Pharm. Final Review Ii

Front 1

Cholinergic Pharmacology

Back 1

**Study the yellow chart about receptors/responses.

Front 2

**Know the Synthesis + Degradation of ACh.

Back 2

(On back of yellow chart)

Front 3

What is ACh?

Back 3

**NT in the:
1) CNS (N and M)
2) Autonomic ganglia (N1)
3) Adrenal medula
=N1-stimulation releases Epi from the adrenal medulla
4) NM junction (N2)
5) Sweat glands (M)

Front 4

Cholinergic Basis of AD:

Back 4

**Seems to involve a deficit of ACh in the CNS

Front 5

Treatment:

Back 5

=carbamate AChase inhibitors --> like Donepezil

Front 6

Metabolism of ACh --> i.e. which drugs POTENTIATE the effects of ACh?

Back 6

"Can't Be Metabolized!"

=Carbachol
=Bethanechol
=Methacholine

**Inhibitors of AChase = potentiates effects of ACh

Front 7

Methacholine

Back 7

**Used for the diagnosis of asthma

=causes flushing, sweating, salivation, GI cramping, and bronchoconstriction

Front 8

What is the function of bethanechol?

Back 8

**Urinary retention in:

1) PD patients being treated w/ benztropine

2) Psychotic patient being treated by typical antipsychotics (=thioridazine)

3) Patient being treated w/ TCAs

Front 9

What is the effect of choline esters (=i.e. acetylcholine, carbachol) on BP??

Back 9

=DECREASE BP via NO released from vascular endothelial cells

**Decreased BP blocked by ATROPINE

Front 10

Pilocarpine

Back 10

=Causes miosis + cycloplegia via contraction of ciliary muscle

**Effect DECREASES IOP via increased outflow of aqueous humor

Front 11

Side Effects of Pilocarpine:

Back 11

=Bronchoconstriction

=Salivation

Front 12

Nicotine

Back 12

=a tertiary amine

NOT hydrolyzed by plasma Achase --> metabolized by LIVER

=induces CYP450 --> so increases drug metabolism

Front 13

Effects:

Back 13

=Increases sympathetic activity w/ INCREASED HR, BP + cutaneous vasoconstriction
=Increased respiration + GI motility

Front 14

What about with very LARGE doses?

Back 14

=muscle fasciculations followed by depolarization blockade

=in the CNS --> convulsions w/ overdose (OD)

Front 15

ACHase Inhibitors:

Back 15

CARBAMATES
=Physostigmine (tertiary)
=Neostigmine (quarternary)
=Edrophonium (quarternary)

Front 16

Use of Edrophonium:

Back 16

**Diagnose MG

**Used to differentiate between "myasthenic" and "cholinergic" crisis in patients treated w/ neostigmine

**Used w/ ATROPINE in reversal of a neuromuscular blockade caused by non-depolarizing drugs
=d-tc or pancuronium

Front 17

Neostigmine:

Back 17

**Treatment of MG
=ALWAYS used w/ atropine to prevent indirect muscarinic S/E's

**Used w/ glycopyrrolate in reversal of NMB caused by non-deplarizing drugs

Front 18

Organophosphates:

Back 18

=Malathion
=Parathion
=Isofluophate (DFP)

Front 19

Symptoms/Signs of Poisoning:

Back 19

=Lacrimation
=Salivation
=Miosis
=Dyspnea
=increased BP (N1)
=skeletal muscle fasciculations (N2)

Front 20

Where would be the places of risk?

Back 20

=Agriculture
=Home
=Biochemistry Laboratory

Front 21

Treatment of poisoning?

Back 21

=atropine + pralidoxime (2-PAM)

**2-PAM regenerates phosphorylated AChase

Front 22

What do humans have that degrade organophosphates and prevent our death?

Back 22

=Carboxylesterases

Front 23

Poisoning w/ Plants:

Back 23

**Increased ACh stimulation
=like giving physostigmine
=treat w/ atropine

**Decreased ACh stimuation:
=like giving atropine
=treat w/ physostigmine

Front 24

Tertiary:

Back 24

=Scopolamine
=Atropine
=Cyclopentolate
=Benztropine

Front 25

Quarternary:

Back 25

**Recall: N-methyl-PIG

=N-methylatropine
=Propantheline (GI spasticity)
=Ipratropium (prevents bronchoconstriction from air pollution/cold air)
=Glycopyrrolate

Front 26

Drugs for the Treatment of Glaucoma:

Back 26

1) Alpha agonists
=Epinephrine
=Brimonidine

2) B-blocckers
=timolol, betaxolol, carteolol

3) Diuretics
=Acetazolamide

4) Cholinomimetics
=Pilocarpine
=Carbachol
=Physostigmine
=Echothiophate

5) Prostaglandin
=Latanoprost

Front 27

Epinephrine

Back 27

Increases outflow of AH

Front 28

Brimonidine

Back 28

Decreases AH secretion

Front 29

Timolol, Betaxolol, Carteolol

Back 29

Decreased AH secretion

Front 30

Acetazolamide

Back 30

=Decreased AH humor secretion due to decreased HCO3- (via inhibition of carbonic anhydrase)

Front 31

Pilocarpine, carbachol, physostigmine, echothiophate

Back 31

**Increased OUTFLOW of AH
=contract ciliary muscle and open trabecular meshwork

Front 32

Prostaglandin

Back 32

Increase outflow of AH

Front 33

Ganglionic Blocking Drugs

Back 33

=Trimethaphan
=Hexamethonium

**Block SNS and PSNS
**Block increase in plasma Epi induced by hypoglycemia

Front 34

Effects of Blocking Sympathetic Ganglia:

Back 34

=Arteriodilation lowers TPR
=Venodilation decreases preload
=Decreased cardiac dp/dt
=Decreased CO
=Decreased TPR and CO = hypotension
=Decreased sweating
=Impotence (no ejaculation)

Front 35

Effects of Blocking Parasympathetic Ganglia:

Back 35

=Tachycardia
=Mydriasis and cycloplegia
=Decreased salivation + lacrimation
=Decreased GI secretion, motility and tone
=Decreased gastric acid secretion
=Decreased release of pancreatic enzymes and bile
=constipation and urinary retension
=impotence (no erection)

Front 36

Neuromuscular Blocking Drugs:

Back 36

**Can either be:
1) Depolarizing (non-competative)

2) Non-depolarizing (competitive)

Front 37

Depolarizing:

Back 37

1) Succinylcholine
2) Decamethonium

**Phase I = MEP depolarized
**Phase II = repolarized but still refractory

=causes fasciculations prior to flaccid paralysis

Front 38

Uses:

Back 38

=NM blockade
=ECT (shock therapy)

Front 39

Non-Depolarizing:

Back 39

1) d-tubocurarine (curare)
2) pancuronium

=the "-curiums and -roniums"

**MEP never depolarized
**NO fasciculations prior to flaccid paralysis

Front 40

Use:

Back 40

NM blockade

Front 41

Changes in Drug Sensitivity w/ Diseases

Back 41

**In MG, the N2 receptor density is DECREASED

**In burns and denervation injury, the N2 receptor density is INCREASED

Front 42

What BLOCKS catecholamine release?

Back 42

=Metyrosine inhibits tyrosine hydroxylase (TH)--> blocks catecholamine release as WELL as the dopamine-B-hydroxylase (DBH) and ATP released w/ NE from nerves

**i.e. tyrosine hydroxylase is the RATE-LIMITING enzyme in the synthesis of catecholamines.

**i.e. used to treat pheochromocytoma

Front 43

What INCREASES the release of NE?

Back 43

1) AngII and B2 stimulation
2) alpha2-BLOCK
3) cocaine
4) TCA's

Front 44

What DECREASES the release of NE?

Back 44

1) muscarinic (ACh) + alpha2-STIMULATION (=clonidine)
2) PGE's

Front 45

Selectivity of each agonist for vascular alpha + beta adrenoceptors:

Back 45

EPI = B2 > B1 > alpha

NE = alpha > B1 > B2

Front 46

Epinephrine

Back 46

**Think FIGHT or FLIGHT!**

=Decreased TPR and DBP
=Increased SV, CO, pulse pressure, and SBP
=Increased cardiac dp/dt and HR
=Decreased hepatic venous resistance w/ increased venous return
=Increased blood flow to the skeletal muscle, liver, myocardium, and brain
=DECREASED flow to the kidneys, GI tract, and skin

Front 47

Epinephrine + Halothane

Back 47

=arrhythmias

Front 48

Epi + B-blocker =

Back 48

ONLY alpha effects = INCREASES BP

Front 49

Epi + alpha-blocker =

Back 49

i.e. Epi + phentolamine

**ONLY beta effects:
=increased HR and RBF
=decreased TPR, BP, and ERP in heart

Front 50

NE

Back 50

**mostly ALPHA w/ a little BETA

**alpha-2 events predominate:
=Increased TPR and increases DBP
=Increased DBP causes a baroreflexly-mediated DECREASE in HR
=Decreased HR --> more time for ventricles to fill = Increased SV
=CO remains the SAME
=Decreased blood flow in the cutaneous bed, kidneys, GI tract, and skeletal muscle

Front 51

How would you BLOCK this decrease in HR?

Back 51

=atropine

Front 52

DA

Back 52

**Adrenoceptor stimulation is DOSE-DEPENDENT

**SMALL DOSE = "renal dose"
=Increases RBF + thus, increases GFR + sodium excretion
=Usually no effect on DBP

**Intermediate Dose:
=Increased dp/dt (B1) w/ little effect on HR
=Increased SV/CO
=Increased DBP (alpha-1)

**Large dose is BAD
=Decreased SV/CO -- can cause tachycardias, worsen ischemia

Front 53

SO...what would you use post-MI to maintain dp/dt?

Back 53

DOPAMINE
=DA increases RBF
=Epi and NE DECREASE RBF

Front 54

What can BLOCK the increase in renal blood flow caused by DA?

Back 54

Haloperidol

Front 55

Phenyephrine (PE)

Back 55

ALPHA-1 AGONIST

**Mydriasis w/o cycloplegia

Front 56

Ritodrine

Back 56

**B-2 AGONIST

=decreases uterine contraction in premature labor

Front 57

BRONCHODILATION

Back 57

**Bronchodilation w/ INCREASED HR:
=Isoproterenol
=i.e. non-selective B1 and B2 agonist

BRONCHODILATION w/ LESS Increase in HR:
=Albuterol
=Terbutaline
=i.e. SELECTIVE B2-agonists

Front 58

Clonidine

Back 58

=pre- and post-synaptic alpha-2 agonist

Front 59

SO...those were the DIRECT adrenergic agonists (=Epi, NE, DA, PE, etc.)--now, let's talk about the INDIRECT:

Back 59

**Will have no effects after pre-treatment w/ RESERPINE

=i.e. ONLY directly-acting agonists increase dp/dt and HR in isolated heart from animals pretreated w/ reserpine

Front 60

What is contraindicated in patients taking phenelzine OR tranylcypromine??

Back 60

**Eating tyramine-containing foods
=drugs non-selectively inhibit MAO-A and MAO-B

Front 61

The increase in BP caused by tyramine can be blocked by:

Back 61

1) Reserpine
2) Guanethidine
3) Cocaine
4) 3 P's
=Phentolamine
=Prazosin
=Phenoxybenzamine

Front 62

Methylphenidate

Back 62

**Used to treat ADHD/ADD

S/E's:
=depression
=insomnia
=decreased appetitie
=decreased linear growth rate

Front 63

Amphetamine Toxicity

Back 63

**Nervous, excited, agitated
**Increased HR/BP
**Toxic Psychosis
=paranoid schizophrenia
=formication w/ excoriations
=convulsions w/ OD

**Difficult to distinguish from effects of cocaine

Front 64

Treatment of psychosis?

Back 64

Chlorpromazine

Front 65

Ephedrine

Back 65

=direct B1 and B2
=indirect alpha

**No alpha effects after reserpine

Front 66

Alpha BLOCKERS

Back 66

**The 3P's:
=Phentolamine
=Prazosin
=Phenoxybenzamine

Front 67

Which drugs increase HR?

Back 67

=Phentolamine
=Phenoxybenzamine

**Prazosin has NO EFFCT on HR

Front 68

What do you use to treat migranes?

Back 68

=Ergotamine, dihydroergotamine

**Partial alpha agonists

Front 69

What are the major S/E's of alpha-blockers?

Back 69

ORTHOSTATIC HYPOTENSION

Front 70

Tamsulosin

Back 70

Blocks alpha IA receptors in the GU tract in patients w/ BPH to enhance voiding

Front 71

Patient w/ pheochromocytoma tumor:

Back 71

Treat w/ phentolamine
=decreases BP = EPI reversal

Front 72

Epinephrine Reversal

Back 72

**Epi reversal by alpha-blockers such as the 3P's:

=vasopressor effect of a large (SUPRAphysiological dose) of Epi is REVERSED to a VASODEPRESSOR effect by an alpha-blocker

Front 73

Explanation:

Back 73

A HUGE dose of Epi increases BP via alpha receptor stimulation.

=treatment w/ an alpha-blocker LOWERS BP
=another injection of a LARGE dose of EPI now causes a large DECREASE in BP because only vascular B2 receptors can be stimulated by Epi
=After treatment w/ the non-selective B-blocker propranolol (=BLOCKS both B1 and B2) --> another injection of a large dose of Epi has NO EFFECT on BP

Front 74

Example: BP during surgery for a pheochromocytoma

Back 74

=Pretreatment w/ an alpha blocker PLUS a non-selective B-blocker would prevent any changes in BP caused by the release of EPI from hte pheochromocytoma during surgery

Front 75

Example: Infusion of a physiological dose of EPI

Back 75

The infusion of a physiological dose of Epi LOWERS DBP and INCREASES SBP.
=this dose vasoconstricts some vascular beds via alpha stimulation and dilates other beds via B2 stimulation

**the NET effect is arteriolar vasodilation w/ a fall in TPR and thus DBP
**SBP is going to INCREASE bc EPI increases CO via increased venous return, cardiac contractility, + decreased afterload.

Front 76

Explanation:

Back 76

**Epi after blockade of vascular alpha-receptors can only stimulate B2 receptors to cause VASODILATION
=large fall in TPR and DBP

**Epi after blockade of vascular B2-receptor can ONLY stimulate vascular alpha-receptors to cause VASOCONSTRICTION and thus a large RISE in TPR and DBP

Front 77

Beta Blockers

Back 77

Atenolol + Metoprolol
=Block B1

Propranolol + Timolol
=Block B1 and B2

Front 78

Uses:

Back 78

=decreased HR, AV conduction, and dp/dt

Front 79

Angina

Back 79

=decreased O2 requirement via decreased dp/dt and HR

=BUT LV-EDV increases

Front 80

SO, a B-blocker decreases O2 demand by decreasing HR, dp/dt/ and afterload--how does nitroglycerin decreases O2 demand by:

Back 80

Decreasing VENOUS RETURN + LV-EDV

Front 81

B-blockers can BLOCk increases in HR caused by:

Back 81

1) Hemorrhage
2) Minoxidil
3) Hydralazine
4) Diazoxide
5) Nitroprusside
6) Nitroglycerin

Front 82

Side Effects of B-Blockers:

Back 82

=CHF
=Bronchospasm
=AV block
=Delayed recovery of glucose in patients w/ Type I DM after s.c. injection of too much insulin

Front 83

Timolol

Back 83

=Decreased IOP w/o cycloplegia

**You would NOT use propranolol because it causes LOCAL ANESTHESIA of cornea

Front 84

A patient is treated w/ a beta-blocker for angina. They abruptly discontinue the drug. What happens?

Back 84

**Beta-Blocker Withdrawl Syndrome:
=tachycardia
=palpitations + tremor
=chest pain

**Increased cardiac B-receptor stimulation --> increased O2 demand --> precipitates angina + MI

Front 85

Patient w/ Hyperthyroidism:

Back 85

**Being treated w/ propranolol
=decrease tachycardia + tremor
=prevent the peripehral conversion of T4 --> T3

Front 86

A type I diabetic patient is being treated w/ a glaucoma drug that causes HYPOGLYCEMIA. Which drug?

Back 86

Timolol

Front 87

Reserpine

Back 87

=DECREASES NE release via depletion of neuronal NE stores --> poisons NE storage vesicles

=NO EFFECT of TAP drugs (=tyramine, amphetamine, phenylpropanolamine) after pretreatment w/ reserpine
=NO alpha effects of ephedrine after reserpine

Front 88

Guanethidine

Back 88

1) Decreased nerve-stimulated NE release
2) Competitive inhibitor of NE uptake
3) anti-HT effect BLOCKED by TCA's
=i.e. TCA's block entry of guanethidine into neuron

Front 89

Cocaine

Back 89

=Blocks uptake of NE, Epi, DA, 5-HT in CNS
=Blocks uptake in peripheral sympathetic neurons --> potentiates effects of NE and Epi but NOT isoproterenol

Front 90

How does it cause euphoria?

Back 90

Via release of DA in the nucleus accumbens

Front 91

How does it cause a local anesthetic effect?

Back 91

=via blockade of Na channels in sensory neurons

Front 92

Toxic Doses/OD Symptoms:

Back 92

=Dilated pupils
=Euphoria
=Hallucinations
=Excitation
=Halo vision
=Itchy skin
=Increased BP/HR

**Difficult to distinguish from amphetamine toxicity

Front 93

Withdrawl Syndrome:

Back 93

1) Sleepiness
2) Depression
3) Anhedonia

Front 94

MAO Inhibitors:

Back 94

**Used to treat depression

=Phenelzine
=Tranylcypromine

**inhibit BOTH MAO-A + MAO-B

Front 95

Selgiline

Back 95

Selectively inhibits MAO-B to prevent breakdown of DA in the CNS

Front 96

"Cheese" Reaction

Back 96

Inhibition of MAO-A in the gut wall allows dietary tyramine to enter the circulation
=tyramine releases NE to cause HT and tachycardia

Front 97

Clonidine + Alpha-Methyldopa

Back 97

=DECREASE SNS activity via stimulation of alpha-2 receptors in the CNS

=DECREASE plasma NE and renin activity
=DECREASE HR

Front 98

S/E's:

Back 98

Sedation, dry mouth, edema

Front 99

S/E's of alpha-methyldopa:

Back 99

=Hepatitis
="Flu" syndrome
=(+) Coomb's Test

Front 100

Clonidine Withdrawl Syndrome

Back 100

=sweating
=increased HR
=abrupt return of BP to HT value
=abdominal pain
=tremor
=HA
=apprehension

Front 101

How does this differ from B-blocker withdrawl syndrome??

Back 101

recall: in B-blocker withdrawl -->
=increased HR w/ palpitations but NO tremor, sweating, abdominal pain, or increased BP

Front 102

Recall: Drugs that DECREASE plasma NE?

Back 102

=clonidine
=alpha-methyldopa
=guanethidine
=reserpine
=ganglionic blockers

Front 103

Recall: Drugs that INCREASE plasma NE?

Back 103

=alpha-blockers
=hydralazine
=minoxidil
=diazoxide
=nifedipine
=HCTZ
=sodium nitroprusside

Front 104

Arterial Vasodilators

Back 104

**Hydralazine, Minoxidil, Diazoxide**

**Dilate resistance vessels
=decreased TPR + BP
=increased HR, dp/dt, CO, PRA, and plasma NE

Front 105

Hydralazine

Back 105

1) Edema
2) SLE-like Symptoms
=arthralgia
=arthritis
=fever
=malar rash
=glomerulonephritis

**Discharge hydralazine + treat w/ steroid

Front 106

Minoxidil

Back 106

1) Hirsutism
2) Edema

**Effect additive w/ finasteride

Front 107

Diazoxide

Back 107

**Inhibition of insulin release
=hyperglycemia
=edema

Front 108

Drugs for a HYPERTENSIVE EMERGENCY:

Back 108

SODIUM NITROPRUSSIDE

Others:
=diazoxide
=labetaolol

Front 109

Sodium Nitroprusside (SNP)

Back 109

**Dilates arteries + veins via release of NO from sodium nitroprusside molecule

**BALANCED VASODILATION
=in a NT patient --> decreases TPR + venous return = NO CHANGE in CO
=in a patient w/ CHF --> decreases preload + afterload --> leads to an INCREASE in CO

Front 110

What happens when you infuse SNP into someone w/ poor renal function?

Back 110

=muscle weakness
=spasm
=disorientation

**treat w/ THIOSULFATE

Front 111

Thiocyanate

Back 111

=combines w/ CN to form thiosulfate which can be eliminated renally

Front 112

CALCIUM-BLOCKERS

Back 112

=Nifedipine
=Diltiazem
=Verapamil

**Block Ca channels at SA/AB nodes, cardiac myocytes, and arterial VSM

Front 113

Effects:

Back 113

1) Decrease BP
=nifedipine > diltiazen > verapamil

2) Decrease AV conduction via increase in ERP
=Verapamil > diltiazem

3) Nifedipine causes a SLIGHT increase in HR

Front 114

Uses:

Back 114

ANGINA
=decrease oxygen demand
=i.e. decreases dp/dt, HR, and afterload w/ increased oxygen delivery via dilation of coronary arteries + arterioles

HTN
AV nodal re-entry tachycardia
=V + D

Front 115

Drugs which DECREASE dp/dt:

Back 115

=B-blockers
=Ca-blockers
=diisopyramide

Front 116

Effects of Angiotension II

Back 116

1) Increased BP
2) Increased SNS activity via CNS
=enhances release of NE
=blocks NE uptake
3) Release of ADH
4) Release of Aldosterone
5) Decreases mesenteric blood flow

Front 117

OTHER DRUGS that decrease mesenteric blood flow

Back 117

**Use these drugs to treat GI bleeding:
=NE + AngII
=ADH
=Octreotide

Front 118

ACE Inhibitors:

Back 118

**Captopril, Enalapril

=prevent conversion of AngI --> AngII

Front 119

Effects:

Back 119

1) Decrease TPR and BP w/ NO CHANGE in HR and CO

2) Block formation of AngII

3) Block enzymatic destruction of bradykinin
=increase plasma [ ] of bradykinin
=i.e. potentiate the decrease in BP caused by IV bradykinin

Front 120

Side Effects:

Back 120

1) Fetal Toxicity
=category X

2) K+ retention

3) COUGH
=caused by BK and PG
=BLOCKED by aspirin

Front 121

Losartan

Back 121

**Angiotensin II receptor antagonist --> NO COUGH

Front 122

Why would you use in the treatment of CHF?

Back 122

=Increae CO by decreasing preload and afterload

=reverses cardiac remodeling caused by angiotension II

Front 123

Why would you treat a hypertensive patient w/ DM with an ACE-inhibitor?

Back 123

=decrease BP and decrease proteinuria (i.e. protects kidneys)

Front 124

DIURETIC DRUGS

Back 124

1) Acetazolamide
2) Furosemide, ethacrynic acid
3) Thiazides
4) Amiloride and triamterene
5) Spironolactone

Front 125

Acetazolamide

Back 125

**Inhibits carbonic anhydrase in PT and DT to prevent reabsorption of bicarbonate
=increased excretion of Na, K, + bicarbonate
=urinary pH increases to 8-8.5
=THEREFORE, can be used to increase urinary pH to enhance renal clearance of acids (=salicylates)

Front 126

OTHER USES:

Back 126

1) Inhibits formation of AH and CSF
=some effect to decrease gastric acid secretion

2) Used to treat glaucoma + altitude sickness
=i.e. acidosis via renal loss of bicarbonate STIMULATES respiration

Front 127

Side Effects

Back 127

HYPERchloremic metabolic acidosis

Front 128

SO, quick review:

What STIMULATES Respiration?

Back 128

=Acetazolamide
=Nicotine
=Epi
=Theophylline, caffeine

Front 129

What INHIBITS respiration?

Back 129

=EtOH
=Opiates--morphine
=Benzo's--diazepam
=Barbiturates

Front 130

SO, how would you make urine ALKALINE?

Back 130

CAI or Na bicarbonate

=increase renal Cl of acidic drugs

Front 131

How would you make urine ACIDIC?

Back 131

=ammonium chloride

=increase renal clearance of BASIC drugs

Front 132

LOOP DIURETIC DRUGS

Back 132

=furosemide
=ethacrynic acid

**Inhibit Na/K/2Cl symporter in the ascecnding limb of hte loop of Henle
=also blocks Na transport in the macula densa of the DT

Front 133

Effects:

Back 133

1) Increased urinary excretion of Na, K, Ca, Mg, Cl, and water
2) Increased delivery of Na to LDT/CD causes K LOSS
3) Cl loss causes hypokalemic, hypochloremic metabolic alkalosis
4) Urine isotonic in presence and absence of ADH
5) Prostaglandin-dependent inccrease in RBF and GFR
6) Increased Hct via decreased plasma volume

Front 134

What does the block of the Na transporter in the macula densa do?

Back 134

**Blocks Na transporter in the macula densa cells of the DT --> no sodium sensed --> INCREASED PRA and AngII --> secondary hyperaldosteronism --> exacerbates K loss

Front 135

Uses:

Back 135

1) Acute pulmonary edema
2) CHF
3) Peripheral edema
4) Hypercalcecmia

Front 136

S/E's:

Back 136

1) Hypokalemia w/ alkalosis
2) Hypomagnesemia
3) Hyperglycemia
4) Dilutional hyponatremia
=i.e. cannot make a dilute urine in order to excrete free water
5) Hyperuricemia
=bad for gout
6) Li toxicity caused by increased reabsorption in PT

Front 137

Drug/Drug Interactions:

Back 137

1) Can cause bilateral hearing loss via toxicity to CNVIII --> potentiated by aminoglycosides (i.e. gentamicin)

2) ENHANCES digoxin toxicity via hypokalemia
=less K+ to compete w/ digoxin for Na-K-ATPase binding sites

Front 138

Thiazides

Back 138

**Hydrochlorothiazide**
=acts in DT and decreases GFR in all patients
=BLOCKS NaCl symporter in principal cells of the DT

Front 139

Effects:

Back 139

1) Increases excretion of Na, K, Mg, Cl, and water
=decreased free water clearance--> urine always hypertonic = dilutional hyponatremia
2) DECREASED secretion of Ca in hypercalcinuria
=used to decrease formation of kidney stones!
3) Increased delivery of Na to LDT/CD causes K+ loss
4) Blocks Na transporter in macula densa --> again, exacerbates K+ loss

Front 140

Uses:

Back 140

1) HT
2) Edema
3) Kidney stones
4) DI
=distal loss of Na and water ENHANCES the reabsorption of filtrate in the PT --> LESS volume sent distally
=decreases urine volume by 50%

Front 141

S/E's:

Back 141

=Hypokalemia w/ alkalosis
=Hypomagnesmia
=Hyperglycemia
=Hyponatremia
=Uniformly decreased GFR
=Hyperuricemia
=Lithium toxicity

Front 142

Drug-Drug Interactions

Back 142

**Also enchances digoxin toxitcity

**Diuretic effect contracts the blood volume = POTENTIATES the fall in BP caused by anti-HT drugs--esp. clonidine and alpha blockers!

Front 143

K+ SPARING Diuretics

Back 143

=TASK

1) Triamterene
2) Amiloride
3) Spironolactone
=aldosterone receptor antagonist

**ALL are contraindicated in renal insufficiency because they can cause fatal hyperkalemia

Front 144

Amiloride and Triamterene

Back 144

1) Block Na channels in principal cells of LDT/CD
=Increased Na excretion w/ decreased K excretion

**Make urine alkaline by inhibiting H+ ion secretion from intercalated cells of the DT

Front 145

Spironolactone

Back 145

**Aldosterone Antagonist**
=also a partial agonist at androgen/progesterone receptors

Front 146

Actions:

Back 146

1) Blocks aldosterone receptors in the principal cells of the LDT/CD
2) Increases urinary loss of Na and water w/ decreased K excretion

Front 147

Who does this drug have NO EFFECT on?

Back 147

=the adrenalectomized patient

Front 148

Uses:

Back 148

1) Secondary hyperaldosteronism associated w/ cirrhosis or nephrotic syndrome

2) Reverses cardiac remodeling caused by aldosterone in patients w/ HF

Front 149

S/E's:

Back 149

=Hyperkalemia
=Gynecomastia (males)
=Menstrual irregularities
=Hirsutism
=Deepend voice (females)

Front 150

A patient treated w/ an OCP containing estrogen and norethindrone develops hirsutism--why?

Back 150

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

Front 151

How would you treat this?

Back 151

Spironolactone

Front 152

A postmenopausal female develops hirsutism--how would you treat it?

Back 152

Spironolactone

Front 153

A patient w/ an adrenal tumor has increased BP and plasma HCO3, and DECREASED plasma K+ and PRA. Plasma Na is normal. What is the diagnosis?

Back 153

**Conn's Syndrome
=aldosterone-secreting adrenal tumor

**Treat w/ spironolactone

Front 154

How would you PREVENT the hypokalemia caused by furosemide and HCTZ?

Back 154

1) K+ sparing diuretics
2) ACE inhibitors
3) Beta-blockers

**AND to a certain extent, p.o. K supplements

Front 155

The Effects of Diuretics on Urinary Flow, pH, and Elecrolyte Composition.

Back 155

**FIRST, look at urine flow rate.

=IF urine flow rate is 8-10 ml/min --> the drug is either furosemide OR mannitol.

=IF the urine flow rate is 2-3 ml/min, the drug is acetazolamide, a thiazide, or a K+ sparing agent

Front 156

NEXT, what should you look at?

Back 156

**Next, look at the QUANTITIATIVE changes in electrolyte excretion.

1) Furosemide can be distinguished from mannitol by the fact that furosemide causes the GREATEST INCREASE in electrolyte excretion.

2)THEN, you have to distinuish between acetazolamide, a thiazide, and a K+ sparing agent.

Front 157

How do you distinguish between these?

Back 157

1) Acetazolamide causes a MASSIVE increase in bicarbonate excretion.

2) The K+ sparing agent decreases K+ excretion.

3) The drug that remains is a thiazide.

Front 158

Cardiac Glycosides

Back 158

=Digoxin
=Digitoxin

Front 159

KINETICS:

Back 159

Digoxin:
=t1/2 = 1-1.5 days
=RENAL clearance
=Decreased GFR decreases Cl and increases t1/2

Digitoxin:
=t1/2 = 7 days
=HEPATIC clearance
=Decreased clearance and increased t1/2 in patients w/ cirrhosis and CHF

Front 160

What if you combine them w/ cholestyramine or antacids?

Back 160

=DECREASED GI absorption

=i.e. decreased plasma digoxin and decreased cardiac effect

Front 161

Dosing in OLDER patients:

Back 161

**Older patients have a decreased Vd, so DECREASE the loading dose

**Also have a decreased GFR, so DECREASE the maintenance dose
=realize that older patients can have decreased GFR even w/ normal serum creatinine

Front 162

Effect of quinidine on digoxin:

Back 162

Quinidine will INCREASE plasma digoxin by displacing digoxin from skeletal muscle and DECREASING renal clearance

Front 163

What is the MOA of digoxin?

Back 163

**Inhibits Na-K-ATPase
=increases dp/dt but decreases resting membrane potential (Vm)
=lack of pumping Na OUT causes cautomaticity in fast fibers

Front 164

LOW K+

Back 164

Potentiates inhibition of ATPase
=causes automaticity and a DECREASED ERP in ventricles

Front 165

Low Mg

Back 165

=Same as a calcium overload inside cells --> causes automaticity

Front 166

HIGH Calcium

Back 166

Ca overload inside cells = causes automatcity

Front 167

How does it work in the CNS?

Back 167

**Acts to INCREASE vagal tone
=decrease HR
=decrease atrial contraction
=decrease AV conduction

Front 168

Uses:

Back 168

=Control (DECREASE) ventricular rate in patients w/ atrial flutter or fibrillation

**Increased vagal tone DECREASES AV conduction --> so fewer atrial signals pass the AV node

Front 169

Side Effects:

Back 169

=Bradycardia
=AV block
=PVC's
=n/v (i.e. CTZ)

**CNS Side effects:
=abnormal color vision + halo vision esp. in elderly

Front 170

Antidysrhythmic Drugs

Back 170

=Quinidine
=Procainamide
=Disopyramide
=Lidocain
=Amiodarone
=Verapamil

Front 171

Quinidine MOA

Back 171

**Blocks Na channels in fast fibers
=Na channel block DECREASES phase 4 automaticity and phase 0 slope --> DECREASED CONDUCTION VELOCITY

**WIDENS the QRS

Front 172

Effects:

Back 172

**Delays ventricular repolarization via K channel block
=Increased APD, ERP, and QT interval

**SA Node:
=NO direct effect
=anticholinergic effect causes tachycardia

**AV Node
=Atropine-like effect INCREASES conduction, but DIRECT effect decreases conduction

Front 173

Uses:

Back 173

**Treat atrial and ventricular dysrhythmias

Front 174

Treatment of Atrial Flutter and Atrial Fibrillation

Back 174

**Give digoxin BEFORE quinidine in tx. of a-fib/flutter SO digoxin can PREVENT the increase in AV conduction from the atropine-like action of quinidine

Front 175

S/E's:

Back 175

=Hypotension (alpha block)
=Decreased dp/dt
=Diarrhea **limits use**
=Tinnitus w/ OD

Front 176

Patient w/ atrial fibrillation is given quinidine to slow ventricular rate but the ventricular rate INCREASES soon after quinidine. WHY?

Back 176

**An immediate atropine-like effect of quinidine INCREASED AV conduction
=treat w/ VERAPAMIL or DILTIAZEM to decrease AV conduction + slow ventricular rate

Front 177

Procainamide

Back 177

**Can cause SLE and arthritis in slow acetylators
=i.e. these people have a genetic defect --> an inactive form of the acetylase enzyme --> SO they cannot clear the drug by hepatic biotransformation

Front 178

Disopyramide

Back 178

**Causes a MARKED decrease in dp/dt
=marked antimuscarinic effects --> dry mouth, constipation

Front 179

When would it be contraindicated?

Back 179

=BPH
=Glaucoma

Front 180

Lidocaine, MOA

Back 180

**Blocks Na channels in fast fibers

**Given IV due to low F

Front 181

Effects:

Back 181

1) Decreases phase 4 automaticity to prevent PVC's
=ONLY USED FOR VENTRICULAR ARRHYTHMIAS

2) NO EFFECT at the SA or AB nodes, on BP or dp/dt

Front 182

Uses:

Back 182

Local anesthetic effect via Na channel block in sensory fibers

Front 183

S/E's:

Back 183

=seizures

**treat w/ benzo's

Front 184

Amiodarone, MOA:

Back 184

**Increase APD, ERP in fast fibers by INHIBITING K+ channels

Front 185

Effects:

Back 185

=POWERFUL suppression of phase 4 automaticity (=blocks Na channels)

=Non-competitive alpha AND beta-blockade (-->can cause hypotension and bradycardia)

=Slows sinus rate and AV conduction

Front 186

Use:

Back 186

Treatment of recurrent ventricular tachycardia/fibrillation

Front 187

S/E's:

Back 187

=Pulmonary fibrosis
=Hypo- OR hyperthyroidism
=Blue, purple, OR slate gray skin
=Corneal microdeposits

Front 188

Verapamil MOA

Back 188

**Blocks L-type calcium channels at hte SA and AV nodes AND cardiac myocytes

Front 189

Effects:

Back 189

1) SA Node
=decrease HR

2) AV Node
=decrease conduction velocity and ERP
=i.e. FEWER atrial signals pass through the AV node to the ventricles

3) Myocardium
=decreased dp/dt = DECREASED CO

Front 190

Uses:

Back 190

**used to treat AV nodal re-entry tachycardia

Front 191

S/E's:

Back 191

Decreased dp/dt and CO in HF

AV block

Front 192

Patient w/ atrial fibrillation and NO HF has palpitations and dizziness

Back 192

Treat w/ Verapamil

=will increase ERP of AV node --> slows ventricular rate --> improved AV filling --> Increased CO

Front 193

Anticoagulatants

Back 193

1) Antiplatelet drugs
2) Heparin
3) LMW Heparins
4) Warfarin

Front 194

Aspirin

Back 194

**Irreversibly inhibits COX-1 of platelets to prevent the synthesis of TXA2

Front 195

Abciximab, Eptifibatide, Tirofiban

Back 195

**Antagonists of the platelet IIb/IIIa which uses fibrinogen to bind platelets together

**Given IV in ER and OR

Front 196

Ticlopidine and Clopidrogrel

Back 196

**Antagonists of platelet purinergic (ADP) receptors

Front 197

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

Back 197

**Use ticlopidine or clopidrogrel

Front 198

Heparin MOA

Back 198

**Accelerates binding of antithrombin III (ATIII) to activated clotting facts 2, 9-12
=increases aPTT

Front 199

Features:

Back 199

1) A glucosaminoglycan
2) NOT effective p.o.
3) NOT metabolized by the liver
=removed from circulation by the reticuloendothelial system
4) INCREASES lipoprotein lipase
=hydrolyzes TG's --> glycerol + FFA to DECREASE postprandial lipemia

Front 200

Uses:

Back 200

Treat MI and DVT's

Front 201

Antagonist:

Back 201

Protamine Sulfate

Front 202

S/E's:

Back 202

=Bleeding
=Antiplatelet effect additive w/ aspirin
=Thrombocytopenia

Front 203

What causes heparin resistance?

Back 203

Heparin resistance results from DECREASED ATIII in blood

Front 204

LMW Heparins

Back 204

=Ardeparin
=Dalteparin
=Enoxaparin

**Acts primarily on Xa --> so little effect to increase the aPTT

Front 205

Antagonist:

Back 205

Anticoagulant effect only PARTIALLY reversed by protamine sulfate

Front 206

Clearance?

Back 206

Cleared by the KIDNEYS instead of the RE system

=longer t1/2 than heparin

Front 207

Warfarin, Dicumarol MOA

Back 207

**Inhibits post-translational vitamin K-dependent gamma-carboxylation of glutamate residues on factors 2, 7, 9, and 10 via inhibtion of enzyme vitamin K epoxide reductase

Front 208

Factors:

Back 208

1) ONLY works in vivo
2) Slow onset of action
=2-3 days --> full effect at 5 days
=INCREASES PT (INR)--> greatest effect on factor 7

Front 209

Uses:

Back 209

=DVT's
=Prevent emboli in patients w/ prosthetic heart values
=Prevent thrombotic strokes in patients w/ A-fib

Front 210

Drug-Drug Interactions

Back 210

**Highly bound to plasma proteins --> MANY drug-drug interactions

**displacement of warfarin from plasma proteins has 2 effects:
=INCREASED PT
=INCREAED Cl of warfarin

Front 211

How is Warfarin metabolized?

Back 211

CYP450

Front 212

SO, inhibition of CYP450 is going to:

Back 212

**INCREASES plasma warfarin and PT

=Cimetidine
=Ketoconazole
=Isoniazid
=Erythromycin
=Grapefruit juice

Front 213

SO, INDUCTION of CYP450...

Back 213

**DECRASES plasma warfarin + PT

=Carbamazepine
=Phenobarbital
=Phenytoin
=Rifampin
=Chronic EtOH
=Benzopyrene (cig. smoke)

Front 214

ANTIDOTE:

Back 214

**Phytonadione
=vitamin K1

Other:
=FFP
=Factor IX concentrate --> contains factors 2, 7, 9, 10

Front 215

Patient overdoses w/ warfarin OR attempts suicide w/ rat poison. Which clotting factors and lab tests are affected?

Back 215

=Decreased activity of factors 2, 7, 9, and 10

=INCREASED aPTT and PT

**NO EFFECT on factors 8, 13, or bleeding time

Front 216

What type of cardiac dysrhythmia requires treatment w/ warfarin?

Back 216

A-fib

Front 217

Thrombolytic (=Fibrinolytic) Drugs

Back 217

**ALL ultimately convert plasminogen --> plasmin
=plasmin destroys fibrin to lyse clots

1) Urokinase
2) tPA
3) Streptokinas

Front 218

Urokinase

Back 218

**Direct activation of plasminogen

Front 219

tPA

Back 219

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

Front 220

Streptokinase

Back 220

**Changes conformation of plasminogen to expose an active protease site that hydrolyzes another plasminogen --> plasmin

Front 221

Side Effects of Fibrinolytic Drugs

Back 221

=Systemic destruction of clotting factors 5 and 8 --> causes bleeding ESP. in CNS (=hemorrhagic stroke)

Front 222

A patient w/ an MI is treated w/ several drugs. He develops intracranial bleeding. Which drug caused it?

Back 222

=streptokinase

Front 223

INHIBITORS of Fibrinolysis

Back 223

=aminocaproic acid

**A lysine analog that binds to hte lysine-binding sites on plasmin which BLOCKS the binding of plasmin to fibrin

Front 224

Antilipemic Drugs

Back 224

1) Statins
2) Ezetimibe
3) Gemfibrozil and Fenofibrate
4) Niacin

Front 225

Statins

Back 225

=i.e. Lovastatin

MOA:
=inhibits HMG CoA reductase --> reduces intracellular hepatic sterol pool --> suppresses teh promotor region of the genes which code for HMG CoA reductase and LDL receptors
=Lack of sterol results in the INCREASED synthesis of HMB CoA reductase and LDL receptors
=THUS, increased hepatic LDL receptors to take up LDL and lower Tc

Front 226

NET Effects:

Back 226

=Decrease Tc
=Decrease LDL and TG's
=Slight increase in HDL

Front 227

S/E's:

Back 227

=myositis/myopathy --> muscle pain and weakness associated w/ an increased CPK

**muscle damage can progress to rhabdomyolysis

Front 228

Ezetimibe

Back 228

MOA
=inhibition of cholesterol absorption from the GI tract DECREASES intracellular hepatic sterol pool
=leads to INCREASED gene expression of hepatic LDL recectprs --> increased receptors take up LDL to lower Tc

Front 229

NET Effect:

Back 229

**Selective for LDL cholesterol
=only Tc and LDL decrease

Front 230

Use:

Back 230

Used in patients who develop muscle weakness on a statin

Front 231

Gemfibrozil and Fenofibrate

Back 231

MOA
=activates lipoprotein lipase (esp. in skeletal muscle) to incrase hydrolysis of VLDL

Front 232

Net Effect

Back 232

=Decrease Tc
=Decrease LDL, VLDL, TG's
=Slight increase in HDL

Front 233

Use:

Back 233

Used to treat hypertriglyceridemia

Front 234

S/E's:

Back 234

=myositis/myopathy --> muscle pain and weakness associated w/ increased CPK

**muscle damage can progress to rhabdomyolysis

Front 235

Niacin

Back 235

MOA = unknown

**Used to increase HDL cholesterol

Front 236

S/E's:

Back 236

Flushing and itching in face and upper body

Front 237

Antianginal Drugs

Back 237

**All DECREASE oxygen demand and/or INCREASE oxygen supply
=ALL increase endocardial blood flow

1) B-blockers
2) Nitrates
3) Calcium channel blockers

Front 238

B-Blockers

Back 238

**Atenolol, metoprolol, propranolol, timolol

Front 239

MOA:

Back 239

**Decreases the rate-pressure product (HR x SBP)

**Also decreases cardiac afterload = decreases DBP

**Net Effect = decreased cardiac O2 demand

Front 240

Nitrates

Back 240

=Nitroglycerin

i.e. glyceryl trinitrate, isosorbide mono and dinitrate

Front 241

MOA:

Back 241

**NO donors which selectively VENODILATE
=venodilation decreases venous return to decrease LV wall tension during diastole and systole

**SO, decreases cardiac oxygen demand!

Front 242

Biggest problem w/ nitroglycerin:

Back 242

DRUG TOLERANCE

Front 243

Calcium Channel Blockers

Back 243

=Verapamil
=Diltiazem
=Amlodipine
=Felodipine

Front 244

MOA of Verapamil + Diltiazem

Back 244

**Negative chronotropic and inotropic effects DECREASES rate x pressure product (HR x SBP)

**Also decreases cardiac afterload = decreased DBP

**ALSO dilates large epicardial vessels + small endocardial resistance vessels

Front 245

MOA of Amlodipine and Felodipine

Back 245

**Decreased cardiac afterload (DBP) and INCREASED blood flow through large epicardial vessels and small endocardial resistance vessels

Front 246

NET EFFECT IN BOTH CASES:

Back 246

**Decreased oxygen demand and increased oxygen supply

Front 247

Treatment of Congestive Heart Failure

=Systolic Dysfunction

Back 247

1) Decrease preload w/ diuretic drugs
2) Decrease both preload + afterload (balanced vasodilation) w/ an ACEI or ARB
3) Enhance cardiac contractility w/ digoxin
4) Reverse cardiac remodeling caused by:
=Ang II --> ACEI or ARB
=Aldosterone --> spironolact.
=SNS --> carvedilol