Pharm Test 3 Flashcards
2 things that cause heart failure
Can’t fill heart with enough blood (diastolic)
Can’t pump enough blood (systolic)
Pumping less than _ constitutes heart failure
40 to 50%
Causes of heart failure (12)
MI Coronary artery disease Valve disease Idiopathic cardiomyopathy Viral/bacterial cardiomyopathy Myocarditis Pericarditis Arrhythmias Chronic hypertension Thyroid disease Pregnancy Septic shock
Class I-IV heart failure
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
Excitation-contraction coupling:
Action potential in skeletal or cardiac muscle triggers muscle contraction
Cardiac muscle contraction is the result of _
Causing _
Which _
Ca influx from depolarization -Causing Release of more Ca from SR -Which Binds to troponin causing interaction b/t actin and tropomyosin
T/F Skeletal and Cardiac muscle get Calcium the same way
False
Depolarization of _ leads to opening of voltage gated Ca channels
Cardiac myocyte
Receptors on SR that, when activated, lead to more Ca release
Ryanodine
Ca binds to _ which alters the interaction b/t _ and _, exposing _ binding sites on _
binds to TROPONIN which alters interaction b/t TROPOMYOSIN and ACTIN exposing MYOSIN binding sites on ACTIN
6 factors that contribute to how well the heart pumps blood
- 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
Inotropic vs. chronotropic drugs
Ino-alter force or energy of muscular contractions
Chrono-change heart rate by affecting nerves controlling heart, or by changing rhythm of SA node
3 positive inotropic drugs to treat heart failure
- cardiac glycosides
- B-adrenergic receptor
- Bipyridines
Cardiac glycosides used in US
Digoxin
Digitalis:
Name for any cardiac glycoside
How does digoxin work
Blocks Na/K ATPase
-internal Na increases, slowing Na/Ca exchanger, slowing removal of Ca
Digoxin, and therefore altering Na/K ATPase messes with
Electrical activity of the heart
Most popular B-1 adrenergic receptor agonists
Dobutamine
T/F B1-adrenergic receptor agonists are the first line of defense
FALSE
4 drugs that treat both systolic and diastolic heart failure
1 for systolic only
ACE inhibitor
Diuretic
Spironolactone
B-blocker
Digitalis
Bipyridines act how
They are phosphodiesterase-3 inhibitors
Main drug w/o positive inotropic effects used to treat heart failure
B-adrenergic receptor ANTAGONISTS (beta blockers)
Medications for CHF can cause
Dry mouth and gingivitis
_% of patients with heart disease also have periodontitis
91
3 types of angina
- Classical/stable-due to fixed and stable plaque
- Variant-spasm of coronary artery
- Unstable-due to unstable plaque
Stable angina vs. acute coronary syndrome
Stable:
Symptoms related to effort
Predictable
Acute coronary:
Unpredictable
Symptoms at rest
5 drugs used to treat angina
Nitrates/nitrites B-adrenergic receptor blockers Ca channel blockers Aspirin, anticoagulant drugs Ranolazine
Nitrates and nitrates are _ that spontaneously produce _
Prodrugs
Nitric oxide
_ compounds are ineffective drugs for angina. Example is _
Inorganic compounds
Na nitrite, used for cyanide poisoning
How is nitroglycerin applied, and what does it treat
Apply under tongue
Acute episodes of angina
Adverse effects of nitrates/nitrites
Headache Hypotension Facial flushing Tachycardia Dangerous if used with viagra
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
Ca channel blockers do what
Same as beta blockers in heart
AND
Increase vasodilation
Increase O2 supply
To treat angina:
Vasodilators:
Cardiac Depressants:
Both:
VD: nitrates
CD: beta blockers
Both: calcium blockers
4 steps in kidney function
Filtration
Resorption
Secretion
Excretion
70% of filtered Na is resorbed in what part of the renal tubule?
Why
PCT
Carbonic anhydride inhibitors
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)
Where do you find osmotic diuretics
What is an OD
PCT, PST
Diuretic that inhibits reabsorption of water and Na
Mannitol is an osmotic diuretic, how does it work?
It isn’t reabsorbed well, it keeps water in urine
Loop diuretics are found where
Thick ascending limb of loop of henle
What do loop diuretics treat and how
Treat hypertension
By
Inhibiting Na, K, 2Cl symporter
(Increases the excretion of these)
Water follows
Loop diuretics are derivatives of what? Why is this important
Sulfonamide derivatives
Many people are allergic to sulfonamides
Thiazide diuretics are found where
Distal convoluted tubule
What do thiazide diuretics do
Block Na/Cl symporter
Increase Na/Cl excretion
Water follows
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+
K sparing diuretics work where
Cortical collecting tubule
MAP=
CO x TPR
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
What cells in kidney have baroreceptors
JG cells
In kidneys, BP decrease causes what
Na decrease in infiltrate
Sympathetic stimulation
And
Renin release from JG apparatus into plasma
Renin does what
Converts angiotensinogen to angiotensin 1
Where is angiotensinogen made and what does it do
Made by liver
Becomes angiotensin 1
What is ACE and what does it do
Angiotensin converting enzyme
Converts angiotensin I to angiotensin II
What effects do:
Angiotensinogen
Angiotensin I
Angiotensin II
Have on Na resorption
Only angiotensin II mediates vasoconstriction, Na resorption, and water retention
Why use an ACE inhibitor? What do they do?
Prevent hypertension
Prevents angiotensin I from becoming angiotensin II
Angiotensin II promotes _ release from _
Aldosterone release from adrenal cortex
4 drugs to treat hypertension
Diuretics
Sympathoplegic agents
Direct vasodilators
Angiotensin II blockers
Person with mild to moderate hypertension is recommended _
Thiazide
Sympathoplegic agents do what
Reduce release of epinephrine from sympathetic nerve endings
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
Suffix -pril usually denotes what
Prodrug, especially ACE inhibitor
Suffix -sartan indicates a drug that does what
Blocks angiotensin II production or activity
4 types of arrhythmias
Extra beats
Supraventricular tachycardia
Ventricular arrhythmia
Bradyarrhythmia
4 places from which arrhythmias can originate
Atria
Ventricle
Junction
AV node (av block)
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
4 causes of arrhythmias
Cardiac ischemia
Excessive discharge or sensitivity to autonomic transmitters
Exposure to toxic substances
Unknown? Other?
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
Why does blocking B-adrenergic antagonists work to treat arrhythmias?
Excess stimulation of beta receptors can lead to arrrhythmias
How does blocking K channels treat arrhythmias
It delays repolarization and prolongs action potential and refractory period
High levels of free fatty acids contribute to what
Insulin resistance Heart disease Atherosclerosis Metabolic syndrome Obesity Cancer
Dyslipidemia:
Disorder of lipoprotein metabolism
Includes overproduction and deficiency
5 types of drugs used to treat dyslipidemia
- Fibric Acid and derivatives
- Nicotinic Acid
- Bile Acid sequestrants
- Inhibitors of HMG CoA reductase (statins)
- Cholesterol Absorption inhibitors
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
Side effects of fibric acid derivatives
Abdominal pain, diarrhea, nausea
Blurred vision
Gallstones
Long prothrombin time
Nicotinic acid, AKA _ can treat dyslipidemia
Niacin
How does nicotinic acid work
Agonist for GPR 109A/B receptor
Inhibits diacylglycerol acyltransferase
What does DGAT do
Takes 1,2 DAG to triacylglycerol
Receptor that niacin agonizes
Activation inhibits what
109A/B
Activation inhibits lipolysis and atherogenic activity
Two major benefits of niacin therapy
More HDL
Less triglyceride
Side effects of nicotinic acid
Flushing
Itching (pruritis)
GI distress
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
Why block HMG CoA reductase?
In pathway to synthesize cholesterol
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
Cholesterol absorption inhibitors overall do what
Inhibit LDL formation
The transport protein that moves cholesterol from lumen into enterocyte:
Blocked by:
NPC1L1
Blocked by ezetimibe
Side effects of cholesterol absorption inhibitors
GI pain/diarrhea
Normal fasting blood glucose
70-100 mg/dL
α cells secrete:
β cells secrete:
δ cells secrete:
α: glucagon
β: insulin
δ: somatostatin
How does glucagon work to raise blood sugar levels (5 steps)
GPCR Elevates cAMP levels Activate PKA Kinase cascade Liberation of glucose from glycogen
Receptor that insulin binds to
3 major biochemical effects that can result
Tyrosine Kinase Receptor
- Decrease in blood glucose levels
- Promotion of storage of fat
- Enhancement of protein anabolism
DM vs DI
DM: metabolic disorder, high blood sugar levels over prolonged period
DI: large amounts of dilute urine and increased thirst
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
What is secondary diabetes
β cells destroyed not by immune cells, but something else like disease or injury
DM type 2:
Sugar?
Insulin?
Causes?
High blood sugar
Insulin resistance, lack of insulin
Obesity and bad lifestyle, genes too
Gestational diabetes:
3 risks?
Risk to baby?
Pre-eclampsia, depression, c-section
Baby can be overweight, low blood sugar, jaundice, getting type 2 diabetes
Peak age for diagnosis of type 1 diabetes
14
3 targets of insulin
Liver, adipose, skeletal muscle
3 acute complications of diabetes
- Diabetic ketoacidosis
- Hypersomolar hyperglycemic state
- Hypoglycemia
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
Hyperosmolar hyperglycemic state:
Features
When?
Hyperosmolar plasma
Dehydration
Hyperglycemia
Type 2 DM, with physiologic stress
How are vascular complications from diabetes induced?
Through diabetes induced endothelial cell dysfunction
ROS
- enhanced in hyperglycemia
- consequence of oxidative rxns
4 tests to diagnose diabetes
- A1C
- Fasting glucose
- Casual Blood glucose
- Oral glucose tolerance test
Normal fasting and post meal blood sugar levels
F: 70-100mg/dL
PM: 70-140mg/dL
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
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
Secretagogues
Molecules/drugs that affect insulin secretion by affecting glucose sensors
Incretins:
Drugs that work on GLP-1 receptors on β cells and stimulate insulin release
First line of treatment for type 2 diabetes
Metformin (Biguanide)
What does metformin do
- Doesn’t stimulate insulin secretion
- Increases glucose uptake and use in sk muscle
- Reduces hepatic glucose production
T/F metformin enhances action of glucagon
FALSE - it opposes glucagon
How does metformin work? (Popular theory)
Activation of AMP-dependent protein kinase
What do thiazolidinediones do
Decrease insulin resistance
How do α-glucosidase inhibitors work
Inhibit the digestion of glucose
3 steps of clot formation
Vessel constriction
Platelet adhesion, activation, aggregation
Cross-linking of fibrin thru coagulation cascade
2 molecules produced by endothelial cells upon injury
What do they do
Prostaglandin F 2α
Τhromboxane A2
Vasoconstriction to limit hemorrhage
In platelet adhesion, what do platelets adhere to
Matrix protein’s collagen
Fibronectin
vWF
What is secreted by activated platelets (4)
PGF2α
Thromboxane A2
ADP
Serotonin
Platelets aggregate as a result of _, forming the platelet plug
Fibrinogen cross-linking
_ is cleaved by _ to form fibrin
Fibrinogen is cleaved by thrombin to form fibrin
Extrinsic pathway (6 steps)
TF
VII->VIIa
IX->IXa
X->Xa
(Xa+Va)
Prothrombin(II) —————>thrombin(IIa)
(Thrombin)
Fibrinogen(I) ——————>fibrin(Ia)In addition to activating I->Ia, thrombin also activates what 3 other factors
V
VIII
XI
What does factor XII do
Starts intrinsic pathway (XII, XI, IX, X)
Cross links fibrin mesh
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
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
Tissue factor pathway inhibitor is a _
It can reversible inhibit _ and _ together
Single chain polypeptide
Xa and VIIa-TF complex
DIC:
Disseminated intravascular coagulation - widespread activation of clotting cascade, clots form in small vessels throughout body
5 fibrinolytics
Streptokinase Urokinase Reteplase Alteplase Tenecteplase
Types of anti-coagulant drugs
- Indirect thrombin inhibitors
2. Direct thrombin inhibitors
Heparin is a _
It acts on _
Indirect thrombin inhibitor
AT
Hirudin is a _
It is found in _
Direct thrombin inhibitor
Leeches
_ is an oral direct thrombin inhibitor. One of these is _
Coumarin
Warfarin
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
What are some drugs that interact with warfarin
Antibiotics Antifungals Antidepressants Antiplatelet agents Anti-inflammatory agents
Amiodarone
Acetaminophen
Alternative remedies
Antidote for warfarin overdose
Vit. K
3 things that block platelet aggregation
1 thing that promotes platelet aggregation
Aspirin
Clopidogrel
Epifibatide
Thromboxane A2
3 essential nutrients for Hematopoiesis
iron
Vit B12
Folic acid
Heme is made where
Mainly in liver and bone marrow. Half in mitochondria, half in cytosol
Iron excretion:
Mostly through blood. Why women lose a lot in menses.
Feces has unabsorbed, lost skin cells another avenue.
Iron is transported into plasma bound to _
It’s stored in _ found in _
Transferrin
Ferritin, liver spleen bone marrow
Anemias from lack of B12 usually reflect a _
Problem with absorption
Folic acid deficiency can cause _ and _
B12 deficiency can cause _
Megaloblastic anemia
Glossitis
Neurologic disease
Treatment of sickle cell
Marrow donor
Erythropoietin (EPO) is used to treat anemia from what
Chronic kidney disease
Inflammatory bowel disease
Myelodysplasia from tx of cancer
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
Ant. Pit hormones that are used as drugs
FSH
LH
GH
A receptor with associated with _ mediates the effects of GH
JAK kinase
What kind of molecule is GH
How big is it
191 aa polypeptide
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
In men:
FSH action
LH action
FSH: spermatogenesis
LH: testosterone production
Vasopressin acts on two different receptors. Which has which effect?
V1: vasoconstriction, increased arterial pressure
V2: increased blood volume
Clinical vasopressin treats 3 things
Diabetes insipidous
Bleeding problems
Nocturnal enuresis
2 causes of diabetes insipid is
Central - can’t make or secrete ADH
Nephrogenic - kidney can’t respond to ADH
Why give/suppress oxytocin
Give: induce labor
Suppress: halt premature labor
ADH or vasopressin does what
Pee less, retain water, higher blood pressure
T4 is dominant in _
T3 is more _
Plasma
Active
3 ways to treat hyperthyroidism
Thioamides-block hormone synthesis
Anion inhibitors - block I transport into thyroid
Iodide
Body is low on Ca. What happens
PTH released
Bone resorption increased
Ca elimination in kidneys decreased
Ca absorption increased in gut
Calcium and _ block PTH release
Vitamin D (thru gene expression)
PTH acts on _ receptor in bone and kidney. Activation causes expression of _. This leads to activation of osteoclasts and bone resorption
PTHR1
RANK ligand
Effects of PTH on kidney
Ca resorption
PO4 decrease resorption
Vitamin D production
The active form of vitamin D is _. _ enhances its production. This enhances _
Calcitrol
PTH
Absorption of Ca from gut
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
Calcitonin is released by _ cells of the _ in response to high serum Ca
Parafollicular cells of thyroid
Dental abnormalities from hyperparathyroidism
Pulp chamber obliteration by pulp stone Alteration in eruption Loosening and drifting of teeth Perio ligament widening Tori
Dental abnormalities from hypoparathyroidism
Enamel hypoplasia Delayed eruption Hypodontia Poorly calcified dentin Widened pulp chambers Ankylosis Caries
(Not enough Ca for teeth)
Osteoporosis can be treated with _.
They do what
Bisphosphonates
Prevent loss of bone mass
Most testosterone (95%) comes from _
Leydig cells of testes
3 natural estrogens
Major product of ovary is _
Estrone (E1)
Estradiol (E2)
Estriol (E3)
Major is E2
Clinical uses of estrogen
Primary hypogonadism
Postmenopausal hormone therapy
Suppress ovulation/ovarian function
What is tamoxifen?
When is it used
Inhibits estrogen receptor positive cell proliferation
Used when cells are estrogen receptor positive to stop cells dividing
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
What is a SERM
Selective estrogen receptor modulator
Can be an agonist or antagonist depending on co-activator availability
Progestins are made in what 3 places
They are precursors to what 3 things
Corpus luteum
Placenta
Adrenal cortex
Androgens
Estrogens
Adrenocortical hormones
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
2 emergency oral contraceptives
- Higher dose of oral contraceptives
2. RU486 (progesterone partial agonist)
