Core 2, Test 1 Pharm Cards

No, small lipid soluble hormones. But, they are made as part of a protein (Thyroglobulin).

See notes.

Needed to make thyroid hormones. Yes, used to inhibit thyroid gland function.

Because hormone stored as colloid can last up to 3 months.

Uptake of Iodine, Peroxidase enzyme, Movement of Iodine into lumen/colloid, Proteolysis of colloid, Conversion of T4 to T3

T4 - it is bound to TGB, more T3 free
T3 is more potent
T3 again, it is more potent

Thyroid Hormone receptor, a nuclear transcription factor.

Stimulates growth/development and metabolism. This leads to inc. O2 consumption and heat production leading to activation of sympathetics.

Non-toxic - thyroid level normal because of increased compensation
Toxic - thyroid level high because of increased compensation

Cretinism, Abnormal mental development

Cold, tired from decreased metabolism.

End-stage myxedema. Life-threatening and need treatment.

Dietary lack - eat more iodine
Hypothyroid - replace thyroid hormone

Typically orally, can be IV. Yes.

Synthetic replacement of T4. Like T4, more protein bound so has long t1/2.

Synthetic replacement of T3. Like T3, less protein bound so rapid action and shorter t1/2.
No, too short t1/2.

Levo, even in emergency.

Yes: cancer, weening or starting of T4. Occasionally for depression w/ T4.

Different bioavailabilities.

Yes, often weeks. Be patient.

Cardiac function.

Elderly, Cardiac disease, Pregnancy.

Give bolus thyroid hormone than bring up slowly while supporting patient.

Hyperthyroid symptoms -- can be dangerous

Thyroid cancer - inhibit TSH release that causes cancer cells to grow.
Non-toxic goiter - give them replacement to suppress TSH and get rid of goiter.

Severe hyperthyroidism. Opposite of Myxedema coma.

Treat Symptoms
Treat underlying cause

B-blocker, Ca+2 channel blocker

Thioamides, Iodides

Suppress thyroid synthesis, do not destroy gland.

No, most patients end up needing surgery or RAI after a year or so.

Orally, typically.

Because get concentrated or trapped in thyroid.

Longer t1/2 than PTU.

Inhibit TPO (thioperoxidase). No, have excess as colloid.

Inhibits conversion of T4 to T3.

Agranulocytosis - no granulocytes, get infection. Watch for signs of infection.

Back off the dose a bit to be sure thyroid hormone levels are adequate. Want hyperthyroid over hypothyroid. PTU better in preg.

Inhibit synthesis and release of thyroid hormone.

Thyroid storm - saturate receptors
Decrease size of thyroid - esp. b/f surgery

Because inhibits effect of RAI. Yes, to reduce TH release and to relieve symptoms.

To decrease uptake of radioactive Iodine.

Burning mouth, sore throat.

I131 contains weak beta radiation that does not travel far (1-2 mm) and does not last long. This minimizes damage to rest of body while destroying thyroid.

Inflammation of thyroid and salivary glands. Hypothyroidism, can treat w/ replacement therapy.

Cancer, pregnancy not responding to anti-thyroid drugs, patients who refuse radioactivity

First, use thioamides and iodine to firm up and shrink gland. Surgery. Then use drugs to decrease thyroid storm from surgery and finally replacement with levo-.

Methimazole
Radioactive Iodide
PTU, radioactive prior is preferred b/f surgery

Iodide (block release), PTU (dec. conversion of T4 to T3), Glucocorticoids (shock?), beta blockers (symptoms of heart)

Blah

Increase metabolism of sugars (glucose), fats, proteins -- hence the name GLUCOcorticoids. Also have anti-inflammatory effects. Also, inc. CO and vasoconstrict.

Yes Yes Yes

Inflammation
Replacement therapy

Effect dosing time and toxicity.

Effects the HPA and can ultimately shut it off!!! Therefore body cannot respond to stress.

Dec. Ca+2, Inc. stomach acid, alter neuronal function, inhibit growth, stim. fetal lung surfactant. Also, you get feedback regulation, duh!

Because of toxicities.

Swelling - vasoconstrict
Pain - inhibit ArachAcid metabolism
Cellular - dec. neutrophils at site
Cytokines - dec. cytokines

Immune system suppression.

Yes, when you want immunosuppression (Ex: leukemias)

Increase Na reabs., Increase K excretion, Increase H+ excretion

Yes, at high doses.

Yes, corticosteroid binding protein
No, some are free to inc. potency

Glucocorticoid receptor which then goes to glucocorticoid response element.
Yes

Blah

Weak anti-inflammatory
Weak Na+ retention
Short t1/2

Better anti-inflammatory
Weaker Na+ retention
Int. t1/2

Strong anti-inflammatory
Very weak Na+ retention
Long t1/2
***lower dose b/c inc. potency

Very weak anti-inflammatory
Strong Na+ retention

Once drug has its effect, effect remains even after it is out of system.

Orally
Yes, water-soluble form
Sustained release bad
Yes, when don't want systemic effect

Arthritis, Skin diseases, Collagen disease (Lupus), Allergies, Asthma, Transplant, Eye, IBS, Nephrotic syndrome

Make use of anti-inflamm. and immunosupp. effects.

Hydrocortisone, relatively weak

-Mineralcorticoid receptor toxicity
-GC Side Effects:
Muscle wasting, thin skin, osteoporosis, growth inhibition, diabetes, weight gain, fat redist., ulcers, cataracts, CNS effects, poor healing, increased infection rate, dec. response to stress

Related to side effects:
Diabetics, ulcers, CV disease, infections, osteoporosis, psychosis

Long term, high dose. Use short term and low dose.

Yes

Yes
Yes

Because mimic diurnal variation.

Need to slowly ween off oral and than go to local, cannot just suddenly switch. Patient still needs some systemic effect.

Yes

Hydrocortison
&
Fludrocortisone

Patient lacks one of the three hydroxylating enzymes of the adrenal cortex. (11, 21, 17)

Even though patient can make corticoids, give replacement so adrenal gland does not have to work overtime and excesses of cortisol, mineralcorticoid, and androgen are not present. Depending, may have to add fludrocortisone.

Give Betamethasone b/f delivery.

Use Prednisone

Cytotoxic to WBCs -- leukemia, myeloma, lymphoma

Reduces adrenal sex steroid synthesis that can cause cancer to grow.

Use Dexamethasone
MG - suppress immune system
Edema - vasoconstriction

Block Aldo. receptor and androgen antagonist?

Inhibits cortisol synthesis.

Dx of Cushing's Syndrome, Treat adrenal carcinoma, Suppress ectopic ACTH release from a tumor

Blocks glucocorticoid receptors and is also the abortion pill.

Decrease blood sugar and increase storage, suppress gluconeogenesis

Tyrosine Kinase Receptor -- mediates internalization and degradation of insulin.

Type 1

Yes, but not in type 1

Type 2

Early - diet, exercise, lifestyle
Late - Insulin, Hypoglycemic drugs

Insulin

No, it is a peptide drug and therefore must be injected IM.

To mimic body patterns in a normal person.

Hypoglycemia, Hyperglycemia -- want balance. Hypoglycemia important!!!

Onset, Duration, Peak. Also, certain preps may have different routes and timing of administration.

Human insulin or exact replica of human insulin. Cloudy, too much Zn+2, mixing issues. Replaced by synthetics.

Regular, NPH

Rapid onset
Short duration
~4 hr. peak

NPH insulin is insulin complexed to a protein to slow its release.
Slow onset
Long duration
~12 hr. peak

No, will clog the line.

For glucose control when eating. Take 1 hr. b/f meal.

For glucose control between meals and at night. Baseline insulin.

No

Lispro, Aspart, Glulisine

Glargine, Detemir

Yes

Because it does not form aggregates like endogenous insulin, it falls apart quickly so it can act rapidly.

You can inject immediately before eating. Don't have to inject 1 hour before.

Yes

Similar to Lispro but with a slightly slower onset and longer duration. Between Lispro and Regular insulin.

Similar to Lispro, but its purpose is to go with Glargine (long-acting compliment)

An ultra-long insulin due to slow absorption and long duration.

pH = 4, this is why they have to go together.

No, they are prepared at pH = 7.

?SubQ? -- slows release

Another ultralong-acting insulin. Its action is so long because it has a fatty tail on it to slow its release.

Detemir has slightly shorter duration.

Lispro/Glulisine/Aspart > Regular > NPH > Detemir/Glargine

Device sucked, complication with asthma/COPD, limited dosing options

Tighter control of diabetes lead to a decrease in risk factors. Loser control led to more complications. However, mortality increased on tighter control.

Hypoglycemia

Similar to increased cortisol levels -- weakness, sweating, hunger, tachycardia, anxiety, tremor, ...

Could be asymptomatic

Eat or drink sugar

Resistance from Anti-Insulin Abs, Insulin allergy, Lipodystrophy

?SubQ? -- slows release

Another ultralong-acting insulin. Its action is so long because it has a fatty tail on it to slow its release.

Detemir has slightly shorter duration.

Lispro/Glulisine/Aspart > Regular > NPH > Detemir/Glargine

Device sucked, complication with asthma/COPD, limited dosing options

Tighter control of diabetes lead to a decrease in risk factors. Loser control led to more complications. However, mortality increased on tighter control.

Hypoglycemia

Similar to increased cortisol levels -- weakness, sweating, hunger, tachycardia, anxiety, tremor, ...

Could be asymptomatic

Eat or drink sugar

Resistance from Anti-Insulin Abs, Insulin allergy, Lipodystrophy, Weight gain

Hypoglycemic episodes

Open K+ channels in beta cells and inhibits the release insulin to help with hypoglycemia.

Prolactin system w/ DA.
GH system w/ Somatostatin.

-Sex Hormones (Progesterone, Estrogen, Testosterone)
-Adrenal Hormones (Glucocorticoids, Mineral Corticoids, Androgens)
-Thyroid Hormones (T4, T3)

GH, Prolactin

Somatomedin, Lymphokines

GPCR

Everything but:
-Adrenal Hormones
-Thyroid Hormones
-Sex Hormones
-Dopamine

Degrade in stomach, difficult to isolate and purify in large amts., Immune reactions, Human form required, Difficult to synthesize, Rapid hydrolysis orally and with injection, blah blah blah

Human genome project

-AA modification (prevents hydrolysis)
-DNA recomb. tech. (make large amt.)
-Many different routes of admin. now possible (inhalation, needle-free, nasal,...)
-Modify AA sequence to get desired properties (Ex: longer duration, quicker action,...)

Desmopressin

Give synthetic GH back to the patient.

Somatropin, Somatrem

Has an extra methionine on it. "-em" = extra methionine.

SC or IM

Stimulates growth (think of a teenager): Decreases fat, increases muscle, increases bone growth (unless plates are closed), increases sense of well-being, physiology maintenance in adults

GH deficiency, Prader-Willi, Turners Syndrome, Short stature, AIDS cachexia, short bowel, renal insufficiency

Debatable

Yes

People with a defect in their GH receptor.
IGF-1 - end organ product of GH since they cannot respond to GH.

Sermorelin

An operational pituitary

IV, SC, Nasally

Analog of Somatostatin
Inhibition of GH system: Acromegaly, metastatic carcinoids (5HT receptor), suppression of VIP and glucagon secretion,

-Longer acting
-Less effective on insulin suppression
-Selective for 5HT receptor

SC

Lantreotide (longer-acting than Octreotide)
Vapreotide, Seglitide

It inhibits the release of prolactin

Anti-Parkinson's drugs
Bromocriptine

Anti-depressants
Anti-psychotics

No, only synthetic analogues

DA agonist

Hyperprolactinemia
Prolactin-secreting tumor
Suppress lactation
Acromegaly (inhibits GH only in acromegaly, stimulates GH in normals)

Orally, Vaginally?

Nausea, dizziness, hypotension
Yes

Parkinson's Disease

Has a longer duration of action

Vasoconstriction
ADH-like effect

Synthetic human Vasopressin

Commonly nasally

V1 and V2

SHORT TERM SITUATIONS
Commonly for bleeding disorders b/c of its V1 effects
May be used for diabetes insipidus following pituitary surgery

Peptide analogue of Vasopressin

Inhaled, Orally (first oral peptide drug)

-Drug of choice for Diabetes Insipidus
-Increase clotting factors in Von-Willibrand's and hemophilia
-Nocturnal Enuresis, AKA - bed-wetting (oral prep only!)

V2

When used for DI!!!
-V1 effects: HTN, GI cramps, headache
-Oxytocin receptor: Uterine contractions and cramps

Arginine Vasopressin

Phase 4 - resting potential (Most channels, except specific type of K+ channel, closed)
Phase 0 - rapid depolarization (Na+ channels open)
Phase 1 - Na+ channels close
Phase 2 - Ca+2 channels open
Phase 3 - K+ channels open (of diff. type than are open in in phase 4)

Fast tissue - fast depolarizing
Slow tissue - slow depolarizing

Fast - atrial & ventricular myocardium, his/perkinje fibers
Slow - AV node, SA node

Many fast Na+ channels
Fewer slow Ca+2 channels

Fewer fast Na+ channels
More slow Ca+2 channels

Fast tissue - block excitability and conduction velocity

Slow tissue - decreases the excitability and conduction velocity of slow tissue

Fast tissue - prolong the AP duration and therefore the refractory period

Modulate GPCR action

- Dec. excitability
- Dec. conduction velocity
- Inc. refractory period (b/c some drug may still be bound to channels thus preventing depolarization)

Resting (closed), Active (open), Inactive (closed)

...the more excitable the cell.

The channel essentially has two gates. An "external" gate ("Martens-ism") and "internal" gate. The external gate allows Na+ in during the active state and is closed in the resting state. The internal gate is like a door that swings shut on the channel during the inactivated state.

The active and inactive states. They do not typically block resting state.

Less -- this is the reason for decreased excitability of the cell.

Dissociation constant -- the longer a Na+ blocker can act, the more effect it will have.

Makes it wider as depolarization is slowed.

- Inc. duration of the AP
- Thus, inc. refractory period

Prolonged Q-T segment -- this is because they slow repolarization.

- Dec. excitability
- Dec. conduction velocity
***Slow tissue only!!!

Prolonged PR interval - this is because Ca+2 channel blockers act mainly on slow tissue (i.e. - the AV node and SA node) so the SA nodes and AV node are slowed resulting in prolonged PR segment.

1. Re-entry - Wolff Parkinson White?
2. Automaticity - ectopic pacemaker
3. Triggered activity - one impulse triggers multiple APs

SDS detergent - "the head bath"

Enhanced - enhanced activity of a normal pacemaker cell
Abnormal - a non-pacemaker cell (not normally a pacemaker) takes over automaticity

Ca+2 blocker - to slow the enhancement of a normal pacemaker
Na+ blocker - to slow the abnormal pacemaker that may arise in ventricular/atrial m., etc...

Early - the AP does not return to baseline before depolarizing again (EAD)
Delayed - the AP does return to baseline again before depolarizing (DAD)

DIGOXIN

K+ channel blocker - because they make the AP so long that often another impulse can be activated before return to baseline

Na+ blocker - blocks depolar.
Ca+2 blocker - blocks depolar.
No K+ blocker - as before, can make worse)
Remove K+ blocker - shorten the AP making a EAD less likely

Na+ blocker - block depolar.
No K+ blocker - ineffective
*Ca+2 blocker - often DADs are due to excess Ca+2 so this is often best

It is a abnormal circuit loop that develops in the heart. TIMING OF THE LOOP IS ESSENTIAL!!!

Too fast: The loop will go around on itself so fast that tissue it has already been through will be depolarized and unable to initiate another AP

Too slow: The pacemaker will pace faster than the loop and take over the conduction of the heart.

Yes

Atria: Afib, Aflutter, Atach
Ventricles: Vfib, Vtach

Paroxysmal Supraventricular Tachycardia - any re-entry involving slow tissue (SA node, AV node, atrial m.) Usually, this is AV nodal re-entry (90% of the time)!!!

Involves fast and slow tissue and uses the AV pathway.

Since it is fast tissue, you would use a Na+ blocker or K+ blocker.

Since it is slow tissue, you would use a Ca+2 blocker.

Yes??? --

No - because it will slow down the pacing of the heart to the point that the WPW pathway will dominate. When the WPW pathway dominates, the ventricles have to work even harder than they did in Afib. This is because not all the signals from Afib get through the AV node in Afib, but they do in WPW. Bad Bad Bad!!!

Terri Spawn's Mobile Clinic with Greg Nissen as the conductor!

Ischemic tissue typically has more channels in the active and inactive state vs. the resting state. Therefore, blockers bind preferentially to ischemic tissue making it electrically silent.

Again, because this tissue has more active/inactive Na+ channels at any given time allowing the blocker to preferentially bind to this area.

Normal tissue often not affected as drugs to block tachycardia are quick dissociating and can dissociate before the next action potential occurs. Therefore, all they do is slow down the tachycardic tissue.

No
No
Yes

A classification schema for Anti-arrhythmics.

Class I - Na+ blocker
Class II - B-blockers
Class III - K+ blockers
Class IV - Ca+2 blockers

Ia - Quinidine, Procainamide, Disopyramide

Ib - Lidocaine

Ic - Propafenone, Flecainide

Metoprolol

Amiodarone, Dofetilide

Verapamil

Adenosine

Fast tissue (Na+ blockers ,K+ blockers)

Slow tissue (Ca+2 blocker, B-blockers, Adenosine)

Quinidine, Procainamide, Disopyramide

Moderate depression
Moderately slow dissociation (1 - 10 sec.)

Yes, often times their activities are not pure. For example, a Na+ blocker may also act as a K+ blocker to some extent.

Yes, they have some K+ blocking activity --> long AP and increased refractory period

Widen QRS
Prolong QT

Lidocaine

Very fast

Depolarized tissue (Ex: ischemic tissue) w/ little effect on normal tissue. This is because their action is to effect active/inactive channels and not resting channels. Also, their dissociation is so fast that they have little affect on tissue at normal resting membrane potential. Therefore, good for ischemic tissue while keeping normal tissue intact.

Propafenone, Flecainide

Yes
Very slow (> 10 sec.)

Widen QRS
Increase the PR interval? (b/c effect Ca+2 channels?)

Cardioversion
ICD
Ablation (for re-entry pathways)

Control ventricular rate - Ca+2 blocker (blocks AV node)

Restore sinus rhythm - cardiovert (reset heart)

Maintain sinus rhythm - Na+ blocer

Amiodarone (but has significant side effects) So...

1st: Class Ic or Solatol
2nd: Class III

Class III agents

Avoid Class Ic agents - become proarrhythmic in this setting

Acutely - AV node blocker: Adenosine & Ca+2 blocker

Chronic -
1st choice: Ca+2 blocker
2nd choice: Class Ic

Acute: Adenosine
Chronic: Na+/K+ blocker

Non-medical: Ablation

w/ Afib: NO Ca+2 BLOCKER
Acutely: Procainamide
Chronic: Na+/K+ blocker
***Basically, don't give anything w/ Ca+2 blocking activity if patient in Afib

Acute:
1) Cardiovert
2) 1st choice - amiodarone
2nd choice Procainamide Lidocaine

Chronic: ICD

Ia

Ventricular and Supraventricular arrhythmias -- 2nd or 3rd line

Anti-muscarinic
Alpha NorE blocker

-SA block

-Torsade de Pointes - K+ blocking effect

-Increased Vent. Rate when given for atrial flutter (because it slows down flutter to the point that more signals get through the AV node making ventricular rate faster)

-Asystole or Arrhythmia (if QRS too wide, toxic levels)

A ventricular arrhythmia that develops from a long duration AP.

GI disturbance -- watch for diarrhea-induced hypokalemia

Ia

- WPW w/ atrial flutter (acutely)
- Supravent. or Ventricular arrhythmias (2nd line drug)

- Liver (fast & slow acetylation)
- Its breakdown product, NAPA, is a K+ blocker and can act as a pro-arryhthmic

Similar to Quinidine but Torsades de Pointes is less common. However, if NAPA levels are high it can occur.

- Hypotension (w/ IV infusion)
- Lupus-like syndrome (esp. in slow acetylators)

Ia

- For supravent. and ventricular arrhythmias

- Anti-muscarinic
- Ca+2 blocking activity

- Same as Quinidine
- Neg. inotropic effect (worsens CHF)
- Anti-muscarinic effects > Quinidine

Enhance the proarrhythmic properties of these drugs.

***A low K+ inactivates K+ channels --> Inc. EADs --> arrhythmia

Ib

Slightly depolarized tissue (Ex: ischemic tissue). Has little affect on tissue at normal resting membrane potential.

- Ventricular arrhythmias
- No effect on atrial arrhythmias

- CNS effects (parethesis, drowsiness)
- Elderly sensitive
- Toxic levels (nystagmus, resp. arrest, convulsions)

- Extensive 1st pass metabolism
- Admin. by IV

Ic

Yes, in patients w/ MI and CHF

- AFib, AFlutter
- AV nodal re-entry (2nd line)

- Vtach
- Heart block
- Bradycardia
- Worsen CHF

Something w/ a B-blocker?

Blurred vision

Extensive 1st pass metabolism by CYP2D6. If person has a CYP2D6 deficiency, be careful.

- Liver > Kidney (Liver disease elevates levels)

- Kidney > Liver (CYP2D6)
- Levels not affected by altered CYP2D6 levels because kidney is main source of metabolism.

II

SNS inhibition, blocks...
- Regulation of Ca+2 and K+ channels
- Enhanced automaticity
- EADs, DADs
And, increases AV node refractory period

- Ventricular Arryhthmias
- After MI (decreases O2 demand)
- Supraventricular Arryhthmias

- SA/AV node block
- Sudden withdraw worsens angina/arrhythmia
- Worsens CHF (short term)

III

- Block K+ channels (Inc. APD)
- Na+ channel blocker
- Ca+2 channel blocker
- B-NE receptor blocker

- Vtach
- Afib/Aflutter w/ heart disease

- Fatal: Pulm & Hepatic toxicity
- Photosensitivity
- Neurologic effects
- Thyroid dysfunction

First off, Amiodarone is extensively tissue bound which significantly increases it's t1/2.

Metabolized by the liver.

It also has active metabolites.

t1/2 = 1-2 mths.

- Increases plasma levels of other anti-arrhythmic drugs
- w/ other drugs (B-blockers, Ca+2 blockers) it can cause sinus arrest, AV block, and worsen CHF

- K+ channel blocker
- B-blocker (esp. L-isomer)

- Maintaining sinus rhythm in Afib after MI
- Vtach

Torsades de Pointes

K+ channel blocker

- Maintain sinus rhythm in afib after MI/CHF
- Requires special training to use

Kidney

Torsades de Pointes

IV

Block L-type Ca+2 channels and therefore mediates slow response tissue (Ex: Depresses AV node conduction)

- Supraventricular tachycardia from AV nodal re-entry
- Reduced ventricular rate in Aflutter

- Contraindicated in CHF, hypotension, sick sinus syndrome?, AV block, Vtach, WPW (esp. if atrial flutter present)

Constipation, nausea, peripheral edema

w/ B-blockers or Digoxin = severe bradycardia or AV block

- Enhances K+ channel activity in SA/AV nodal tissue --> hyperpolarization
- Inhibits Ca+2 currents in AV node
- Increases AV node refractory period

Block re-entry!!!
- AV nodal re-entry
- WPW w/ no afib/aflutter

- Short t1/2
- Relatively safe

Not for cardiac transplant patients

Apoptosis, Abnormal Ca+2 handling, Altered protein structure blah blah blah

High levels of hormones and SNS present in a CHF patient: AII, Aldo, Vasopressin, Symp. stimulation,...

Symptomatic relielf

Dec. volume load (Dec. filling pressure, Dec. wall stress) --> Dec. pulmonary symptoms

If you use too much you can reduce volume to the point that you reduce SV.

Loops - common use, can dec. K+
Thiazides - rare use, can dec. K+
K-sparing - rare use, weak agents

Yes -- because it blocks one of the hormones (Aldosterone) that leads to re-modeling

Inhibits conversion of AI to AII by blocking the action of ACE.

Increases survival -- again, it blocks one of the hormones directly responsible for re-modeling.

- Potent vasoconstrictor
- Blocks aldo. release
- Re-modeling
- Catecholamine release?

AII levels return to baseline -- but have no fear, ACE inhibitors are still effective.

Penguin

Degrades Bradykinin -- so if you block ACE --> Inc. bradykinin --> vasodilation & reduced re-modeling

Angiotensin receptor blocker -- acts by blocking the AT1 recpetor

ACE-like effect

When patients are intolerant of ACE. It also avoids ACE escape.

Reduces mortality -- again, it inhibits the action of a hormone directly responsible for re-modeling

Nitrates (venodilation > vasodilation)
Hydralizine (Ca+2 blocker?)
Combo of the two above

No -- only symptomatic relief

Yes -- almost always

Yes, but more importantly they prevent re-modeling by inhibiting the SNS activity on the heart.

"Start low, go slow"

Yes, actually it does -- f'd up

ACE or ARB
B-blocker
Diuretic
Maybe Digoxin, not typical

Aldo. blocker
Hydralazine/Nitrate Combo

Digoxin
You better believe it

They are talking about Digoxin's effect directly on the heart -- impt. for CHF Tx

Effects mediated through the nervous system -- impt. for arrhythmia Tx

Positive Inotrope/Inc. CO -- this will shut off SNS & hormonal response to CHF

Block Na+/K+ channel --> increase intracellular Na+ --> Dec. Na+ gradient for the Na+/Ca+2 exchanger (helps get Ca+2 out of cell after contraction) --> Inc. in intracellular Ca+2 --> Increase contractility

DADs -- recall these are often due to increases in Ca+2

- Inc. parasymp. activity
- Inc. sensitivity of heart to parasymp.

This leads to an increased refractory period at the AV node thus preventing Vtach in atrial flutter

Increases SNS activity -- BAD

Yes

- K+ depletion enhances Digoxin binding (Ex: diuretics)
- K+ depletion enhances excitability

***Watch for K+ depletion situations

- Ventricular extra systoles (riggered activity from Ca+2 overload)
- SA block/AV block
- AV nodal arrhythmia

Anorexia, Nausea/Vomit, Diarrhea (can make K+ depletion worse)

- Monitor ECG
- Monitor K+/correct K+
- Monitor Digoxin levels
- Lidocaine for Vtach
- Digibind (Ab to Digoxin)

Do not use w/ K+ depleting diuretics

Other anti-arrhythmics increase Digoxin levels in the blood

Systolic CHF w/ Aflutter

Systolic CHF not being managed by B-blockers, diuretics, ACE

Dihydropyridines (Nifedipine)
Non-dihyrdopyridines (Verapimil)

"-dipine"

L-type

- Dec. Ca+2 current
- Dec. afterload via vasodilation and therefore reduce O2 demand of heart. Therefore, relieve angina.

Preload
Afterload

Yes

N-site on L-type Ca+2 channel

V-site on L-type Ca+2 channel

Yes

Yes

- Brady (verapamil)
- Reflex tachy
- Cardiac depression (verapamil)
- Flushing, edema (nifedipine)
- Constipation (verapamil - blocks Ca+2 in gut as well)

Propanolol

Antagonize B1 (and B2)
- Dec. rate
- Dec. contractility

No -- could make it worse.

Mechanism unknown -- could be blocking B2 in CA and letting Alpha receptors dominate.

- Worsen ventricular function
- Inc. airway resistance
- Precipitate MI via acute withdrawal
- Fatigue, sexual dysfunction, depression
- DO NOT use B1 agonists. I have no idea why this is here, but anywho...

- Nitrates + B-blockers
- CCBs + B-blockers
- Nitrates + CCBs
- All three together

Basically, any combo you can think of to control it!!!

New antianginal agent

Na+ channel blocker IN ISCHEMIC TISSUE!!! This prevents Ca+2 overload and thus an increase in O2 consumption. Therefore, anginal symptoms are relieved.

Late phase Na+2 channel (I - Na+ channel)

Prevents acute anginal attacks w/ no change in HR or BP

- Prolong QT - can lead to Torsades
- CYP3A4 interference

ED

Selective inhibitor of PDE5 --> prolongs activity of NO/cGMP --> relaxation of smooth muscle --> inc. blood flow --> erection

*Sexual stimulation must be present

30-60 min.

headache, abnormal vision, dyspepsia, diarrhea, flushing, nasal congestion, boner > 4 hrs (priapism)

- Nitrates
- Alpha blockers

- Vardenafil
- Tadalafil

-Diuretics (Thiazide, Loop, ...)
-RAAS blockers (ARB, ACE, Aldo-blocker,...)
-CCB (Verapamil, etc...)
-Vasodilators
-Sympatholytics (Clonidine, Terazosin,...)

-Primary (essential)
-Secondary (ex: renal artery stenosis, pheochromocytoma, primary aldosteronism)

Primary (essential)

Asymptomatic and insiduous

CVA, CAD, Renal failure

BP = CO x TPR

SNS

Kidneys - days
RAAS - hours

You bet

Yes

Hydrocholorothiazide

-Acutely - dec. blood volume
-Long-term - decrease TPR (dec. Na+ long term --> vasculature less responsive to SNS)

- Mild to moderate HTN
- Alone or in combo (causes synergistic effect of other drugs)
- Good for volume dependent HTN
- Shallow dose-response curve (do not increase dose or will inc. side affects)

- Hypokalemia (inc. Na+ to distal nephron)
- Gout (dec. UA secretion)
- Hyperglycemia (dec. secretion of insulin)
- ED

Furosemide

- Modest BP effect
- Malignant HTN
- Volume dependent

- Same as thiazide
- Hearing loss

"-pril"

Inhibits ACE that converts Ang. I --> Ang. II

- Inhibits vasoconstriction
- Inhibits bradykinin degradation
- Inhibits release of Renin
- Prevents re-modeling

- HTN
- Cardiovasc. reflexes not affected -- can still exercise normally
- Safe in asthma, no sexual dysfunction
- CHF, diabetic nephropathy, MI, CAD

First dose hypotension
Cough

Rash, loss of taste
Angioedema (fatal)
Hyperkalemia

Pregnancy (2nd, 3rd trimesters)
Bilateral renal stenosis

NSAIDs - the decreased breakdown and excess of breakdown of bradykinin from ACE will be blocked by aspirin

Captopril

Losartan (all end in "-sartan")

*Notes, everything for ARB very similar to ACE

- Blocks renin
- Prevents vasoconstriction

*Does not inhibit bradykinin as ACE

Anti-HTN
Others: CHF, MI, diabetic nephropathy

Same as ACE

Eplerenone (sounds like the prototype spironolactone)

Blocks the action of aldo:
- Na+ wasting
- K+ retention
- Prevents re-modeling

Anti-HTN

Hyperkalemia

Directly blocks the enzyme renin and therefore prevents conversion of angiotensinogen --> Ang. I

Aliskiren

Anti-HTN

Hyperkalemia

Non-Dihyrdopyridines (Heart > VSM)
Dihydropyridines (VSM > Heart)

Verapamil (non-dihyro.)
Nifedipine (dihyro.)

Block L-type Ca+2 channels and therefore prevent contraction of VSM

No

Anti-HTN

Reflex tachy, bradycardia

A molecule that is has a covalently bound NO molecule that is released once it gets degraded in the body.

Yes, venous and arterial.

You can titrate it at any level and get the blood pressure to wherever you want it. Plus, the action is quick so the effect may be lifted quickly.

CN portion metabolized by liver rhodanase to thiocyanate

Thiocyanate excreted in kidney

Emergency hypertension
Surgery
Give Furosemide as adjunct

Excessive hypotension
Cyanide toxicity
Hypothyroid from CN-

Unknown -- reduces bp by reducing TPR

Extensive 1st pass
Reduce dose in slow acetylators as it is acetylated in liver by NAT2

Essential HTN
Hypertensive crisis
Heart failure

Reflex tachy
Lupus-like syndrome

A drug which opens K+ channels thereby hyperpolarizing the cell and inhibiting contraction

Yes

Reflex inc. in HR and contractility

Hepatic Sulfotransferase to the active drug

HTN
Promotes hair growth (Topical form of this drug is Rogaine)

Edema -- from Na+ and H2O retention
Reflex tachy
Hypertrichosis (hair growth)

Clonidine, Methyldopa

Decreased overall sympathetic outflow:
- Decrease HR
- Decrease TPR
- Dec. Renin

Related to sympathetic dec.:
- Dry mouth
- Sedation
- Impotence

Yes, very abrupt. Rebound HTN, headache, tachycardia

False transmitter that gets metabolized to Methylnorepinephrine.

***All MOA and adverse effects similar to Clonidine

Propanolol

Beta 1 blockade:
- Dec. HR
- Dec. contractility
- Dec. Renin
- Dec. SNS outflow

Has both SNS blocking and activating activity. Also, blocks B-1 and B-2.

Therefore, if patients get too low of SNS activity, this drug can rev them up.

Block A-1 as well as B-1,2.

Anti-HTN -- block reflex tachy

Hypotension
Bradycardia
Bronchoconstriction
Sexual dysfunction

"-osin"

Terazosin

Block A-1 receptors on VSM

Salt/H2O retention - combine w/ diuretic

Anti-HTN - not 1st line

1st dose effect, reflex tachy, nasal congestion, inhibition of ejaculation

***Somewhat similar to B-blocker

All are vasodilators...

Nifedipine - Ca+2 blocker
Epoprostenol - acts like prostacyclin
Bosentan - Endothelin 1 antagonist
Sildenafil - PDE 5 inhibitor