Exam 2 Flashcards
Where is autonomic NS; draw a picture of the central, peripheral, and autonomic
It is in both the peripheral and central nervous system, but largely located in peripheral
What is the somatic nervous system apart of
The peripheral NS
Sympathetic has what and what are they close to
Sympathetic ganglia; and they are close to the CNS (spinal cord) and distant from the organs they are going to effect.
Parasympathetic has what and what are they close to? and why?
The ganglia are usually imbedded in the organs; really close. This system is designed for fast global responses… broadcasting signals
why are they called post ganglionic
They are postsynaptic to the pre-ganglionic with its cell body in the gray matter of spinal cord
Pre-ganglion sends process out to post ganglion
What kind of system is the autonomic NS
A two neuron system
whether sympathetic or parasympathetic
What kind of system is the somatic system
a one neuron system — skeletal muscle
What are the four parts of the autonomic system drawn out
(brain/spine)—Pre-ganglionic neuron, mylenated and part of CNS–Autonomic ganglion—-Post-ganglionic neuron, unmylenated and part of PNS—Smooth muscle
Draw the autonomic NS diagram with cholinergic and adernergic
sympathetic nervous system is cholinergic from pre-ganglionic to post-ganglionic
T or F
False
Where do drugs target in the autonomic NS?
the pre or post ganglionic or post ganglionic tissue
What are the two kinds of receptors in the cholinergic synapse
muscarnic and nicotinic
The neurotransmitter is acetycholine
Draw out the anatomical location of ANS neurotransmitters; with nicotinic/mucarinic, adenergic receptors
Cholernergic all throughout but nicotinic at what synapse, and what synapse is it muscarinic?
Draw and label
What are the muscarnic receptor agonist and antagonists
Agonist:
Bethanechol
Pilocarpine
Antagonist:
Atropine
Scopolamine
Ipratroprium
What does Bethanechol do/ what is it
Activates muscarinic but NOT nicotinic acetocholine, so it causes smooth muscle but not skeletal muscle contraction or general activation of the autonomic nervous system.
-direct agonist for all muscarinic receptors
-does nto cross bbb
-stimulates GI, bladder, eye, sweating
-resists hydrolysis by cholinesterase or butyrylcholinesterase
-is a modified version of acetylcholine (note; acetylcholine is unstable and hard to work with)
-very stable
What kind of receptor resides in the smooth muscle
M3
M2 receptor tissue, responses and mechanism
Tissue: cardiac muscle
Responses: Slow heart rate decreases atrial force, slow A-V conduction velocity
Mechanism: activation of K channels and inhibition of adenylyl cyclase through G-i
M3; what tissue; responses; mechanism
Tissue: Smooth muscle, secretory glands, blood vessels
Responses: Smooth muscle contraction, Increases secretion from secretory glands, dilation vis endothelial factors of blood vessels
What is one of the major effects from the M3 receptors
contraction of bladder; parasympathetic stimulation causes the bladder evacuation
Effect of M3 on vascular smooth muscle and what does it release
-both vascular smooth muscle and endothelial cells have m3 receptors
-stimulation of m3 in VSM causes contraction
-Stimulation of m3 in endothelial cells cause release of NO, which causes VSM to relax
What kind of drugs do not pass through endothelial cells
injected, water-soluble drugs like bethanechol do not pass through and do not impact smooth muscle directly. Even if they did; the relaxing impact from the NO would overide it. The effects of the relaxation are always present
How are pilocarpine and bethanechol the same/ different
They react the exact same on M3 receptors; not degraded by cholinesterases
Difference: Pilocarpine crosses the BBB while bethanechol does not; there is CNS arousal: hallucinations/delirium
Do blood vessels receive parasympathetic input?
no, they only receive sympathetic input which can cause them to contract (and is important for BP)
What creates the BBB, what are the properties, and what does it mean
Endothelial cells create
-Large molecules cant cross
- lipid (fat) soluble can
-Charged molecules cant cross
-Knowing if something crosses or not is a key point in deciding which drug to use for what purpose
How does pilocarpine alleviates glaucoma
M3 receptors in the eye in the iris sphincter and ciliary muscle
(local application; ex: eyedrops to have a localized effects is really good)
What slows the heart down/ speeds up?
parasympathetic outflow; there are muscarinic receptors
Sympathetic increase HR
What does the M2 receptor activate on cellular level
potassium channels and that causes a hyper polarization
Bethanechol and reflex tachycardia and what is the reflex tachcardia
-Decreases HR through M2
-causes drop in blood pressure by impacting M3 in vascular endothelial cells
-Usually, the drop in bp would trigger baroreflex, where the sympathetic output to the heart is increased. Counteracting the effect of M2 receptor activation which causes HR to go up
-The net effect of bethanechol (or OD of pilocarpine) cab be a drop in BP AND tachycardia even though there is activation of M2 cardiac receptors
The parasympathetic NS
decreases HR and increases bowl motility
M3 muscarinic acetylcholine receptors are activated
Primary by the parasympathetic nervous system
Bethanechol can most readily affect blood pressure by
activating M3 muscarinic receptors in the cells lining the arteries
atropine
“deadly nightshade”
-direct agonist for all muscarnic receptors
-crosses BBB but need a lot to do so… high dose
-rapid treatment of bradycardia
-overcoming effects of cholmesterase block following anethetic or poising
-decreased bladder spasm
Side effects:
-Urinary retention
-can exacerbate narrow-angle glaucoma
Can be treated with physostigmine which blocks the cholinesterase enzyme (CNS and peripheral)
Scopolamine
-competitive antagonist for all M3 receptors; does the same thing as atropine but readily crosses the BBB and is longer acting.
Low-dose CNS effects in inhibition of motion sickness and induction of amnesia. CNS effects at higher doses include excitation, irritability, delirium, coma
Clinical uses: Decrease motion sickness
Side effects:
Flushed dry skin, dry mouth, tachycardia, dilated pupil, uniary retention, constipation, CNS disturbances
Ipratropium
Direct antagonist for all muscarnic receptors
-really bad at crossing BBB
-can use it for local application as an inhaler, treating asthma or COPD
-Can be used as an alternative to sympathomimetic therapy
-low system absorption from lung decreases side effects
Side effects
-minimal when used as inhaler, dry mouth sometimes can occur
What is the nicotinic receptor made out of and what does this mean
various subunits; there 5; they can be 5 of the same or a combination of tissue-specific. This means that they exist in neurons; and they can be different in neurons vs skeletal muscle and you can target skeletal muscle instead of neurons
Where are the nicotinic receptors
always in postganglionic structure; it doesn’t matter if it in parasympathetic or sympathetic, they all receive acetylcholine and target nicotinic receptors
in skeletal muscle
Nicotine
Expressed in a lot of plants
It is an insecticide (kills)
wet and squishy think of
muscarinic receptor over-activation; excess saliva, bronchorrhea, diaphoresis, diarrhea, abdominal cramping
Sympathetic activation symptoms
tachycardia, hypertension
therapeutic use of nicotine
wean people off cigs
why can symptoms present as both sympathetic and parasympathetic
because nicotinic receptors are on both parasympathetic and sympathetic parts of the NS
Why can symptoms change from hypertension/tachycardia to hypotension and less tachycardia
Nicotinic receptors depolarize cells; they are very powerful. They go through 2 phases of blocking. / desensitization
Phase one: Na channel inactivation
Phase 2 block: receptor desensitization.. not fully understood
happens quickly
Nicotinic activation and the heart
First increases all autonomic outflow- HR BP
Then with excessive cholinergic activation they desensitize through Phase 1/2
Then, it decreases all autonomic outflow because the post-ganglionic neuron nicotinic receptors are less active without the output
-turning off both sympath + para
Blood vessels receive sympathetic but not parasympathetic innervation
what is an indirect activator of nicotinic receptors and what are it’s inhibitors
they target Acytycholinesterase; its inhibitors are:
Edrophonium
Neostigmine/Physostigmine
Organophosphates (sarin, isofluorane)
what is sevin and what does it do
Insecticide and it has the active ingredient methylcarbamate which is an acetylcholinesterase inhibitor; in mammals tends to be eliminated quickly
carbamates… drugs + their use
longer acting modification but still reversible.. the two most common drugs used medically are:
Neostigmine: does not cross BBB
Physostigmine: does cross BBB
same mechanism
used to treat diseases in communication of nerve and muscle cells or the amount of nicotinic receptors and you can increase the amount by using them
Oganophosphates + drug and its use
Acts as long-term inhibitor by generating permanent non-functional phosphorylated intermediate
drug: Isofluophate
Use: isofluophate is an indirect agonist which increases the amount of natural acetylcholine at muscarinic receptors there.
pilocarpine is a direct agonist for the receptors in the ciliary in the eye, but it acts similar
What is a way to reverse organophosphate poisoning
Pralidoxime, only case where it can’t: if you wait too long
Organophosphates; nerve agents
They block acetylcholinesterase (enzyme in nerve terminals)
Exposure: inhalation, skin, ingestion
Persistence: low to high
some can be treated with pralidoxime
Adrenergic receptors
all g-protein-coupled receptors
Alpha 1 tissue target, responses and mechanism
Tissue: smooth muscle
Responses: contraction, including: blood vessels iris (has a similar effect from M3)
Mechanism: Stimulation of PLC through gq. Release of IP and DAG lead to increased CA2+. Similar to M3
Beta-1 tissue, responses, mechanism
Tissue: Cardiac muscle
Responses: increased force and rate of contraction (similar to M2)
Mechanism: Stimulation of adenylyl cyclase through Gs increases Ca2+ causes cardiac stimulation
Beta-2 Tissue, response, mechanism
Tissue: Smooth muscle in vasoculature, bronchioles, GI
Responses: Relaxation
Mechanism: Stimulation of adenylyl cyclase through Gs leads to smooth muscle relaxation
The adrenergic synapse
removal of adrenergic transmitters by re-uptake… drugs CAN target synthesis and release of adrenergic transmitters;
Releases: Norepinepherine (noradrenaline) in sympathetic NS
Adrenal gland
A post-ganglionic structure; releases 80% epinephrine and 20% norepinephrine directly into blood stream
Think of it post-ganglionic neuron with no axons
Epinephrine vs pilocarpine
ep: reduces intraocular pressure by affecting aqueous humor production from ciliary epithelium; does they by activating alpha-1 adrenergic receptors on blood vessels
pilocarpine (increases drainage) does not cause any significant muscle contraction at therapeutic doses
Epinephrine: low and high does and what it does
Low dose: B1 + B2
High dose: B1 + B2 + A1
A1: glaucoma target
(plus usual tissue, responses, and mechanism of b1/2, a)
is epinephrine going to increase or decrease BP at high doses
Increase
it can also be used to open airways
Norepinephrine: agonist or antagonist? what are its receptors and where is it released and what does it do
agonist for: a1, b1, b2
released in nerve terminals; covers blood vessels
It keeps it at constant steady state; it has a very high affinity for a1 and b1 and not as much for b2 which is good
a1 control Bp, they can cause constriction and raise bp
what are two endogenous NTs and what is a disadvantage
epinephrine and norepinephrine
acetylcholine is also one but it is never administered clinically unlike NE and E (destroyed too fast)
a disadvantage of using endogenous NT is that they are not strongly subtype-specific
Isoproterenol
non-selective beta-agonist for B1/B2
B1: increases heart function
B2: dilates bronchial smooth muscle
can be used as inhaler
Phenlephrine
Selective a1 agonist
Constricts vascular smooth muscle
It doesn’t cross BBB
can increase BP
Nasal spray + stop runny nose
Very versatile
Phenylephrine misuses
Selective a1 agonist
does not work when taken orally
Pseudoephedrine is the oral version; makes too much money to take off the market
Prasozin
selective a1 antagonist
Used for:
-open up blood vessels (treat people with heart failure)
-hypertension (decrease BP)
-improve urine flow… benign prostatic hyperplasia
-Does not readily cross BBB, but can and have mild CNS effects
Propanolol
Nonselective Beta antagonist (b1+2)
Block beta receptors
Used for:
Cardiac and BP problems, a decrease in HR and contractility…decrease oxygen the heart needs
helps arrhythmias, migraines
Possibly also for anxiety, the HR, the body thinks you’re calm
adrenomimetic drugs
can mimic effects of sympathetic nervous system
-can stimulate neurotransmitter release or block uptake
Pseudoephedrine/ephedrine
-both an agonist, but also
causes an INCREASE OF RELEASE
-helps with colds
-came from a weed
-Penetrates the BBB
controlled because it can be turned into amphetamine
What does organophosphate nerve gas do
It disrupts autonomic function by indirectly hyperactivating both nicotinic and muscarinic receptors
A patient comes into the emergency room exhibits inhibitor poisoning, excessive salivation with fluid in the lungs. The patient is being treated for a muscle disorder with physostigmine. The patient is showing signs of confusion what should you do?
inject scopolamine to block muscarinic receptors
There is no connection between the airway and the sympathetic NS. However, the fight/flight response does cause an increase in the diameter of bronchial airways by relaxing bronchial smooth muscle.. what processes contribute to this?
Increased sympathetic outflow causes the release of epinephrine, which activates beta-2 adrenergic receptors on the bronchial smooth muscle, causing them to relax
A patient on prazosin to treat high BP. Has a cold and wants to use an over-the-counter drug to relieve her runny nose, what should she use?
Pseudoephedrine taken as a nasal spray
Phenylephrine taken as a nasal spray
both work great to treat cold symptoms
Cardiovascular system + Cardiovascular disease
heart, blood vessels, and blood
20% of all hospital admissions are patients over 65 have to do with heart failure
drugs and heart failure: whats the aim
Decrease hospitalizations and mortality rather than improve quality of life, physical function, or symptoms
lots have severe side effects
What is congestive heart failure what is survival rate
The heart can’t pump out enough blood to the body’s other organs.
symptoms: Shortness of breath (blood backs up… creates back pressure in tissue which causes fluid to leak in the lungs), fatigue, swollen ankles or legs
5-year morality, which is worse than most cancers
Basics of human heart function; systole and diastole
Right side: smaller and weaker and pumps to the lungs
Left ventricle: bigger and stronger pumps to the whole body
Systole (pumping, the BP comes from contractions of left ventricle)
Diastole (filling, resting between beats, BP comes from slowly depressurizing arteries)
Chronic/ acute heart failure
Chronic: long term.. if you have chronic failure, you also have… compensation by the body
Acute: rapid onset, can be immediately life-threatening
Compensation phase in chronic heart failure; what are mechanisms one and two
It can fail– and lead to acute heart failure…
-in heart failure, what your body tries to do is make your heart work harder/faster
-it affects kidney function and increases BP
Compensation Mechanism 1: Sympathetic outflow increases HR and force of contraction VIA B1. It also causes vasoconstriction, increasing BP.
Compensation mechanism 2: Angiotensin (ACE): peptide hormone that causes vasoconstriction and increased BP
Angiotensin receptors cause what
vasoconstriction
Decompensation
failure of compensation, a sudden heart failure
What is a positive inotropic drug
Any drug that increases cardiac contractility
Catecholamines: epinephrine
Agonist for B1 B2 and A1 and A2
it affects A1 in the blood vessels (constricts) not really want because it increases BP and puts more work on the heart
Still best to have a drug without the vasoconstrictive effect
Adverse effects: arrhythmias, tachcardia
Dobutamine
selective B1 agonist
It is used to stimulate the heart by activating to B1, which has the same side effects as epinephrine.
Issues: tolerance is likely to develop with prolonged use because of receptor desensitization
Bipyridines: Milrinone
Used only within the first 48 hours… overtime it is toxic so it is only for acute heart failure
Increases stroke volume and cardiac output via two mechanisms that BYPASS the B1 receptor
Positive Inotropic agent- increases cardiac contractility but decreases of smooth muscle.
Vasodilator- reduces impedance to blood flow.
How does it do this: PDE increases cAMP
in cardiac cells: increase cAMP causes INCREASE in Ca and INCREASE cardiac contractility
Digoxin
Increases Ca2+ levels within cardiac myocytes to enhance contractility
-comes from plants-
Mech of action: inhibition (not completely) of Na+/K+
leads to an increase of Na+
Increases cytosolic Ca2+ levels within cardiac
myocytes to enhance contractility
does not cross BBB
Clinical effects: decreased rate of hospitalization, decreased symptoms of heart failure, increased exercise tolerance
Does not increase survival… just makes what time is left is easier
Adverse effects:
Narrow therapeutic index…
CNS confusion, fatigue… nausea, vomiting
have vision disturbances: yellowed vision or blurred vision
Therapies that target the angiotensin system will….
Do one or both of:
Ace inhibitors to reduce angii levels
AT1 receptor antagonist to reduce angii effects
ACE inhibitors: decrease mortality rates in patients with heart failure
Captopril effects
Ace inhib
decreases total peripheral resistance because there is less BP
so as a result there is an increase in heart performance
Decreases water reabsorption in kidneys…
Improves survival in patients with heart failure
Side effects: Dry cough, hypotension, anaphylactoid reactions, fetal malformations
What does it mean if it ends in pril
it is an ace inhibitor.. prototype is captopril
IT INHIBITS angiotensin-converting enzymes
Angiotensin 2 receptor blockers: Losartan
Helps BP.. blocks effects of angiotensin 2 at the receptor.
It doesn’t impact ACE activity
Side effects: hypertension, fetal malforms
if it ends in LOL what does it mean
It is a beta-blocker…
B1 cardiac (kidney)
also has impacts in kidney
increases force and rate of contraction in the heart + HR
Beneficial effects of B-blockers + adverse effects
decreases O2 + HR, contractility
Improved survival
Adverse effects:
Balance, fatigue, heart failure, bradycardia, asthma (blockade in lung), depression, insomnia, nightmares, impotence, tachycardia
Propranolol
nonselective beta antagonist
Sir James Black
Metoprolol and bisoprolol
relatively selective beta antagonist
Carvedilol
combined non-selective beta and a1 antagonist
has antioxidant properties
not good for patients with asthma, or COPD
Angina is
the result of ischemia, it is pain… that is the result of ischemia in the heart tissue
Ischemia
reduced blood supply.. less oxygen; it is a build-up of plaque inside the blood vessels and restricts the normal flow of blood.
Atherosclerosis
build-up of plaque
what are anginas symptoms
Chest pain; the pain is severe and crushing.
It can accompany or be a precursor to a heart attack
Unstable angina
can happen at rest it comes on and off; it is unstable because it is a plaque becoming unstable… the plaque can start to break apart. It is often a prelude to a heart attack
What helps: nitrodilators, beta-blockers
Angina pectoris
can happen when sitting at rest
Caused by a spasm of the coronary arteries
Drug therapy: calcium channel blockers
Classic/ stable angina
triggered by physical activity, emotional stress, something where heart is beating faster
-always there under the right circumstances
-pain isn’t super long
therapy: Nitrocasodialators, Ca2+ blockers, beta-blockers, ranolazine
Etiology of angina + reactive hypermia
as cardiac work increases; need more flood flow to keep up with the O2 demand
In angina: the coronary arteries cannot widen enough to let O2
reactive hyperemia: When artery dilation occurs to match O2 supply with demand
it results in hypoxia-induced vasodilator production
Stable angina pectoris treatments
exercise
invasive surgeries
Pharmacological: Organic nitrates, Ca2+, Ranolazine
Organic nitrates how does it get into the cell; and uses; and how does it work
converted to nitric oxide, which can then go into the smooth muscle… which then it can activate GTP, activates cGMP and when activates PKG
In SMOOTH MUSCLE, PKG phosphorylates Ca channels, which reduces Ca entry… which reduces contraction
USE: vascular smooth muscle but not a lot of effects in the heart
Main effect: opens up the veins and the volume of the venous system; feedback is slower to the heart (decrease cardiac O2 demand through action on veins) it does also open the coronary heart arteries but it’s not the main effect
Nitroglycerin
Organic nitrate drug
There is a short and long-lasting form; under tongue, transdermal is long (/ointment)
Primary use: treatment of acute angina or peaks of pain in stable angina
pretty fast onset of action
Tolerance can occur; but they change time dosing
Longest form: a chemical derivative of nitro glycerin
-long onset of time; tolerance still a problem
Side effects: headache
anything that drops BP
you can have reflex tachycardia
Nitrate interactions with sidenafil (viagra)
Causes a build up of cAMP
can lead to extreme low BP and can cause heart attack because of decreased perfusion of heart
summary points of nitrovasodilators
treatment of angina
They do not cause dilation of coronary arteries,
Major action is decreasing myocardial oxygen demand through venodilation
Ca2+ inhibitors
PKA increases increases contractility (activation of Ca2+)
PKG decreases it (Inhibits Ca2+)
contrast to smooth muscle where they both decrease contractility (both inhibit)
they are good targets
what do you want to do to help the heart
decrease blood flow and decrease demand
Ca2+ channel blockers
dilate coronary arteries, and peripheral dilation to decrease BP
Ca2+ in the heart: Spike in sodium, and then a huge Ca2+ spike
so blocking decreases ability of heart to generate force
They can also slow the heart
Uses: treat stable angina, heart failure
Nifedipine
treatment of angina
Ca2+ channel inhibitor
vascular version; impacts without heart rhythm disruption
less impact on cardiac calcium channels
diltiazem/verapamil
treatment of angina
Ca2+ channel inhibitor
similar potency on arterial and cardiac muscle
Uses: angina, hypertension, arrhythmias
Adverse effects Ca2+ channels
headache, dizzy, hypotension, peripheral edema, heart failure
Beta-blockers impact with ca2+ in treating angina
Activation of b1 receptors increases PKA which increases the strength of contraction; beta-blockers block this impact which then DECREASES HR and cardiac contractility to decrease oxygen demand
Ranolazine
treatment of angina
inhibitor of cardiac sodium and potassium channels
opposite of digoxin
more Na+ into the cell and therefore more Ca2+ out of the cell.
The lower amounts of Ca2+ cause a decrease in cardiac muscle contractility and O2 demand
No effect on HR or BP
DOES cross BBB
Sife effects: nausea and constipation.. but not a lot
What are the two major types of blood flow
systemic and pulmonary
Systemic circulation
Left ventricle of the heart, Every time the heart contracts, pressure shoots up, when it relaxes it almost goes to 0.
Fluctuation is limited to 120 and 80 in the arteries
After the capillaries, pressure is less and less
How to calculate BP
cardiac output X vascular resistance
Increasing either increases BP
What can impact BP Cardiac output factors
Preload (pressure that fills the heart)
Afterload (Pressure the heart needs to work against)
Neuroendocrine control of cardiac function (stress (HR increase), physical activity)
What can impact BP Peripheral vascular resistance
Dilation/constriction of resistance arterioles (Neuroendocrine control, hormones, local regulation (running hard- dilates for O2))
Vascular diseases (arteriosclerosis)
the relationship of blood volume and blood pressure
Blood volume is regulated by kidneys by adjusting urine production
-Increases blood volume=increases preload, increases cardiac output… then peripheral blood vessels contrast to maintain normal blood flow, which then you get higher BP.
If kidneys are unable to restore this then there is hypertension; damaging heart and kindey
Cycle of: vicious cycle, hypertension, peripheral edema, pulmonary edema
Normal BP and what an increase means
normal: less than120 and less than 80
any tiny changes are impactful
Hypertension factors
Primary hypertension: genetic, age, Risk factors: stress, smoking, obesity, physical inactivity
secondary: renal, endocrine, hormone treatment
others: Pregnancy induced pre-eclampsia, coarctation of the aorta
Complications of hypertension in: cardiac
Left ventricle hypertrophy
Heart failure
Ischemic heart disease
Arrhythmias
Complications of hypertension in: vasular
Arteriosclerosis
Complications of hypertension in: cerebral
stroke
transient ischemic attack
Encephalopathy
Complications of hypertension in: Renal and eye
Renal: Nephropathy
Eye: Retinopathy
Consequences of Heart failure
kidney failure, Na+ water retention, excess amount of extracellular fluid, increased venous pressure, peripheral and pulmonary edema
Leg edema: fluid buildup in periphery
When does stroke mortality risk double
for every 20/10 hg increase above 115/75
Diuretics
drugs that increase urine output by kidneys they help get rid of extra Na+ and water which helps reduce: extracellular fluid volume, blood volume, edema, and BP
BLOCKS NA+
categorized by where they act
What is nephron
it is the functional unit of the kidney, starts with the glomerulus and goes to the collecting tubule which has a cortical and medullary
What are the steps of exretion
Filtration: movement of water from glomerulus to tubules
reabsorption: transport from urine to blood: from the outside world to the body
secretion: Transport of blood to urine, from body to outside world
Proximal convoluted tubule; carbonic anhydrase inhibitor: acetazolamide
By Lumen, there is a reabsorption of NA+ and bicarbonate.
Mild diuretic, used for GLAUCOMA, not hypertension
increases urinary excretion of bicarbonate
Side effects: Acidosis, K+ depletion, avoid in ppl with hepatic cirrhosis risk of hepatic encephalopathy
Loop diuretics; Furosemide
actions: inhibits reabsorption of Na+, K+, Mg2+, Ca2+ in the thick ascending limb
oral or parenteral, FAST
MOST POTENT DIURETIC
drug of choice for acute pulmonary edema due to heart failure
SIDE EFFECTS:
hypotension, hypovolemic shock
Distal convoluted tubule- Thiazides
Na+/Cl- transporter inhibitor
Chlorothiazide is blcoed
Actions: orally active
MOST COMMONLY PRESCRIBED
Drug of choice for HYPERTENSION + Heart failure
reduces Ca2+ excretion
SIDE EFFECTS: thirst, increased blood cholesterol and glucose levels
Collecting duct- potassium-sparing diuretcs
The antagonist: Spironolactone– it reduces Na+ reabsorption but INHIBITS the loss of K+
Action:
Oral
inhibits reabsorption of Na+ and secretion of K+
mild effect but if used in combination with others it can prevent K+ loss
Decreases mortality of heart failure
SIDE EFFECTS:
drug interaction
tummy hurt
Mannitol- osmotic diuretics
Action:
intravenous
Used to reduce intracranial pressure, and remove of renal toxins.
Osmotically active.. filtered through glomerulus, but not reabsorbed
Mannitol promotes water diuresis
Side effects: dehydration, hypoantremia
What does a blockage of the angiotensin system do
It has a similar effect to potassium-sparing diuretics; increases Na+ reabsorption…
Spironolactone is an aldosterone antagonist
Angiotensin-converting enzyme (ACE) Captopril
Actions: effective antihypertensive agent
-increases K+ reabsorption, decreases aldosterone, decreases hypokalemia in patients on diuretics
-decreases proteinuria and slows the progression of renal insufficiency of renal insuff especially in patients with diabetes
Side effects: Dry cough, hyperkalemia, renal failure, skin reactions, contraindicated during pregnancy, angioedema
good bioavailability, eliminated by kidneys 2 hours,
Renin- angiotensin system (angiotensin 2 receptor blockers ARBs) LOSARTAN
Actions: get rid of cough
selective to actions of Ang2, no effect on bradykinin
No effect on levels
more effective blockage of Ang2–AT1R
Side effects:
Hyperkalemia
renal failure
contraindicated during pregnancy
angiodemia
Indications and complications of ACE inhibitors and ARBs
Indications: hypertension, heart failure, left ventricle hypertrophy, acute MI, renal disease, diabetes
Contraindications: Hyperkalemia, pregnancy, Bilateral renal artery stenosis
Sprint trial
Examine the effect of intensive high blood pressure treatment, looking at intensive treatment and standard treatment
Intensive care has a 25% lower cardiovascular disease risk
Serious adverse events: way higher chance of hypotension and syncope when there is intensive care
Management of high blood pressure- lifestyle
Physical activity, healthy diet, and weight reduction, less alcohol reduction can impact and make significant changes in bp.
Hemostasis
Control of blood loss from a damaged vessel
It is initiated by vasospasm
rapid platelet adhesion to collagen and platelet aggregation
Reinforcement of platelet plug by fibrin
What is secondary hemostasis
Clot formation to stabilize the plug
What is primary hemostasis
damaged endothelial cells
transient vasoconstriction induced by endothelium secretion from endothelium
Exposed subendothelial components con Willebrand factor and collagen
Formation of the platelet plug
Thrombosis what is it and what are the effects
Happens at site
Blockage of a blood vessel by formation of a blood clot inside the lumen
It depends on where thrombosis is..
effects:
Arterial (ischemia, infarction)
Venous (congestion, edema, ischemia, infarction)
What is an embolism
Blockage of a blood vessel by solid, liquid, or gas at site..
when a clots breaks off and causes a problem
how the blockage leads to a stroke
clot enters blood stream and travels towards brain
Blocks blood flow to part of the brain… starved of oxygen, it leads to a stroke
It can also lead to pulmonary embolism
Anticlotting drugs work on
heart failure
pulmonary embolism
myocardial infarction
ischemic stroke
Anti-clotting drug classes
Anti-platelet agents
Anticoagulants
Fibrinolytic agents
antiplatelet Aspirin… mechanism of action
inhibits COX-1 (cox-1 is important for synthesis of platelet thromboxane)
Irreversible inhibitor
inhibits platelet aggregation
Adverse effect: Bleeding
antiplatelet drug: Clopidogrel
Inhibtsi ADP binding which leads to inhibition of platelet actatioin
Oral
Prodrug, converted to active metabolite by CYP450
Adverse effect: bleeeding
Coagulation cascade
Involves a lot of blood clotting; these are all proteolytic enzymes.
They are typically inactivated but can get activated, which can amplify the reaction to activate prothrombin, which then activates thrombin.
Anticoagulants: Heparins
has negative charge
Parenteral administration: cant be oral
Adverse effect: Bleeding
have to monitor aPTT
Antidote: Protamine sulfate (positive charge)
Mech of action: Binds and activates antithrombin and increases the activity by 1000x
Uses: there is a low-molecular-weight heparin can be given outside of hospital
Oral Anticoagulants: Warfarin
Action: inhibits of Vitamin K
It inhibits the re-activation of Vitamin K
ORAL
Binds to albumin (99%), and clearance is slow, and onset of action is delayed
narrow therapeutic index
Adverse effect: bleeding, can cross the placenta
Reversal is done by: stop taking, vitamin K, fresh frozen plasma, prothrombin complex concentrate
Drug interactions:
Asprin and heparin enhance the effects.
CYP450 activators reduce the effects
What is cholesterol and what are its phases of absorption
Waxy, sterol lipid molecule
How it is absorbed: enzymes are in the mouth, stomach, and intestines
How does micelles impact cholesterol
Critical for how cholesterol is absorbed.
What are lipoproteins and what do they do
They are balls that carry and store cholesterol around..
It is a structure that is made up of lipids, cholesterol, and apolipoproteins (which is just a protein)
LDL (low density) is a major store of cholesterol in the body
HDL: high density
What are some facts about the population for cholesterol
Millions of deaths (4.4) every year
37% / 78 million adults have “bad” cholesterol
7% of adolescents have high cholesterol
people with high = 2x the desk of heart disease
what is artherocslerosis
It is BAD
can lead to the complete closure of arteries
unstable; can rupture and cause thromboembolic event
Drugs that treat hyperlipidemia… what is their goal/ what are the two types
Reduce LDL blood levels
1- lower LDL… by inhibiting de novo production in liver
2- lower LDL and triglycerides
Drugs that inhibit de novo cholesterol synthesis
drugs that end in statin
main: Atorvastatin, rosuvastin, simvastatin
how do satin drugs work
HMG-coA reductase is blocked.
Lower de novo synthesis
decreases synthesis of LDL receptor
no effect on HDL
they also have other benefits: reduced inflammation, plaque stabilization
Adverse effects: Stomach disturbances, rash, headache, muscle toxicity, acute renal failure, cognitive difficulties, pregnancy issues
guidelines for cholesterol
GOOD:
less than 40mg is low and a major risk factor
60 mg is lowers risk
LDL: raises heart disease risk
Borderline or high (130-160…165 or higher)
Rhabdomyolysis… what is it
Breakdown of skeletal muscle tissue
What is cholesterol like in the brain
accounts for 1/4th of total cholesterol
brain must produce its own cholesterol… like the liver it uses HMG-coA
Statins can cross BBB and can have cognitive effects.. (simvastatin, atorvastatin)
Less cognitive effects: rosuvastatin
