Pharm Test 3 Flashcards
1
Q
2 things that cause heart failure
A
Can’t fill heart with enough blood (diastolic)
Can’t pump enough blood (systolic)
2
Q
Pumping less than _ constitutes heart failure
A
40 to 50%
3
Q
Causes of heart failure (12)
A
MI Coronary artery disease Valve disease Idiopathic cardiomyopathy Viral/bacterial cardiomyopathy Myocarditis Pericarditis Arrhythmias Chronic hypertension Thyroid disease Pregnancy Septic shock
4
Q
Class I-IV heart failure
A
1-mild-normal
2-mild-slight limitation of physical activity
3-moderate-limitation of activity, less than normal activity causes fatigue
4-severe-can’t do any physical activity w/o discomfort
5
Q
Excitation-contraction coupling:
A
Action potential in skeletal or cardiac muscle triggers muscle contraction
6
Q
Cardiac muscle contraction is the result of _
Causing _
Which _
A
Ca influx from depolarization -Causing Release of more Ca from SR -Which Binds to troponin causing interaction b/t actin and tropomyosin
7
Q
T/F Skeletal and Cardiac muscle get Calcium the same way
A
False
8
Q
Depolarization of _ leads to opening of voltage gated Ca channels
A
Cardiac myocyte
9
Q
Receptors on SR that, when activated, lead to more Ca release
A
Ryanodine
10
Q
Ca binds to _ which alters the interaction b/t _ and _, exposing _ binding sites on _
A
binds to TROPONIN which alters interaction b/t TROPOMYOSIN and ACTIN exposing MYOSIN binding sites on ACTIN
11
Q
6 factors that contribute to how well the heart pumps blood
A
- Sensitivity of contractile proteins to Ca
- Amount of Ca that is released
- Amount of Ca stored in SR
- Amount of Ca that enters cell at depolarization
- Activity of Na/Ca exchanger
- Intracellular Na conc. And activity of Na/K ATPase
12
Q
Inotropic vs. chronotropic drugs
A
Ino-alter force or energy of muscular contractions
Chrono-change heart rate by affecting nerves controlling heart, or by changing rhythm of SA node
13
Q
3 positive inotropic drugs to treat heart failure
A
- cardiac glycosides
- B-adrenergic receptor
- Bipyridines
14
Q
Cardiac glycosides used in US
A
Digoxin
15
Q
Digitalis:
A
Name for any cardiac glycoside
16
Q
How does digoxin work
A
Blocks Na/K ATPase
-internal Na increases, slowing Na/Ca exchanger, slowing removal of Ca
17
Q
Digoxin, and therefore altering Na/K ATPase messes with
A
Electrical activity of the heart
18
Q
Most popular B-1 adrenergic receptor agonists
A
Dobutamine
19
Q
T/F B1-adrenergic receptor agonists are the first line of defense
A
FALSE
20
Q
4 drugs that treat both systolic and diastolic heart failure
1 for systolic only
A
ACE inhibitor
Diuretic
Spironolactone
B-blocker
Digitalis
21
Q
Bipyridines act how
A
They are phosphodiesterase-3 inhibitors
22
Q
Main drug w/o positive inotropic effects used to treat heart failure
A
B-adrenergic receptor ANTAGONISTS (beta blockers)
23
Q
Medications for CHF can cause
A
Dry mouth and gingivitis
24
Q
_% of patients with heart disease also have periodontitis
A
91
25
3 types of angina
1. Classical/stable-due to fixed and stable plaque
2. Variant-spasm of coronary artery
3. Unstable-due to unstable plaque
26
Stable angina vs. acute coronary syndrome
Stable:
Symptoms related to effort
Predictable
Acute coronary:
Unpredictable
Symptoms at rest
27
5 drugs used to treat angina
```
Nitrates/nitrites
B-adrenergic receptor blockers
Ca channel blockers
Aspirin, anticoagulant drugs
Ranolazine
```
28
Nitrates and nitrates are _ that spontaneously produce _
Prodrugs
| Nitric oxide
29
_ compounds are ineffective drugs for angina. Example is _
Inorganic compounds
| Na nitrite, used for cyanide poisoning
30
How is nitroglycerin applied, and what does it treat
Apply under tongue
| Acute episodes of angina
31
Adverse effects of nitrates/nitrites
```
Headache
Hypotension
Facial flushing
Tachycardia
Dangerous if used with viagra
```
32
Beta adrenergic receptor blockers (beta blockers)
Do what at the SA node?
Do what at the ventricular myocardium?
SA: decrease heart rate
VM: decrease contractility
BOTH: decrease O2 demand
33
Ca channel blockers do what
Same as beta blockers in heart
AND
Increase vasodilation
Increase O2 supply
34
To treat angina:
Vasodilators:
Cardiac Depressants:
Both:
VD: nitrates
CD: beta blockers
Both: calcium blockers
35
4 steps in kidney function
Filtration
Resorption
Secretion
Excretion
36
70% of filtered Na is resorbed in what part of the renal tubule?
Why
PCT
Carbonic anhydride inhibitors
37
What does carbonic anhydrase do specifically?
SO, CA inhibitors end up doing what
Facilitates Na and HCO3 reabsorption (and therefore H2O retention
Inhibitors enhance fluid loss (water follows Na)
38
Where do you find osmotic diuretics
What is an OD
PCT, PST
Diuretic that inhibits reabsorption of water and Na
39
Mannitol is an osmotic diuretic, how does it work?
It isn’t reabsorbed well, it keeps water in urine
40
Loop diuretics are found where
Thick ascending limb of loop of henle
41
What do loop diuretics treat and how
Treat hypertension
By
Inhibiting Na, K, 2Cl symporter
(Increases the excretion of these)
Water follows
42
Loop diuretics are derivatives of what? Why is this important
Sulfonamide derivatives
| Many people are allergic to sulfonamides
43
Thiazide diuretics are found where
Distal convoluted tubule
44
What do thiazide diuretics do
Block Na/Cl symporter
Increase Na/Cl excretion
Water follows
45
Why are K sparing diuretics necessary
Loop and thiazide diuretics increase Na delivery to distal segment of Distal tubule which increases potassium loss.
This happens because the aldosterone sensitive Na pump increases Na conc. in exchange for K and H+
46
K sparing diuretics work where
Cortical collecting tubule
47
MAP=
CO x TPR
48
How does the baroreflex regulation system work?
Baroreceptors send BP info to _
Symp. Nerves adjust _ to regulate vasoconstriction, heart beat and CO
Baroreceptors send BP info to medulla
Catecholamines
49
What cells in kidney have baroreceptors
JG cells
50
In kidneys, BP decrease causes what
Na decrease in infiltrate
Sympathetic stimulation
And
Renin release from JG apparatus into plasma
51
Renin does what
Converts angiotensinogen to angiotensin 1
52
Where is angiotensinogen made and what does it do
Made by liver
Becomes angiotensin 1
53
What is ACE and what does it do
Angiotensin converting enzyme
Converts angiotensin I to angiotensin II
54
What effects do:
Angiotensinogen
Angiotensin I
Angiotensin II
Have on Na resorption
Only angiotensin II mediates vasoconstriction, Na resorption, and water retention
55
Why use an ACE inhibitor? What do they do?
Prevent hypertension
Prevents angiotensin I from becoming angiotensin II
56
Angiotensin II promotes _ release from _
Aldosterone release from adrenal cortex
57
4 drugs to treat hypertension
Diuretics
Sympathoplegic agents
Direct vasodilators
Angiotensin II blockers
58
Person with mild to moderate hypertension is recommended _
Thiazide
59
Sympathoplegic agents do what
Reduce release of epinephrine from sympathetic nerve endings
60
4 types of direct vasodilators
Nitric oxide pro-drugs
Drugs that reduce Ca influx into vascular smooth muscle
Drugs that cause Hyperpolarization of vascular smooth muscle
Drugs that activate dopamine receptors
61
Suffix -pril usually denotes what
Prodrug, especially ACE inhibitor
62
Suffix -sartan indicates a drug that does what
Blocks angiotensin II production or activity
63
4 types of arrhythmias
Extra beats
Supraventricular tachycardia
Ventricular arrhythmia
Bradyarrhythmia
64
4 places from which arrhythmias can originate
Atria
Ventricle
Junction
AV node (av block)
65
AV blocks:
1˚, 2˚, 3˚
Conduction b/t atria and ventricles is blocked or slowed causing arrhythmia
1˚- PR interval beyond 0.2 seconds
2˚-disturbance, delay or interruption of atrial impulse conduction through AV node to ventricles
3˚- complete heart block. Impulse from SA node doesn’t propagate to ventricles
66
4 causes of arrhythmias
Cardiac ischemia
Excessive discharge or sensitivity to autonomic transmitters
Exposure to toxic substances
Unknown? Other?
67
4 classes of antiarrhythmic drugs
I-block Na channels
II-Block B-adrenoceptor antagonists
III-prolong action potential and refractory period (K channel blockers)
IV-Block Ca channels
68
Why does blocking B-adrenergic antagonists work to treat arrhythmias?
Excess stimulation of beta receptors can lead to arrrhythmias
69
How does blocking K channels treat arrhythmias
It delays repolarization and prolongs action potential and refractory period
70
High levels of free fatty acids contribute to what
```
Insulin resistance
Heart disease
Atherosclerosis
Metabolic syndrome
Obesity
Cancer
```
71
Dyslipidemia:
Disorder of lipoprotein metabolism
Includes overproduction and deficiency
72
5 types of drugs used to treat dyslipidemia
1. Fibric Acid and derivatives
2. Nicotinic Acid
3. Bile Acid sequestrants
4. Inhibitors of HMG CoA reductase (statins)
5. Cholesterol Absorption inhibitors
73
What does fibric acid do
How
Reduce levels of triglycerides
Agonists of PPARalpha
-combined with RXR-alpha regulate gene expression
—Those genes regulate cell differentiation & development and carb and lipoid and protein metabolism
74
Side effects of fibric acid derivatives
Abdominal pain, diarrhea, nausea
Blurred vision
Gallstones
Long prothrombin time
75
Nicotinic acid, AKA _ can treat dyslipidemia
Niacin
76
How does nicotinic acid work
Agonist for GPR 109A/B receptor
Inhibits diacylglycerol acyltransferase
77
What does DGAT do
Takes 1,2 DAG to triacylglycerol
78
Receptor that niacin agonizes
Activation inhibits what
109A/B
Activation inhibits lipolysis and atherogenic activity
79
Two major benefits of niacin therapy
More HDL
| Less triglyceride
80
Side effects of nicotinic acid
Flushing
Itching (pruritis)
GI distress
81
How do bile acid sequestrants work? Why sequester bile acid?
Drugs keep bile acids from getting absorbed in intestines, are pooped out
Why?
-Bile acids are made when liver converts cholesterol to bile acid, more pooped out, more will be metabolized
82
Why block HMG CoA reductase?
In pathway to synthesize cholesterol
83
Who should take statins
Men
Over 65
No Hx of heart disease
Don’t have current problems
1+ risk factors (high cholesterol, diabetes, etc)
10% risk of heart attack in next 10 years
84
Cholesterol absorption inhibitors overall do what
Inhibit LDL formation
85
The transport protein that moves cholesterol from lumen into enterocyte:
Blocked by:
NPC1L1
Blocked by ezetimibe
86
Side effects of cholesterol absorption inhibitors
GI pain/diarrhea
87
Normal fasting blood glucose
70-100 mg/dL
88
α cells secrete:
β cells secrete:
δ cells secrete:
α: glucagon
β: insulin
δ: somatostatin
89
How does glucagon work to raise blood sugar levels (5 steps)
```
GPCR
Elevates cAMP levels
Activate PKA
Kinase cascade
Liberation of glucose from glycogen
```
90
Receptor that insulin binds to
3 major biochemical effects that can result
Tyrosine Kinase Receptor
1. Decrease in blood glucose levels
2. Promotion of storage of fat
3. Enhancement of protein anabolism
91
DM vs DI
DM: metabolic disorder, high blood sugar levels over prolonged period
DI: large amounts of dilute urine and increased thirst
92
DM type 1:
What’s going on w/insulin
Blood sugar?
Cause:
- Not enough insulin produced
- High blood sugar
- Immune system destroys β cells in pancreas
93
What is secondary diabetes
β cells destroyed not by immune cells, but something else like disease or injury
94
DM type 2:
Sugar?
Insulin?
Causes?
High blood sugar
Insulin resistance, lack of insulin
Obesity and bad lifestyle, genes too
95
Gestational diabetes:
3 risks?
Risk to baby?
Pre-eclampsia, depression, c-section
Baby can be overweight, low blood sugar, jaundice, getting type 2 diabetes
96
Peak age for diagnosis of type 1 diabetes
14
97
3 targets of insulin
Liver, adipose, skeletal muscle
98
3 acute complications of diabetes
1. Diabetic ketoacidosis
2. Hypersomolar hyperglycemic state
3. Hypoglycemia
99
What is diabetic ketoacidosis
Liver converts pyruvate to glucose
Liver gets pyruvate from skeletal muscle
Results in excess keto acid
ALSO
Liver oxidizes fatty acid to Acetyl CoA
Liver converts ACoA to ketone bodies
100
Hyperosmolar hyperglycemic state:
Features
When?
Hyperosmolar plasma
Dehydration
Hyperglycemia
Type 2 DM, with physiologic stress
101
How are vascular complications from diabetes induced?
Through diabetes induced endothelial cell dysfunction
ROS
- enhanced in hyperglycemia
- consequence of oxidative rxns
102
4 tests to diagnose diabetes
1. A1C
2. Fasting glucose
3. Casual Blood glucose
4. Oral glucose tolerance test
103
Normal fasting and post meal blood sugar levels
F: 70-100mg/dL
PM: 70-140mg/dL
104
A1C test measures what
Why is it good
Glycation of hemoglobin
Hemoglobin lasts 115 days, so its value is an average over a longer time
105
How to administer oral glucose tolerance test?
Normal baseline
1 hr
2 hr
Draw blood
Give 75 g of glucose
Draw blood after 1 and 2 hr
Normal:<110mg/dL
1hr: <180 mg/dL
2hr: <140mg/dL
106
Secretagogues
Molecules/drugs that affect insulin secretion by affecting glucose sensors
107
Incretins:
Drugs that work on GLP-1 receptors on β cells and stimulate insulin release
108
First line of treatment for type 2 diabetes
Metformin (Biguanide)
109
What does metformin do
- Doesn’t stimulate insulin secretion
- Increases glucose uptake and use in sk muscle
- Reduces hepatic glucose production
110
T/F metformin enhances action of glucagon
FALSE - it opposes glucagon
111
How does metformin work? (Popular theory)
Activation of AMP-dependent protein kinase
112
What do thiazolidinediones do
Decrease insulin resistance
113
How do α-glucosidase inhibitors work
Inhibit the digestion of glucose
114
3 steps of clot formation
Vessel constriction
Platelet adhesion, activation, aggregation
Cross-linking of fibrin thru coagulation cascade
115
2 molecules produced by endothelial cells upon injury
What do they do
Prostaglandin F 2α
Τhromboxane A2
Vasoconstriction to limit hemorrhage
116
In platelet adhesion, what do platelets adhere to
Matrix protein’s collagen
Fibronectin
vWF
117
What is secreted by activated platelets (4)
PGF2α
Thromboxane A2
ADP
Serotonin
118
Platelets aggregate as a result of _, forming the platelet plug
Fibrinogen cross-linking
119
_ is cleaved by _ to form fibrin
Fibrinogen is cleaved by thrombin to form fibrin
120
Extrinsic pathway (6 steps)
```
TF
VII->VIIa
IX->IXa
X->Xa
(Xa+Va)
Prothrombin(II) —————>thrombin(IIa)
(Thrombin)
Fibrinogen(I) ——————>fibrin(Ia)
```
121
In addition to activating I->Ia, thrombin also activates what 3 other factors
V
VIII
XI
122
What does factor XII do
Starts intrinsic pathway (XII, XI, IX, X)
| Cross links fibrin mesh
123
Antithrombin is a _
It is produced by _
It’s activity is increased by _, which enhances binding of _ to _ and _
Serine protease inhibitor
the liver
Heparin which enhances binding of antithrombin to factor II (thrombin) and factor X
124
Protein C inactivates what two proteins
It is classified as a _
How is it activated
Factor Va and VIIIa
Serine protease
Activated by binding to thrombin
125
Tissue factor pathway inhibitor is a _
It can reversible inhibit _ and _ together
Single chain polypeptide
Xa and VIIa-TF complex
126
DIC:
Disseminated intravascular coagulation - widespread activation of clotting cascade, clots form in small vessels throughout body
127
5 fibrinolytics
```
Streptokinase
Urokinase
Reteplase
Alteplase
Tenecteplase
```
128
Types of anti-coagulant drugs
1. Indirect thrombin inhibitors
| 2. Direct thrombin inhibitors
129
Heparin is a _
It acts on _
Indirect thrombin inhibitor
AT
130
Hirudin is a _
It is found in _
Direct thrombin inhibitor
Leeches
131
_ is an oral direct thrombin inhibitor. One of these is _
Coumarin
Warfarin
132
For thrombin to become catalytically competent, it needs to undergo a _ rxn
This requires the _ of _
Coumarins block _
Without this, the body runs out of reduced vitamin K and thrombin won’t become active.
Carboxylation
Oxidation of vitamin K
The conversion of oxidized vit. K back to reduced form
133
What are some drugs that interact with warfarin
```
Antibiotics
Antifungals
Antidepressants
Antiplatelet agents
Anti-inflammatory agents
```
Amiodarone
Acetaminophen
Alternative remedies
134
Antidote for warfarin overdose
Vit. K
135
3 things that block platelet aggregation
1 thing that promotes platelet aggregation
Aspirin
Clopidogrel
Epifibatide
Thromboxane A2
136
3 essential nutrients for Hematopoiesis
iron
Vit B12
Folic acid
137
Heme is made where
Mainly in liver and bone marrow. Half in mitochondria, half in cytosol
138
Iron excretion:
Mostly through blood. Why women lose a lot in menses.
Feces has unabsorbed, lost skin cells another avenue.
139
Iron is transported into plasma bound to _
It’s stored in _ found in _
Transferrin
Ferritin, liver spleen bone marrow
140
Anemias from lack of B12 usually reflect a _
Problem with absorption
141
Folic acid deficiency can cause _ and _
B12 deficiency can cause _
Megaloblastic anemia
Glossitis
Neurologic disease
142
Treatment of sickle cell
Marrow donor
143
Erythropoietin (EPO) is used to treat anemia from what
Chronic kidney disease
Inflammatory bowel disease
Myelodysplasia from tx of cancer
144
G-CSF, GM-CSF, IL-11 are what
Used to do what
Hematopoietic growth factors
Stimulates bone marrow to make granulocytes and stem cells and release them
145
Ant. Pit hormones that are used as drugs
FSH
LH
GH
146
A receptor with associated with _ mediates the effects of GH
JAK kinase
147
What kind of molecule is GH
How big is it
191 aa polypeptide
148
FSH and LH:
Regular actions
Follicular stage actions
Luteal stage actions
Regular:
- (FSH) Ovarian follicle development
- (Both) Ovarian steroidogenesis
Follicular:
- (LH) Androgen production
- (FSH) conversion of androgens to estrogens
Luteal:
-(LH) estrogen and progesterone production
149
In men:
FSH action
LH action
FSH: spermatogenesis
LH: testosterone production
150
Vasopressin acts on two different receptors. Which has which effect?
V1: vasoconstriction, increased arterial pressure
V2: increased blood volume
151
Clinical vasopressin treats 3 things
Diabetes insipidous
Bleeding problems
Nocturnal enuresis
152
2 causes of diabetes insipid is
Central - can’t make or secrete ADH
Nephrogenic - kidney can’t respond to ADH
153
Why give/suppress oxytocin
Give: induce labor
Suppress: halt premature labor
154
ADH or vasopressin does what
Pee less, retain water, higher blood pressure
155
T4 is dominant in _
| T3 is more _
Plasma
| Active
156
3 ways to treat hyperthyroidism
Thioamides-block hormone synthesis
Anion inhibitors - block I transport into thyroid
Iodide
157
Body is low on Ca. What happens
PTH released
Bone resorption increased
Ca elimination in kidneys decreased
Ca absorption increased in gut
158
Calcium and _ block PTH release
Vitamin D (thru gene expression)
159
PTH acts on _ receptor in bone and kidney. Activation causes expression of _. This leads to activation of osteoclasts and bone resorption
PTHR1
RANK ligand
160
Effects of PTH on kidney
Ca resorption
PO4 decrease resorption
Vitamin D production
161
The active form of vitamin D is _. _ enhances its production. This enhances _
Calcitrol
PTH
Absorption of Ca from gut
162
Vitamin D does more than influence Ca. Other things it does
```
Brain development/function
Reduce inflammation
Heart function
Blood pressure
Reduce colon cancer
Muscle strength
```
163
Calcitonin is released by _ cells of the _ in response to high serum Ca
Parafollicular cells of thyroid
164
Dental abnormalities from hyperparathyroidism
```
Pulp chamber obliteration by pulp stone
Alteration in eruption
Loosening and drifting of teeth
Perio ligament widening
Tori
```
165
Dental abnormalities from hypoparathyroidism
```
Enamel hypoplasia
Delayed eruption
Hypodontia
Poorly calcified dentin
Widened pulp chambers
Ankylosis
Caries
```
(Not enough Ca for teeth)
166
Osteoporosis can be treated with _.
They do what
Bisphosphonates
Prevent loss of bone mass
167
Most testosterone (95%) comes from _
Leydig cells of testes
168
3 natural estrogens
Major product of ovary is _
Estrone (E1)
Estradiol (E2)
Estriol (E3)
Major is E2
169
Clinical uses of estrogen
Primary hypogonadism
Postmenopausal hormone therapy
Suppress ovulation/ovarian function
170
What is tamoxifen?
When is it used
Inhibits estrogen receptor positive cell proliferation
Used when cells are estrogen receptor positive to stop cells dividing
171
How do estrogen nuclear receptors work
Agonist exposes AF-2 region of receptor
Co-activators can only bind if it is exposed
Agonists bind well but don’t cause conformation change
172
What is a SERM
Selective estrogen receptor modulator
Can be an agonist or antagonist depending on co-activator availability
173
Progestins are made in what 3 places
They are precursors to what 3 things
Corpus luteum
Placenta
Adrenal cortex
Androgens
Estrogens
Adrenocortical hormones
174
Two types of oral contraceptives
How do they work
Estrogen + progesterone
-block LH and FSH release from pit
Progesterone only
- thickening of cervical mucus (blocks sperm)
- block release of eggs from ovary
175
2 emergency oral contraceptives
1. Higher dose of oral contraceptives
| 2. RU486 (progesterone partial agonist)
