MCMP 408 Final

increased serum succinyl choline leading to respiratory apnea

peripheral neuropathy

auto immune disease

MAO-B; DAT; parkinsons like sx; MAO-B inhibitor or DAT inhibitor

2E1, a reactive intermediate which can bind cell components leading to hepatotoxicity

2E1

N-Acetylcysteine

CYP 2C9

Barbiturates, carbamazepine, rifampin, griseofulvan

Azo antifungals, Metronidazole, sulfapyrazone

2C19

1A1,2

metabolism of procarcinogens to carcinogens

3A4; cardiotoxicity

Erythromycin, ketoconazole

• blocks VMAT
• diarrhea, cramps, acid secretion, sedation, nightmares, depression

• alpha 2 agonist at slpha 2 and imidazoline receptors
• transient increase in BP
• dry mouth, sedation, depression, withdrawal

• alpha 2 agonist, PRODRUG
• sedation, mental impairment, lactation, positive coombs test

• alpha 2 agonist at imidazole and alpha 2 receptor
• Dry mouth, sedation, depression, withdrawal

• alpha 1 antagonist
• first dose effect (orthostatic hypotension)--> take at night, Na/H20 retention, relfex tachycardia

• beta blocker
• CI in diabetes, asthma, COPD, class 4 CHF
• ^ VLDL, decrease HDL, inhibit lypolysis, glycogenolysis, glucose release, bronchile resistance, sedation

• beta 1 blocker
• less SE

• beta block, alpha 1 block
• no reflex tachycardia

• alpha 1 block, beta block
• no reflex tachycardia

Proximal conveluted Tubule; carbonic anhydrase

• Acetazolamide
• K wasting, hyperchloremic metabolic acidosis, paresthesia, drowsiness, renal stones

• acute mountain sickness, metabolic alkalosis, glaucoma, urine alkalinization
• Hepatic Cirrosis

lose sodium/potassium and bicarb

thick ascending loop of henle; Na/K/2Cl transport

• Furosemide, Bumetanide, Ethacrinic Acid
• K wasting, dehydration, hypokalemic metabolic alkalosis, ototoxicity, hyperuricemia, hypomagnesemia

• edema, hypercalcemia, hyperkalemia, renal fail, anion OD
• Lose NA, K, Cl, Mg, Ca

Na/Cl; distal conveluted tubule

K wasting, hypokalemic metabolic alkalosis, hyperuricemia, impaired carb tolerance, hyperlipidemia, hyponatremia

HTN, CHF, hypercalciuria, diabetes insipidus

• Lose Na/Cl
• Keep Ca

collecting tubule; Na channel

• kidney stones, hypokalemia, hyperchloric metabolic acidosis
• K supplements, ACEi

maintains K

Collecting tubule; aldosterone

hyperkalemia, hyperchloremic metabolic acidosis, gynecomastia, impotence, BPH

HTN, CHF, mineralcorticoid excess, aldosteroneism

• Lose Na
• Keep K

Renin

ACE

aminopeptidase

little to none

release of aldosterone and vasoconstriction

increase in peripheral resistance due to direct vasoconstriction, enhanced NE action, increase sympathetic discharge, release of NE from adrenals

Na reabsorption, synthesis/release of aldosterone, altered hemodynamics

increased preload/afterload, increased cascular wall tension, increased expression of protooncogenes, growth factors and ECM proteins

same release of aldosterone but less vasoconstriction

yes by a work around pathway

• Macula densa
• Blood pressure of pre-glomerular blood vessels
• sympathetic activation of beta receptors

binds active site of ACE and inhibit it

htn, lv systolic dysfunction, MI, diabetic neuropathy

hypotension, dry cough, hyperkalemia, acute renal failure, skin rash

antacids (decreased ba), NSAIDs (reduced effectiveness), k supplements, digoxin (^levels)

2nd/3rd trimester, neutropenia in renal insufficient patients

altered taste, rash

prodrug that requires cleavage to enalaprilat and is eliminated hepatically

Lysine derivative of enaloprilat NOT prodrug

Prodrug that rquires hepatic esterase activation and has extensive hepatic metabolism

antagonize ang 1-3

HTN, CHF, progressive renal impairment,

hypotension, hyperkalemia, teratogen

Losartan, Valsartan, Irbesartan, Candesartan, Temisartan, Eprosartan

tekturna, prevents formation of ANG 1-3

pregnancy

• voltage gated Ca channels
• receptor activated Ca channels
• pharmaco mechanical coupling

natural vasoconstrictors

antagonize endothelin causing vasodilation to treat pulmonary arterial hypertension

ca channel activation, release of intracellular ca, ca binds calmodulin, MLCK phorphorylates MLC, myosin can interact with actin, contraction

HTN, control blood flow (procedures), shock, anesthesia, chronic orthostatic hypotension, hemostasis, decongestants

phenylephrine, pseudophedrine, ephedrine, naphazoline, tetrahyrdocoline, oxymetazoline

severe debilitating ha

stress, decreased levels of estrogen, increased PGE

aura, photophobia, hyperacusis, polyuria, diarrhea, mood appetite disturbances

initial vasoconstriction then vasodilation followed by edema and inflammation

5-HT 1D agonist causing vasoconstriction and inhibiting release of inflammatory neuropeptides

• high incidence of reoccurence
• MAO-A inhibitor

CI in Wolff parkinson white syndrome

• Slow onset, longer duration
• CI in severe hepatic/renal impairment or peripheral vascular disease

CI in patients with PKU

warmth/tingling, vertigo, malaise, fatigue, feelings of heaviness, sense of pressure in chest

5-HT 2A agonists

diarrhea, nausea, vomiting, prolonges vasospasm, uterine contractions

beta blockers and macrolides increase ergot levels and may result in ischemia

ergonovine, methylergonovine, methylsergide

ergotamine, dihydroergotamine

ergots, beta blockers, CCB, antidepressents, antiseizures, melatonin, ACEi, NSAIDs

in

outside

outside, wants to come in!

Decreased blood pressure and provides relief of angina pectoris as well as antiarrhthmic effects

isradipine, felodipine, amlodipine, nifedipine, nislopidine, nicardipine, nimodipine

binds to closed channels to prevent opening

vasoselective

reduce O2 demand in heart . effective to tx angina

binds inside pore to prevent ion passage--> frequency dependent block

cardioselective

slows conduction through SA/AV nodes to decrease HR and force of contractility

some tonic block, some frequency dependent block

cardio and vaso

slows conduction but less than PAA

selective for cerebral arteries used to treat brain bleeds

slow onset of action and long DOA, no reflex tachycardia

Diltiazem

Verapamil

reflex tachycardia, facial flushing, ankle edema

ankle edema

ankle edema, constipation

predictable. Gets worse with exercise, exertion

sudden transient constriction typically at night

new or sudden worsening of angina at rest

• dilate coronary arteries and increase perfusion to the heart
• decrease oxygen demand of the heart
• decrease afterload and preload

increase NO which activates guanylate cyclase leading to relaxation dilating veins, minor artery dilation

decreased preload

sublingial for acute attacks

oral/transderm for prophylaxis

oral/transderm for prophylaxis

occurs due to inhibition of aldehyde dehydrogenase which activates NO to dilate blood vessels

hypotension, flushing, HA

reflex tachycardia, decreased preload leads to decreased blood pressure causing the baroreceptors to increase HR

decrease influx of Ca which causes contraction causing dilation of arteries (decreased afterload)

reflex tachycardia, decreased afterload leads to decreased blood pressure causing the baroreceptor to increase HR

Block epi stimulation of myocardium, decreasing the oxygen demand (decrease HR and force)

can increase preload due to increase pr intercal and filling time which increases LV-EDV

verapamil--> too much depression of the heart

Blocks Na channels responsible for Na overload (which leads to ca overload) to PREVENT angina

PDE3 breaks down cAMP which causes contraction. PDE3 inhibitors will allow cAMP to stick around causing contraction of myocardium. In vessels it causes vasodilation by decreased MLCK

PDE5 breaks down cGMP which causes relaxation. inhibitors allow sustained relaxation of smooth muscle allowing the CC to stay full of blood

causes dilation

synthetic human type b naturetic peptide

endogenous peptide vasoconstrictor

open k chennels so potassium leaves resulting in hyperpolarization

k agonists, hydralazine

PDE3 for CHF

longest onset, longest duration, more selective

Shortest onset, shortest duration, most selective

Medium onset, medium duration, least selective

blocks ETa and ETb for primary arterial hypertension

blocks ETa receptor for primary arterial hypertension

prodrug k agonist for severe htn

K agonist for acute htn

interferes with release of ca from er, can induce lupus

binds to the A1 receptor leading to increased camp and increase relaxation, Minimal clinical use as a vasodilator

pumps Ca out of cells

pumps Ca into SR

major route of Ca clearance

more sodium is in the cell so the NCX pump works less so Ca will remain in cell. SERCA will pump more into the SR.

Digoxin

delerium, fatigue, malaise, confusion, anorexia, N/V, ab pain, PROARRHTHMIC EVENTS

digibind--> goes straight to untreated HF

neomycin, antacids, bran

Erythromycin, omeprazole, tetracycline

Potassium and dig compete for the same receptor. less potassium means glycosides are more able to bind --> TOX

MI, HTN, genetic predisposition

inability of heart to pump out enough blood to support the body's O2 demand

heart cant fill with enough blood (cant expand adequatley, stiff walls)

heart cant contract well enough

tachycardia, cardiomeglia, arrythmia, fatigue (heart tries to pump harder and faster), shortness of breath, pulmonary edema Cyanosis, orthopnea (decreased lung function due to pulmonary edema due to preload being large and leaking into the pulmonary interstitum)

systemic vascular resistance causes increase contraction to compensate. heart needs more oxygen. doesnt get it. preload increases causing back up in lungs. blood is oxygenated less. gets worse and worse.

decrease oxygen demand and increase oxygen supply

diuretics (furosemide) , venodilators (nitrates), angiotensin inhibiotrs (ACEi, ARBs)

decrease MAP

organic nitrates, hydralazine, ACEi, ARBs NOT CCB

glycosides, pde inhibitors, beta agonists (dobutamine, dopamine)

Milirone and amirone, beta agonists

diuretics, vasodilators

inotropes and vasodilators

FIRTS LINE reduce preload, reduce afterload, prevent/reverse remodeling

desensitize baroreceptors, decrease remodeling

aldosterone antagonists, beta blockers, ACEi

ACEi, beta blockers, aldosterone antagonists

normal origin of AP

depolarization of atria

depolarization of ventricles

repolarization of ventricles

• obstacle to conduction
• unidirectional block
• slow enough conduction time

depolarization

Na channels

Ca channels

K channels

ca

Na channel blockers

beta blockers

potassium channel blockers

CCB

phase 4 (HCN/GIRK), 0(Ca, slow), 3(K)

esmolol, acebutolol, propranolol

• na and k mixed
• procanamide, quinidine, disopyramide
• lengthen QT, slow 0, prolonged AP, increase refractoryness

• Na
• lidocaine, tocainide, mexilentine
• NO ekg change
• blocks bad

• na block
• fleconide propfenone
• marked slow 0

• K block
• amiodrone, bretylium, sotalol, bronedorne, dofetilide
• prolonged AP increased QT inverval
• Can cause torsade de pointes

• CCB
• verapamil and diltiazem
• slow 0, lengthen APD

• beta blockers
• esmolol acebutolol, propranlol
• incresed PR interval