
Q
Where are peptide hormones degraded?
A
Kidney (some liver and lung)
11
Q
Where are steroid hormones degraded?
A
Liver by cytochrome p450s
12
Q
These hormones criculate bond to plasma proteins, activity depends on free (not total) concentration
A
Steroid
13
Q
These hormones are released as soon as they are synthesized
A
Steroid
14
Q
Steroid hormone that is not released as soon as it is synthesized
A
Thyroid hormone stored as precursor in lumen gland
15
Q
Why is IGF-1 an exception to its hormone class?
A
It is a peptide hormone that is bound to plasma proteins
16
Q
Which hormones share an alpha chain?
A
LH, FSH, TSH, hCG
17
Q
What is the mechanism for pseudohypoparathyroidism type 1b?
A
PTH resistance because of a mutated Gs (no increase in cAMP)
18
Q
Why do diabetics need more insulin during times of stress?
A
Hormones and cytokines released inhibit secretion and action of insulin
19
Q
Why will patients with kidney disease develop hyperparathyroidism?
A
Impaired Vit D metabolism (no conversion of 25OHD3 to 1,25OHD3)
20
Q
Why does aspirin cause hyperthyroid?
A
It displaces the thyroid hormone from its binding protein, increasing free concentration
21
Q
Why does pregnancy cause hypothyroid?
A
Increased serum globulin proteins cause lower levels of free thryroid hormone
22
Q
Why do post-menopausal women secrete FSH and LH in their urine?
A
They don’t produce estrogen to generate a negative feedback on FSH and LH production
23
Q
Explain estrogen’s role in cross-coupling
A
Estrogen increases oxytocin receptors on uterine muscle during late pregnancy (better contractions). Estrogen also activates expression of progesterone receptor.
24
Q
Glucose transporter in ____ is insulin-independent
A
Liver
25
Somatotropin
GH (human recombinant) SQ
GHD, Turner's, CKD, AIDS, short
X: malignancy, ICU
SE: SCFE in heavy boys, HTN & headache; edema, arthalgia & carpal tunnel in adults
26
Octreotide
Somatostatin analog (long-lasting) SQ
Acromeg, P-HTN, carcinoid, VIPomas, hyperisulin
SE: gallstones & sludge, GI
27
Pedvisomant
GH variant (pegylated), blocks GHR SQ
Acromegaly
SE: hepatitis, tumor
*cross-reacts with GH is assays (use IGF-1)
28
Bromocriptine
D2 receptor agonist PO
Hyperprolactin, acromegaly, Parkinson's
SE: GI, orthostasis & syncope, less efficient antipsychotics
29
Cabergoline
D2 receptor agonist PO
Hyperprolactin, acromegaly, PArkinson's
SE: cardiac valvular lesion @ highdose
*more specific & expensive than bromocriptine
30
hCG
stimulate ovluation, cryptochordism (undescended testes) SQ/IM
acts as LH substitute
Evaluate pregnancy (beta-subunit)
SE: multiples, Ovarian hyperstimulation syndrome (OHSS): hypotension, ascites, pleural effusions, coag abnormalities (risk: high E & >3 big follicles)
31
Leuprolide
```
GnRH agonist (long-acting synthetic) IM
central precocious puberty (no LH/FSH release after single dose), endometriosis (E-dependent), fibroids (E-dependent), prostate cancer (chemical castration)
```
32
FSH
fertility treatment SQ/IM
| Evaluate precocious or delayed pubery
33
Cosyntropin
```
ACTH analog (synthetic)
Diagnose 1 vs 2 adrenal insufficiency
```
34
GH direct effects
Lipolysis, anti-hypoglycemia
35
GHR is in a family that also includes the
EPO and IL receptors (cytokines receptor family)
| NO kinase activity
36
GH-GHR pathway
GHR recruites JAK2 kinase, STAT5 phosphorylated, transcription of IGF-1
37
What is the problem in Laron's? How are they treated?
GHR mutation.
| Treat with IGF-1
38
GH indirect effects (IGF-1)
Activation of insulin receptor (high concentrations), lower glucose concentrations
39
Why dodes IGF-1 have a long half-life?
It is associated with IGFBP-3 and ALS
40
Positive stimulator of GH release?
GHRH (+synthesis), protein, hypoglycemia, stress (catelcholamines), sleep, excercise, a-adrenergic (block SST)
41
Where is GHRH produced?
Arcuate nucleus
42
Negative regulator of GH release?
Somatostatin, glucose, FA, b-adrenergics
43
Where is somatostatin produced?
Hypothalamus (widely dispersed)
44
What is the most common anterior pituitary deficiency?
GH
45
How is the GH feedback loop completed?
IGF-1 feeds back to hypothalamus and anterior pituitary to prevent release of GH
46
Genes implicated in GH defficiency
HESx1m PIT1, PROP1 (all needed for pituitary development)
47
What are some causes of acquired GH deficiency?
Brain trauma, GBHS infancy, iatrogenic (after surgery to remove craniopharyngioma)
48
3 ways to diagnose GH deficiency
Arginine: protein (+GH)
Clonidine: a-adrenergic (+GH)
Insulin: hypoglycemia (+GH)
49
Diagnosing GH excess
- Elevated IGF-1
- Failure of glucose load to suppress GH
- MRI for pituitary adenoma
50
Mechanism of PRL action
Similar to GH
| Cytokine receptor family, JAK2/STAT5 pathway
51
Major regulator of PRL
Dopamine via D2R (inhibit secretion), secreted by hypothalamus
52
Why do patients with hypothyroid have excess PRL?
TRH activates the PRL receptor at high concentrations and causes lactotroph hypertrophy
53
Common etiologies for hyperPRL (4)
- Pituitary adenoma
- antipsychotics (D2R antagonists)
- 1ry hypothyroid (TRH spillover to PRL-R)
- PCOS
54
Which hormones share a very similar beta subunit?
LH and hCG
55
Gonadotrope mechanism of action
Gs, AC, cAMP
56
Which gonadotropins share a receptor?
LH and hCG both bind to the LH receptor
57
FSH function in males and females
F: follicle growth, +inhibin, +estrogen
M: Spermatogenesis, +inhibin
58
FSH targets in males and females
F: granulosa cells
M: sertoli cells
59
LH targets in males and females
F: theca, corpus luteum, follicles
M: leydig cells
60
LH effects in males and females
F: +estrogen & progesterone
M: +testosterone
61
hCG targets & effects in females
T: corpus luteum
E: +progesterone
62
How does FSH stimulate estrogen production in females?
Via effects on aromatase (test-est)
63
Which gonadotropin can exert positive feedback? When?
Estrogen during ovulation
64
Where is GnRH made?
Arcuate nucleus of the hypothalamus
65
How does GnRH stimulate production of LH and FSH?
Through GPCRs
66
What happens if GnRH delivery is constant?
The GnRH receptor is down-regulated, less gonadotropin secretion (how long-acting GnHR agonists prevent precocious puberty)
67
What are negative feedback molecules for gonadotropins?
Estrogen, progesterone, testosterone, inhibin
68
What phase?
| Gn stimulate follicles, + estrogen, + endometrium. Gn has small, frequent pulses.
Follicular
69
Follicular phase
Gn stimulates follicles to make estrogen, which builds up endometrium. Pulses are small and frequent.
70
Ovulation phase
Estrogen rises and exerts positive feedback, LH surge causes ovulation, follicle produces corpus luteum, which makes E&P
71
Luteal Phase
Progesterone causes vascularization & mucus production in endometrium, feedback causes bigger but less frequent pulses.
72
Fertilization
Trophoblasts secrete hCG, +P&E by corpus luteum, >9 wks P&E by placenta
73
Menstration
Corpus luteum progresses, no more endometrial support
74
Ganirelix
GnRH receptor antagonist
IVF, prostate & breast cancer
Shut off Gn release with no flares seen in GnRH long-term agonists
75
Which are the most common insulin types in pumps?
Rapid acting
76
What type of insulin is lispro?
Rapid-acting
77
What type of insulin is aspart?
Rapid-acting
78
Wahat type of insulin is glulisine?
Rapid-acting
79
What type of insulin is regular?
Short-acting
80
What type of insulin is NHP?
Intermediate-acting (basal)
81
Which is the only insulin that is cloudy?
NPH
82
What type of insulin is glargine?
Long-acting
83
What type of insulin is Levemir?
Long-acting
84
What do gamma or F-cells secrete?
pancreatic polypeptide
85
What enzyme processes the preprohormone of insulin itnto disulfide-linked alpha and beta chains?
carboxypeptidase
86
What percentage of insulin is released at unproteolyzed proinsulin?
6%
87
What is the insulin concentration in the portal blood? In peripheral blood?
50-100 uU/mL vs 12 uU/mL
| Differential not achieved with insulin therapy
88
What is the earliest defect in T2D?
Priming phase of insulin secretion
89
How many units of insulin are released daily from a normal pancreas?
20-30
90
Which insulin cannot be combined with any others in a single injection?
Glargine and Determir (long-acting basal insulins)
91
When should regular insulin be taken?
30 min before a meal
92
When are long-acting insulins given?
Once a day, usually at bedtime
93
Why is glargine long-acting?
Mutation causes polypeptide soluble at pH 4 but precipitates at physiological
94
Why is determir long-acting?
Myristolated which increases self-association and binding to albumin.
95
What is the rule of 15 for correcting hypoglycemia?
Injest 15 g of glucose, wait 15 min, repeat.
96
What are the side effects of using insulin therapy?
Hypoglycemia, allergic rxns (uncommon), lipoatrophy (immune response), lipohypertrophy (insulin), weight gain, worse retinopathy
97
What is the mechanism of action of sulfonylureas?
Stimulate b cell secretion by inhibiting ATP-sensitive K channel. Delivery independent of glucose levels.
98
What are the disadvantages of sulfonylureas?
Hypoglycemia, weight gain, sulfa allergies, fail when beta cells fail
99
Glyburide class
Sulfonylurea
100
Glipzide class
Sulfonylurea
101
Glimepiride class
Sulfonylurea
102
Pioglitazone class
Thozolidinediones (TZD)
103
How does pioglitazione work?
Binds PPARs in fatty tissue and increases insulin sensitivity.Promote differentiation of adipocytes, so fat is stored subq instead of in organs. Also increase iver & muscle sensitivity
104
Advantages of pioglytazione
Increases HDL, lower TG, no hypo, may improve fatty liver
105
Disadvantages of pioglytazione
Takes weeks, weight gain, worse HF, worse osteo, increases LDL, bladder cancer, p450's
106
How does metformin work?
Improves insulin sensitivity, mainly in liver. Lower glucose output, improve uptake. Slows glucose absorption from gut
107
Advantages of metformin
Rapid, no weight gain, no hypo, better lipids
108
Disadvantages of metformin
lactic acidosis in renal/liver fail, GI effects when starting, B12 deficiency
109
Metformin class
biguanide
110
Liraglutide class
GLP-1 analog
111
How does liraglutide work?
GLP-1 analog. Incretin effect.Stimulates insulin release and beta cell growth. Suppresses gastric emptying, glucagon secretion & appetite.
112
Liraglutide advantages
Only works if glucose is high, increase beta cell mass, weight loss
113
Liraglutide disadvantages
Injected, nausea, acute pancreatitis, nto for those with MEN muts of medullary carcinoma of thyroid
114
Sitagliptin mdoe of action
DPP-IV inhibitor (less degrade of GLP-1 and GIP)
115
Difference in GLP-1 levels between liraglutide and sitagliptin.
Liraglutide has pharmacological concentrations (analog) and sitagliptin had phyisiological concentrations (DPP-IV inhibitor)
116
Sitagliptin advatages
Oral, no hypo unless with sulfonylureas, less nausea than liraglutide
117
Sitagliptin disadvantages
Not as potent as liraglutide, no weight loss
118
How does canaglifozin work?
SGLT2 inhibitor. Lowers renal threshold for glucose=urine glucose loss & osmotic diuresis
119
Advantages of canagliflozin
Weight loss, rare hypo, oral, independent of islet cells, improve BP
120
Diadvantages of canagliflozin
Need renal function, more genital infections, hypotension, increased LDL
121
Cosyntropin
Synthetic ACTH, screening for adrenocortical insufficiency
122
Dexamethasone
Gluccocorticoid w/o mineralocorticoid (long-acting)
123
Fludrocortisone
Mineralocorticoid (Aldo analog)
124
Hydrocortisone
Glucco/mineralocorticoid (short-acting)
125
Fluticasone
Gluccocorticoid (nasal spray)
126
Methylprednisolone
Gluccocorticoid (intermediate)
127
Prednisone
Gluccocorticoid (converted to prednisolone in vivo by HSD11B1, doesn't work with liver disease, use during pregnancy, intermediate)
128
Prednisolone
Gluccocorticoid (use instead of prednisone in liver disease, intermediate)
129
Triamcinolone
Gluccocorticoid w/no mineralocorticoid, causes muscle weakness.(intermediate)
130
Long-acting gluccocorticoid with no mineralocoirticoid activity
Dexamethasone
131
Intermediate-acting gluccocorticoid with no mineralocorticoid activity
Triamcinolone
132
Which zone of the adrenal cortex is not stimulated chronically by ACTH?
Zona glomerulosa
* *ACTH does activate Ald production acutely
* *region is regulated by AngII & K+
133
Treu androgens are formed in the
Periphery. Zona fasciculata makes precursors (DHEA & androstenedione)
134
Will zona glomerulosa aterophy with HP axis failure?
No
135
Will zona fasciculata atropy under HP axis failure?
yes
136
Steroid synthesis is regulated by trophic hormones via ___, which controls ____
cAMP controls flux of cholesterol into mitochondria
137
How does ACTH acutely stimulate aldo production?
Via cholesterol delivery
138
How does ACTH stimulate the adrenal gland?
Binds to Gs, AC, cAMP (increase P450 SCC and StAR)
139
Which enzyme is responsible for the transfer of cholesterol fom the outer mitochondrial membrane into the inner mitochondrial membrane/
StAR
140
Low dose cosyntropin can be used to
Secondary adrenal insufficiency
141
High dose cosyntropin test is used to
Differentiate enzymatic defects that cause primary adrenal insufficiency
142
What is a good measure of adrenal function because it is only made in the adrenals?
DHEA
143
Coricosteroids have __ carbons
21
144
Androgens have __ carbons
19
145
Only the ___ can feed back on the anterior pituitary to repress ACTH secretion
Gluccocorticoids
146
Will changes is plasma proteisna ffect adlo or cortisol levels?
Cortisol. Aldo is not mainly bound to proteins.
147
Gluccocorticoids are inactivated in
liver
148
What is the function of renin?
Converts angiotensinogen to ANGI
149
What is the function of ACE?
Converts AngI to AngII
150
Prior to binding, corticosteroid receptors are ina complex with
HSP70, HSP90, immunoophilins
151
What receptor family do corticosteroid receptors belong to?
Nuclear hormone receptors
152
Aldosterone increases the expression of ___ and ___ in the distal tubule
ENaC adnd SGK1 (acitvates ENaC)
153
Name 2 ways that aldo affects K homeostasis.
- Activates Na/K ATPase
| - SGK1 activates ROMK
154
Where is the MR found?
kidney, sweat glands, salivary glands, exocrine pancreas, GI mucosa
155
What are the effects of gluccos on protein and carb metaolism?
- gluconeogenesis (PEPK in liver)
- protein catabolism
- reduce peripheral gluc uptake
- glycogen synthesis (only anabolic effect)
-
156
effects of gluccos on fat
- lipolysis & fat distribution
- steroids increase number of enzymes and stimulate FA relase
- catecholamines increase enzyme activity
157
Effects of gluccos on immune system
- lympho/monocytopenia (distribute from vascular into spleen, lymph and BM)
- prevent neutrophil adeherence, demargination
- inhibit chemotactic factors
158
Which is a side effect of triamcinolone?
Muscle weakness
159
Which glucco shoudl eb used during pregnancy?
prednisone (fetal liver can convert it to active form)
160
Spirinolactone
Mineralocorticoid antagonist, treats HTN due to CHF. Also antagonizes angroen and progesterone receptor (hirtuism).
161
Eplerenone
More selective mineralocorticoid antagonist.
162
How do antacids affect corticosteroid use?
Inhibit oral absorption
163
What are some symptoms of Addisonian crisis?
hypoglycemia, hyponatremia, hypotension, weakness, Gi stress, hyperkalemia (late), hyperpigmentation (chronic)
164
What is the treatment for an Addisonian crisis?
Fluids and stress-dose gluccocorticoids (will spill over and have mineralo effects)
165
Steroid used for RA
Prednisone, triamcinolone in acute cases
166
Steroid used for asthma
Fluticasone, methyl-prednisolone for severe
167
Steroid used for cerebral edema
dexamethasone
168
Steroid used for ocular disease
dexamethasone, or prednisone
169
Steroid used for rashes
hydrocortisone, triamcinolone
