Pharmacology Unit 5

Card Set Information

Author:
Leon
ID:
240212
Filename:
Pharmacology Unit 5
Updated:
2013-10-16 20:45:46
Tags:
Pharmacology Unit
Folders:

Description:
Pharmacology Unit 5
Show Answers:

Home > Flashcards > Print Preview

The flashcards below were created by user Leon on FreezingBlue Flashcards. What would you like to do?


  1. 1) Difference between inotropic, chronotropic and dromotropic effect.
    • a) Inotropic effect – influences contractility or force of contraction
    •  i) May be + or – inotropic effect
    •  ii) (Na+)
    • b) Chronotropic effect – influences rate
    •  i) May be + or – chronotropic effect
    •  ii) (Ca++ )
    • c) Dromotropic effect – influences conduction through specialized conducting tissues
    •  i) May be + or – dromotropic effect
    •  ii) (K+ )
  2. 2) What are the types of arrhythmias?
    • a) –disorders of rate, abnormal impulse formation, and electrical conduction (Rate, Impulse formation, & Patterns of electrical conduction)
    •  i) Functional refractory period:
    •  (1) –time when heart may not be stimulated again
    •   (a) Av node limited to about 200 beats/minute
    •   (b) Explains use of electroshock for:
    •    (i) Ectopic foci
    •     1. Out of place “pacemaker”
    •     2. “escape” beats are lifesavers
    •    (ii) Circus movements
    •     1. Same impulse travels around and around
    •      a. [diminish refractory period = inhibits resting/refilling phase]
    •     2. Reentry- the same impulse reactivates tissue that it has already stimulated
    •      a. Requires:
    •       i. Normal conduction to be slowed
    •       ii. Refractoriness to be shortened
    •       iii. both
    •    (iii) Fibrillation
    •     1. Cells fire individually w/ no unified beat
    •      a. [firing/depolarization all over the place]
    •  ii) Rate & abnormal impulse formation
    •  (1) Bradycardia (under 50-60 BPM)
    •  (2) Tachycardia (100-200 impulses/minute)
    •  (3) Flutter (200-300 imulses/minute)
    •   (a) (Some beats usually ectopic)
    •  (4) Fibrillation (probably over 300/minute)
    •   (a) Can’t measure pulse because contraction non-effective.
    •   (b) (Many ectopic sites are active
    •  iii) Conduction issues
    •  (1) A-V block –form tissue damage, coronary infarction, vagal stimulation
    •   (a) Pulse less than 50-60 beats/minute often a warning sign but depends upon the patient
    •   (b) Major reason for bradycardia
    •  (2) Circus movements of entire muscle mass in unison

    • b) What are the most dangerous?
    •  i) Those in ventricles:
    •  (1) PVC – premature ventricular contraction
    •   (a) 1 PVC/hr increased mortality risk
    •   (b) 10/hr see 20% mortality the 1st year
    •  (2) Highly lethal arrhythmias have
    •   (a) 80% in the 1st year if not treated
    •   (b) 50% mortality w/ treatment
    •  (3) Meds are dangerous w/ multiple side effects
    •  (4) Implantable defibrillators an option
  3. Kinds of hypertension?
    • a) Specific or 2nd degree: less than 15%: only curable kinds
    •  i) Pheochromocytoma- adrenal medulla tumor
    •  ii) Cushing's disease
    •  (1) + adrenal cortex secretion
    •  (2) + Na+ retention
    •  iii) Renal disease
    •  (1) + retention of fluid
    •  (2) also renin-angiotensin-aldosterone release
    • b) Essential or primary hypertension: +85%
  4. 3) Difference between antipressor and pressor agent
    • a) Antipressor/Antihypertensive agent
    •  i) Mechanism–decrease BP
    •  ii) Classes
    •  (1) Autonomic (ANS) modifiers
    •   (a) -Lack sympathetic (SNS)- either Alpha or Beta or both
    •    (i) Parasympathetic (PNS) stimulators not used
    •   (b) Alpha blockers: prazosin, phenoxybenzamine, terazonsin
    •    (i) Mechanism of action
    •     1. Block action of epi or norepi (NE) on receptors
    •     2. Inhibits vasoconstriction
    •    (ii) Side or toxic effects
    •     1. Postural hypotension (dizziness, weakness, fainting)
    •     2. Reflex tachycardia
    •   (c) Beta blockers: names that ends with –lol; metroprolol & atenolol (more Beta1)
    •    (i) Mechanism of action
    •     1. Decrease HR & force of contraction= so decreases CO
    •     2. Inhibits renin release
    •    (ii) Side or Toxic effects
    •     1. GI – nausea, vomiting, diarrhea
    •     2. Heart – uncommon, but may cause:
    •      a. Serious cardiac depression
    •      b. A-V block
    •     3. Bronchioles – constrict airway
    •    (iii) Contradictions – asthma or A-V block
    •     1. Beta blockers most useful in patients under 40
    •     2. Patients over 60 do poorly but respond well to calcium channels blockers
    •   (d) Ganglionic blocker (Hexamethonium)- no longer recommended
    •    (i) Mechanism of action
    •     1. Anti-nicotinic drug
    •     2. Inhibition of sympathetic ganglia decreases BP
    •      a. Decreases CO & vasoconstriction
    •     3. Inhibition of parasympathetic ganglia
    •      a. May increase HR
    •    (ii) Therapeutically, these drugs are as good as many others, but too many annoying side effects
    •   (e) Central (CNS- SNS) or Central & Peripheral sympathetic (CNS & PNS- SNS) blockers
    •    (i) CNS: Methylodopa (Aldomet ®), clonidine, guanabenz, guanfacine-
    •     1. In general, shouldn’t be used for initial treatment – withdrawal can cause rebound hypertension
    •      a. Do not miss a dose; withdraw slowly
    •     2. Sedation, dry mouth, dizziness occur frequently
    •     3. Transdermal Clonidine (Catapres ® patch) has duration of 1 week w/ minimal side effects
    •      a. Shows experimental promise in # of conditions w/ a disturbance of catecholaminergic function
    •       i. Promotes growth in children
    •       ii. Drug withdrawal
    •       iii. Treatment of psychiatric disorders
    •       iv. Control of antipsychotic drug induced reactions including tardive dyskinesias
    •    (ii) Rauwolfia Alkaloids (reserpine) –originally to treat psychoses [mental disorder]
    •     1. Mechanism of action
    •      a. Depletes Norepi in brain & heart
    •     2. Side or toxic effects
    •      a. CNS- sedative effect, psychic depression
    •      b. GI – (less sympathetic so parasympathetic seen)
    •       i. Increase tone & motility – cramps and diarrhea
    •       ii. Increased gastric secretion
    •      c. Nasal congestion (especially in 1st weeks)
    •     3. Contraindications
    •      a. Patients w/ depressive episodes
    •      b. Gastric ulcers
    •      c. Pregnant women (babies born w/ respiratory problems)
    •   (f) Monoamine Oxidase (MOA) Inhibitors – Paraglyne Hydrochloride
    •    (i) Mechanism of action – confusing
    •     1. In CNS: increases norepinephrine (as needed)
    •      a. (good antidepressant)
    •      b. Because the MAO can’t break it down
    •     2. In SNS:
    •      a. first increase
    •       i. Because the MAO isn’t breaking ti down as much (expected)
    •      b. Then decrease norepi (making it an effective antihypertensive)
    •       i. Excess of tyrosine (no GI breakdown) replaces some of the NE as transmitter & it is less effective at stimulating the receptor (false transmitter)
    •      ii. This effect doesn’t occur in CNS due to BB Barrier
    •    (ii) Side or Toxic Effects
    •     1. NA++ (Sodium) fluid retention in some individuals
    •      a. Must use w/ a diuretic
    •     2. Reflex tachycardia due to decrease BP
    •      a. Must given w/ beta blockers
    •     3. Some CNS & GI effects - mechanism? Very common
    •      a. Headache
    •      b. Nausea, loss of appetite
    •      c. Dizziness, sweating
    •     4. Note: Does not get postural hypotension – SNS still functional
    •    (iii) Contraindications
    •     1. Angina or coronary artery disease (tachycardia)
    •     2. Hypersensitive reaction to drug
    •     3. May develop rheumatism and blood diseases
    •      a. Skin rash, anemia indicate drug should be discontinued
    •  (2) Non-autonomic (ANS) inhibitors of smooth muscle of vessels
    •   (a) Direct acting, ACE (angiotensin converting enzyme) inhibitors, Angiotensin receptor antagonists, Calcium channel blockers
    • ----
    •  ii) Direct Peripheral Vasodilators – hydralazine, minoxidil, pinacidil
    •  (1) Mech of action: relax smooth muscle of vessels
    •  (2) Side or Toxic effects
    •   (a) Na++ fluid retention in some individuals
    •    (i) Use w/ diuretic
    •   (b) Reflex tachycardia due to decrease BP   (i) Give w/ Beta blockers
    •   (c) Some CNS & GI effects – mechanism? – very common
    •    (i) Headache
    •    (ii) Nausea, loss of appetite
    •    (iii) Dizziness, sweating
    •   (d) Do not get postural hypotension- SNS still functional
    •  (3) Contraindications
    •   (a) Angina or coronary artery disease  (tachycardia)
    •   (b) Hypersensitive reaction to drug
    •   (c) May develop rheumatism and blood diseases
    •    (i) Skin rash, anemia indicate drug should be discontinued
    • ----
    •   (b) ACE (Angiotensin Converting Enzyme) Inhibitors: (ends w/ -pril)
    •    (i) Mechanism: Inhibits ACE
    •     1. Less vasoconstriction & aldosterone secretion = less fluid retention
    •    (ii) Adverse Effects:
    •     1. Less concern about severe effects
    •      a. Fatal bone marrow depression & renal damage occur chiefly in patients w/ renal disease
    •     2. Persistent cough, rash, proteinuria, headache, myalgia, dyspepsia, diarrhea
    •     3. Contraindicated in pregnancy:
    •      a. 2nd & 3rd trimester death or injury to fetus
    •     4. Less effective in black patients
    •    (iii) Especially effective w/ a small dose of hydrochlorothiazide
    •    (iv) Recommended for other use are therapeutic uses
    •     1. Often the 1st drug given for CHF (Cardiac Heart Failure)
    •      a. Digitalis & diuretics are often prescribed as well
    •      b. Less likely to cause potassium depletion and cardiac arrhythmias
    •      c. More likely to cause first dose hypotension & dizziness, decreased renal function and severe persistent cough
    •     2. Has been recommended post MI to decrease chances of slow onset of heart failure
    •      a. Improves perfusion of cardiac muscle
    •     3. Being used to reduce diabetic nephropathy
    •      a. Relaxes efferent arteriole lowering glomerular pressure & presumably damage
    •   (c) Angiotensin receptor antagonists (ends w/ -tan)
    •    (i) Mechanism of action – Blocks Angiotensin II Receptor
    •     1. Prevents angiotensin II from constricting smooth muscle
    •     2. Prevents stimulating adrenal cortex for aldosterone release
    •    (ii) Therapeutic Use:
    •     1. Only recommended for hypertension control (CHF, etc)
    •    (iii) Adverse Effects:
    •     1. Essentially same as ACE inhibitors except no persistent cough
    •      a. Rash, proteinuria, headache, myalgia, dyspepsia, diarrhea
    •      b. Contraindicated in pregnancy:
    •       i. 2nd & 3rd trimester death or injury to fetus
    •      c. Less effective in black patients
    •   (d) Aldosterone receptor antagonists (ends w/ -one)
    •    (i) Mechanism of action – Blocks Aldosterone Receptor
    •     1. In renal epithelial cells (especially distal tubule)
    •     2. In non-epithelial cells of heart, blood vessels, brain
    •    (ii) Therapeutic Use:
    •     1. Hypertension control
    •     2. CHF (refer back to CHF alternatives in notes)
    •    (iii) Adverse Effects:
    •     1. Few so far
    •      a. Diarrhea
    •      b. Rare liver enzyme increases
    •      c. Rare kidney marker increases (BUN, creatinine, uric acid)
    •     2. Cations: monitor potassium levels for hyperkalemia
    •   (e) Calcium channel blockers (verapamil, ditiazem, -dipine)
    •    (i) All cause vasodilation
    •    (ii) Usually a rflex tachycardia also occurs
    •    (iii) Direct action on blocking heart still makes these useful to treat atrial tachycardias
    •    (iv) Therapeutic uses:
    •     1. Hypertension
    •     2. Supraventricular tachycardia, angina
    •     3. Better choice for black patients (along w/ diuretics)
    •    (v) Adverse effects
    •     1. Prepheral edema, dizziness, fatigue, flushing
    •     2. Constipation, nausea, diarrhea
    •    (vi) Contradiction in CHF (weakens contraction)
    •     1. Note: compare/contrast w/ ACE inhibitors
    •  (3) Drugs acting on blood volume
    •   (a) Diuretics [modifying circulating volume] 
    •    (i) Use thiazide type (eg. Chlorothiazide)
    •    (ii) Useful in combinations
    •    (iii) Useful in black patients
    •    (iv) Mechanism of action – prevents hypervolemia
    •      1. Initially decreases blood volume and fluid in tissues
    •       a. Cause increase Na+ excretion and water follows
    •     2. Appears to also relax blood vessels
    •    (v) Side or toxic effects
    •     1. Potassium depletion (cause arrhythmias)
    •     2. May aggravate diabetes mellitus
    •      a. Thiazides seem to inhibit insulin secretion
    •    (vi) Contraindications or Cautions
    •     1. Possibly diabetes
    •     2. Renal or liver disease (somehow thiazides aggravate condition)
    •     3. Cardiac arrhythmias (because of K+ depletion)
    •  iii) Summary of Antihypertensive drugs
    •  (1) Control of hypertension difficult
    •   (a) All effective agents produce significant side effects
    •   (b) Mild hypertension use – weigh control, avoid salt, possible exercise
    •   (c) When drug therapy required, usually use 2 or more drugs – helps avoid side effects
    •    (i) Hydralazine (relaxes vessels directly but causes reflex tachycardia) w/ propranolol (Beta blocker – lower BP and also reduces tachycardia)
    •    (ii) Or a diuretic w/ any other kind of agent
    •  iv) Hypertensive emergencies
    •  (1) Classically use IV medicines that relax blood vessels
    •   (a) Diazoxide (Hyperstat ®) – given IV push or drip
    •    (i) – used w/ a diuretic, relaxes arteries and venules possibly by antagonizing Ca++
    •   (b) Sodium Nitroprusside (Nipride®) – IV drip
    •    (i) Requires constant attention – relaxes arteries and venules
    •   (c) Labetolol IV (alpha and beta blockers)
    •    (i) Easily countered w/ specific antidotes, can be followed w/ oral form

    • b) Pressor agent/Hypertensive agent
    •  i) Mechanism of action: –increase BP, given to some1 w/ hypotension (only if it causing clinical symptoms) by:
    •  (1) Increased peripheral resistance: Alpha agonist
    •   (a) Phenylephrine (for spinal anesthesia) or dopamine
    •  (2) Increased cardiac output: Beta agonists
    •   (a) Isoproterenol (a Beta agonist – for shock)
    •   (b) Sometimes use drugs that are both Alpha & Beta agonists
    •    (i) Eg: ephedrine (for spinal anesthesia) or norepinephrine (for myocardial shock following myocardial infarction)
    •  (3) Replace blood volume
    •   (a) Whole blood, blood constituents (like cells, plasma, or proteins), & plasma substitutes (like dextran)
    •  ii) Therapeutic uses
    •  (1) Chronic hypotension – not defined as a specific BP
    •   (a) Treated only if symptomatic, i.e. fainting, increase HR
    •   (b) Might phenylephrine – alpha agonist
    •  (2) Acute hypotension –usually in hospital – often an emergency
    •   (a) Spinal anesthesia – ephedrine (alpha and beta), metaraminol (alpha), phenylephrine (alpha)
    •   (b) During surgery – pick alpha agonist (beta may cause cardiac arrhythmias)
    •   (c) Cardiac surgery – dopamine (mild beta & alpha agonist w/ added vasodilator effects that help increase sodium ion elimination)
    •   (d) Hypovolemic shock
    •    (i) Replace blood volume
    •    (ii) Then drugs that mildly dilate and increase CO (dopamine, isoproterenol)
    •  iii) No contraindication (emergency uses)
    •  (1) Caution: not for chronic therapy
  5. 4) What are the conductivity cells in the heart and where are they located?
    • a) SA node: pace maker; right supra-arteriole area
    • b) AV node: relay & slower: arterial-ventricular area
    • c) Bundle of His: a slender bundle of modified cardiac muscle that passes from the atrioventricular node in the right atrium to the right and left ventricles by way of the septum and that maintains the normal sequence of the heartbeat by conducting the wave of excitation from the right atrium to the ventricles—called also atrioventricular bundle, His bundle
    • d) Purkinje system: a network of Purkinje fibers that carry the cardiac impulse from the atrioventricular node to the ventricles of the heart and causes them to contract

    • e) Automacity
    •  i) -capacity for spontaneous, repetitive self- excitation usually only found in SA & AV nodes & in Bundle of His & Purkinje system. 
    •  ii) Due in part, to a slow influx of Na+ & Ca++ ions, but ultimately triggered by time-dependent "pacemaker" current that opens the sodium ion channels
    •  (1) Adrenergic stimulation: increase b/g influx of Na+ ion & calcium ion & seems to + the rate of the "pacemaker" current
    •  (2) Vagal stimulation: increase K+ efflux & hyperpolarize the cells
  6. 5) What is the refractory period?
    • a) –time when heart may not be stimulated again
    •  i) Av node limited to about 200 beats/minute
    •  ii) Explains use of electroshock for:
    •  (1) Ectopic foci
    •   (a) Out of place “pacemaker”
    •   (b) “escape” beats are lifesavers
    •  (2) Circus movements
    •   (a) Same impulse travels around and around
    •    (i) [diminish refractory period = inhibits resting/refilling phase]
    •   (b) Reentry- the same impulse reactivates tissue that it has already stimulated
    •    (i) Requires:
    •    (ii) Normal conduction to be slowed
    •    (iii) Refractoriness to be shortened
    •    (iv) both
    •  (3) Fibrillation
    •   (a) Cells fire individually w/ no unified beat
    •    (i) [firing/depolarization all over the place]
  7. 6) Indications/ Contraindications for the use of a cardiac glycoside? (Digitalis)
    • a) Background
    •  i) Structure of Chemical Group
    •  (1) All have sugar structural group (glycoside)
    •  (2) Attach various other chemical groups  (aldehyde, hydroxyl, etc)
    •  (3) Some can be extracted from plants
    •   (a) Digoxin (Lanoxin®): form white foxglove
    •    (i) (Caution: renal failure)
    •   (b) Digitoxin: from purple foxglove (Digitalis Purpura)
    •    (i) Note: different cardiac glycosides have different pharmacokinetics & shouldn’t be used interchangeably. Dosages, durations, etc differs: longer name = long 1/2 life
    • b) Actions: -C:HR, +I:SV, -D:CV
    •  i) + inotropic action (strength of contraction)
    •  ii) – dromotropic effect in the heart
    •  iii) – chronotropic action
    • c) Mechanism:
    •  i) Increase Ca++ release w/in cardiac muscle (stronger: SV)
    •  ii) Moves calcium into muscle (w/ slower conduction: -CV)
    •  iii) Increases vagal tone-slows HR (= +PNS: muscarinic effect)
    •  (1) This is a significant feature in later discussions
    • d) Therapeutic Uses:
    •  i) Congestive heart failure (CHF) heart fails to pump adequate amount of blood
    •  (1) Mechanism of action: + inotropic effect
    •   (a) Supportive treatment: decreased weight, physical activity, and Na intake, and treat hypertension if present
    •   (b) Result: heart size decreased to normal, lower HR, diuresis
    •  ii) Atrial flutter (200-300 beats/minute) or Fibrillation (moer than 300 beats/minute) or Paroxysmal tachycardia (irregular beats)
    •  (1) Usually requires higher dose than treating CHF
    •  (2) Mechanism of action (protect ventricles):
    •   (a) Depresses electrical conduction in atria and AV node
    •   (b) Increased refractory period
    • e) Issues to Consider: Cardiac Glycosides Can be Dangerous!
    •  i) Commonly prescribed yet poor margin of safety
    •  (1) Low therapeutic index*
    •   (a) (= Digitoxicity: one of most adverse effect)
    •  ii) Order of appearance unpredictable
    •  iii) Dose must be carefully adjusted for each  patient
    •  (1) (ex: ppl w/ renal failure)
    •  iv) Very small dose required (low T.I.)
    •  (1) = Errors are significant
    •  v) Poisoning usually due to “cumulative effect”
    •  (1) (drug level goes up: not getting eliminated fast enough)
    •  vi) "Digitalizing” dose* = priming dose or loading dose
    •  (1) (strong bound w/ plasma proteins)
    •  (2) Otherwise would take at least one week to reach therapeutic levels
    • f) Side Effects or Toxic Effects
    •  i) GI – loss of appetite, nausea, vomiting, diarrhea (due to + PNS)
    •  (1) Partly due to GI irritation; also may be due to toxicity
    •  (2) May take w/ food or immediately after food but absorption may be altered
    •  ii) Visual – single color vision *(yellow or green tinged vision), white halos around objects, blurred or double vision
    •  iii) Nervous irritability, restlessness, weakness, headache (usually not serious – cut dosage)
    •  iv) Arrhythmias* – many kinds – watch ventricles
    •  (1) Ventricular tachycardia (more ectopic beats)
    •  (2) “Bigeminy” – indicates toxicity
    •  (3) Ventricular fibrillations – most common cause of death
    •  (4) A-V block – due to negative dromotropic effect
    • g) Contraindications or Cautions: Note precautions are relative
    •  i) Recent myocardial infarction
    •  (1) Prone to developing arrhythmias
    •  (2) Digitalis may have additive or synergistic effect
    •  ii) Ventricular tachycardia – may throw into fibrillation
    •  (1) Increased ectopic foci & automaticity
    •  iii) Partial heart block – may produce complete block
    •  (1) Pacemaker is better option
    •  iv) Cardioversion (electroshock)
    •  (1) May cause fibrillation that will not respond to further shocks
    •  v) Calcium administration
    •  (1) – Ca++ synergistic w/ digitalis – toxic effect
    •  vi) Potassium depletion
    •  (1) – increases toxicity
    •  vii) Renal or hepatic disorders or older patient
    •  (1) Lower maintenance dose required
    • h) Drug Interactions
    •  i) Phenobarbital
    •  (1) Causes increased degradation, thus decreased effect
    •  ii) Diuretics (indirect only)
    • (1) Decrease K+ which increases digitalis toxicity
    •  iii) Calcium ion
    •  (1) Increase in Ca++ will increase toxicity
    • i) Other Meds for Heart Failure:
    •  i) ACE inhibitors are now recommended 1st for cases of heart failure
    •  ii) Diuretics often used to control edema
    •  iii) Beta Blockers (early only)
    •  (1) Slows progression in some patients
    •  (2) Later in disorder is contraindicated
    •  iv) Flosequinan (a flouroquinolone) –uncommon
    •  (1) Approved 1993 for cases resistant to ACE inhibitors
    •  v) Aldosterone blockers
    •  (1) Aldosterone produced peripherally in heart & major vessels
    •  (2) Aldosterone directly induces myopathy
    •  (3) Aldosterone blocks reuptake epi/Norepi so induces symp. Arrhy.
    •  vi) Phosphodiesterase Inhibitors (amrinone & milrinone)
    •  (1) Positive inotropic, dilates veins (less return)
    •  (2) Dilates arteries (decreases afterload)
    •  (3) Not supported by follow-up studies
    •  (4) Too many cautions but try short term
    • j) Major side effects
    •  i) GI – loss of appetite, nausea, vomiting, diarrhea (due to + PNS)
    •  (1) Partly due to GI irritation; also may be due to toxicity
    •  (2) May take w/ food or immediately after food but absorption may be altered
    •  ii) Visualsingle color vision *(yellow or green tinged vision), white halos around objects, blurred or double vision
    •  iii) Nervous irritability, restlessness, weakness, headache (usually not serious – cut dosage)
    •  iv) Arrhythmias* – many kinds – watch ventricles
    •  (1) Ventricular tachycardia (more ectopic beats)
    •  (2) “Bigeminy” – indicates toxicity
    •  (3) Ventricular fibrillations – most common cause of death
    •  (4) A-V block – due to negative dromotropic effect
  8. 7) Indications/ Contraindications for the use of antiarrythmics (quinidine)
    • a) Prototype anti-arrhythmic drug
    •  i) Originally for malaria
    •  ii) Used less frequently than digitalis for arrhythmias
    •  iii) (Anti-muscarininc: block PNS = + excitability of AV node)
    •  iv) Effective orally*
    • b) Mechanism of Action: an overview: -C:HR:Na, -I:SV:Ca, -D:CV:K
    •  i) Chiefly a cardiac depressant: (anti-muscarinic effect)
    •  (1) (Explains therapeutic effects)
    •  (2) Decreased excitability, conduction velocity, and contractility
    •  (3) More effective on His & Purkinje than SA node
    •  (4) Prolongs effective refractory period (blocks K+ ch)
    •  ii) Also anticholinergic (atropine-like) action – AV node
    •  (1) (Explains negative effects)
    •  (2) (antimuscarinic: block PNS = + excitability of AV node)
    •  (3) Prevents cardiac slowing w/ muscarinic drugs
    •  (4) May be hazard when used to treat flutter or fibrillation
    •   (a) Atrial flutter may be transmitted to ventricles
    •    (i) (all arrhythmias cause another arrhythmia)
    •  (5) Solution: often used after digitalis because digitalis does inhibit conduction through A-V node
    • c) Therapeutic Uses
    •  i) Atrial fibrillation – converts to normal sinus rhythm
    •  (1) Hospital setting
    •  (2) Electrical conversion more commonly used than drug
    • (3) Sometimes used to prevent reoccurrence  of fibrillation
    •  ii) Atrial flutter – used if digitalis fails to work
    •  iii) Ventricular tachycardia
    •  (1) Common complication of myocardial infarction
    •  (2) Electroshock – implantable defibrillators
    •  (3) Lidocaine used in hospital if episodes repeatedly occur
    •   (a) Really good Na+ blocker vs ventricular arrhtmias
    •    (i) Intravenous
    •    (ii) –C, none I, -D
    •    (iii) Slow conduction
    •   (b) Given only IV in emergenciesrapid onset, short duration
    •   (c) An antiarrythmic agent that is used for ventricular arrhythmias in emergency situations because it has a rapid onset and a short duration of action and does not have an anticholinerigc effect
    •  iv) Premature systoles (PVC)
    •  (1) Usually only treat if thin will lead to more serious arrhythmias (tachycardia, flutter, fibrillation)
    • d) Side or Toxic Effects
    •  i) Cinchonism* (quinidine for cinchona bark)
    •  (1) (ringing in ears, dizziness (vertigo), blurred vision)
    •  (2) Relate to malaria treatment
    •  (3) Aspirin
    •  ii) Mild to moderate symptoms
    •  (1) Gi – nausea, vomiting, diarrhea, abdominal pain
    •  (2) Ears- ringing, decreased hearing
    •  (3) Eyes – blurred vision, night blindness
    •  (4) CNS- headache
    •  iii) Most toxic
    •  (1) Low BP (due to alpha blockade = intense vasodilation = hypotension)
    •  (2) Respiratory depression, respiratory arrest
    •  (3) Low temperature
    • e) Contraindications/Cautions
    •  i) Complete A-V block
    •  ii) Cardiac failure
    •  iii) Allergy to drug or idiosyncracy
    •  iv) Due to anticholinergic properties
    •  (1) Caution glaucoma, urinary retention
    •  v) Serum K+ must be normal
    •  (1) Hypokalemia decreased drug effectiveness
    •  (2) Hyperkalemia increases it
    • f) [Other Antiarrhythmics
    •  i) You should know:
    •  (1) Quinidine*
    •  (2) Lidocaine*
    •   (a) Given only IV in emergencies – rapid onset, short duration
    •   (b) An antiarrythmic agent that is used for ventricular arrhythmias in emergency situations because it has a rapid onset and a short duration of action and does not have an anticholinerigc effect is:Premature systoles (PVC)
    •  (3) Beta blockers
    •  (4) Ca++ ch blockers]
    • g) Major side effects
    •  i) Cinchonism* [quinidine from cinchona bark]: (toxic effect too severe*)
    •  (1) (ringing in ears, dizziness (vertigo), blurred vision)
    •  (2) Relate to malaria treatment
    •  (3) Aspirin
    •  ii) Mild to moderate symptoms
    •  (1) Gi – nausea, vomiting, diarrhea, abdominal pain
    •  (2) Ears- ringing, decreased hearing
    •  (3) Eyes – blurred vision, night blindness
    •  (4) CNS- headache
    •  iii) Most toxic
    •  (1) Low BP (due to alpha blockade = intense vasodilation = hypotension)
    •  (2) Respiratory depression, respiratory arrest
    •  (3) Low temperature
  9. 8) Indications/ Contraindications for the use of cardiac stimulants
    • a) -Treating Arrythmias that are slow
    •  i) Therapy is only a temporary measure
    •  (1) Heart starts
    •  (2) Electrical pacemaker fitted (overcome A-V block)
    • b) Mechanism of action
    •  i) Adrenergic Agents – Stimulates Beta activity of heart
    •  (1) Epinephrine (Alpha & Beta agonist)
    •  (2) Isoproterenol (Beta agonist) – can be given orally or sublingually
    •  ii) Anticholinergic Agents
    •  (1) Block muscarinic slowing
    • c) Therapeutic Uses
    •  i) –for most therapeutic uses try adrenergic agonist
    •  ii) Cardiac arrest
    •  iii) Hypotensive crisis
    •  iv) A-V block
    •  v) Bradycardia
    •  (1) –for bradycardia, chiefly use anticholinergic agent
    • d) Side Effects
    •  i) Not crucial –drug used acutely
    • e) Toxic Effects
    •  i) Heart
    •  (1) Palpitations, tachycardia, ventricular arrhythmias
    •  ii) CNS
    •  (1) Headache, fear, anxiety, restlessness
    •  iii) BP
    •  (1) May rise alarmingly
    • f) Contraindications
    •  i) Not for chronic use
    •  (1) Make heart work too hard & increase its O2 use
    •  ii) Congestive heart failure
    •  iii) Angina pectoris
    •  iv) High blood pressure… unless cardiac  arrest
    • g) Major side effects
    •  i) Heart
    •  (1) Palpitations, tachycardia, ventricular arrhythmias
    •  ii) CNS
    •  (1) Headache, fear, anxiety, restlessness
    •  iii) BP
    •  (1) BP may rise alarmingly
  10. 9) Indications/ Contraindications for the use of anti-anginal meds
    • a) (Angina Pectoris: Heart Pain caused by mismatch of O2 supply vs. O2 demand (coronary arteries)
    •  i) Causes related to O2 supply
    •  (1) Atheroscleoris
    •  (2) Spasms of coronary arteries (Prinzmetal’s variant angina)
    •  (3) Anemia
    •  ii) Causes related to O2 demand
    •  (1) Hypertension
    •  (2) Pulmonary hypertension
    •  (3) Heart valve disease
    •   (a) Note: when severe these conditions may also affect supply
    •  iii) Attacks precipitated by exercise or strong emotions)
    • b) Nitrates & nitrites
    •  i) Nitroglycerine – a nitrate, is DRUG OF CHOICE
    •  (1) –relaxes smooth muscle: decreasing workload of heartslight increase O2 supply
    •  ii) Routes of admin
    •  (1) Sublingually (must bypass liver)
    •   (a) Onset: 1-2 min
    •   (b) Duration: 15060 min
    •  (2) Ointment for longer lasting effect
    •   (a) Onset: 15 min – 1hr
    •   (b) Duration: 2-12 hr
    •  (3) Patch for 24 hr duration
    •  (4) IV controls BP during surgery
    •  iii) Therapeutic uses
    •  (1) Angina pectoris
    •  (2) BP during surgery or hypertensive
    •  iv) Side or Toxic Effects
    •  (1) Tachycardia (not serious)
    •  (2) Headache (disappears w/ use – tolerance)
    •   (a) Dilation cerebral blood vessels
    •  (3) Postural hypotension* – dizziness & weakness upon standing
    •  v) Contraindications or Cautions
    •  (1) Storage of medicine deteriorates in light, high temperature, moisture; keep away from body heat: (fragile)
    •  (2) Glaucoma – dilated eye vessels may increase intra-ocular pressure
    •  (3) Head trauma – cerebrovascular hemorrhage, intracranial pressure
    • c) Beta blockers (-lol)
    •  i) Doesn’t help during attach
    •  ii) Used to prevent attack (decrease workload of heart)
    • d) Ca++ channel blocking agents (verapamil, nifedipine, diltiazem, nicardipine, nimodipine)
    •  i) Mech: blocks extracellular Ca++ into cells
    •  (1) Dilation of coronary & peripheral vessels
    •  (2) Decrease in cardiac contractility
    •   (a) Useful chiefly in Prinzmetal’s “variant” angina due to coronary artery spasm
    •   (b) Not better than nitrates
    •   (c) Not very useful in coronary vessels are occluded
    •  ii) Side effects: From relaxation of smooth & cardiac muscle
    •  (1) Hypotension, peripheral edema
    •  (2) Dizziness, headache
    •  (3) Bradycardia & possible CHF if patient susceptible
    •  (4) Constipation, nausea, diarrhea, fatigue
    •  iii) Dipyridamole (Persantine®)
    •  (1) Not for acute attacks
    •  (2) Causes selectively vasodilation of coronary arteries
    •  (3) Seems to reduce nitrate requirements in some patients
    •  (4) Adverse effects minimal and transient
    •   (a) Headache
    •   (b) Nausea, GI distress
    •    (i) Not very popular as an antianginal agent but being used as an anticoagulant due to its inhibition of platelet aggregation
    • e) Major side effects
    •  i) Nitrate: nitroglycerine
    •  (1) Tachycardia (not serious)
    •  (2) Headache (disappears w/ use – tolerance)
    •   (a) Dilation cerebral blood vessels
    •  (3) Postural hypotension – dizziness & weakness upon standing
    •  ii) Ca++ channel blocker
    •  (1) Hypotension, peripheral edema
    •  (2) Dizziness, headache
    •  (3) Bradycardia & possible CHF if patient susceptible
    •  (4) Constipation, nausea, diarrhea, fatigue
  11. 10) Indications/ Contraindications for the use of antihypertensive
    • a) Automomic modifiers
    •  i) Block (SNS) sympathetic – either Alpha or Beta or both
    •  (1) PNS stimulator not used
    •  ii) Alpha blockers: prazosin, phenoxybenzamine, terazosin
    •  (1) Mech of action:
    •   (a) Block action of Epi & NE on receptors in peripheral arterioles (very useful lowering BP)
    •   (b) Inhibits vasoconstriction
    •  (2) Side or Toxic effects
    •   (a) 1st dose = Postural hypotension* (stand up = dizzy/weakness/fainting)
    •   (b) Reflex tachycardia
    •   (c) fluid retention
    •  iii) Beta blockers (-lol)
    •  (1) Mech of action: for HTN & arrythmia
    •   (a) decrease HR & (SV) force of contraction = decrease CO
    •   (b) inhibit renin release
    •   (c) decrease in vascular resistance & dilation arterioles
    •  (2) Side or Toxic effects
    •   (a) GI:(PNS stronger)- nausea, vomiting, diarrhea
    •   (b) Heart: uncommon, but may cause:
    •    (i) Serious cardiac depression; decrease in contractility of heart*
    •    (ii) A-V block
    •    (iii) rebound tachycardia*
    •   (c) Bronchioles – constrict airway
    •  (3) Contradictions: Asthma* or A-V block
    •   (a) Most useful in patients under 40*
    •   (b) Patients over 60 do poorly, but better w/ Ca++ channel blockers
    •  iv) Ganglionic blocker- no longer recommended (Hexamethonium)
    •  (1) Mech of action
    •   (a) Antinicotinic drug
    •   (b) Inhibition of sympathetic ganglia decreases BP
    •    (i) Decreases CO & vasoconstriction
    •   (c) Inhibition of parasympathetic ganglia
    •    (i) May increase HR
    •  (2) Therapeutically, these drugs are as good as many others, but TOO many annoying side effects
    •  v) Central or CNS & PNS blockers
    •  (1) CNS:Clonidine*, methyldopa (aldomet®), guanabenz, guanfacine
    •   (a) Mech of action:
    •    (i) Block Alpha-2 in brain = block all SNS out flow
    •     1. = decrease CO & vascular resistance = lower BP
    •   (b) In general, shouldn’t be used for initial treatment. Withdrawal = rebound hypertension. Don’t miss dose; withdraw slowly.
    •   (c) S/E: Sedation/depression, dry mouth, dizziness occur frequently: Rebound HTN
    •  (2) CNS&PNS- Reserpine (Rauwolfia Alkaloids): (originally for psychoses) (& Guanefidine)
    •   (a) Mech of action
    •    (i) Depletes NE in brain & heart (prevent release of NE in nerve terminals) = decrease vascular resistance & CO
    •   (b) Side or Toxic effects
    •    (i) CNS (Resperine can cross BB & cause depletion of catecholamines): sedative effect/psychic depression
    •    (ii) GI: (less SNS = more PNS)
    •     1. + tone & motility = cramps & diarrhea
    •     2. + gastric secretion
    •    (iii) Nasal congestion (esp in 1st weeks)
    •    (iv) Severe hypotension
    •   (c) Contraindications
    •    (i) Patients w/ depressive episodes
    •    (ii) Gastric ulcers
    •    (iii) Pregnant women (babies born w/ respiratory problems)
    •  vi) Monoamine Oxidase (MOA) Inhibiotors – Paraglyne Hydrochloride
    •  (1) Mechanism of action – confusing
    •   (a) In CNS: increases norepinephrine (as needed)
    •    (i) (good antidepressant)
    •    (ii) Because the MAO can’t break it down
    •   (b) In SNS:
    •    (i) first increase
    •     1. Because the MAO isn’t breaking ti down as much (expected)
    •    (ii) Then decrease norepi (making it an effective antihypertensive)
    •     1. Excess of tyrosine (no GI breakdown) replaces some of the NE as transmitter & it is less effective at stimulating the receptor (false transmitter)
    •     2. This effect doesn’t occur in CNS due to BB Barrier
    •  (2) Side or Toxic Effects
    •   (a) Acute:
    •    (i) CNS (excess) stimulation= hallucination, agitation, convulsions
    •    (ii) Hypo/hypertension
    •   (b) Chronic
    •    (i) CNS (excess) stimulation- tremors, insomnia, nightmares, mood elevation
    •    (ii) Rarely confusion & hallucinations
    •    (iii) Inhibition of SNS
    •     1. GI: nausea, constipation (common, but cause unknown)
    •     2. Postural hypotension
    •     3. Decreased sexual function
    •     4. Hypertensive crisis may occur (see contradictions)
    •  (3) Contradictions: Food, drugs, renal failure & accumulation

    • b) Non-autonomic (ANS) inhibitors of smooth muscle of vessels
    •  i) Direct acting, ACE (angiotensin converting enzyme) inhibitors, Angiotensin receptor antagonists, Calcium channel blockers
    •  ii) Direct Peripheral Vasodilators – hydralazine, minoxidil, pinacidil
    •  (1) Mech of action: relax smooth muscle of vessels
    •  (2) Side or Toxic effects
    •   (a) Na++ fluid retention in some individuals
    •    (i) Use w/ diuretic
    •   (b) Reflex tachycardia due to decrease BP
    •    (i) Give w/ Beta blockers
    •   (c) Some CNS & GI effects – mechanism? – very common
    •    (i) Headache
    •    (ii) Nausea, loss of appetite
    •    (iii) Dizziness, sweating
    •   (d) Do not get postural hypotension- SNS still functional
    •  (3) Contraindications
    •   (a) Angina or coronary artery disease  (tachycardia)
    •   (b) Hypersensitive reaction to drug
    •   (c) May develop rheumatism and blood diseases
    •    (i) Skin rash, anemia indicate drug should be discontinued
    •  iii) ACE (Angiotensin Converting Enzyme) Inhibitors: (ends w/ -pril)
    •  (1) Mechanism: Inhibits ACE. For HTN
    •   (a) Less vasoconstriction & aldosterone secretion = less fluid retention = decrease BP
    •  (2) Adverse Effects:
    •   (a) Less concern about severe effects
    •    (i) Fatal bone marrow depression & renal damage occur chiefly in patients w/ renal disease
    •   (b) Persistent cough*, rash, proteinuria, headache, myalgia, dyspepsia, diarrhea
    •   (c) Contraindicated in pregnancy:
    •    (i) 2nd & 3rd trimester death or injury to fetus
    •   (d) Less effective in black patients
    •  (3) Especially effective w/ a small dose of hydrochlorothiazide
    •  (4) Recommended for other use are therapeutic uses:
    •   (a) Often the 1st drug given for CHF (Cardiac Heart Failure)
    •    (i) Digitalis & diuretics are often prescribed as well
    •    (ii) Less likely to cause potassium depletion and cardiac arrhythmias
    •    (iii) More likely to cause first dose hypotension & dizziness, decreased renal function and severe persistent cough
    •   (b) Has been recommended post MI to decrease chances of slow onset of heart failure
    •    (i) Improves perfusion of cardiac muscle
    •   (c) Being used to reduce diabetic nephropathy
    •    (i) Relaxes efferent arteriole lowering glomerular pressure & presumably damage
    •  iv) Angiotensin receptor antagonists (ends w/ -tan)
    •  (1) Mechanism of actionBlocks Angiotensin II Receptor
    •   (a) Prevents angiotensin II from constricting smooth muscle
    •   (b) Prevents stimulating adrenal cortex for aldosterone release
    •  (2) Therapeutic Use:
    •   (a) Only recommended for hypertension control (CHF, etc)
    •  (3) Adverse Effects:
    •   (a) Essentially same as ACE inhibitors except no persistent cough*
    •    (i) Rash, proteinuria, headache, myalgia, dyspepsia, diarrhea
    •    (ii) Contraindicated in pregnancy:
    •    (iii) 2nd & 3rd trimester death or injury to fetus
    •    (iv) Less effective in black patients
    •  v) Aldosterone receptor antagonists (ends w/ -one)
    •  (1) Mechanism of actionBlocks Aldosterone Receptor
    •   (a) In renal epithelial cells (especially distal tubule)
    •   (b) In non-epithelial cells of heart, blood vessels, brain
    •  (2) Therapeutic Use:
    •   (a) Hypertension control
    •   (b) CHF (refer back to CHF alternatives in notes)
    •  (3) Adverse Effects:
    •   (a) Few so far
    •    (i) Diarrhea
    •    (ii) Rare liver enzyme increases
    •    (iii) Rare kidney marker increases (BUN, creatinine, uric acid)
    •   (b) Cautions: monitor potassium levels for hyperkalemia
    •  vi) Calcium channel blockers (verapamil, ditiazem, -dipine)
    •  (1) All cause vasodilation
    •  (2) Usually a reflex tachycardia also occurs
    •  (3) Direct action on blocking heart still makes these useful to treat atrial tachycardias
    •  (4) Therapeutic uses:
    •   (a) Hypertension
    •   (b) Supraventricular tachycardia, angina
    •   (c) Better choice for black patients** (along w/ diuretics)
    •  (5) Adverse effects
    •   (a) Prepheral edema, dizziness, fatigue, flushing
    •   (b) Constipation, nausea, diarrhea
    •  (6) Contradiction: not for patients w/ CHF: (drug weakens contraction*)
    •   (a) Note: compare/contrast w/ ACE inhibitors

    • c) Drugs acting on blood volume
    •  i) Diuretics [modifying circulating volume]- often 1st line therapy
    •  (1) Use thiazide type (eg. Chlorothiazide)
    •  (2) Useful in combinations
    •  (3) Useful in black patients
    •  (4) Mechanism of action – prevents/reduce hypervolemia
    •   (a) Initially decreases blood volume and fluid in tissues
    •    (i) Cause increase Na+ excretion and water follows
    •   (b) Appears to also relax blood vessels
    •  (5) Side or toxic effects
    •   (a) Potassium depletion (cause arrhythmias)
    •   (b) May aggravate diabetes mellitus
    •    (i) Thiazides seem to inhibit insulin secretion
    •  (6) Contraindications or Cautions
    •   (a) Possibly diabetes
    •   (b) Renal or liver disease (somehow thiazides aggravate condition)
    •   (c) Cardiac arrhythmias (because of K+ depletion)

    • d) Summary of Antihypertensive drugs
    •  i) Control of hypertension difficult
    •  (1) All effective agents produce significant side effects
    •  (2) Mild hypertension use – weigh control, avoid salt, possible exercise
    •  (3) When drug therapy required, usually use 2 or more drugs – helps avoid side effects
    •   (a) Hydralazine (relaxes vessels directly but causes reflex tachycardia) w/ propranolol (Beta blocker – lower BP and also reduces tachycardia)
    •   (b) Or a diuretic w/ any other kind of agent
    • e) Hypertensive emergencies
    •  i) Classically use IV medicines that relax blood vessels
    •  (1) Diazoxide (Hyperstat ®) – given IV push or drip
    •   (a) – used w/ a diuretic, relaxes arteries and venules possibly by antagonizing Ca++
    •  (2) Sodium Nitroprusside (Nipride®) – IV drip
    •   (a) Requires constant attention – relaxes arteries and venules
    •  (3) Labetolol IV (alpha and beta blockers)
    •   (a) Easily countered w/ specific antidotes, can be followed w/ oral form

    • f) Major side effects
    •  i) Autonomic modifier
    •  (1) Alpha blocker
    •   (a) Postural hypotension (stand up = dizzy/weakness/fainting)
    •   (b) Reflex tachycardia
    •  (2) Beta blocker
    •   (a) GI: nausea, vomiting, diarrhea
    •   (b) Heart: uncommon, but may cause:
    •    (i) Serious cardiac depression
    •    (ii) A-V block
    •   (c) Bronchioles – constrict airway
    •  (3) Ganglionic blocker
    •   (a) Too many side effects
    •  (4) CNS, CNS & PNS
    •   (a) Central blocker: Clonidine
    •    (i) Sedation/depression, dry mouth, dizziness occur frequently
    •   (b) Reserpine: Ruawolfia Alkaloids
    •    (i) CNS: sedative effect/psychic depression
    •    (ii) GI: (less SNS = more PNS)
    •     1. + tone & motility = cramps & diarrhea
    •     2. + gastric secretion
    •    (iii) Nasal congestion (esp in 1st weeks)
    •   (c) MAO inhibitor
    •    (i) Acute:
    •     1. CNS stimulation= hallucination, agitation, convulsions
    •     2. Hypo/hypertension
    •    (ii) Chronic
    •     1. CNS stimulation- tremors, insomnia, nightmares, mood elevation
    •    2. Rarely confusion & hallucinations
    •    3. Inhibition of sympathetic nervous system
    •     a. GI: nausea, constipation (common, but cause unknown)
    •     b. Postural hypotension
    •     c. Decreased sexual function
    •     d. Hypertensive crisis may occur (see contradictions)
    •  ii) Non-Autonomic inhibitors of smooth muscle
    •  (1) Direct Peripheral vasodilators
    •   (a) Na++ fluid retention in some individuals
    •    (i) Use w/ diuretic
    •   (b) Reflex tachycardia due to decrease BP
    •    (i) Give w/ Beta blockers
    •   (c) Some CNS & GI effects – mechanism? – very common
    •    (i) Headache
    •    (ii) Nausea, loss of appetite
    •    (iii) Dizziness, sweating
    •   (d) Do not get postural hypotension- SNS still functional
    •  (2) Renin-Angiotensin-Aldosterone System
    •   (a) Angiotensin Converting Enzyme (ACE) inhibitors
    •    (i) Less concern about severe effects
    •     1. Fatal bone marrow depression & renal damage occur chiefly in patients w/ renal disease
    •    (ii) Persistent cough, rash, proteinuria, headache, myalgia, dyspepsia, diarrhea
    •    (iii) Contraindicated in pregnancy:
    •     1. 2nd & 3rd trimester death or injury to fetus
    •    (iv) Less effective in black patients
    •   (b) Angiotensin receptor antagonist
    •    (i) Essentially same as ACE inhibitors except no persistent cough
    •     1. Rash, proteinuria, headache, myalgia, dyspepsia, diarrhea
    •     2. Contraindicated in pregnancy:
    •     3. 2nd & 3rd trimester death or injury to fetus
    •     4. Less effective in black patients
    •   (c) Aldosterone receptor antagonist
    •    (i) Few so far
    •     1. Diarrhea
    •     2. Rare liver enzyme increases
    •     3. Rare kidney marker increases (BUN, creatinine, uric acid)
    •    (ii) Cations: monitor potassium levels for hyperkalemia
    •  (3) Calcium Channel blockers
    •   (a) Prepheral edema, dizziness, fatigue, flushing
    •   (b) Constipation, nausea, diarrhea
    •  iii) Modifying Circulating Volume
    •  (1) Diuretics
    •   (a) Potassium depletion (cause arrhythmias)
    •   (b) May aggravate diabetes mellitus
    •    (i) Thiazides seem to inhibit insulin secretion

    • g) Main difference between the different mechanisms of action for the antihypertensives
    •  i) Autonomic modifier
    •  (1) Alpha blocker
    •   (a) Block action of epi & Norepi on receptors
    •   (b) Inhibits vasoconstriction
    •  (2) Beta blocker
    •   (a) Decreases HR & force of contraction so decreases CO
    •   (b) Inhibits renin release
    •  (3) Ganglionic blocker
    •   (a) Antinicotinic drug
    •   (b) Inhibit SNS ganglia = decrease BP: lower CO & vasoconstriction
    •   (c) Inhibit PNS ganglia = may increase HR
    •  (4) CNS, CNS & PNS
    •   (a) Central: Clonidine
    •    (i) Decrease BP, but take away too fast = rebound hypertension
    •   (b) Reserpine: Ruawolfia Alkaloids
    •    (i) Depletes Norepi in brain and heart
    •   (c) MAO inhibitor
    •    (i) In CNS: increases norepinephrine (as needed)
    •     1. (good antidepressant)
    •     2. Because the MAO can’t break it down
    •    (ii) In SNS:
    •     1. first increase
    •      a. Because the MAO isn’t breaking ti down as much (expected)
    •     2. Then decrease norepi (making it an effective antihypertensive)
    •      a. Excess of tyrosine (no GI breakdown) replaces some of the NE as transmitter & it is less effective at stimulating the receptor (false transmitter)
    •      b. This effect doesn’t occur in CNS due to BB Barrier
    •  ii) Non-Autonomic inhibitors of smooth muscle
    •  (1) Direct Peripheral vasodilators
    •   (a) Relaxes smooth muscle of vessels
    •  (2) Renin-Angiotensin-Aldosterone System
    •   (a) Angiotensin Converting Enzyme (ACE) inhibitors
    •    (i) Less vasoconstriction & less aldosterone secretion = less fluid retention
    •   (b) Angiotensin receptor antagonist
    •    (i) Prevent angiotensin II from constricting smooth muscle
    •    (ii) Prevent stimulating adrenal cortex for aldosterone release
    •   (c) Aldosterone receptor antagonist
    •    (i) In renal epithelial cells (especially distal tubule)
    •    (ii) In non-epithelial cells of heart, blood vessels, brain
    •    (iii) For: hypertension control & CHF
    •  (3) Calcium Channel blockers
    •   (a) All cause vasodilation
    •   (b) Usually reflex tachycardia occurs
    •   (c) Direct action on blocking heart still makes these useful to treat atrial tachycardia
    •  iii) Modifying Circulating Volume
    •  (1) Diuretics
    •   (a) Prevent hypervolemia
    •   (b) Initially decreases blood volume & fluid in tissues
    •    (i) Causes increase Na+ excretion & water follows
    •   (c) Appears to also relax blood vessels
  12. 11) Indications/ Contraindications for the use of hemopoietic(anti-anemic) agents
    • a) Mech of action: replace missing factor
    •  i) Iron – microcytic – component of hemoglobin
    •  ii) Vitamin B-12 – macrocytic anemia
    •  (1) Coenzyme for synthesis of DNA and other cell component
    •  iii) Folic acid – macrocytic anemia
    •  (1) needed for amino acid & DNA synthesis)
    •  iv) RBC, whole blood
    •  v) Erythropoietin: available as drug Epoetin Alfa (Epogen®)
    • b) Therapeutic use: treat anemia
    • c) Side or Toxic effect: chiefly w/ iron
    •  i) Headache & GI symptoms
    •  ii) Some overdoses in children have caused death
    • d) Cautions
    •  i) Iron, human blood components, folic acid
    • e) Major side effects
    •  i) Headache & GI symptoms
    •  ii) Some overdoses in children have caused death
  13. 12) Indications/ Contraindications for the use of antiarrythmics (quinidine & others)
    • I) Quinidine: Na+ ch blocker
    • a) Prototype anti-arrhythmic drug
    •  i) Originally for malaria
    •  ii) Used less frequently than digitalis for arrhythmias
    • b) Mechanism of Action:
    •  i) Chiefly a cardiac depressant; Na+ ch blocker; there is an antimuscarinic effect
    •  (1) (Explains therapeutic effects)
    •  (2) Decreased excitability, conduction velocity, and contractility: -C,-I,-D
    •  (3) More effective on: His & Purkinje than SA node
    •  (4) Prolongs effective refractory period
    •  ii) Also anticholinergic (atropine-like) action – AV node
    •  (1) (Explains negative effects)
    •  (2) Prevents cardiac slowing w/ muscarinic drugs
    •  (3) May be hazard when used to treat flutter or fibrillation
    •   (a) Atrial flutter may be transmitted to ventricles
    •  (4) Solution: often used after digitalis* because digitalis does inhibit conduction through A-V node (due to anticholinergic effect)
    • c) Therapeutic Uses
    •  i) Atrial fibrillation – converts to normal sinus rhythm
    •  (1) Hospital setting
    •  (2) Electrical conversion more commonly used than drug
    •  (3) Sometimes used to prevent reoccurrence of fibrillation
    •  ii) Atrial flutter – used if digitalis fails to work
    •  iii) Ventricular tachycardia
    •  (1) Common complication of myocardial infarction
    •  (2) Electroshock – implantable defibrillators
    •  (3) Lidocaine used in hospital if episodes repeatedly occur (-C,none I, -D): only IV in emergencies- rapid onset, short duration
    •  iv) Premature systoles (PVC)
    •  (1) Usually only treat if thin will lead to more serious arrhythmias (tachycardia, flutter, fibrillation)
    • d) Side or Toxic Effects
    •  i) Cinchonism* (quinidine for cinchona bark)
    •  (1) Relate to malaria treatment
    •  (2) similar to Aspirin toxicity
    •  ii) Mild to moderate symptoms
    •  (1) Gi – nausea, vomiting, diarrhea, abdominal pain
    •  (2) Ears- ringing, decreased hearing
    •  (3) Eyes – blurred vision, night blindness
    •  (4) CNS- headache
    •  iii) Most toxic
    •  (1) Low BP
    •  (2) Respiratory depression, respiratory arrest
    •  (3) Low temperature
    •  iv) Contraindications/Cautions
    •  (1) Complete A-V block
    •  (2) Cardiac failure
    •  (3) Allergy to drug or idiosyncracy
    •  (4) Due to anticholinergic properties
    •   (a) Caution glaucoma, urinary retention
    •  (5) Serum K+ must be normal
    •   (a) Hypokalemia decreased drug effectiveness
    •   (b) Hyperkalemia increases it

    • II) Lidocaine: Na+ ch blocker
    •    (i) Given only IV in emergencies (intravenously: 1st pass metabolism) – rapid onset, short duration
    •    (ii) An antiarrythmic agent that is used for ventricular arrhythmias in emergency situations because it has a rapid onset and a short duration of action and does not have an anticholinerigc effect: effective w/ less tendency for cardiotoxicity

    • III) Amiloridorane: -C, +I, -D
    • K+* & Na+: ch blocker.
    • • Also blocks calcium ch & beta adrenergic receptors.
    • • Effective in orally suppressing arrythmias.
    • Less likely to produce arrythmias.
    • • Has a very long half life and has a tendencyto go crystalize in the tissue
    •      – Pulmonary fibrosis is the limiting side effect
    • As K+ ch blocker
    • • Prolongs the action potential and refractory period.
    • • If you lengthen the AP it takes longer to get back to the resting potential and longer until the cells can fire again.
    • • Produces the same arrythmias asquinidine.

    • IV) Beta blockers: -C,-I,-D
    • • Slow the heart down and suppresses arrythmias
    • Decrease catecholamine induced automaticity
    • Use:
    •   a) treat atrial fibrillation & flutter
    •   b) counteract digitalis toxicity

    • V) Ca++ ch blockers (veramil): -C, -I, -D
    • -stop 90% of supraventricular tachycardias w/ a single IV dose
    • • Works the same way as the sodium channels blockers, they have a preference for open/active channels.
    •        – But they works at the SA & AV node,places where calcium currents are driving the current
    • Effective for atrial arrythmias and circus movements
    • • Can weaken the cardiac muscle overtime

    • Major side effects:
    • I)Quinodine
    • a)        Cinchonism* (quinidine for cinchona bark)
    •  (1)   Relate to malaria treatment
    •  (2)   like Aspirin toxicity
    •  ii)      Mild to moderate symptoms
    •  (1)   Gi – nausea, vomiting, diarrhea, abdominal pain
    •  (2)   Ears- ringing, decreased hearing
    •  (3)   Eyes – blurred vision, night blindness
    •  (4)   CNS- headache
    •  iii)    Most toxic
    •  (1)   Low BP
    •  (2)   Respiratory depression, respiratory arrest
    •  (3)   Low temperature
  14. 13) Indications/ Contraindications for the use of anticoagulants.
    • a) Summary:
    •  i) Hemostatics: hasten blood clotting
    •  (1) Mech of action
    •   (a) Mechanical coagulants (for use during surgery) – gelfoam or oxidized cellulose causes platelets to disintegrate
    •   (b) Actual clotting factors: thrombin (topical application) or platelets (tranfusions)
    •   (c) Vitamin K: essential to prothrombin synthesis by liver
    •  ii) Anticoagulants: retard blood clotting
    •  (1) mechanism
    •   (a) Vs Prothrombin
    •    (i) Herapin
    •   (b) Vs prothrombin -> thrombin; & vs fibrinogen -> fibrin
    •    (i) Coumarin Derivatives: P1.Protein Binding- P450
    •   (c) Vs platelets
    •    (i) Aspirin
    •     1. Note: ibuprofen (Advil et.al.) & especially COX-2 inhibitors are NOT to be substituted for aspirin
    •    (ii) Dipyridamole
    •    (iii) Pentroxifylline
    •  (2) Therapeutic uses
    •   (a) Venous thrombosis (prevention or treatment)
    •    (i) Preventative circulation sluggish, i.e. bed rest, myocardial infarction, polycythemia
    •   (b) Prevention coronary thrombosis- especially if atherosclerosis present
    •   (c) Atrial fibrillation or valve disease where blood not emptied from heart
    •  (3) Side or Toxic Effects
    •   (a) Hemorrhage – clotting time should be closely monitored
    •   (b) Bleeding may occur from GI tract, gums, nose, uterus, etc
    •   (c) 25% of deaths from GI bleeding
    •  (4) Cautions or Contraindications
    •   (a) Patients w/ bleeding tendencies
    •   (b) Ulcers or carcinomas of GI tract
    •   (c) Pregnancy – risk of abortion
    •   (d) Severe liver or kidney disease
    •   (e) Avoid IM injections: muscle too vascular and may hematoma
    •   (f) Note: patients should carry MEDALERT in case of emergency
    •   (g) Drug interactions may be very serious
    •    (i) Phenobarbital – incr. deactivation by liver – need more anticoagulant to prevent thrombosis
    •    (ii) Phenyllbutazone (treats gout) – displaces anticoagulant from plasma protein
    •     1. 97% bound: may cause hemorrhage
    •     2. Special caution: any drug that binds to plasma proteins. Interactions often occur.
    •  iii) Thrombolytics: dissolve clots that have already formed:
    •    Mech of action: cause plasminogen to convert to plasmin
    •   (1) Therapeutic uses
    •    (a) Acute pulmonary embolism
    •    (b) Coronary thrombosis
    •    (c) Some strokes
    •    (d) Deep venous thrombosis
    •    (e) Arterial clots
    •  (2) Contraindications
    •   (a) Active bleeding tendencies
    •   (b) Cerebrovascular accidents 2 hours old or more (approximately)
    •   (c) Tumor
    •  (3) Cautions
    •   (a) Surgery or childbirth in the last few months
    •   (b) Watch for bleeding tendencies
    •   (c) Anaphylactic reactions possible
    • b) Major side effects
    •  i) Anticoagulants: Side or Toxic Effects
    •  (1) Hemorrhage – clotting time should be closely monitored
    •  (2) Bleeding may occur from GI tract, gums, nose, uterus, etc
    •  (3) 25% of deaths from GI bleeding
  15. 14) Indications/ Contraindications for the use of antilipemic
    • a) Summary:
    •  i) Controversial drugs
    •  (1) Most have severe side effects
    •  (2) Overall unproven usefulness, general population
    •   (a) Do lower heart attack/stroke risk but… cause other problems
    •  ii) Study June 1987
    •  (1) Atherosclerosis can be reversed in less than ¼ of the population
    •  iii) Cholesterol is associated w/ heart disease
    •  iv) Serum triglycerides alone are less significant
    •  (1) Must be studies as their type
    •   (a) HDL is chiefly protein & soluble phospholipids
    •    (i) Increases w/ exercise & moderate alcohol consumption
    •    (ii) Decreases w/ smoking and diabetes
    •    (iii) Inhibits cellular uptake of LDL
    •    (iv) Moves other lipids to liver for degradation
    •     1. (“reverse cholesterol Transport”)
    •   (b) LDL contains 2/3 body’s cholesterol
    •    (i) Liver removes all it can metabolize
    •    (ii) Remainder processed peripherally
    •     1. Ingestion by macrophage in vessel begins damage
    •    (iii) Harmful because: excess must be processed in tissues where damage occurs
    •   (c) VLDL- chiefly triglycerides
    •    (i) Made by liver to transport fats already in body
    •    (ii) Burned for fuel or stored as fat
    • b) Fibroic Acid Derivatives: triglycerides
    •  i) Clofibrate (Atromid-S®)
    •  (1) (Decreasing in popularity
    •  (2) More effective at lowering triglycerides than cholesterol
    •  (3) Patients have increase cancer, GI problems, especially gallsontes)
    •  ii) Gemfibrozil (Lopid®)
    •  (1) (inhibits peripheral lipolysis & decreases hepatic triglyceride production = lowers triglycerides
    •  (2) Increase HDL by ? mechanism
    •  (3) Severe side effects as bile sequastriant
    •  (4) Use only if strongly indicated
    •  (5) Makes statin drugs more toxic)
    • c) Niacin: often used in combination
    •  i) Common skin flushing
    •  (1) Minimized by taking aspirin 30 min. prior to dose
    •  ii) Watch liver function tests
    •  iii) Rare muscle pain if used in combination w/ statin
    • d) Bile sequestratn: binds cholesterol
    •  i) Cholestyramin: note side effects
    •  ii) New Category approved (2003)
    •  (1) Ezetimibe (Zetia®) prevents absorption cholesterol and decreased LDL by 25% if used w/ Statins
    •  iii) Severe side effects: constipation, nausea, flatulence, diarrhea, interference w/ GI, absorption of other drugs, cardiac arrhythmias, flushing, itching, hyperpigmentation, glucose intolerance, hyperruricemia, liver toxicity, nephrotoxicity, permanent nerve deafness
    •  e) Statin* (HMG-CoA reductase inhibitors): Inhibits enzyme for cholesterol production
    •  i) Lovastatin (formerly mevinolin) approved late 1987 can lower cholesterol by 30-40%
    •  ii) Adverse effects: uncommon but may be severe
    •  (1) Early cataract formation reported
    •  (2) Some liver function test abnormal but no severe liver disease noted yet
    •  (3) Myalgia, weakness, rhabdomyolysis
    •  iii) Similar drugs show no advantages over lovastatin so far, and some may be slightly less effective
    •  (1) Other agents include name-statin
    • f) Policosanol- dietary supplement made from sugar can wax
    •  i) 5-20 mg/day can lower total cholesterol by 20%
    •  (1) Compared to 60% for statin when given higher dosages
    •  ii) Appears to protect from endothelial damage
    •  (1) May have value in mild cases including in some diabetic patients
    •  iii) Seems to be well tolerated (no documentation n of liver enzyme changes)
    •  iv) Caution – do not self medicate:
    •  (1) May have antiplatelet effect
    •  (2) Interaction w/ other medications in unknown
    • g) Problem
    •  i) Even when antilipemic agens are used, comparison w/ control grops indicates:
    •  (1) Fatal myocardial inarctions are not decreased
    •  (2) & in fact, other fatalities increase!
    •   (a) This is why the use of antilipemic agents is very controversial unless serum cholestoerl levels clearly indicate usage
    •  ii) Try dietary & lifestyle changes for 6 months before considering drug therapy
    •  iii) Possible explanation:
    •  (1) Antilipemic agents may cause a loss of tissue cholesterol (that seems to persist even after drug use is stopped)
    •  (2) This loss might then impair cell function
    • h) Major side effects
    •  i) Fibroic Acid Derivatives: triglycerides
    •  (1) Clofibrate (Atromid-S®)
    •   (a) Patients have increase cancer, GI problems, especially gallsontes
    •  (2) Gemfibrozil (Lopid®)
    •   (a) Severe side effects as bile sequastriant
    •   (b) Use only if strongly indicated
    •   (c) Makes statin drugs more toxic
    •  ii) Niacin: often used in combination
    •  (1) Common skin flushing
    •   (a) Minimized by taking aspirin 30 min. prior to dose
    •  (2) Watch liver function tests
    •  (3) Rare muscle pain if used in combination w/ statin
    •  iii) Bile sequestrant: binds cholesterol
    •  (1) Severe side effects: constipation, nausea, flatulence, diarrhea, interference w/ GI, absorption of other drugs, cardiac arrhythmias, flushing, itching, hyperpigmentation, glucose intolerance, hyperruricemia, liver toxicity, nephrotoxicity, permanent nerve deafness
    •  iv) Statin*
    •  (1) Adverse effects uncommon but may be severe
    •  (a) Early cataract formation reported
    •  (b) Some liver function test abnormal but no severe liver disease noted yet
    •  (c) Myalgia, weakness, rhabdomyolysis
    •  v) Policosanol-
    •  (1) Caution – do not self medicate:
    •  (a) May have antiplatelet effect
    •  (b) Interaction w/ other medications in unknown
    •  vi) overall
    •  (1) Even when antilipemic agents are used, comparison w/ control groups indicates:
    •   (a) Fatal myocardial inarctions are not decreased
    •   (b) & in fact, other fatalities increase!
    •    (i) This is why the use of antilipemic agents is very controversial unless serum cholestoerl levels clearly indicate usage
    •  (2) Try dietary & lifestyle changes for 6 months before considering drug therapy
    •  (3) Possible explanation:
    •   (a) Antilipemic agents may cause a loss of tissue cholesterol (that seems to persist even after drug use is stopped)
    •   (b) This loss might then impair cell function
    • i) Main difference between the mechanisms of action for the different types of antilipemics
    •  i) Fibrioc Acid Derivatives
    •  (1) Clofibrate:
    •   (a) lower triglycerides than cholesterol
    •  (2) Gemifibrozil:
    •   (a) inhibits peripheral lipolysis & decrease hepatic triglyceride
    •  ii) Niacin: often used in combination
    •  iii) Bile sequestrant: binds cholesterol
    •   (1) Cholestyramin: note side effects
    •   (2) New Category approved (2003)
    •    (a) Ezetimibe (Zetia®) prevents absorption cholesterol and decreased LDL by 25% if used w/ Statins
    •  iv) Statin* (HMG-CoA) reductase inhibitors): Inhibits enzyme for cholesterol production
    •  (1) Lovastatin (formerly mevinolin) approved late 1987 can lower cholesterol by 30-40%
    •  v) Policosanol-
    •  (1) 5-20 mg/day can lower total cholesterol by 20%
    •   (a) Compared to 60% for statin when given higher dosages
    •  (2) Appears to protect from endothelial damage
    •   (a) May have value in mild cases including in some diabetic patients
    •  (3) Seems to be well tolerated (no documentation n of liver enzyme changes)

What would you like to do?

Home > Flashcards > Print Preview