Pharm Final Part Two

Front 1

Synthesis of ACh?

Back 1

Synthesized in nerve terminals by the cytoplasmic enzyme CHOLINE ACETYLTRANSFERASE, which catalyzes transfer of an acetate group from acetyl CoA to choline

Front 2

Degradation of ACh?

Back 2

Rapidly hydrolyzed and inactivated by tissue ACETYLCHOLINESTERASE (AChase),

Also by non-specific pseudocholinesterase (inactivates more slowly than AChase)

Front 3

Where do we find ACh as a neurotransmitter?

Back 3

CNS (N and M)

autonomic ganglia (N1)

adrenal medulla (N1-receptor stimulation releases Epi from adrenal medulla),

NM junction (N2)

sweat glands (M)

Front 4

Alzheimer’s disease and ACh? How is ACh implicated in treatment?

Back 4

ALZ involves a deficit of ACh in CNS

TX: w/ carbamate AChase inhibitors like DONEPAZIL (DOC)

Front 5

ACh agonists?

Back 5

Carbachol

Bethanechol

Methacholine

“Can’t Be Metabolized” – more slowly metabolized and thus longer duration of action than ACh

Front 6

Methacholine therapeutic use?

Back 6

Dx of asthma, causes:
Flushing
Sweating
Salivation
GI cramping
Bronchoconstriction

Tiny dose given

Front 7

Choline esters…?

Back 7

Nicotinic/muscarinic effects = ACh and CARBACHOL

Muscarinic effects = METHACHOLINE and BETHANECHOL

Front 8

Bethanechol therapeutic use?
-is it tertiary or quaternary?

Back 8

Urinary retention, bowel stasis, postop paralytic ileus

Quartenary – doesn’t cross BBB

Front 9

Choline esters given i.v. will cause…?

Back 9

Decreasd BP via NO released from vascular endothelial cells (muscarinic receptors)

↓BP can be blocked by atropine

Front 10

Therapeutic use of pilocarpine?

Back 10

MUSCARINIC AGONIST
Causes miosis and cycloplegia via contraction of ciliary muscle
-- effect decreases IOP via increased outflow of aqueous humor
-- treatment for open angle glaucoma

If treating acute narrow angle glaucoma, given w/ physostigmine (indirectly acting muscarinic agonist)

Front 11

Pilocarpine S/Es?

Back 11

Bronchoconstriction

Salivation

Bradycardia

Front 12

Nicotine?

Back 12

A tertiary amine
-- not hydrolyzed by plasma AChase
-- metabolized by liver
-- induces cytochrome CYP450, so increases drug metabolism (actually, benzypyrene in cigarettes)

Front 13

Nicotine effects?

Back 13

1. ↑ sympathetic activity with ↑ HR and BP, cutaneous vasoconstriction (cold hands/fingers)

2. increased respiration and GI motility

3. large doses - muscle fasciculations, followed by depolarization blockade

4. CNS - convulsions with overdose (OD)

Front 14

AChase Inhibitors?

Back 14

CARBAMATES

ORGANOPHOSPHATES

Front 15

Name the carbamates

Back 15

Physostigmine (tertiary)

Neostigmine (quaternary)

Edrophonium (quaternary)

Front 16

Physostigmine therapeutic use?

Back 16

Eye drops cause miosis
-- lower IOP in glaucoma

Front 17

Edrophonium therapeutic use?

Back 17

1. Diagnosis of myasthenia gravis (MG)
-- differentiate between “myasthenic” and “cholinergic” crisis in patients
-- reduces brkdwn of ACh in NMJ; eyelids open
-- tx MG w/ neostigmine


2. Used w/ atropine in reversal of neuromuscular blockade (NmB) caused by non-depolarizing drugs (d-tc, pancuronium)

Front 18

What are the organophosphates?

Back 18

Malathion

Parathion

Isofluophate (DFP)
-- agriculture
-- home
-- biochem lab chem. (commonly used in protein chemistry)

These are IRREVERSIBLE inhibitors of ACHases that form covalent bonds w/ AChase active site

Front 19

Signs and symptoms of OP poisoning?

Back 19

Lacrimation
Salivation
Miosis
Dyspnea
NO change in BP (N1)
Skeletal muscle fasciculations (N2)

Front 20

OP poisoning treatment?

Back 20

1. Pralidoxime (2-PAM)
-- regenerates phosphorylated ACHase
-- must be admin quickly after OP poisoning b/c not able to break bond once it has aged

2, Atropine
-- muscarinic antagonist that can be used to treat cholinomimetic symptoms or OP toxicity, but b/c of its transient effects, is NOT curative

**Carboxylesterases in humans degrade organophosphates and prevent our death

Front 21

Plant poisoning?

Back 21

Increased ACh stimulation
-- treat w/ atropine

Decreased ACh stimulation
-- mydriasis, bronchodil, tachy, no sweating, no peeing
-- treat w/ physostigmine

Front 22

What is the effect of a muscarinic receptor blockade?

Back 22

DRY AS A BONE
-- no saliva, sweat, urine

MAD AS A HATTER
-- confusion, delirium

HOT AS A HARE
-- increased core temp

BLIND AS A BAT
-- mydriasis and cycloplegia (lack of accommodation)

Front 23

What are the muscarinic antagonists?

Back 23

TERTIARY
-- scopolamine
-- atropine
-- cyclopentolate
-- benztropine

QUARTENERY
-- N-methylatropine
-- propantheline
-- ipratropium
-- glycopyrrolate

Front 24

Scopolamine use?

Back 24

Used orally or topically as a remedy for motion sickness

Front 25

Atropine use?

Back 25

Atropine causes muscarinic receptor blockade.

Used for bradycardia, heart block, and to reverse cholinergic poisoning

Front 26

Cyclopentolate use?

Back 26

Topical eyedrops for ciliary paralysis
-- mydriasis
-- allows fundoscopic exam
-- inhibits accommodation (↓ near vision)

Front 27

Benztropine use?

Back 27

Penetrates CNS well (tertiary), so used for Parkinson’s disease
-- ↓ cholinergic signaling
-- helps restore dopaminergic/cholinergic balance in the brain

Front 28

Propantheline use?

Back 28

Decreased ACh-stimulated secretion and motility in the GI tract
-- help w/ GI spasticity

Front 29

Ipratropium use?

Back 29

Prevent bronchoconstriction from air pollution/cold air by inhibiting ACh mediated constriction of bronchial airways

Front 30

Glycopyrrolate use?

Back 30

Used to suppress bronchiolar secretions during surgery via inhibiting ACh-mediated secretion

Front 31

Approaches toward treatment of Glaucoma?

Back 31

1. Decrease formation of aqueous humor
-- B-blocker
-- Carbonic anhydrase inhibitor
-- alpha2 receptor agonist

2. Increase outflow of aqueous humor
-- alpha1 receptor agonists
-- pilocarpine, isofluophate
-- PGF2 analogs (uveoscleral flow)

Front 32

B-blockers that decrease formation of aqueous humor?

Back 32

BETAXOLOL – better choice b/c relatively selective for B1-adrenoceptors, thus little effect on bronchial smooth muscle

TIMOLOL

Both by unknown MOA

Front 33

Carbonic anhydrase inhibitor for glaucoma?

Back 33

Acetazolamide

Dorzolamide

Front 34

Alpha2 receptor agonists for glaucoma?

Back 34

Apraclonidine

Brimonidine

Both used post-surgically, and not generally as outpt

Front 35

Alpha1 receptor agonists for glaucoma?

Back 35

Epinephrine

Dipivefrin

Both stimulate the radial muscle of the iris to cause mydriasis and increase outflow

Front 36

Pilocarpine and isofluophate for glaucoma?

Back 36

Organophosphate Cholinesterase Inhibitors

Lower IOP by ↑ amt of ACh avb to contract meridional fibers of the ciliary muscle

Front 37

PGF2 analogs for glaucoma?

Back 37

ONLY ones to increase UVEOSCLERAL outflow

Latanoprost
Unoprostone

Will have ADDITIVE effect w/ any other drug

Front 38

What are the ganglionic blocking drugs?

Back 38

Trimethaphan – used to produce controlled hypotension during head and neck surgery

Hexamethonium

Front 39

What do the ganglionic blocking drugs do?

Back 39

Block Sympth NS and Parasympth NS

Block increase in plasma Epi induced by hypoglycemia

Front 40

What is the effect of a ganglionic (N1-cholinergic receptor) blockade?

Back 40

Blocks ALL of the nervous system

SYMPATHETIC BLOCK
-- arteriodilation lowers TPR
-- venodilation decreases preload
-- decreased cardiac dp/dt
-- ↓TPR and CO = hypotension
-- decreased sweating
-- impotence (no ejaculation)

PARASYMPATHETIC BLOCK
-- tachycardia (intrinsic HR is 70-100)
-- mydriasis and cycloplegia
-- ↓ salivation and lacrimation
-- ↓ GI secretion, motility, tone
-- ↓ gastric acid secretion
-- ↓ release of panc enzymes and bile
-- constipation and urinary retention
-- impotence (no erection)

Front 41

Depolarizing, non-competitive neuromuscular blocking drugs?

Back 41

Succinylcholine, decamethonium

Phase 1 = MEP depol
Phase 2 = repolarized but still refractory

Causes fasciculations prior to flaccid paralysis

Front 42

Succinylcholine use?

Back 42

NM blockade, Electroshock therapy

Front 43

Non-depolarizing, competitive neuromuscular blocking drugs?

Back 43

d-tubocurarine (curare)
pancuronium (the –curiums and –curoniums)

MEP never depolarized

No fasciculations prior to flaccid paralysis

Front 44

-curium and –curonium use?

Back 44

NM blockade

Front 45

Changes in changes in NM blockade drug sensitivity?

Back 45

Changes in drug sensitivity with diseases

1. myasthenia gravis (MG) the N2-receptor density is decreased
-- succinylcholine ↓ effect
-- curare ↑ effect

2. in burns and denervation injury, the N2-receptor density is increased
-- succinylcholine ↑ effect
-- curare ↓ effect

Front 46

NE and Epi synthesis?

Back 46

Tyrosine --> L- Dopa --> Dopa --> NorEpi --> Epi

Tyr to Dopa via tyrosine hydroxylase
-- rate-limiting step in NE/Epi synthesis
-- inhibited by METYROSINE

L- Dopa to Dopa via dopa decarboxylase

Dopa to NorEpi via dopamine β-hydroxylase
-- inhib by METYROSINE

NorEpi to Epi via phenylethanolamine-N-methyltransferase

METYROSINE also inhibits NE release from nerves

Front 47

Presynaptic receptors affecting NE release?

Back 47

See image pg 209 Module 1

INCREASED overflow of NE
1. Ang II stimulation
2. β2 stimulation
3. α2 block (prejxnal)
4. cocaine
5. TCAs

DECREASED overflow of NE
1. muscarinic (ACh) stimulation (prejxnal)
2. α2 stimulation (clonidine)
3. PGEs

Front 48

α1-adrenoceptors are found at…?

Back 48

POSTjxnal sites on effector organs, tissues and glands innervated by sympathetic nerves

(IP3 and DAG)

These adrenoceptors are usually excitatory, except in the GI tract.

Front 49

α2 adrenoceptors are found at…?

Back 49

1. POSTjxnal sites on effector organs, tissues, and glands innervated by the sympathetic nerves (↑ intracellular inhib of adenyl cyclase --> ↓[cAMP])

2. PREjxnal sites on sympathetic neurons (autoreceptors for increased K conductance)

3. PREjxnal sites on parasympathetic neurons of
-- SA node
-- sphincter muscle of iris
-- GI tract

These adrenoceptors are usually excitatory, except in the GI tract.

Front 50

β1-adrenoceptors are found at…?

Back 50

POSTjxnal sites of
-- cardiac muscle and cardiac conduction tissue
-- adipocytes
-- JG cells of the renal afferent arteriole

β receptors are generally inhibitory, except for effects on lipolysis, heart, and renin secretion

Front 51

β2-adrenoceptors are found at…?

Back 51

1. POSTjxnal sites of the
-- arterioles & venules
-- bronchioles
-- uterus
-- GI tract
-- liver

2. PREjxnal sites on sympathetic neurons (heteroceptors)

Mediate vasodilation and intestinal and bronchial smooth muscle relaxation

Front 52

D1-receptors are found at…?

Back 52

vascular smooth muscle of the renal afferent arterioles where they cause vasodilation (adenyl cyclase)

Front 53

D2-receptors found at…?

Back 53

synapses in the CNS
-- corpus striatum
-- hypothalamus
-- CTZ
-- limbic system

(inhibition of adenyl cyclase; increase K conductance)

Front 54

General: Increase in parasympathetic activity has the following effects...

Back 54

1. HR ↑
2. BP ↓ slightly
3. GI secretions and movements are increased
4. Gall bladder is contracted
5. Glucose is stored in the liver
6. Retina is protected from excessive light
7. Urinary bladder and rectum are emptied

Via Cholinergic (ACh) activity at muscarinic receptors

Front 55

General: Increase in sympathetic activity has the following effects…

Back 55

INCREASED
1. HR and dp/dt
2. BP
3. Blood flow to liver and skeletal muscles
4. Blood glucose concentration via glycogenolysis and gluconeogenesis
5. Glucagon release as insulin release inhibited

DECREASED
1. Renal and cutaneous blood flow
2. Splanchnic blood flow
3. Visceral activity

Also, bronchioles are dilated

Front 56

Know the site of action of drugs on a sympathetic nerve jxn = uptake1, MAO-A & MAO-B, storage granule

Back 56

MAO-A
-- located in outer mbrn of mitochondria
-- removes the amine group of the side-chain to metabolize 5-HT and NE
-- found mostly in liver, GI tract, and placenta

MAO-B
-- located in outer mbrn of mitochondria
-- found mostly in blood platelets

Uptake1
-- found on presynaptic neuron
-- blocked by TCAs and SSRIs

PREsynaptic α2 receptor
-- feedback inhibition which can modulate NE or 5-HT release
-- Mirtazapine blockade amplifies release for any given frequency of neuronal stim

Front 57

CV effects of Norepi?

Back 57

SYMPATHETIC response to Norepi

ATRIA
-- ↑ dp/dt

VENTRICLES
-- ↑ dp/dt

SA NODE
-- ↑ HR

ATRIA
-- ↑ conduction velocity
-- ↓ AP duration, refractory period

AV NODE, HIS-PURKINJE, VENTRICLES
-- ↑ automaticity, conduction velocity
-- ↓ conduction time, refractory period, AP duration

Front 58

Drug Z is given i.v. and ↑BP, and ↓HR.

After treatment w/ atropine, Drug Z will then cause ↑BP, and ↑HR

What is Drug Z?

Back 58

Norepinephrine

Initially, it increases BP, and the HR decreases due to baroreceptor reflex.

When given atropine, this blocks muscarinic receptors, so NO vagal response is available. The body isn’t able to mount a baroreceptor reflex, so the NE increases BOTH BP and HR

Front 59

CV effects of Epi?

Back 59

↑HR, dp/dt, CO, SBP, and PP

↓DBP with physiological doses

(Think fight or flight)

Front 60

CV effects of Dopa?

Back 60

↑dp/dt (β1)

↑DBP (α1)

Front 61

Epi general effects?

Back 61

increased skeletal muscle BF

decreased skin, renal and GI BF

↑ HR, dp/dt, CO, SBP and PP, decreased DBP with physiological doses

Front 62

Dopa general effects?

Back 62

increased RBF/mesenteric BF (block by haloperidol)

increased dP/dT (beta1), increased DBP (alpha1)

Front 63

How do we control dp/dt post MI?

Back 63

Use Dopa instead of NE or Epi to maintain dp/dt post MI b/c Dopa ↑RBF, whereas NE and Epi ↓RBF

Front 64

Epi + halothane = ?

Back 64

arrhythmias

Front 65

Epi + α-blocker = ?

Back 65

Use α-blocker (Epi + phentolamine) so that you only get β effects
-- ↑HR, dp/dt, CO, SBP, and PP
-- ↓ DBP w/ physiological doses

Front 66

Epi + β-blocker = ?

Back 66

will get you only α effects
-- ↑BP

Front 67

Why do we add Epi to local anesthetics?

Back 67

Prevents systemic absorption because it causes skin vasoconstriction to keep the local local

Also, you won’t bleed as much and it enhances platelet aggregation

Front 68

Phenylephrine?

Back 68

(PE)
alpha1-agonist = mydriasis without cycloplegia
-- will still have light response

useful for fundoscopic exam (actually, we use tropicamide)

Front 69

Ritodrine?

Back 69

(beta2-agonist) decreases uterine contraction in premature labor

can also use NSAIDs b/c they block PGs which cause uterine contraction

Front 70

Bronchodilate and ↑HR?

Back 70

isoproterenol (non-selective beta1 & beta2-agonist)

Front 71

Bronchodilation with less  HR?

Back 71

albuterol, terbutaline (selective beta2-agonists)

Front 72

Clonidine?

Back 72

pre- and post-synaptic alpha2-adrenoceptor agonist
-- activate prejxnal receptors in the vasomotor center of the medulla to reduce sympathetic tone
-- ↓BP, w/ decrease in TPR, and minimal long-term effects on cardiac output and HR

Front 73

List examples of indirect adrenergic agonists.

Back 73

1. tyramine-containing foods
2. methylphenidate
3. ephedrine

No effect after pre-tx w/ RESERPINE (destroys NE storage granules)
-- Only directly acting agonists increase dp/dt and HR in isolated heart from animals treated w/ reserpine

Front 74

Tyramine-containing foods?

Back 74

Contraindicated in pts taking phenelzine or tranylcypromine which non-selectively inhibit MAO-A and MAO-B

increase in BP caused by tyramine blocked by reserpine
guanethidine (sympathetic blocking agent)
cocaine
3 P’s

Front 75

Methylphenidate?

Back 75

tx ADHD/ADD

S/E's = depression, insomnia, decreased appetite
and linear growth rate

Front 76

Amphetamine toxicity?

Back 76

nervous, excited, agitated, ↑ HR/BP, toxic psychosis = paranoid schizophrenia, formication w excoriations, convulsions w OD
-- difficult to distinguish from effects of cocaine

Treat psychosis w CHLORPROMAZINE

Front 77

Ephedrine?

Back 77

Direct beta1 and beta2,

Indirect alpha
-- no alpha after reserpine

Front 78

What are the 3 P’s?

Back 78

Phentolamine
Prazosin
Phenoxybenzamine (PBZ)

Alpha blockers

Front 79

Phentolamine, PBZ, Prazosin, and HR?

Back 79

Phentolamine, PBZ
-- increases HR via baroreflex

Prazosin
-- no effect on HR

Front 80

Ergotamine, dihydroergotamine?

Back 80

partial alpha agonists

Used for tx of migraine

Front 81

What is the major S/E of alpha blockers?

Back 81

orthostatic hypotension

Front 82

Tamsulosin?

Back 82

blocks alpha1A-receptors in GU tract in patients w BPH to enhance voiding

Front 83

Epinephrine and alpha blockers?

Back 83

Epinephrine-reversal by alpha-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 alpha-blocker (only β effects)

Front 84

How do we control BP during surgery for pheochromocytoma?

Back 84

Pretreat w/ alpha and beta-blockers to prevent any changes in BP caused by the release of EPI from the pheo during surgery

Front 85

What if we infuse a physiological dose of EPI?

Back 85

Lowers DBP and increases SBP.
-- vasodilates some vascular beds via beta2-receptor stimulation and
-- constricts other vascular beds via alpha2-receptor stimulation.

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).

Front 86

Effect of SBP and DBP with:
1. Epi
2. Epi and alpha block
3. Epi and beta block

Back 86

Epi alone:
-- Lowers DBP and increases SBP.

Epi and alpha block
-- can only stim vascular β2 receptors to cause vasodilation
-- large fall in TPR and DBP

Epi and beta block
-- can only stimulate vascular α receptors to cause vasoconstriction
-- large rise in TPR and DBP

Front 87

Atenolol & metoprolol

Back 87

Beta blockers that block β1

Front 88

Propanolol & timolol

Back 88

Beta blockers that block β1 and β2

Front 89

Beta blocker used for…?

Back 89

Angina
-- decreased O2 requirement via ↓dp/dt and HR
-- but LV-EDV increases

Causes ↓ HR, AV conduction, dp/dt

Blocks increase in HR caused by hemorrhage, minoxidil, hydralazine, diazoxide, nitroprusside, NTG

Front 90

Beta blockers vs. NTG and oxygen demand

Back 90

beta-blocker (BB) decrease oxygen demand by decreasing HR, dp/dt and afterload (DBP)

NTG decreases oxygen demand by decreasing venous return and LV-EDV

Front 91

Beta blocker S/Es?

Back 91

CHF

bronchospasm

AV block

delayed recovery of [glucose] in pts w/ Type 1 DM after s.c. injection of too much insulin

Front 92

Timolol?

Back 92

Decreased IOP w/ cycloplegia
-- does not affect visual accommodation OR papillary size

(do not use propranolol b/c it causes local anesthesia of cornea)

Front 93

What causes Beta-blocker withdrawal syndrome?

Back 93

patient tx w beta-blocker for angina…

d/c drug --> increased cardiac -receptor stimulation --> increased O2 demand --> angina and MI (tachycardia, palpitations, tremor, chest pain)

Receptors will downregulate w/in a few days

Front 94

How do we treat the symptoms of hyperthyroidism?

Back 94

Tx with Propranolol to ↓ tachycardia and tremor and prevent the peripheral conversion of T4 to T3,

Propanolol is the only beta-blocker to have the effect on T4 and T3

Front 95

Reserpine?

Back 95

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;

3. no alpha effects of ephedrine after reserpine

Front 96

Guanethidine?

Back 96

1. decreased nerve-stimulated NE release
2. competitive inhibitor of NE uptake1
3. anti-HT effect blocked by TCA’s b/c TCA’s block entry of guanethidine into neuron

Front 97

Cocaine?

Back 97

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 (and causes hemostasis w/o Epi addition like other locals)

Front 98

Cocaine toxicity?

Back 98

dilated pupils, euphoria, hallucinations, excitation, halo vision, itchy skin, ↑ BP/HR, convulsions
-- difficult to distinguish from amphetamine

Front 99

Cocaine w/d syndrome?

Back 99

sleepiness, depression, anhedonia

Front 100

MAO inhibitors?

Back 100

PHENELZINE, TRANYLCYPROMINE - inhibit MAO-A and MAO-B

SELEGILINE – selectively inhibits MAO-B to prevent breakdown of DA in CNS
-- can be used to treat Parkinson’s
-- NO adverse food rxns

Front 101

MAO “cheese rxn”?

Back 101

Inhibition of MAO-A in gut wall allows dietary tyramine to enter the circulation

Tyramine releases NE to cause HT and tachycardia

Front 102

Clonidine and α-methyldopa?

Back 102

Antihypertensive drugs

↓ SNS activity via stimulation of alpha2-receptors in CNS
-- ↓ plasma NE
-- ↓ plasma renin activity (PRA) --> usually proportional to sympth tone and Na/H2O balance
-- ↓ HR
MIMICS BARORECEPTOR INPUT

Clonidine has off-label use by psych

α-methyldopa goes into the brain, then becomes α-NE

Front 103

S/E’s of clonidine & α-methyldopa?

Back 103

sedation, dry mouth, edema

alpha-MD = hepatitis, “flu” syndrome, (+) Coomb’s test

Front 104

What is clonidine w/d syndrome?

Back 104

sweating, ↑ HR, abrupt return of BP to HT value, abdominal pain, tremor, headache, apprehension
= REBOUND SYMPTH ACTIVITY

(differs from beta-blocker withdrawal syndrome = ↑ HR with palpitations but no tremor, sweating, abdominal pain or ↑ BP)

Front 105

Drugs that DECREASE plasma NE?

Back 105

ACT AT BRAIN
-- clonidine
-- alpha-MD

↓NE AT NERVES
-- guanethidine

DEPLETE NE STORAGE GRANULES
reserpine

ganglionic blockers

Front 106

Drugs that INCREASE plasma NE?

Back 106

alpha blockers, hydralazine, minoxidil, diazoxide, nifedipine, HCTZ, sodium nitroprusside

VASODILATORS – baroreflex ↑ in sympth tone, thus ↑ plasma NE

Front 107

Name the arterial vasodilators.

Back 107

hydralazine

minoxidil

diazoxide

Dilate resistance vessels
-- ↓ TPR & BP
-- ↑ HR, dp/dt, CO, PRA, and plasma NE

Front 108

S/E hydralazine?

Back 108

SHIP drug!
1. edema

2. SLE-like syndrome
-- arthralgia
-- fever
-- arthritis
-- malar rash
-- (+) ANA

Front 109

S/E minoxidil?

Back 109

1. hirsutism; effect additive w/ finasteride

2. edema

Front 110

S/E diazoxide?

Back 110

1. Inhib of insulin release
-- hyperglycemia

2. edema

Front 111

Which drugs do we use in a hypertensive emergency?

Back 111

1. diazoxide
-- arterial vasodilator

2. sodium nitroprusside (SNP)
-- nitrate vasodilator
-- dilates arteries & veins

3. labetalol
-- beta blocker to ↓HR

Front 112

Sodium Nitroprusside?

Back 112

1. dilates arteries and veins via release of nitric oxide (NO) from SNP molecule

2. balanced vasodilation

Front 113

Sodium Nitroprusside in normotensive pt?

Back 113

decreases TPR and venous return
-- NO change in CO

Front 114

Sodium Nitroprusside in CHF pt?

Back 114

decreases preload and afterload
-- leads to INCREASE in CO

Front 115

Thiocyanate toxicity?

Back 115

Toxicity of Sodium Nitroprusside

1. anorexia, nausea, delirium, hallucinations and psychosis
2. usually occurs after several days of therapy and assoc w/ decreased renal fxn

EARLIEST SIGNS
-- mental disorientation and metabolic acidosis in assoc. w/ increased dose requirement

Front 116

How do we treat thiocyanate toxicity?

Back 116

(pic on pg 232 of cardio syllabus)

DC the sodium nitroprusside

Give furosimide to improve renal fxn (gets rid of the thiocyanate)

Tx with thiosulfate

Front 117

Cyanide toxicity?

Back 117

(pic on pg 232 of cardio syllabus)

occurs when thiosulfate becomes depleted

-- muscle weakness, spasm, disorientation

Front 118

How do we treat cyanide toxicity?

Back 118

Treat w/ nitrite or thiosulfate

Front 119

What are the Ca channel blockers?

Back 119

Nifedipine – primarily affects vessels

Diltiazem – primarily affects heart

Verapamil – primarily affects heart

Front 120

Ca channel blocker action?

Back 120

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

Front 121

Therapeutic uses of Ca channel blockers?

Back 121

HT

exertional and vasospastic angina

AV nodal re-entry tachycardia (V+D)

Front 122

Which drugs DECREASE dp/dt/

Back 122

B-blockers
Ca blockers
diisopyramide

Front 123

What are the effects of Ang II?

Back 123

1. ↑ BP (via increased water reabsorp)

2. increases SNS activity via CNS

3. presynaptic enhancement release of NE

4. blocks NE uptake1 -- ↑dp/dt

5. causes release of ADH

6. release of aldosterone

7. decreases mesenteric BF

RAAS reinforces the sympathetic NS; each enhances the other’s release

Front 124

Which drugs decrease mesenteric blood flow to treat GI bleeding?

Back 124

NE and Ang III (get escape)

ADH and octreotide (no escape)
-- retain Na to ↑ Aldo and ↑H20
-- octreotide is a somatostatin agonist

Front 125

What are the ACE inhibitors?

Back 125

-prils

captopril
enalopril

Prevent conversion of Ang I to Ang II

Front 126

What are the effects of ACE inhibitors?

Back 126

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. ACEI’s potentiate the decrease in BP caused by i.v. bradykinin

4. ACEI's increase the plasma concentration of BK

Front 127

ACEi side effects?

Back 127

1. fetal toxicity (category X)

2. K+ retention

3. cough
-- cough caused by BK & PG and is blocked by aspirin (ACEI’s block metabolism of bradykinin)

Front 128

Losartan?

Back 128

Ang II receptor antagonist - no cough

Front 129

Therapeutic use of ACE inhibitors?

Back 129

1. MOA in tx of CHF
-- increase CO by decreasing preload and afterload
-- reverses cardiac remodeling caused by angiotensin II (ang II)

2. HT patient with DM
-- tx w ACEI to ↓ BP and ↓ proteinuria (protects kidneys)

Front 130

What are the diuretic drugs?

Back 130

Acetazolamide

Furosemide, ethacrynic acid

HCTZ

Amiloride and Triamterene

Spironolactone

Mannitol

Front 131

Acetazolamide MOA?

Back 131

1. Inhibits carbonic anhydrase in PT and DT to prevent reabsorption of bicarbonate

2. Inhibits formation of aqueous humor and CSF, some effect to ↓ gastric acid secretion

3. Increased excretion of Na+, K+, bicarbonate - urinary pH increases to 8-8.5

Front 132

Therapeutic use of acetazolamide?

Back 132

1. used to increase urinary pH to enhance renal clearance of acids, e.g., salicylates,

2. used to tx glaucoma and altitude sickness

3. tx of acidosis, via renal loss of bicarbonate

4. stimulates respiration

Front 133

Acetazolamide S/Es?

Back 133

hyperchloremic metabolic acidosis

Front 134

Respiration: stimulants vs. inhibitors?

Back 134

STIMULATION
-- acetazolamide
-- nicotine
-- Epi
-- theophylline, caffeine

INHIBITION
-- EtOH
-- opiates – morphine
-- benzo’s – diazepam
-- barbiturates

Front 135

How do you make urine alkaline?

Back 135

CaI or Na bicarbonate

Increases renal clearance of acidic drugs

Ex: OD w/ aspirin

Front 136

How do you make urine acidic?

Back 136

ammonium chloride

Increases renal clearance of basic drugs

Ex: OD w/ amphetamine

Front 137

What are the loop diuretic drugs?

Back 137

Furosemide

Ethacrynic acid

Front 138

MOA of loop diuretics?

Back 138

Inhibit Na,K,2Cl symporter in ascending L of H

Also blocks Na transport in macula densa of DT

Front 139

Effect of loop diuretics?

Back 139

1. Increased urinary excretion of Na, K, Ca, Mg, Cl, 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

Front 140

Therapeutic use of loop diuretics?

Back 140

acute pulmonary edema

CHF

peripheral edema

hypercalcemia

bilateral hearing loss via toxicity to CN VIII; potentiated by aminoglycosides (e.g., gentamicin)

Front 141

Loop diuretics S/E’s?

Back 141

1. hypokalemia w alkalosis

2. hypomagnesemia

3. hyperglycemia

4. dilutional hyponatremia
-- cannot make a dilute urine in order to excrete free water

5. hyperuricemia (bad for gout)

6. Li toxicity caused by their enhanced reabsorption in PT

7. enhances digoxin toxicity via hypokalemia
-- less K+ to compete w digoxin for Na+-K+ ATPase binding sites

Front 142

Thiazides?

Back 142

HCTZ

Front 143

HCTZ MOA?

Back 143

Acts in the distal tubule and ↓ GFR in all pts

Blocks NaCl symporter in principal cells of DT

Front 144

HCTZ effect?

Back 144

1. ↑ 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

Front 145

HCTZ therapeutic use?

Back 145

HT

edema

kidney stones

DI
-- distal loss of Na and water enhances the reabsorption of filtrate in the PT
-- less volume sent distally
-- urine vol ↓ by 50%

Front 146

HCTZ S/E’s?

Back 146

1. hypokalemia w alkalosis

2. hypomagnesemia, hyperglycemia, hyponatremia;

3. uniformly decreases GFR

4. hyperuricemia (bad for gout)

5. Li+ toxicity caused by their enhanced reabsorption in PT

6. enhances digoxin toxicity via hypokalemia
-- less K+ to compete w ith digoxin for Na-K ATPase binding sites

7. diuretic effect contracts the blood volume & therefore potentiates the fall in BP caused by anti-HT drugs
-- especially sympatholytic drugs (e.g., clonidine and alpha-blockers like prazosin)

Front 147

What are the K sparing diuretics?

Back 147

TASK

triamterene

amiloride

spironolactone (aldo receptor antagonist)

Front 148

K sparing diuretics contraindication?

Back 148

All are contraindicated in renal insufficiency b/c they can cause fatal hyperkalemia

Front 149

Amiloride and triamterene MOA?

Back 149

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

Front 150

Spironolactone MOA?

Back 150

1. Aldo antagonist

2. Partial agonist at androgen/progesterone receptors

3. Blocks aldosterone receptors in the principal cells of the LDT and CD

Front 151

Spironolactone therapeutic use?

Back 151

1. NO effect in adrenalectomized patient

2. Secondary hyperaldosteronism
-- associated w/ cirrhosis

3. nephrotic syndrome;

4. reverses cardiac remodeling caused by aldosterone in patients with HF

Front 152

Spironolactone S/E’s?

Back 152

hyperkalemia

gynecomastia (males)

menstrual irregularities

hirsutism

deepened voice (females)

Front 153

CLINICAL: Patient tx with OCP containing estrogen + norethindrone develops hirsutism. Why? Tx?

Back 153

Hirsutism results from androgenic effects of the progestin norethindrone which is a derivative of 19-nortestosterone;

Tx: Spironolactone

Front 154

CLINICAL: Postmenopausal female develops hirsutism - how to tx?

Back 154

Spironolactone

Front 155

CLINICAL: Patient with an adrenal tumor has ↑ BP and plasma [HCO3], ↓ plasma [K] and PRA; plasma [Na] is normal  dx? and tx?

Back 155

Conn’s syndrome – aldo secreting adrenal tumor
-- zona glomerulosa causes Na retention
-- ADH causes water retention
-- but plasma Na will be NORMAL

Tx w/ spironolactone

Front 156

Review: What stimulates Aldo?

Back 156

1. ACTH

2. Ang II

Front 157

Hypokalemia from furosemide and HCTZ can be prevented by…?

Back 157

K+-sparing diuretic drugs

ACE inhibitors – blocks Ang action

B-blockers – inhib renin release of Ang

To a certain extent, by p.o. K+ supplements

Front 158

When trying to determine which diuretic drug was used, you must consider the following…?

Back 158

1. First look at urine flow rate

2. Then look at the changes in electrolyte excretion

3. Finally, you can also consider pH

Front 159

The effects of diuretics on urinary flow…?

Back 159

URINE FLOW RATE
1. 8-10ml/min
-- furosemide OR
-- mannitol

2. 2-3ml/min
-- acetazolamide
-- thiazide
-- K-sparing agent (TASk)

Front 160

The effects of diuretics on quantitative changes in electrolyte excretion?

Back 160

1. FUROSEMIDE is distinguished from MANNITOL by the fact that FUROSEMIDE causes greatest increase in electrolyte excretion

2. ACETAZOLAMIDE causes massive increase in bicarb excretion

3. K-sparing agent decreases K excretion

4. Drug that remains is thiazide

Front 161

What are the cardiac glycosides?

Back 161

digoxin

digitoxin

Front 162

Cardiac glycoside kinetics?

Back 162

DIGOXIN
-- Half-life= 1-1.5 d
-- renal Cl
-- decreased GFR decreases Cl and increase half-life

DIGITOXIN
-- Half-life = 7 d
-- hepatic Cl
-- ↓ Cl and ↑ half-life in patient w cirrhosis and CHF

1. ↓ GI absorption w cholestyramine (ion exch resin) or antacids
-- ↓ plasma [dig] and ↓ cardiac effect

2. older patients
-- ↓ Vd, so ↓ loading dose
-- ↓ GFR, so ↓ maintenance dose
-- older patients can have decreased GFR with normal serum [Cr] (b/c Cr byproduct of skel m.; if ↓skel m., then ↓ Cr, so [Cr] doesn’t change

3. QUINIDINE ↑ plasma digoxin by displacing digoxin from skeletal muscle and ↓ renal Cl

SMALL THERAPEUTIC WINDOW
-- binds to skel muscle
-- Vd determines loading dose
-- Cl determines maintenance dose

Front 163

Cardiac glycoside MOA?

Back 163

DIGOXIN, DIGITOXIN

1. Inhibition of Na-K ATPase
-- increases dp/dt, but decreases resting membrane potential (Vm)
-- lack of pumping Na out causes automaticity in fast fibers
-- low K: potentiates inhibition of ATPase: causes automaticity and ↓ERP in ventricles (K and dig compete for same binding site on ATPase)
-- low Mg: same a Ca overload inside cells - causes automaticity
-- high Ca: Ca overload inside cells causes automaticity

2. Acts in CNS to ↑ vagal tone
-- ↓ HR, atrial contraction and AV conduction

Front 164

Therapeutic use of cardiac glycosides?

Back 164

DIGOXIN, DIGITOXIN

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

Good for heart failure and no adverse effect on dp/dt

Front 165

Glycoside S/E’s?

Back 165

bradycardia

AV block

PVC’s

n/v (CTZ)

CNS-abnormal color vision, halo vision, esp. in elderly

Front 166

What are the antidysrhythmic drugs?

Back 166

Quinidine

Procainamide

Disopyramide

Lidocaine

Amiodarone

Verapamil

Front 167

Quinidine MOA?

Back 167

blocks Na+ channels in fast fibers

Front 168

Quinidine effects?

Back 168

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
-- gets rid of automaticity (PVCs)

3) SA node
-- no direct effect
-- anticholinergic effect causes tachycardia

4) AV node
-- atropine-like effect ↑ conduction (increases HR)
-- but direct effect ↓ conduction (P-R increases)

Front 169

Quinidine therapeutic use?

Back 169

Atrial and ventricular dysrhythmias

Give digoxin before quinidine to tx A flutter and A fib so digoxin prevents increase in AV conduction from atropine-like action of quinidine

ATROPINE -- ↑HR and takes away inhibition of AV conduction by vagus

Front 170

Quinidine S/E’s?

Back 170

hypotension (-blockade)

↓ dp/dt

diarrhea (limits use)

tinnitus w OD

Front 171

CLINICAL: Pat w atrial fibrillation given quinidine to slow ventricular rate, but ventricular rate ↑ soon after quinidine. Why? What to do about it?

Back 171

Immediate atropine-like effect of quinidine ↑ AV conduction

TX: Verapamil or Diltiazem to ↓ AV conduction and slow ventricular rate.

Front 172

Procainamide S/E’s?

Back 172

SLE and arthritis in slow acetylators
-- genetic defect
-- inactive form of acetylase enzyme
-- cannot clear drug by hepatic transformation

Front 173

Disopyramide effects?

Back 173

1. marked increase in dp/dt

2. marked antimuscarinic effects
-- dry mouth
-- constipation
-- contraindicated in BPH & glaucoma

Front 174

Lidocaine MOA?

Back 174

block of Na+ channels in fast fibers

given i.v. due to low F

Front 175

Lidocaine effects?

Back 175

1. ↓ phase 4 automaticity to prevent PVC’s

2. no effect at SA or AV nodes, BP or dP/dT

3. local anesthetic effect via Na+ channel block in sensory fibers

DOES NOT widen QRS (primarily affects ischemic tissue)

Front 176

Lidocaine therapeutic effects?

Back 176

1. ventricular arrhythmias

2. local anesthetic

Front 177

Lidocaine S/E’s?

Back 177

Seizures
-- Tx w/ BZ

Front 178

Amiodarone MOA?

Back 178

1. Inhibition of K channels

2. Blocks Na channels

3. Non-competitive alpha and β blockade

Front 179

Amiodarone effects?

Back 179

K INHIBITION:
-- ↑ APD, ERP interval in fast fibers
-- ↑ Q-T (but doesn’t precip torsade)

Na BLOCK:
-- powerful suppression of phase 4 automaticity

NON-COMPETITIVE - and -BLOCKADE:
-- hypotension & bradycardia
-- slows sinus rate and AV conduction (P-R increased)

Almost perfect antidysrhythmic except for S/Es

Front 180

Amiodarone therapeutic use?

Back 180

recurrent ventricular tachycardia/fibrillation

Front 181

Amiodarone S/E’s?

Back 181

1. pulmonary fibrosis

2. hypo- or hyperthyroidism

3. blue, purple or slate gray skin
-- purple man
-- 30% iodide by wt

4. corneal microdeposits

Front 182

Verapamil MOA?

Back 182

blocks L-type Calcium channels at SA and AV nodes and cardiac myocytes

Works primarily at the heart! (VD)

Front 183

Verapamil effects?

Back 183

SA node
-- ↓HR

AV node
-- ↓ conduction velocity
-- ↑ ERP
-- fewer atrial signals pass through the AV node to the ventricles
-- myocardium = ↓ dp/dt = ↓ CO

Front 184

Verapamil therapeutic use?

Back 184

AV nodal re-entry tachycardia

Front 185

Verapamil S/E’s?

Back 185

1. ↓ dp/dt

2. decreased CO in HF

3. AV block

Front 186

CLINICAL: Patient with atrial fibrillation and no HF has palpitations and dizziness. Tx and MOA?

Back 186

Tx w/ VERAPAMIL

MOA: ↑ ERP of AV node slows ventricular rate --> improved AV filling --> ↑ CO

Front 187

Antiplatelet drugs?

Back 187

Aspirin

Abciximab, Eptifibatide, Tirofiban

Ticlopidine, Clopidogrel

Front 188

ASA?

Back 188

Irreversibly inhibits COX-1 of platelets to prevent the synth of TXA2

Front 189

Abciximab, Eptifibatide, Tirofiban?

Back 189

1. antagonist of the platelet IIb/IIIa which uses fibrinogen to bind platelets together

2. given in OR and ER via i.v.

Front 190

Ticlopidine, Clopidogrel?

Back 190

antagonist of platelet purinergic (ADP) receptors

Front 191

CLINICAL: A patient requires an antiplatelet drug after MI or stroke, but the patient has aspirin hypersensitivity. How to Tx?

Back 191

Use ticlopidine or clopidogrel

Front 192

Heparin MOA?

Back 192

1. accelerates binding of antithrombin III (AT III) to activated clotting factors 2, 9-12

2. increases aPTT

Front 193

Heparin kinetics?

Back 193

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

Front 194

Heparin therapeutic use?

Back 194

Treat MIs and DVTs

Front 195

Heparin antagonist?

Back 195

protamine sulfate

Front 196

Heparin S/E’s?

Back 196

antiplatelet effect additive w aspirin

thrombocytopenia

Front 197

Heparin resistance?

Back 197

results from decreased [ATIII] in blood

Front 198

LMW heparins?

Back 198

ardeparin

dalteparin

enoxaparin

Front 199

LMW heparin MOA?

Back 199

LMW = 2-6 K

LMW acts primarily on Xa, so little effect to increase the aPTT

Front 200

LWM heparin reversal of anticoagulant effect?

Back 200

Can only be PARTIALLY reversed by protamine sulfate

Front 201

LMW heparin clearance?

Back 201

Cleared by kidneys instead of RE system

Longer half-life than heparin

Front 202

Warfarin, dicumarol MOA?

Back 202

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

Only works in vivo, slow onset of action
-- (2-3 d, full effect at 5 d) increases PT (INR) (greatest effect on factor 7)

Front 203

Therapeutic use of warfarin?

Back 203

1. to treat DVT’s

2. prevent emboli in patients with prosthetic cardiac valves

3. prevent thrombotic stroke in patients with atrial fibrillation

Front 204

Warfarin interactions?

Back 204

1. Highly bound to plasma proteins
-- many drug-drug interactions

2. Displacement of warfarin from plasma proteins has two effects
-- ↑ PT and ↑ clearance of warfarin

3. metabolized by CYP450

Front 205

CYP450 inhibitors?

Back 205

cimetidine
ketoconazole
isoniazid
erythromycin
grapefruit juice

Inhibition will INCREASE plasma warfarin and PT

Front 206

CYP450 inducers?

Back 206

carbamazepine
phenobarbital
phenytoin
rifampin
chronic EtOH
benzopyrene (cigarette smoke)

Induction will DECREASE plasma warfarin and PT

Front 207

Warfarin antidote?

Back 207

Vit K1 (phytonadione)

Fresh frozen plasma

Factor IX concentrate (contains factors 2,7,9 & 10)

Front 208

CLINICAL: Patient OD's with warfarin are attempts suicide with rat poison --> which clotting factors and lab tests affected?

Back 208

↓ activity of factors 2,7,9 and 10

↑ aPTT and PT (usually doesn’t affect aPTT but will w/ OD)

no effect of factors 8 or 13 or bleeding time

Front 209

CLINICAL: Which type of cardiac dysrhythmia requires tx with warfarin?

Back 209

Atrial fibrillation

Front 210

What are do thrombolytic drugs do? Name them.

Back 210

all ultimately convert plasminogen to plasmin
-- plasmin destroys fibrin to lyse clots

Urokinase
tPa
Streptokinase

Front 211

Urokinase MOA?

Back 211

Direct activation of plasminogen

Front 212

tPA MOA?

Back 212

When tPA and plasminogen bind to fibrin in close proximity, plasminogen is converted to plasmin by tPA
-- normal, intrinsic activation of plasmin

Front 213

Streptokinase MOA?

Back 213

changes conformation of plasminogen to expose an active protease site that hydrolyzes another plasminogen molecule to plasmin

Front 214

S/E’s of fibrinolytics?

Back 214

systemic destruction of clotting factors 5 & 8 causes bleeding, esp. in CNS (hemorrhagic stroke)

Front 215

CLINICAL: Patient with MI treated with several drugs and develops intracranial bleeding. Which drug caused it?

Back 215

Streptokinase (or choose other thrombolytic in list)

Front 216

Inhibitors of fibrinolysis?

Back 216

Aminocaproic acid

A lysine analog that binds to the lysine-binding sites on plasmin which blocks the binding of plasmin to fibrin

Front 217

What are the antilipemic drugs?

Back 217

Statins (lovastatin)
Ezetimibe
Gemfibrozil and Fenofibrate
Niacin

Front 218

MOA of statins?

Back 218

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

Front 219

Net effect of statins?

Back 219

↓Tc, LDL, VLDL, and TG

slight ↑ in HDL

Front 220

S/E’s of statins?

Back 220

myositis/myopathy = muscle pain and weakness assoc with ↑ CPK
-- damage can progress to rhabdomyolysis which can cause renal shut-down
-- give mannitol + i.v. fluids to flush out the toxic myoglobin

Front 221

Ezetimibe MOA?

Back 221

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

Front 222

Net effect of ezetimibe?

Back 222

selective for LDL cholesterol
-- so only Tc and LDL decrease

Front 223

Therapeutic use of ezetimibe?

Back 223

used to tx patients who develop muscle weakness on a statin

So switch to EZE OR
↓ statin dose and add EZE to get beneficial LDL equal to the highest statin dose

Front 224

Gemfibrozil and Fenofibrate MOA?

Back 224

activates lipoprotein lipase (esp. in skeletal muscle) to increase hydrolysis of VLDL

Front 225

Net effects of Gemfibrozil and Fenofibrate?

Back 225

↓ Tc, LDL, VLDL and TG's

slight ↑ in HDL

Front 226

Gemfibrozil and Fenofibrate therapeutic use?

Back 226

Hypertriglyceridemia
-- common in DMII

Front 227

S/E’s of Gemfibrozil and Fenofibrate?

Back 227

myositis/myopathy = muscle pain and weakness assoc w/ ↑ CPK
-- muscle damage can progress to rhabdomyolysis

Front 228

Niacin MOA?

Back 228

unknown

Front 229

Niacin therapeutic use?

Back 229

↑ HDL cholesterol

Front 230

Niacin S/E’s?

Back 230

flushing and itching in face and upper body

Front 231

What do antianginal drugs do?

Back 231

all ↓ oxygen demand and/or ↑ oxygen supply

all ↑ endocardial blood flow

Front 232

What are the beta blockers?

Back 232

atenolol

metoprolol

propanolol

timolol

Front 233

B-blocker MOA?

Back 233

Negative chronotropic & inotropic effects decreases the rate-pressure product (HR x SBP)

Also decrease cardiac afterload (= decreased DBP)

↓HR, ↓dp/dt, ↓ afterload

Front 234

Net effect of B-blockers?

Back 234

Decreased cardiac oxygen demand

Front 235

What are the nitrates?

Back 235

nitroglycerin
-- glyceryl trinitrate
-- isosorbide mono- and dinitrate

Front 236

MOA of nitrates?

Back 236

NO donors which selectively venodilate
-- venodilation ↓ venous return to ↓ LV wall tension during diastole and systole (↓preload)

Front 237

Net effect of nitrates?

Back 237

decreased cardiac oxygen demand

Front 238

Problem w/ nitrates?

Back 238

Drug tolerance is a big problem

Front 239

What are the calcium channel blockers?

Back 239

verapamil

diltiazem

amlodipine

felodipine

Front 240

MOA of verapamil and diltiazem?

Back 240

1. negative chronotropic & inotropic effects decreases the rate-pressure product (HR x SBP)

2. also decreases cardiac afterload (= decreased DBP)

3. also dilates large epicardial vessels and small endocardial resistance vessels

4. Decreased oxygen demand and increased oxygen supply

Front 241

MOA of amlodipine and felodipine?

Back 241

1. Decreased cardiac afterload (DBP)

2. Increased blood flow through large epicardial vessels and small endocardial resistance vessels

3. Decreased oxygen demand and increased oxygen supply

Front 242

Treatment of CHF?

Back 242

1) decrease preload with diuretic drugs
-- ↓ blood volume

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 fibrillation