Lecture Part 2 - 9.13.

23
Wednesday, September 13, 2023 15:33

Cardiovascular
• Good place to start to learn about PMH = med list
• Memorize chart on 3rd slide!!
○ Shows what happens when alpha and beta receptors are stimulated
○ When stimulated --> stress response
• Alpha 1
○ Vasoconstriction of BV of
§ Skin
§ GIT
§ Kidney
§ Brain
○ Contract of smooth muscles of
§ Ureter
§ Vas deferens
§ Urethral sphincter
§ Uterus
§ Ciliary body
○ Glucose metabolism
§ Glucogenesis
§ Glucolysis
• Alpha 2
○ Glucose metab
§ Inhibits insulin release
§ Stimulates glucagon release
○ Contraction of sphincter
○ Inhibits release of NE
• Beta 1
○ Increase in
§ HR
§ Impulse conduction
§ Contraction
§ Renin release
§ Hunger
• Beta 2
○ Smooth muscle relaxation of
 § Impulse conduction
§ Contraction
§ Renin release
§ Hunger
• Beta 2
○ Smooth muscle relaxation of
§ Bronchus
§ Bronchioles
§ Detrusor muscles
§ Uterine muscle
○ Contraction of urethral sphincter = not peeing
○ Increase in renin
○ Glucose metabolism
§ Increase in BS and decrease in insulin
○ Lipolysis
○ Thickened salivary gland

Alpha 2 agonist
• Ex: Clonidine, precedex
• Acts centrally in the brain
• Targeting the inhibition of NE
• Specific to A2
• SE
○ HA

Alpha blockers
• -osins
• Ex of alpha blockers used to treat high BP
○ Doxazosin
○ Prazosin
○ Terazosin
• Can be used in GU (flomax = tamsulosin)
○ Used for BPH to relax the ureter, vas deferens, and urethral sphincter to help th

BB
• -lols
• MOA : occupies beta receptor and prevents occupancy of catecholamines --> decreaed
contractility
• Highest concentration of B1 receptors are located in the heart
• Beta 2 are in (more peripheral)
○ Lungs
○ GU
○ Kidneys
○ Eyes
• 2 types
hem urinate

d HR and
• Beta 2 are in (more peripheral)
○ Lungs
○ GU
○ Kidneys
○ Eyes
• 2 types
○ Cardioselective
§ Targets beta 1
§ Ex: atenolol, metoprolol, esmolol
○ Non-cardioselective
§ MC = propranolol
§ Ex: labetalol
□ If trying to decrease BP, considered non-cardioselect
• If treating
○ Tremors = non-cardio
○ HA = non-cardio
○ Anxiety = non-cardio
• Contra
○ Resp conditions that includes bronchospasms
§ Ex: asthma, COPD
○ Av block
○ Cautions
§ DM
□ Causes lower blood sugar
® Response of body will usually be increased HR, anxiety, tremo
◊ If on BB, you wont get any of this--will mask hypoglycem
• ADRs
○ Bradycardia
○ hypoTN
○ CHF
○ Fatigue
§ Large complaint
○ Weakness
○ Dizziness
○ Exercise intolerance bc BB is blunting cardiac activity
§ Ex: going up the stairs will normally increase HR and conduction and cont
it will stay the same
○ Unstable glucose
○ Impotence/libido changes
§ Large complaint (mainly impotence in men)
• Indications
○ HTN
§ 3rd line (ex metoprolol)
○ Angina
ors, etc.
mia

traction but with BB,

 ○ Impotence/libido changes
§ Large complaint (mainly impotence in men)
• Indications
○ HTN
§ 3rd line (ex metoprolol)
○ Angina
○ Post MI prophyl
○ Migraine prophyl
§ Ex propranolol
○ Glaucoma--BB drops (topical)
○ Hyperthyroidism
• Dosing
○ Abrupt withdrawal can be life threatening
§ Body gets used to having it
§ Can shock cardiovascular system---v dangerous!
○ Long-half life to allow for daily dosing
○ Certain drugs are indicated for certain conditions
○ Atenolol dosed once per day

RAAS
• Kidney makes renin + angiotensinogen --> ang 1 + ACE from lungs --> ang 2 --> stimu
• Ang 2 goes to
○ Kidneys - hold on to water and Na
○ Pituitary - secrete ADH --> hold on to water
○ Arteries - vasoconstrict
○ Heart - increase HR

ACEI
• Block ACE (no conversion between ang 1 into ang 2)
• SE
○ Angioedema = worrisome!
○ Dry/hacking cough (also caused by increased bradykinin levels)
§ Pt needs to be taken off ACEI
• Bradykinin and prostaglandins get broken down by ACE
§ Giving ACEI --> bradykinin and prostaglandins levels increase --> they cause inf
□ Bradykinin = triggering factor of angioedema
® AA are more sensitive to bradykinin --> they get more angioedema
□ Prostaglandins can be helpful bc they are protective of the kidneys
® ACEI can help protect kidneys in people with DM
• -prils
• MOA: inhibit action of ACE decreasing ang 2 --> stops vasoconstriction and Na retenti
breakdown of bradykinin
• Usually 6-12 hr half lives
§ Steady state in a few weeks
• Daily or BID/TID dosing
ulates RAAS

flammation

ion, prevents
 • -prils
• MOA: inhibit action of ACE decreasing ang 2 --> stops vasoconstriction and Na retenti
breakdown of bradykinin
• Usually 6-12 hr half lives
§ Steady state in a few weeks
• Daily or BID/TID dosing
• NO for preggos or for anyone in childbearing age
§ Pick CCB (safer)

ARBS = angiotensin receptor blockers

• Found on
○ Arteries
○ Kidneys
○ Pit gland
• Will block all these^^^ receptors
• -sartans
• MOA: blocks ang 2 receptors --> stops vasoconstriction and Na retention
• Usually 6-12 H half lives, steady state in a few weeks
• Daily dosing
• NO change in dose for renal impairment
• Don’t protect kidneys as well BUT they don’t really give the cough/angioedema that A
○ Can happen still but not as much
• Alternative to ACEI
• Will not be on ACEI and ARBS at same time--they are either/or meds

Direct Renin Inhibitor

• Directly works on kidney and inhibits production of renin
• Ex: Alsikren
• 24 hour half life, steady

ACEIs, ARBS, and DRIs

• Contra
○ Bilat renal artery stenosis
□ Need to have REALLY good renal blood flow to take these meds
○ Angioedema
○ Pregnancy
• ADRs
○ Angioedema
□ Usually within 1st mo of use--> dc
□ hypoTN
□ Dry/hacking cough
• Cautions
○ Anything leading to decreased BF to kidneys
○ hyperK
ion, prevents

ACEIs give
 □ Usually within 1st mo of use--> dc
□ hypoTN
□ Dry/hacking cough
• Cautions
○ Anything leading to decreased BF to kidneys
○ hyperK
□ Need to monitor this while on these meds
○ Hepatic impairment
○ Pregnancy category c--don’t give
• Indications
○ HTN
○ HF
○ Post MI
○ Diabetic nephropathy (with ACEI)
• Interactions
○ K supplements, salt subs, K-sparing diuretics --> hyperK
○ Diuretics or other antiHTN --> hypoTN
○ Others that commonly interact
□ NSAIDS
□ Allopurinol
□ Probenecid
□ Fluconazole
□ Indomethacin
• Drug selection
○ consider
□ Long acting vs short acting
□ Cost
□ Generic = good cost!
□ Administration
□ Sprinkled or crushed = only certain meds you can do this with
• Monitoring
○ BP
○ Weight and fluid status
○ Renal function
○ K level
○ Proteinuria = early indication of kidney failure
○ Hepatic function
• Patient edu
○ Administration
○ ADR
○ Childbearing and contraception initiation
○ Lifestyle management

CCBs
 • Monitoring
○ BP
○ Weight and fluid status
○ Renal function
○ K level
○ Proteinuria = early indication of kidney failure
○ Hepatic function
• Patient edu
○ Administration
○ ADR
○ Childbearing and contraception initiation
○ Lifestyle management

CCBs
• Prevents release of calcium stores --> Heart muscle wont respond as quickly
or as strongly
• -pines
○ All type 2's
• Type 1 (non-dhp)
○ V strong cardiac effect
○ Impacts contraction of heart
○ Ex: diltiazem, verapamil
○ SE:
□ Weaker contraction
□ Decreased conduction --> HR slower (a little bit--not as much
compared to BB)
□ LV dysfunction
□ AV block
○ Considered class 4 antiarrythmics
• Type 2 (dhps)
○ More peripheral
○ Strong vasodilation effect
○ Ex: amlodipine, nicardipine, nifedipine
○ SE:
□ (Orthostatic) hypoTN
□ LE edema
□ d/t vasodilation leaks
□ Reflex tachycardia
□ d/t vasodilation --> decreased BP --> increase HR (reflex
tachy)
□ Should not change more than 10 BPMs from baseline
• Some brands have short acting forms and sustained release forms
• MOA = inhibits movement of calcium causing depressed contraction and/or
vasodilation
 □ d/t vasodilation --> decreased BP --> increase HR (reflex
tachy)
□ Should not change more than 10 BPMs from baseline
• Some brands have short acting forms and sustained release forms
• MOA = inhibits movement of calcium causing depressed contraction and/or
vasodilation
• Cautions
○ Hepatic impairment
• ADRs
○ hypoTN
○ HF
○ GI s/s
□ Verapamil causes constipation in all
□ Will also cause pill to come out in poo (fully--will come out
as an orange pill😂)
○ Hyperglycemia
○ Photosensitivity and pigmentation changes
○ Decreased ADRs with sustained release forms and esp amlodipine
• Interactions
○ Other antiHTN meds (BB)
○ Cyp34a inhibitors = grapefruit
○ NSAIDS
○ H2 blockers
○ Azoles
○ Dig
• Contra
○ HF -- gonna make it worse
• Antidote: beta agonist
• Look at indications and selection
○ Can use with BB if they need mult meds to control HR/BP
○ Black people respond really well with CCBs and diuretics
○ Ok for HTN in preggos

Diuretics
• Loop
○ Work on ascending loop of henle
○ Gets rid of
□ K
□ Na
□ Mg
□ Ca
□ Water
○ Ex: furosemide, bumetanide
○ MOA: inhibits Na reabsorption in ascending loop
 □ Na
□ Mg
□ Ca
□ Water
○ Ex: furosemide, bumetanide
○ MOA: inhibits Na reabsorption in ascending loop
○ Short acting
○ Quick diuresis
○ Increased K secretion
○ Lasts 6 hours = la six
○ If on these, usually also getting K supplement
○ Needs to be dosed in the morning so that theyre not getting up to pee
□ If 2 per day, needs to be taken 6 hours apart
• Thiazide
○ Moa: inhibits sodium reabs (increase excretion) in distal renal
tubule --> decreases circulating vol
○ Lasts longer
○ Less brisk diuresis
○ Increased K excretion--need to monitor K level but usually don’t need
K supplement
○ Lasts 12-24 hours--slow process over that
○ Once per day
○ Will sometimes see ACEI + thiazide combo pill
□ Ex: lisinopril/hctz 20/25 mg daily
□ ACEI increase K
□ HCTZ decrease K
□ Balances out so don’t worry as much about K
• Aldosterone antagonist (aka K sparing)
○ Ex: spironolactone (used for PCOS and acne--blocks testosterone in
females --> helps acne, preventing hair growth, helps PCOS s/s),
amiloride, triamterene (most common), eplerenone
○ Moa = blocks mineral corticosteroid receptor that aldosterone binds to
so there is decreased aldosterone effect, inhibits excretion of K
○ WEAK diuretics
□ Often used in combo with thiazides
□ Ex: hctz/triamterene 25/37.5 mg daily
® Hctz = decreasing BP and K
® Triamterene increases K
◊ Only there to help increase K while on HCTZ
med
○ Contra in renal impairment d/t hyperK (even more)
• Osmotic
○ Ex: mannitol
○ Used for
□ Increased ICP or intraocular pressure
 med
○ Contra in renal impairment d/t hyperK (even more)
• Osmotic
○ Ex: mannitol
○ Used for
□ Increased ICP or intraocular pressure
○ Works in loop of henle --> gets rid of water (sodium goes with it)
○ Look at slide
• Diuretics
○ Cautions
□ Gout bc will increase risk d/t dehydration
□ Renal stones bc will increase risk d/t dehydration
□ hypoTN esp in OA
□ Tinnitus or hearing loss
□ Electrolyte imbalances
○ Interactions
□ antiHTN
□ Aldosterone antagonists with ACEI bc of K
□ These both cause hyperK
□ NSAIDS
□ Lithium
□ Warfarin
□ Aminoglycosides, etc,
• Indications
○ HTN
□ Best = thiazide
□ Not loop bc too any SE
○ Edema
□ Best = loop
○ Fluid overload
• Monitoring
○ Clinical indicators
□ BP
□ HR
□ Weight

Cardiac glycosides
• Ex: dig
• Moa = strong and highly selective inhibitors of ATPase (sodium pump)
○ Na and Ca build inside cell --> increased force of contraction,
decreased activation of sympathetic nervous system --> more effective
heart beat
• 10% of people have gut bacteria that inactivates dig requiring much higher
doses
 • Moa = strong and highly selective inhibitors of ATPase (sodium pump)
○ Na and Ca build inside cell --> increased force of contraction,
decreased activation of sympathetic nervous system --> more effective
heart beat
• 10% of people have gut bacteria that inactivates dig requiring much higher
doses
• Old ass drug (1785)
• Increases SV
• ADRs
○ GI s/s
○ CNS adverse response
□ Esp in OA
○ Tox
○ hypoK
• Contra
○ Heart block
• Indications
○ Afib
○ SVT
○ CHF with poor contractility
• Interactions - a lot!
• Monitoring

Antiarrythmic classes
• Class I - Na channel blocker - "some
• Class II - BB - body
• Class III - K channel blocker - please
○ Ex
□ Amio
□ Moa: prolongs potential phase 3 (IV or PO)
□ For
® Vent arrhythmias
® Pulseless vt
® Tachy
® Afib cardioversion
□ Dronedarone
○ Used for
□ Vt
□ Vfib
□ afib
• Class IV - CCB - call (911)"

Vasodilators/nitrates
• Ex: nitroglycerin, isosorbide dinitrate/mononitrate, nipride
• ROA:
 □ afib
• Class IV - CCB - call (911)"

Vasodilators/nitrates
• Ex: nitroglycerin, isosorbide dinitrate/mononitrate, nipride
• ROA:
○ Oral
○ Buccal
○ SL
□ Quick acting nitro
□ Needs to be kept in a brown bottle bc light exposure deactivates
it
○ Transdermal
□ Long acting nitro ointment
• Moa: produce arterial and venous dilation by relaxing vascular smooth
muscle with nitric oxide
• Contra
○ Head trauma or cerebral hemorrhage
□ Already worried swelling and bleeding into brain--if give
nitrates --> gonna get worse
○ Closed-angle glaucoma --> angle in eye to close --> acute glaucoma
crisis
• STRONG vasodilation effect
• ADRs
○ hypoTN and tachycardia
○ Syncope
○ HA
○ Tolerance develops after 18-24 H of exposure
• Indications
○ Acute angina
○ Stable/unstable angina
• Dosing
○ Short acting
○ Long acting is available but has a nitrate-free interval d/t tolerance
(eccentric schedule)
□ Need 24 hour window where you don’t get any nitro
○ Start low and go slow advancing slowly over 1-2 weeks

Hydralazine
• Moa: directly dilates peripheral vessels
• Indicated for HTN
○ Off label
□ HFrEF
□ HTN crisis
Hydralazine
• Moa: directly dilates peripheral vessels
• Indicated for HTN
○ Off label
□ HFrEF
□ HTN crisis
□ Htn emergency (preg-assoc)
• Most important

Inotropes/pressors
• Ang 2, dobut, NE, epi, midodrine, milrinone, vaso
• Moa = varies based on drug; in general, stimulates alpha and beta
receptors --> vasoconstriction, antidiuresis to bring BP up
• Indications
○ Shock
○ Decomp HF
○ Anaphylaxis
○ hypoTN
• Monitoring
○ Electrolytes
○ I/O
○ Renal function
○ Bp
○ Hr

Colloids
• Ex: albumin
• Used for
○ Hypovol
○ Hypoalbumenia
○ ARDS
○ Burns
○ Nephrotic syndrome

Dyslipidemics
• Exogenous path = prevent absorption of cholesterol
• Endogenous path = increase LDL receptors
• HMG-CoA reductase inhibitors
○ Statins---gold standard, 1st line
□ Diff statins have diff strenfths
□ Strongest = rosuvastatin
□ Will have stronger/more SE
□ Weakest = lovastatin
□ Will have weaker/less SE
 ○
□ Diff statins have diff strenfths
□ Strongest = rosuvastatin
□ Will have stronger/more SE
□ Weakest = lovastatin
□ Will have weaker/less SE
○ Moa = block synthesis of cholesterol in liver by inhibiting HMG-CoA
reductase activity; increase ldl receptors; anti-inflam properties
○ decrease in ldls
○ decrease in trigly
○ Increases hdls
○ Significant hepatic metabolism and CYP action
○ Pregnancy category X - do not give
□ Do not give to childbearing age
○ Take at night bc cholesterol is usually made at night
○ SE
□ Rhabdo d/t Myopathy = inflammation of muscles -- rare! But
concerning
□ Muscle aches
□ Can lower dose will help with muscle aches
□ Co-q 10 can help too
○ Labs to check for muscle inflammation
□ CK = creatinine kinase
○ Monitor
□ Liver function

Fibric-acid Derivatives
• Ex: gemfibrozil
• Great for triglys (>800)
○ Normal <150
• Moa = increase lipolysis of trigly via lipoprotein lipase in liver --> 50%
decrase in triglys

Bile acid sequestrants

• Ex: colestipol
• Moa = promote 10x increase in excretion of bild-acid in bowel
• Used for post-GB sx or GI issues
○ For dumping syndrome/diarrhea--these meds help bulk stool
• ADRs
○ Major GI s/s
○ Decrease folate levels
• Only antilipidemic that can be used in liver dz bc ???

Niacin -- no longer used for HLD

• Moa
 ○ Major GI s/s
○ Decrease folate levels
• Only antilipidemic that can be used in liver dz bc ???

Niacin -- no longer used for HLD

• Moa
• Type of b vitamin

Ezetimbe
• Moa = blocks absorption of cholest across intestinal border
• Small decrease in ldl

Omega 3 fish oil

• Prescription ones help decrease cholesterol
• Not v strong OTC to bring down cholest
• Used to treat hypertrigly or adjunct HLD

Antilipidemics
• Interactions
○ Warfarin
○ Increase dig levels
○ Azoles increases reductase inhibitor level x20
○ Increased rhabdo
○ Grapefruit + statins
• Indications for cholesterol -- always statins

PCSK9 inhibitors (monoclonal antibodies)

• Ex: evolocumab
• Moa = inhibits PCSK9--> decreases LDL receptor degradation --> increases
clearance
○ Makes it easier to breakdown LDLs
• Indications--all after they have failed other things
○ HLD adjunct tx
○ Familial HLD
○ CV risk reduction
• Monitoring/cautions = no routine monitoring, angioedema, no interactions
• $500 per injection--need to prove to insurance that this is the only thing that
works for you

PCSK9 small interfering RNA

• Ex: inclisiran
• Moa = small interfering RNA directs breakdown of mRNA for PCSK9
synthesis and subsequent binding to ldl receptors --> decreases ldls
• Indications
○ Hld adjunct tx