Pharmacology

What are the transmitters of the autonomic nervous system?

acetylcholine, norepinephrine, epinephrine

What releases ACh?

all preganglionic neurons and all parasympathetic postganglionic neurons

What releases norepinephrine transmitters?

most sympathetic postganglionic neurons

except Sweat glans (Ach) and renal arteries (dopamine)

What releases epinephrine?

also called adrenaline, comes from adrenal medulla

What are routes for termination of (nor)epinephrine?

all work in parallel

reuptake into presynaptic nerve ending, COMT, MAO and presynaptic α2 receptors

What is the effect of cocaine?

it inhibits the reuptake of epinephrine into the presynaptic nerve ending

What are adrenergic receptors?

α1, α2, β1, β2, β3

What are alpha 1 receptors?

in most vascular smooth muscles

activate PLCβ → increase in calcium → contraction

What are alpha 2 receptors?

mostly presynaptic, inhibit adenylate cyclase (AC)

What are beta 1 receptors?

mostly in the heart

activate adenylate cyclase

What are beta 2 receptors?

in respiratory and uterine smooth muscle

activate adenylate cyclase

What are beta 3 receptors?

mostly in adipocytes (fat cells)

activate adenylate cyclase → lipolysis

What is the mechanism behind MAO inhibitors?

MAO metabolizes dopamine and serotonin → MAO inhibits trigger increase in these “happy hormones” → used as antidepressants

What are MAO inhibitors?

is a indirect sympathomimetic, inhibition causes increase in free norepinephrine

irreversible inhibition of MAO → long-lasting effect (weeks)

What are some examples of MAO inhibitors?

tranylcypromine and moclobemide

What is ephedrine?

an indirect sympathomimetics, in herbal preparations (Ma Huang and Ephedra) and dietary supplements

displace norepinephrine in storage vesicles → forces norepinephrine release → increase heart rate

What are amphetamines?

displace norepinephrine in storage vesicle → forced epinephrine release

inhibit norepinephrine re-uptake and degradation by MAO

What is the triple action of amphetamines?

1. forced epinephrine release

2. inhibit norepinephrine re-uptake

3. degradation by MAO

What is methylphenidate (Ritalin)?

an amphetamines and treatment for ADD

What is fenfluramine?

an amphetamines, an appetite suppressant that was combined with phentermine (FenPhen)

What is Methamphetamine/MDMA?

am amphetamines, also called ecstasy, effectiveness disappears due to norepinephrine depletion of vesicles

What are examples of indirect sympathicomimetics?

amphetamines, ephedrine, and MAO inhibitors

What are the non-selective agonists of adrenergic system?

epinephrine and norepinephrine

What are the effects of epinephrine?

activates both alpha and beta receptors

increases in blood pressure and dilates bronchii

What are medicines that uses epinephrine?

sympathetic treatment of anaphylactic shock (Epi-Pen)

adjuvant in local anesthetic (increases duration, reduces bleeding)

What are the effects of norepinephrine?

activates mostly a receptors → systolic and diastolic blood pressure increase

very potent vasopressor → clinical uese limited to severe shock treatment

What is methoxamine?

an alpha 1 agonist, treats a hypotensive state

What is phenylephrine?

an alpha 1 selective agonist, local vasoconstrictor nasal decongestant

What drugs have the ending -zoline?

is an alpha 1 selective agonist, specifically nasal, should not be used less than 10 days since its causes damage to tissue due to alpha 1 receptors downregulation

What are alpha 2 selective agonists?

sympathomimetics, inhibit presynaptic alpha 2 receptors in the cardiovascular center in the CNS → reduced sympathetic nervous system activity → blood pressure decrease

What are clinical applications for alpha 2 agonists?

hypertension ex. clonidine and guanfacine

What are beta 1 receptors effects?

mostly in heart, increase in contractility and increase in heart rate

What are beta 2 receptors effects?

• respiratory system - located in bronchial smooth muscle

• produce bronchial dilation

What is dobutamine?

strong inotropic effect with little chronotropic effect

used mostly for short term treatment of impaired cardiac function after cardiac surgery

What is the dobutamine stress test?

used in sonogram tests to mimic exercise

How are beta 2 agonists used to treat asthma?

since they mostly target the respiratory system they are best used for asthma

used mostly as aersols

What are drug that end in -terol and erenol?

they are aerosols used for asthma

What are drugs that end in -zosin?

they are alpha 1 selective inhibitors used to treat hypertension

ex. prazosin was the prototype

What are the effects of alpha selective antagonists?

they promote vasodilation → decreased peripheral resistance → decreased blood pressure

What is the side effect of all vasodiliatiors?

reflex tachycardia and postural hypotension

What is the clinical applications of the alpha selective antagonists?

hypertension and urinary retention

What are examples of non selective alpha antagonist?

phentolamine and ergot alkaloids

What is yohimbine?

an alpha-2 selective antagonists, is an ingredient in many weight loss products and has extensive use in treatment of male sexual dysfunction

What is the mechanism behind yohimbine?

enters CNS → increased sympathetic output → increased heart rate, blood pressure and can cause severe tremors

What are beta selective antagonists?

sympatholytic, noncardioselective, contain intrinsic agonist activity

What drugs have the ending -olol or alol?

are beta antagonists

labetalol- also has antagonists on a1

What is propranolol?

the protype for beta antagonists

What is esmolol?

an beta 1 specific cardio selective antagonist, has an quick onset/short duration → used in urgent settings

What are venules?

collect blood from capillaries

What are veins?

transport blood back to heart

What does resistance to flow depend on?

vessel diameter, length and viscosity of the blood

What does the right side of the heart do?

operates as a low pressure system and delivers de-oxygenated blood to the lungs

What does the left side of the heart do?

functions as a high pressure system and delivers oxygenated blood to the rest of the body

How do the walls of the ventricles differ on the right and left side?

the walls of the right ventricle are much thinner than those on the left due to the workload of the right side of the heart

What is the cardiac output?

how much blood is being pumped in the heart

What is the cardiac output dependent on?

heart rate, stroke volume, preload and afterload

What is the sterling’s law?

Ventricular contraction is proportional to muscle stretch

What are the consequences of hypertension?

heart failure, kidney damage, stroke and blindness

What are the 4 major drugs to fix hypertension?

sympathetic nervous system suppressors, direct vasodilators, renin-angiotensin system targeting drugs and diuretics

What effects do calcium channel blockers have on the heart?

Since they inhibit calcium entry into cells they cause there to be a decreased afterload

What are dihydropyridines?

calcium channel blockers that specifically inhibit L-type channels on vascular smooth muscles

they are Vasoselective but can cause peripheral edema

What drugs end id -dipine?

dihydropyridines, L-type calcium channel blockers

ex. nifedipine

How do potassium channel agonists affect the heart?

increases outward K channel → membrane hyperpolarization → Ca channel activity is inhibited → decreased afterload

What is minoxidil?

a potassium channel agonist that was originally used to treat severe, treatment-resistant hypertension but was then used topically to treat baldness

What is nitroprusside?

very unstable, but converts into NO and causes rapid vasodilation but is very short

What is renin-angiotensin system?

regulates blood volume, arterial pressure and cardiac and vascular function

What is the function of angiotensin 2?

constricts vessels, stimulates adrenal cortex, stimulates vasopressin (fluid retention), facilitates norepinephrine release and stimulates cardiac hypertrophy

What drugs end in -pril?

ACE inhibitors

Captopril

What is the role of ace inhibitors?

an vasodilator, however has an side effect of an cough

What drugs end in -sartan?

AT 2 receptors, no side effects

What is the treatment for stable angina?

nitrates and b-blockers

What is the treatment for unstable angina?

nitrates

What is the treatment for variant angina?

Ca++ channel blockers

What are nitrates used to treat anginas?

nitroglycerin, ISDN, nitroprusside

What is atrial fibrillation?

the atria quivers rather than contract normally because of rapid and irregular electrical signals, risk of blood clots

What is ventricular fibrillation?

life threatening that causes heart to quiver rapidly- 350 bpm leading to cardiac arrest

What are the classes of drugs used to treat arrhythmias?

sodium channel blockers, beta-blockers, potassium channel blockers, calcium channel blockers

What is congestive heart disease?

inadequate contractility → ventricles have difficulty expelling sufficient blood → rise in venous blood pressures → impaired fluid damage causing heart failure

What is right sided heart failure?

causes lower limb edema leading to intravascular clotting

What is left sided heart failure?

produces pulmonary edema and respiratory distress

What are the classification of heart failure?

1- no limitation of physical activity

2- slight limitation

3- marked limitation

4- symptoms occur at rest

What are the treatment options of congestive heart failure?

diuretics, Ace inhibitors, AT 2 antagonist, vasodilators and cardiac glycosides

What are the two categories of cardiac glycosides?

cardenolides and bufadienolides

What are cardiac glycosides?

the main treatment of heart failure, they slow the heart, increase the force of contraction and urine output but they do not prolong life

What is the mechanism of cardiac glycosides?

they inhibit the Na/ atpase pump → increase in extra Na → slow of Na/Ca exchanger → increase in intra Ca → more calcium pumped for contraction

What is digitalis?

drug of choice for heart failure associated with atrial fibrillation

What is the antidote for cardiac glycoside overdose?

potassium since they compete for binding the Na/K Atpase

What are the types of diuretics?

carbonic anhydrase inhibitors, thiazides, loop diuretics, potassium-sparing diuretics

What are the main mechanism of diuretics?

block reabsorption of sodium and chloride → water will stay in the nephron

those that target the early nephron have the greatest effect since they block more sodium

What is a acetazolamide?

an cardiac anhydrase inhibitor that is primarily used for glaucoma and is not in use as a diuretic anymore

What is an carbonic anhydrase inhibitors?

an diuretic that works by blocking hydrogen exchange so sodium cant be removed from the lumen therefor more water is excreted

What is an loop diuretic?

strong and brief diuretic, used for moderate to severe fluid retention and hypertension

inhibits the Na/K/2Cl symporter in the ascending limb in the loop of henle

What is the major side effects of loop diuretics?

there is a major loss of K, Ca and Mg

What is Furosemide?

a loop diuretics

What is a thiazide diuretics?

used for mild to moderate hypertension, mild heart failure

inhibits the Na/Cl symporter in the distal tubule

What is the major side effect of thiazide diuretics?

loss of K

What is the hydrochlorothiazide?

the prototype for thiazide diuretics

What are potassium-sparing diuretics?

used in combination with high ceiling diuretics or thiazides due to potassium effects however they produce little diuresis on their own

aldosterone promotes reabsorption of Na in exchange for K

What is spirinolacetone?

prevents aldosterone build up, onest of action requires several days

What are the osmotic diuretics?

small, non-reabsorbable molecules that inhibit passive reabsorption of water

used to prevent renal failure, reduction of intracranial pressure