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105 Cards in this Set

  • Front
  • Back
NT in CNS (N and M), autonomic ganglia (N1) adrenal medulla (N1-receptor stimulation releases Epi from adrenal medulla), NM junction (N2), sweat glands (M)

Alzheimer’s disease appears to involve a deficit of ACh in CNS – tx w carbamate AChase inhibitors like donepezil
Metabolism of ACh
acetylcholinesterase (AChase) vs plasma (pseudo)cholinesterase
Carbachol, bethanechol, methacholine more slowly metabolized than ACh
mnemonic = Can’t Be Metabolized, inhibitors of AChase only potentiate effects of ACh
used for dx of asthma: causes flushing, sweating, salivation, GI cramping, bronchoconstriction
Choline esters
nicotinic/muscarinic effects = acetylcholine, carbachol
- muscarinic effects = methacholine, bethanechol (trans = β-carbon substitution)
- bethanechol for urinary retention in PD patient tx w benztropine, psychotic
patient tx w typical antipsychotic drug (e.g., thioridazine) or a patient tx w TCA
- choline esters i.v. decrease BP via nitric oxide (NO) released from vascular
endothelial cells (muscarinic receptors) - ↓ BP blocked by atropine
causes miosis and cycloplegia via contraction of ciliary muscle, effect decreases IOP via increased outflow of aqueous humor
- S/E = bronchoconstriction, salivation
a tertiary amine: not hydrolyzed by plasma AChase, metabolized by liver
- induces cytochrome CYP450, so increases drug metabolism
- ↑ sympathetic activity with ↑ HR and BP, cutaneous vasoconstriction
- increased respiration and GI motility
- large doses - muscle fasciculations, followed by depolarization blockade
- CNS - convulsions with overdose (OD)
AChase inhibitors
know physostigmine (3°), neostigmine (4°), edrophonium (4°)
medical uses
diagnosis of myasthenia gravis (MG)
- to differentiate between “myasthenic” and “cholinergic” crisis in patients tx w
- used w atropine in reversal of neuromuscular blockade (NmB) caused by
non-depolarizing drugs (d-tc, pancuronium)
- tx of MG (always used w atropine to prevent indirect muscarinic S/E’s)
- used w glycopyrrolate in reversal of NMB caused by non-depolarizing drugs.
malathion, parathion, isofluophate (DFP)

- agriculture, home, biochemistry laboratory (DFP = diisopropyl fluorophosphate)
- Tx poisoning w atropine and pralidoxime (2-PAM) (regenerates phosphorylated
Carboxylesterases in humans degrade organophosphates and prevent our death.

Poisoning with plants: (increased ACh stimulation) (decreased ACh stimulation)
(like giving physostigmine) (like giving atropine)
(tx w atropine) (tx w physostigmine)
S/S of poisoning with organophosphates
= lacrimation, salivation, miosis, dyspnea, nc BP (N1), skeletal muscle fasciculations (N2)
Muscarinic Antagonist

Quaternary (N-methyl-PIG)

propantheline - GI spasticity

ipratropium - prevent bronchoconstriction from air pollution/cold air

Ganglionic Blocking drugs
trimethaphan, hexamethonium - block SNS and PSNS
Block increase in plasma Epi induced by hypoglycemia
Neuromuscular blocking drugs
Types: Depolarizing (non-competitive)
succinylcholine, decamethonium

phase I = Moter end plate (MEP) depolarized
phase 2 = repolarized, but
still refractory

causes fasciculations prior
to flaccid paralysis

Uses: NM blockade, ECT
Neuromuscular blocking drugs
Types: Non-depolarizing (competitive)
d-tubocurarine (curare), pancuronium
(the -curiums and -roniums)

MEP never depolarized

no fasciculations prior
to flaccid paralysis

Uses: NM blockade
changes in drug sensitivity with diseases
In myasthenia gravis (MG) the N2-receptor density is decreased: in burns and denervation injury, the N2-receptor density is increased
changes in drug sensitivity with diseases
(ACh receptor density) (succinylcholine) (curare)
MG (↓) (effect ↓) (effect ↑)
burns (↑) (effect ↑ (hyperkalemia)) (effect ↓)
denerv. (↑) (effect ↑ (hyperkalemia)) (effect ↓)
Adrenergic Pharmacology
NE/Epi synthesis - metyrosine inhibits tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) & ATP released w NE from nerves
Know presynaptic (prejunctional) receptors affecting NE release
(Increased overflow of NE) (Decreased overflow of NE)
(Ang II & β2-stimulation,) (muscarinic (ACh) & α2-stimulation (clonidine))
(α2-block, cocaine, TCA’s) (PGE’s)
Know site of action of drugs a sympathetic nerve junction
= α1, α2, β1,& β2; uptake1; MAO-A & MAO-B; storage granule; NE release mechanism; NE synthesis (metyrosine inhibits tyrosine hydroxylase – the rate-limiting E in the synthesis of CA’s
Direct adrenergic agonists 1
1) Know CV effects of Epi, NE, DA. NB: i.v. NE ↓ HR via baroreflex, ↓ HR blocked
by atropine
Direct adrenergic agonists 2
2) DA = increased RBF/mesenteric BF (block by haloperidol), increased dP/dT (β1),
increased DBP (α1)
Direct adrenergic agonists 3
3) Epi = increased skeletal muscle BF; decreased skin, renal and GI BF; ↑ HR, dp/dt,
CO, SBP and PP, decreased DBP with physiological doses
Direct adrenergic agonists 4
4) DA used instead of NE or Epi to maintain dp/dt post-MI bx DA ↑ RBF whereas NE
and Epi ↓ RBF.
Direct adrenergic agonists 4a
4) Epi + halothane = arrhythmias
Direct adrenergic agonists 5
5) Epi reversal with an α-blocker, e.g., Epi + phentolamine = only β effects = ↑ HR and
RBF, ↓ TPR, BP, and ERP in heart
Direct adrenergic agonists 6
6) Epi + β-blocker, e.g., propranolol = only α effects = increased BP
Direct adrenergic agonists 7
7) Epi added to local anesthetic agent to prevent systemic absorption
Direct adrenergic agonists 8
8) phenylephrine (PE) = α1-agonist = mydriasis without cycloplegia
Direct adrenergic agonists 9
9) ritodrine (β2-agonist) decreases uterine contraction in premature labor
Direct adrenergic agonists 10
10) bronchodilation with ↑ HR = isoproterenol (non-selective β1 & β2-agonist)
bronchodilation with less ↑ HR = albuterol, terbutaline (selective β2-agonists)
Direct adrenergic agonists 11
11) clonidine = pre- and post-synaptic α2-adrenoceptor agonist
Indirect adrenergic agonist
no effects after pre-tx with reserpine
Indirect adrenergic agonist 1
1) tyramine-containing foods contraindicated in patients taking phenelzine or
tranylcypromine which non-selectively inhibit MAO-A and MAO-B
Indirect adrenergic agonist 2
2) increase in BP caused by tyramine blocked by reserpine, guanethidine, cocaine, 3 P’s
Indirect adrenergic agonist 3
3) only directly-acting agonists increase dp/dt and HR in isolated heart from animals
pretreated w reserpine
Indirect adrenergic agonist 4
4) methylphenidate - tx ADHD/ADD - S/E's = depression, insomnia, decreased appetite
and linear growth rate
Indirect adrenergic agonist 5
5) amphetamine toxicity = nervous, excited, agitated, ↑ HR/BP, toxic psychosis =
paranoid schizophrenia, formication w excoriations, convulsions w OD; difficult to
distinguish from effects of cocaine
- tx psychosis w chlorpromazine
Indirect adrenergic agonist 6
6) ephedrine = direct β1 and β2, indirect α - no α after reserpine
Alpha blockers 1
1) 3 P’s - phentolamine, prazosin, phenoxybenzamine
Alpha blockers 2
2) phentolamine/PBZ increases HR via baroreflex; prazosin = no effect on HR
Alpha blockers 3
3) ergotamine, dihydroergotamine = partial α agonists - tx of migraine
Alpha blockers 4
4) major S/E of alpha blockers = orthostatic hypotension
Alpha blockers 5
5) tamsulosin - blocks α1A-receptors in GU tract in patients w BPH to enhance voiding
Alpha blockers 6
6) patient with pheo tumor - tx with phentolamine = decreases BP = EPI reversal
Alpha blockers 7
7) Epinephrine-reversal by α-blockers such as phentolamine, phenoxybenzamine and
prazosin = The vasopressor effect of a large (supraphysiological dose) of EPI is
reversed to a vasodepressor effect by an α-blocker
Example 1 *see graph*
A pharmacological (supraphysiological) dose of EPI increases BP via α-receptor stimulation. Treatment with an α-blocker lowers BP. Another injection of a large dose of EPI now causes a large decrease in BP because only vascular β2-receptors can be stimulated by EPI. After treatment with the non-selective β-blocker propranolol (blocks both β1 and β2-receptors), another injection of a large dose of EPi has no effect on BP.
Example 2 = BP during surgery for a pheochromocytoma *see graph*
Pretreatment with an α-blocker plus a non-selective β-blocker would prevent prevent any changes is BP caused by the release of EPI from the pheochromocytoma during surgery.
Example 3 = infusion of a physiological dose of EPI *see graph*
The infusion of a physiological dose of EPI lowers DBP and increases SBP. This physiological dose of EPI vasoconstricts some vascular beds via α-receptor stimulation and dilates other vascular beds via β2-receptor stimulation. The net effect is arteriolar vasodilation with a fall in TPR and thus DBP. SBP increases because EPI increases cardiac output via increased venous return, and cardiac contractility and decreased afterload (DBP). What happens to these responses after either α- or nonselective β-receptor blockade.

EPI after blockade of vascular α-receptor can only stimulate vascular β2-receptors to cause vasodilation and thus a large fall in TPR and DBP.

EPI after blockade of vascular β2-receptor can only stimulate vascular α-receptors to cause vasoconstriction and thus a large rise in TPR and DBP.
Beta blockers:
atenolol/ metoprolol = block β1; propranolol/timolol = block β1 & β2
Beta blockers
1) angina = decreased oxygen requirement via decreased dP/dT and HR, but LV-EDV
2) decreased HR, AV conduction, dp/dt
3) block increase in HR caused by hemorrhage, minoxidil, hydralazine, diazoxide,
nitroprusside, nitroglycerin
4) β-blocker (BB) decrease oxygen demand by decreasing HR, dp/dt and afterload
(DBP) [NTG decreases oxygen demand by decreasing venous return and LV-EDV]
6) S/E = CHF, bronchospasm, AV block, delayed recovery of [glucose] in pats
w Type 1 DM after s.c. injection of too much insulin
7) timolol - decreased IOP wo cycloplegia (do not use propranolol bx it causes local
anesthesia of cornea)
Beta blockers *clinical*
Clinical: patient tx w beta-blocker for angina → d/c drug → increased cardiac β-receptor
stimulation → increased O2 demand → angina and MI = beta-blocker withdrawal syndrome
(tachycardia, palpitations, tremor, chest pain)
Clinical: patient with hyperthyroidism → tx with propranolol to ↓ tachycardia and tremor and
prevent the peripheral conversion of T4 to T3,
Clinical: type I diabetic patient treated with glaucoma drug which causes hypoglycemia. Which
drug? = timolol
1) ↓ NE release via depletion of neuronal NE stores, poisons NE storage vesicles
2) no effect of TAP drugs (tyramine, amphetamine, phenylpropanolamine) after
pretreatment w reserpine; no α effects of ephedrine after reserpine
1) decreased nerve-stimulated NE release
2) competitive inhibitor of NE uptake1
3) anti-HT effect blocked by TCA’s bx TCA’s block entry of guanethidine into neuron
1) blocks uptake1 of NE, Epi, DA, 5-HT in CNS
2) blocks uptake1 in peripheral sympathetic neurons - potentiates effects of NE and Epi,
but not isoproterenol (ISO)
3) Euphoria via release of DA in nucleus accumbens
4) local anesthetic effect via blockade of Na+ channels in sensory neurons
5) toxic doses/OD = dilated pupils, euphoria, hallucinations, excitation, halo vision,
itchy skin, ↑ BP/HR, convulsions - difficult to distinguish from amphetamine
6) withdrawal syndrome = sleepiness, depression, anhedonia
MAO inhibitors - used to tx depression
1) drugs = phenelzine, tranylcypromine - inhibit MAO-A and MAO-B
2) selegiline – selectively inhibits MAO-B to prevent breakdown of DA in CNS
3) “cheese” reaction - inhibition of MAO-A in gut wall allows dietary tyramine to enter the
circulation; tyramine releases NE to cause HT and tachycardia
Antihypertensive drugs
clonidine and alpha-methyldopa (α-MD)
- ↓ SNS activity via stimulation of α2-receptors in CNS: ↓ plasma NE & renin activity
(PRA) , HR
- S/E = sedation, dry mouth, edema
- S/E of α-MD = hepatitis, “flu” syndrome, (+) Coomb’s test
- clonidine withdrawal syndrome = sweating, ↑ HR, abrupt return of BP to HT value,
abdominal pain, tremor, headache, apprehension (differs from β-blocker withdrawal
syndrome =↑ HR with palpitations but no tremor, sweating, abdominal pain or↑ BP)
Drugs that decrease plasma NE
clonidine, α-MD, guanethidine, reserpine,
ganglionic blockers
Drugs that increase plasma NE
alpha blockers, hydralazine, minoxidil, diazoxide,
nifedipine, HCTZ, sodium nitroprusside
Arterial vasodilators = hydralazine, minoxidil, diazoxide
- dilate resistance vessels = ↓ TPR & BP; ↑ HR, dP/dT, CO , PRA and plasma NE;
S/E - hydralazine - edema ;SLE = arthralgia, arthritis, fever, malar (butterfly) rash,
glomerulonephritis- d/c hydralazine and tx with steroid
- minoxidil = hirsutism, effect additive w finasteride; edema
- diazoxide = inhibition of insulin release = hyperglycemia; edema
Drugs for HT emergency
diazoxide, sodium nitroprusside (SNP), labetalol
sodium nitroprusside (SNP)
1) dilates arteries and veins via release of nitric oxide (NO) from SNP molecule
2) balanced vasodilation
NT patient = decreases TPR and venous retrun → CO = n.c.
CHF = decreases preload and afterload → leads to increase in CO
3) review thiocyanate (tx w thiosulfate) and CN (tx w nitrite/thiosulfate) toxicity
thiocyanate toxicity after SNP infusion in patients w poor renal function = muscle
weakness, & spasm, disorientation)
Ca++ blockers = nifedipine, diltiazem, verapamil
1) block Ca++ channels at SA/AV nodes, cardiac myocytes, arterial VSM
2) decrease in BP: nifedipine>diltiazem>verapamil
3) decrease AV conduction via increase in ERP: verapamil>diltiazem
4) nifedipine - slight increase in HR with increase or n.c. in AV conduction
5) angina - decrease oxygen demand (decrease dp/dt, HR and afterload) w increased
oxygen delivery via dilation of coronary arteries and arterioles
6) tx uses: HT, exertional and vasospastic angina, AV nodal re-entry tachycardia (V+D)
Drugs which decreased dP/dT =
β-blockers, Ca++ blockers, diisopyramide
Effects of Ang II
↑ BP, increases SNS activity via CNS, presynaptic enhancement
release of NE, blocks NE uptake1, release of ADH, release of aldosterone, decreases mesenteric BF. NB: Drugs which decrease mesenteric BF to tx GI bleeding =
NE & Ang II (get escape), ADH (a.k.a. AVP) & octreotide (no escape)
ACE inhibitors = captopril, enalapril - prevent conversion of Ang I to Ang II
1) decrease TPR and BP with no change in HR and CO
2) block formation of Ang II, block enzymatic destruction of bradykinin (BK)
3) S/E = fetal toxicity (category X) , K+ retention, cough; cough caused by BK & PG and
is blocked by aspirin (ACEI’s block metabolism of bradykinin)
4) ACEI’s potentiate the decrease in BP caused by i.v. bradykinin
5) ACEI's increase the plasma concentration of BK
5) losartan = Ang II receptor antagonist - no cough
ACE inhibitors *clinical*
clinical: MOA in tx of CHF = increase CO by decreasing preload and afterload;
reverses cardiac remodeling caused by angiotensin II (ang II)
clinical: HT patient with DM - tx w ACEI to↓ BP and ↓ proteinuria (protects kidneys)
Diuretic drugs

inhibits carbonic anhydrase in PT and DT to prevent reabsorption of bicarbonate
1) inhibits formation of aqueous humor and CSF, some effect to↓ gastric acid secretion
2) increased excretion of Na+, K+, bicarbonate - urinary pH increases to 8-8.5
3) used to increase urinary pH to enhance renal clearance of acids, e.g., salicylates,
4) used to tx glaucoma and altitude sickness - acidosis, via renal loss of bicarbonate,
stimulates respiration
5) S/E - hyperchloremic metabolic acidosis
Diuretic drugs
NB: (Stimulation of respiration) (Inhibition of respiration)
(acetazolamide) (EtOH)
(nicotine) (opiates - morphine)
(Epi) (benzodiazepines - diazepam)
(theophylline, caffeine) (barbiturates)
Diuretic drugs
To make urine alkaline = CAI or Na bicarbonate = increase renal Cl of acidic drugs

To make urine acidic = ammonium chloride = increase renal Cl of basic drugs
Loop diuretic drugs = furosemide, ethacrynic acid
inhibit Na+:K+:2Cl- symporter in
ascending limb of the loop of Henle; also blocks Na+ transport in macula densa of DT
1) increased urinary excretion of Na+, K+, Ca++, Mg++, C- l, and water
2) Increased delivery of Na+ to LDT/CD causes K+ loss
3) blocks Na+ transporter in macula densa cells of DT → no sodium sensed → ↑ PRA
and Ang II → secondary hyperaldosteronism → exacerbates K+ loss
4) Cl- loss caused hypokalemic, hypochloremic metabolic alkalosis
5) urine isotonic in presence and absence of ADH
6) PG-dependent increase in RBF and GFR
7) increases hematocrit via decreased plasma volume
8) used in tx of acute pulmonary edema, CHF, peripheral edema, hypercalcemia
9) bilateral hearing loss via toxicity to CN VIII; potentiated by aminoglycosides (e.g.,
10) S/E - hypokalemia w alkalosis, hypomagnesemia, hyperglycemia, dilutional
hyponatremia = cannot make a dilute urine in order to excrete free water
11) S/E - hyperuricemia (bad for gout) and Li+ toxicity caused by their enhanced
reabsorption in PT
12) enhances digoxin toxicity via hypokalemia - less K+ to compete w digoxin for
Na+-K+ ATPase binding sites
Thiazides = hydrochlorothiazide
acts in distal tubule and ↓ GFR in all patients
1) block NaCl symporter in principal cells of DT: ↑ excretion Na+, K+, Mg++, Cl- and water
2) ↓ excretion of Ca++ in hypercalcinuria: used to decrease formation of kidney stones
3) ↓ free water clearance: urine always hypertonic; causes dilutional hyponatremia
4) Increased delivery of Na+ to LDT/CD causes K+ loss
5) blocks Na+ transporter in macula densa cells of DT → no sodium sensed → ↑ PRA
and Ang II → secondary hyperaldosteronism → exacerbates K+ loss
6) used in tx of HT, edema, kidney stones and DI (distal loss of Na and water enhances
the reabsorption of filtrate in the PT; less volume sent distally; urine vol ↓ by 50%)
7) S/E - hypokalemia w alkalosis, hypomagnesemia, hyperglycemia, hyponatremia;
uniformly decreases GFR
8) S/E - hyperuricemia (bad for gout) and Li+ toxicity caused by their enhanced
reabsorption in PT
9) enhances digoxin toxicity via hypokalemia - less K+ to compete w ith digoxin for
Na+-K+ ATPase binding sites
10) diuretic effect contracts the blood volume & therefore potentiates the fall in BP
caused by anti-HT drugs, especially sympatholytic drugs (e.g., clonidine and
α-blockers like prazosin
K+-Sparing diuretics
TASK = triamterene, amiloride, spironolactone (aldosterone
receptor antagonist)
All are contraindicated in renal insufficiency bx they can cause fatal hyperkalemia
amiloride and triamterene
1) block Na+ channels in principal cells of LDT/CD
2) increased Na+ excretion with decreased K+ excretion
3) make urine alkaline by inhibiting H+ ion secretion from intercalated cells of DT
aldo antagonists; partial agonist at androgen/progesterone receptors
1) blocks aldosterone receptors in the principal cells of the LDT and CD
2) increases urinary loss of Na+ and water w decrease in K+ excretion
3) no effect in adrenalectomized patient
4) used in tx of secondary hyperaldosteronism ass w cirrhosis, nephrotic syndrome;
5) reverses cardiac remodelling caused by aldosterone in patients with HF
6) S/E - hyperkalemia, gynecomastia (males), menstrual irregularities, hirsutism, deeped
voice (females)
spironolactone *clincal*
clinical: patient tx with OCP containing estrogen + norethindrone develops hirsutism - why? how to tx? A: hirsutism results from androgenic effects of the progestin norethindrone which is a derivative of 19-nortestosterone; tx with spironolactone
clinical: postmenopausal female develops hirsutism - how to tx? A: spironolactone
clinical: patient with an adrenal tumor has ↑ BP and plasma [HCO3-], ↓ plasma [K+] and PRA; plasma [Na+] is normal → dx? and tx? A:Conn's syndrome = aldosterone-secreting adrenal tumor; tx with spironolactone

NB: hypokalemia from furosemide and HCTZ prevented by K+-sparing diuretic drugs,
ACE inhibitors, β-blockers, and, to a certain extent, by p.o. K+ supplements
The effects of diuretics on urinary flow, pH and electrolyte composition.
A. First look at urine flow rate
1. If urine flow rate is 8-10 ml/min, the drug is either furosemide or mannitol.
2. If urine flow rate is 2-3 ml/min, the drug is acetazolamide, a thiazide
or a K+-sparing agent.
B.. Next look at the quantitative changes in electrolyte excretion.
1. Furosemide is distinguished from mannitol by the fact that furosemide
causes the greatest increase in electrolyte excretion.
2. Acetazolamide, a thiazide and a K+-sparing agent are distinguished as
a. Acetazolamide causes a massive increase in bicarbonate excretion.
b. The K+-sparing agent decreases potassium excretion.
c. The drug that remains is a thiazide.
C. Ignore theophylline because standardized tests never include hemodynamic
diuretic drugs

*Large doses of the thiazide diuretic drugs can inhibit carbonic anhydrase. The dose is usually kept small to prevent hypokalemia, so urinary pH usually does not increase during treatment with thiazides.
Cardiac Gylcosides = digoxin, digitoxin
1) kinetics:
digoxin = t1/2β = 1-1.5 d: renal Cl, decreased GFR decreases Cl and ↑ t1/2β .
digitoxin = t1/2β = 7 d: hepatic Cl, dec Cl and ↑ t1/2β in patient w cirrhosis and CHF
2) ↓ GI absorption w cholestyramine or antacids:↓ plasma [dig] and↓ cardiac effect
3) older patients:↓ Vd, so ↓ loading dose: ↓ GFR, so ↓ maintenance dose
older patients can have ↓ GFR with normal serum [Cr]
4) quinidine↑ plasma digoxin by displacing digoxin from skeletal muscle and ↓ renal Cl
5) MOA: inhibition of Na+-K+ ATPase - increases dp/dt, but decreases resting membrane
potential (Vm) and lack of pumping Na+ out causes automaticity in fast fibers
- low K+: potentiates inhibition of ATPase: causes automaticity and ↓ ERP in
- low Mg++: same a Ca++ overload inside cells - causes automaticity
- high Ca++: Ca++ overload inside cells causes automaticity
6) MOA - acts in CNS to↑ vagal tone:↓ HR, atrial contraction and AV conduction
7) Used to control (decrease) ventricular rate in patients w atrial flutter or fibrillation:
↑ vagal tone decreases AV conduction, so fewer atrial signals pass the AV node
8) S/E - bradycardia, AV block, PVC’s; n/v (CTZ); CNS-abnormal color vision, halo
vision, esp. in elderly
Antidysrhythmic drugs
MOA: blocks Na+ channels in fast fibers
1) Na+ channel block ↓phase 4 automaticity and phase O slope (↓ conduction velocity
so it widens the QRS)
2) Delays ventricular repolarization via K+ channel block:↑ APD, ERP and Q-T interval
3) SA node: no direct effect, anticholinergic effect causes tachycardia
4) AV node: atropine-like effect increases conduction, but direct effect decreases
conduction (P-R increases)
5) used to Tx atrial and ventricular dysrhythmias
6) give digoxin before quinidine in tx of atrial flutter and atrial fibrillation so digoxin
prevents increase in AV conduction from atropine-like action of quinidine
7) S/E - hypotension (α-blockade),↓ dp/dt, diarrhea (limits use), tinnitus w OD
SLE & arthritis in slow acetylators (genetic defect; inactive form of acetylase enzyme) bx they cannot clear the drug by hepatic biotransformation
marked decrease in dp/dt
marked antimuscarinic effects: dry mouth, constipation; contraindicated in BPH & glaucoma
MOA: block of Na+ channels in fast fibers - given i.v. due to low F
2) ↓ phase 4 automaticity to prevent PVC’s: only used for ventricular arrhythmias
3) no effect at SA or AV nodes, BP or dP/dT
4) local anesthetic effect via Na+ channel block in sensory fibers
5) S/E’s = seizures, tx w benzodiazepine (BZ)
1) MOA:↑ APD, ERP interval in fast fibers by inhibiting K+ channels: ↑ Q-T
- powerful suppression of phase 4 automaticity (blocks Na+ channels)
- non-competitive α- and β-blockade (hypotension & bradycardia)
- slows sinus rate and AV conduction (P-R increased)
2) tx of recurrent ventricular tachycardia/fibrillation
3) S/E: pulmonary fibrosis, hypo- or hyperthyroidism; blue, purple or slate gray skin;
corneal microdeposits
1) blocks L-type Calcium channels at SA and AV nodes and cardiac myocytes
2) effects: SA node = ↓ HR; AV node = ↓ conduction velocity &↑ ERP = fewer atrial
signals pass through the AV node to the ventricles; myocardium = ↓ dp/dt = ↓ CO
3) used to tx AV nodal re-entry tachycardia
4) S/E = ↓ dp/dt; decreased CO in HF, AV block
verapamil *clinical*
clinical: patient with atrial fibrillation and no HF has palpitations and dizziness → tx with
verapamil → MOA? A: ↑ ERP of AV node slows ventricular rate → improved AV filling → ↑ CO

antiplatelet drugs
1) aspirin - see notes on NSAID's: irreversibly inhibits COX-1 of platelets to prevent the
synthesis of TXA2
2) antagonists of the platelet IIb/IIIa which uses fibrinogen to bind platelets together;
= abciximab, eptifibatide, tirofiban = given i.v. in ER and OR
3) antagonist of platelet purinergic (ADP) receptors = ticlopidine and clopidogrel
clinical: a patient requires an antiplatelet drug after MI or stroke, but the patient has aspirin
hypersensitivity. How to Tx? use ticlopidine or clopidogrel
MOA: accelerates binding of antithrombin III (AT III) to activated clotting
factors 2, 9-12, increases aPTT
1) a glucosaminoglycan, HMW = 5-30 K
2) not effective p.o.; works in vivo and in vitro
3) not metabolized by the liver: removed from circulation by reticuloendothelial system
4) ↑ lipoprotein lipase (hydrolyzes TG’s to glycerol + FFA) to↓ postprandial lipemia
5) Used to treat MI and DVT’s
6) antagonist = protamine sulfate
7) S/E - bleeding, antiplatelet effect additive w aspirin, thrombocytopenia
8) Heparin resistance results from decreased [AT III] in blood
LMW heparins
ardeparin, dalteparin, enoxaparin,
1) LMW = 2-6 K; LMW acts primarily on Xa, so little effect to increase the aPTT
2) anticoagulant effect only partially reversed by protamine sulfate
3) cleared by the kidneys instead of the RE system; longer half-life than heparin
warfarin, dicumarol
MOA: inhibits post-translational vitamin K1-dependent gamma-carboxylation of glutamate residues on factors 2,7,9 & 10 via inhibition of enzyme
vitamin K1 epoxide reductase
1) Only works in vivo, slow onset of action (2-3 d, full effect at 5 d) increases PT (INR)
(greatest effect on factor 7)
2) Used to treat DVT’s, prevent emboli in patients with prosthetic cardiac valves, prevent
thrombotic stroke in patients with atrial fibrillation
3) highly bound to plasma proteins: many drug-drug interactions: displacement of
warfarin from plasma proteins has two effects: ↑ PT and ↑ clearance of warfarin
4) metabolized by CYP450

inhibition of CYP450 increases plasma warfarin and PT =
cimetidine, ketoconazole, isoniazid, erythromycin and grapefruit juice

induction of CYP450 decreases plasma warfarin and PT =
carbamazepine, phenobarbital, phenytoin, rifampin, chronic EtOH,
benzopyrene (cigarette smoke)

5) antidote: vit K1 (phytonadione), fresh frozen plasma, factor IX concentrate (contains
factors 2,7,9 & 10)
warfarin, dicumarol
clinical: patient OD's with warfarin are attempts suicide with rat poison → which clotting factors
and lab tests affected? A: ↓ activity of factors 2,7,9 and 10; ↑ aPTT and PT; no effect of
factors 8 or 13 or bleeding time
clinical: Which type of cardiac dysrhythmia requires tx with warfarin? A: atrial fibrillation
Thrombolytic (fibrinolytic) drugs:
: all ultimately convert plasminogen to plasmin: plasmin destroys fibrin to lyse clots
direct activation of plasminogen
when tPA and plasminogen bind to fibrin in close proximity, plasminogen
converted to plasmin by tPA = normal, intrinsic activation of plasmin
changes conformation of plasminogen to expose an active protease
site that hydrolyzes another plasminogen molecule to plasmin
S/E of fibrinolytic drugs: systemic destruction of clotting factors 5 & 8 causes bleeding,
esp. in CNS (hemorrhagic stroke)
streptokinase *clinical*
clinical: pat with MI treated with several drugs → develops intracranial bleeding → which drug
caused it? A: streptokinase
Inhibitors of fibrinolysis
aminocaproic acid:
MOA: a lysine analog that binds to the lysine-binding sites on plasmin which blocks the binding of plasmin to fibrin
Antilipemic drugs

statins, e.g., lovastatin
1) MOA: the inhibition of hepatic HMG CoA reductase reduces an intracellular hepatic
sterol pool which suppresses the promotor region of the genes which code for HMG
CoA reductase and LDL receptors; lack of sterol results in the increased synthesis of
HMG CoA reductase and LDL receptors; increased hepatic LDL receptors take up
LDL cholesterol to lower Tc
2) net effect = ↓ Tc, LDL and TG's; slight ↑ in HDL
3) S/E's = myositis/myopathy = muscle pain and weakness ass with ↑ CPK; muscle
damage can progress to rhabdomyolysis
1) MOA: the inhibition of cholesterol absorption from the GI tract decreases an
intracellular hepatic sterol pool leading to increased gene expression of hepatic LDL
receptors; increased hepatic LDL receptors take up LDL cholesterol to lower Tc
2) net effect: selective for LDL cholesterol, so only Tc and LDL decrease
3) used to tx patients who develop muscle weakness on a statin
gemfibrozil and fenofibrate
1) MOA: activates lipoprotein lipase (esp. in skeletal muscle) to increase hydrolysis of
2) net effects = ↓ Tc, LDL, VLDL and TG's; slight ↑ in HDL
3) used to tx hypertriglyceridemia
4) S/E's = myositis/myopathy = muscle pain and weakness ass with ↑ CPK; muscle
damage can progress to rhabdomyolysis
1) MOA: unknown
2) used to increase HDL cholesterol
3) S/E = flushing and itching in face and upper body
Antianginal drugs
- all↓ oxygen demand and/or↑ oxygen supply; all increase endocardial blood flow
Antianginal drugs
β-blockers = atenolol, metoprolol, propranolol, timolol
1) MOA: negative chronotropic & inotropic effects decreases the rate-pressure product
(HR x SBP); also decrease cardiac afterload (= decreased DBP)
2) net effect is decreased cardiac oxygen demand
Antianginal drugs
nitrates = nitroglycerin a.k.a. glyceryl trinitrate, isosorbide mono- and dinitrate
1) MOA: NO donors which selective venodilate; venodilation ↓ venous return to
decrease LV wall tension during diastole and systole
2) net effect: decreased cardiac oxygen demand
3) drug tolerance is a big problem
Antianginal drugs

calcium channel blockers = verapamil, diltiazem, amlodipine, felodipine
1) MOA of verapamil and diltiazem: negative chronotropic & inotropic effects decreases
the rate-pressure product (HR x SBP); also decrease cardiac afterload (= decreased
DBP); also dilates large epicardial vessels and small endocardial resistance vessels
2) MOA of amlodipine and felodipine: decreased cardiac afterload (DBP) and increased
blood flow through large epicardial vessels and small endocardial resistance vessels
3) net effect in both cases: decreased oxygen demand and increased oxygen supply
Tx of Congestive Heart Failure = systolic dysfunction
1) decrease preload with diuretic drugs
2) decrease both preload and afterload (balanced vasodilation) with an ACEI or ARB
3) enhance cardiac contractility (dp/dt) with digoxin
4) reverse cardiac remodeling caused by ang II with an ACE or ARB
5) reverse the cardiac remodeling caused by aldosterone with spironolactone
6) reverse the cardiac remodeling caused by the SNS with carvedilol
7) add digoxin to tx when ACEI + diuretic not working or when patient is in chronic atrial