pmcol 200 final

What is atherosclerosis

A disease where plaque is formed in the arteries (reduced blood flow to organs) + plaque dislodgement and flow to other locations

Why atherosclerosis only in arteries and not veins

Because they experience higher pressure

Clinical manifestations of atherosclerosis (5)

1. Coronary artery disease (heart attacks)

2. Carotid artery disease (stoke) brain

1. Peripheral artery disease (intermittent claudication)

2. Renal artery stenosis (chronic kidney disease)

3. Mesenteric artery ischemia (abdominal pain)

What are the risk factors of atherosclerosis

Metabolic: modifiable + non-modifiable

Lifestyle + environmental: modifiable

What causes plaque development

1. Lipids (LDL-C MAJORRR, cholesterol, triglycerides)

2. Blood clots after plaque formation

3. Inflammation

What is the main approach to reducing atheroscelrotic cardiovascular disease

Lowering LDL-C

How does atherosclerosis start

Damage to the endothelium in the arteries (lipids can pass through intima) → inflammation + macrophage activation of LDL → turn into foam cells → accumulation > plaque stabilization by smooth muscle —> clot dislodge = further damage = blood clot

Embolus

Made of the clot that is formed in response to plaque

Cholesterol + triglycerides are ______ in the blood and need ____ to carry them

Insoluble; lipoprotein transporters

What are the types of lipoproteins transporters (4)

1. Chylomicrons

2. Very low-density lipoproteins

3. Low-density lipoproteins

4. High-density lipoproteins.

proteins makes things denser

Exogenous pathway of lipid metabolism

1. dietary triglycerides broken down → (glycerol + FA) by (bile acids + pancreatic lipase)

2. enters enterocyte by simple diffusion assembled into chylomicron

3. chylomicron → lymphatic → jugular vein

any steps not work = atherosclerosis

what treatments of other 3 disease that can reduce the risk of atheroscleorsis

hypertension

chronic kidney disease

diabetes

systolic blood pressure

pressure in arteries during heart contraction

diastolic bp

pressure in arteries during heart relaxation

formula for blood pressure

bp = cardiac output (CO) * total peripheral resistance

cardiac output

volume of blood pumped out by the heart in one minute

CO= Stroke volume (mL/ beat) * heart rate (beats/min)

total peripheral distance

total resistance in blood in systemic circulation in peripherals

what are the short term regulation of BP

baroreceptors in carotid artery and aorta by regulating SNS and PSNS

baroreceptors when bp low

activate sympathetic, inhibit PSNS

baroreceptors on cardiac output of SNS

baroreceptors on total peripheral distance of SNS

baroreceptors when BP is high

activate PSNS inhibit SNS

decrease norepinephrine release to decrease force of contraction on beta1 receptors on SA node + cardiomyocytees

decrease NR on alpha1 receptors on smooth muscle to decrease vasoconstriction

short term regulation of low blood pressure RAS

BP low → intrarenal receptors in renal artery sense low pressure OR low NaCl filtrate in macula densa —> release renin → activate RAS

long-term regulation of blood pressure

pressure natruiresis (Na secretion in response to pressure

long term high blood pressure

renal artery pressure increase + Na reabsorption decrease (excreted in urine) → draws water out → low BP due to low water in blood

long term low blood pressure pressure natruiresis

renal pressure decreases, Na reabsorption increases (less excretion in urine —> draw water in → high BP

what are the lifestyle changes to reduce risk of atherosclerosis

healthy diet, exercise, limit alcohol/ no smoking

only for those who are at risk, those who have it need meds

orthostatic hypotension

reudced bp when standing because gravity decrease amount of venous return to heart

why do we drugs to treat hypertension if we have our own defense mechanisms

1. baroreceptors reset to higher BP (they would only bring it back to the HTN “normal” BP)

2. RAAS is overactivated due to artery thickness and stiffness (due to low pressure in kidney renin thinks person has low BP)

3. pressure natruiresis (kidney) shifts right

thiazides what and what

diuretic hypertension drugs

includes hydrocholorthiazide, chlorthalidone, indapamide

what is the mechanisms of thiazide

blocks Na/Cl TP in distal tubule → dec. Na+ reabsorption → dec. blood volume → decrease cardiac output /BP

what are the side effects of thiazides

hyponatremia and hypokalemia

amiloride

potassium sparing duretic that bloacks ENaC in distal tubule + collecting ducts → decrease cardiac output → decrease BP

K+ wont leave blood because lumen is not negative from Na being reabsorbed

furosemide

loop diuretic that blocks NKCC in thick ascending limb

ONLY IN PATIENTS WITH HEART FAILURE OR CHRONIC KIDNEY DISEASE

ACE inhibitors

a group of RAAS inhibitors that include (captopril, enalapril, lisinopril, ramipril)

what is the mechanims of RAAS inhibitors

inhibit angiotensin II and aldosterone production → decrease BP

increase bradykinin (vasodilator) → decrease BP

why do we need to inhibit RAAS pathway

because it secretes aldosterone and is overactive in hypertensive patients

what are the adverse effects of RAAS inhibitors

dry cough and angiodema from bradykinin effects (sensitize neurons)

ARBs

angiotensin receptor blockers that inhibit RAAS (includes: losartan, valsartan, telmisartan)

what is the mechanism or ARBs

they block the AT1 receptor of Ang II

indication of ARBs

first line class for hypertension meds when ACE inhibitors are not tolerated

what are the adverse effects of ARBs

hyperkalemia (aldoesterone effects, inhibit sodium will increase potassium in blood)+ acute kidney injurt

what is the indication of ACE inhibitors

first line class for HTM (great benefit if pateint has heart failure or chronic kidney disease)

ACE inhibitors and ARBs (should/should not)be combined together

SHOULD NEVER it will completely abolish RAAS (mega hyperkalemia), kidney problems

aldoesterone antagonists

RAAS inhibitors that include spironolactone and elprenolone block aldoesteron receptor

mechanissm of aldoesterone antagonists

block aldoesterone receptor to inhibit synthesis of ENaC chanenels→ dec. Na+ reabs

indication of aldosterone antagonists

best add on for resistant HTN (especially good for patients with primary aldosteronism)

adverse effects of spironolactone

gynecomastia (similar to sex hormone)

dihydropyridines

calcium channel blockers that include (nifedipine, amlodipine, felodipine)

mechanism of dihydropyridines

block L-type calcium channels in smooth muscle of arteries → increase vasodilation → decrease BP

what is the indication for DHP + adverse effect

first line class for HTN

edema (increased pressure in capillaries only not venules → hydrostatic pressure difference)

non-dihydropyridines (nonDHP)

calcium channel blockers that include diltiazem and verapamil

mechanisms of calcium channle blockers

1. block L type Ca channels in SA node in heart → decrease heart rate

2. block L type Ca channels in cardiomyocytes in heart → decrease contraction

indication + adverse effects of non DHP

HTN pateints with arrythmia

adverse: bradycardia

betablockers

metoprolol, esmolol, bisoprolol

mechanisms of beta blockers

1. block beta 1 receptors in SA node in heart → decrease heart rate

2. block beta 1 receptors in cardiomyocytes in heart → decrease heart rate

Gs coupled

indication of betablockers

not first line for HTN pateints but effective in HTN pateints with heart failure (HFrEF)

adverse effects of betablockers

bradycardia, heart block

what should beta blockers not be combined with

nonDHP both are reducing heart rate and contraction SEVERE BRADYCARDIA (heart shut down)

alpha 1 receptors

prazosin, terazosin, doxazosin

mechanism of alpha 1 blockers

1. block alpha 1 receptors in smooth muscle arteries and venules → vasodilate → decrease cardiact out put → decrease blood pressure

both decrease cardiac out put

indication of alpha 1 blockers

not first line for HTN pateints only an add on therapy due to less faviorable ourcomes (HTN has benign prostatic hyperplasia + urination problem)

adverse effects of alpha 1

orthostatic hypotension

it vasodilates arteries and veins (decreasing the blood flow back to heart)

alpha 2 agonists

clonidine + methyldopa

mechanism of alpha 2 agonists

inihibit sympathetic outflow (ddecrease norepinephrine) → decreaes BPi

indication of alpha 2 agonists

not first line, only in resistant HTN

pregnancy (preeclampsia)- methyldopa (good for pregnancy)

hydralazine + mioxidil

direct vasodilators

what are the mechanisms of hydralazine

increase NO → increase vasodilation → decrease BP

what is the mechansism of minoxidil

open K channels → hyperpolarization of smooth muscle → vasodilation → decrease BP

indication of direct vasodilators

not first line, only in resistant HTN (last resort)

pregnancy preeclampsia- hydralazine

adverse effects of direct vasodilators

vasodilation of carotid arteries → baroreceptor activation → reflex tachycardia (inc. sympathetic innervation to heart)

alpha 1 vs alpha 2 receptors

alpha 1 = Gq vs alpha 2 =Gi

what are the first line drugs of HTN`

thiazide, ACE inhib, ARBs, DHPs

either alone or in combo (never ACE with ARB)

gram negative vs gram pos cell memb

what is the peptidoglycan structure made of

glycan or N-acetylglucosamine and N-acetylmuramic acid (GlcNAc and MurNAc)

glycosyltransferase

(GT) an enzyme that polymerizes indivudal glycan strands together

transpeptidase

TP cross linking strads (main target of antibioticss)

what are the 4 types of bacterial illnesses

food borne illnesses

sexually transmitted diseases

skin infections

highly infectious disease

what bacteria was cephalosporins derived from

the fungus Acremonium

how do beta lactams work

interrupt cell wall synthesis by inhibitng DD-transpeptidase (penicillin binding protein) enzyme that is responsible for cross linking cell wall → holes → bactericidal

effectiveness of different beta lactams on gram bacteri

only gram-positive at first but now has increased activity to negative

vancomycin

inhibits peptidoglycan cross inking produced by Actinobacteria

what do bacteria use to synthesize nucleic acids

folic acids

PABA

para-aminobenzoic acid is a nutrient obtained from the environment that is a folate precursor

sulfonamides and trimethoprim

resemble PABA and dihydrofolic acid and interfere with PABA pathways

blocking only = bacteriostatic

transpeptidation

tRNA t6 transfers aa to growing aa chain on 70s ribosome

chloramphenicol and macrolides

bind to 50s subunit and block transpeptidation

tetracyclines

bind 30s ribosomal subunit and prevent tRNA binding

aminoglycosides

bind 30s ribosomal subunit that has 3 methods of function

1. block initiation

2. cause misreading of mRNA code

3. block translocation

stevens-johnson syndrome and toxic epidermal necrolysis

rare conditions that skin becomes detached from underlying tissues and sloughs off body

what are some methods of antibiotic resistance 4

1. drug inactivation or modificaiton

2. alteration of binding site

3. alteration of metabolic pathways

4. reduced drug accumulation (efflux) (elimination + distribution)

what are antibiotics

soluble compounds that are produced and released by microorgnanisms and that inhibit the growth or kill other microorganisms

what are viruses

obligate itracellular parasites

virions

viruses when they are not inside an infected cell, an independent particle

bacteriophage

a virus that only infects bacteria

viral range

a group of cell types or species that a virus can infect

most animal viruses ____ cros phyla

do not (some infect only closely related species)

pathogenicity

ability of viruses to causes disease

virulence

degree of pathogenicity

latency

ability of virus to remain formant in organisms