Usmle Pharmacology

Front 1

What is pharmacokinetics?

Back 1

Deals with what the body does to the drug: absorption, distribution, sites of action, tissue storage, metabolism and excretion.

Front 2

What factors are involved in drug permeation/absorption?

Back 2

Solubility, concentration gradient, surface area, vascularity, ionization.

Front 3

In what form can drugs cross cell membranes?

Back 3

Non-ionized form (lipid soluble).

Front 4

In what form are drugs excreted?

Back 4

Ionized form (water soluble) are better renally excreted

Front 5

What factors affect renal clearance of drugs?

Back 5

The drug must be in free form, ionized or nonionized. Only nonionized drug can be actively secreted or reabsorbed.

Front 6

What effect does acidification of urine have on drugs?

Back 6

Increases ionized fraction of weak bases and increases their renal elimination. NH4Cl, vitamin C, cranberry juice.

Front 7

What effect does alkalinization of urine have on drugs?

Back 7

Increases ionized fraction of weak acids and increases their renal elimination. NaHCO3, acetazolamide.

Front 8

Urine alkalinization agents

Back 8

NaHCO3, acetazolamide

Front 9

Urine acidification agents

Back 9

NH4Cl, vitamin C, cranberry juice

Front 10

What is Cmax?

Back 10

Maximal drug level obtained with the dose

Front 11

What is Tmax?

Back 11

Time at which Cmax occurs

Front 12

What is the lag time?

Back 12

Time from administration to appearance in blood

Front 13

What is onset of activity?

Back 13

Time from administration to blood level reaching minimal effective concentraion

Front 14

What is duration of action?

Back 14

Time that the plasma concentration remains above minimial effective concentration

Front 15

What is time to peak?

Back 15

Time from administration to Cmax.

Front 16

What is bioavailability?

Back 16

Is the fraction of a dose that reaches the systemic circulation after 1st pass metabolism

Front 17

What is the first-pass effect?

Back 17

Is the decrease in bioavailability of an oral drug after passing through intestines or from the portal blood through the liver. Portal blood will always have a higher concentration of the drug before passing for the first time through the liver.

Front 18

What is bioequivalence and what factors are involved?

Back 18

Bioequivalence is the similarity between two formulations of the same drug. To be bioequivalent they must have the same bioavailability and the same rate of absorption.

Front 19

How are rate of absorption, Tmax and Cmax related?

Back 19

The faster the rate of absorption the smaller Tmax and larger Cmax. Tmax and Cmax are rate dependant.

Front 20

What is distribution?

Back 20

Is the process by which a drug reaches the target tissues from systemic circulation.

Front 21

What factors affect distribution of a drug?

Back 21

Protein-binding capacity and competition between drugs for protein-binding sites, barriers such as placenta or brain.

Front 22

What is volume of distribution?

Back 22

Correlates dose given with the plasma level at time X. Vd=Dose/C0. C0=[plasma] at zero time.

Front 23

What is the significance of the volume of distribution?

Back 23

It's needed to calculate a loading dose; when Vd is low, a high fraction of the drug is bound to proteins; when Vd is high, a big fraction of the drug is being sequestered in tissues.

Front 24

Relationship between plasma concentration and volume of distribution

Back 24

Inversely proportional. The higher the plasma concetration, the lower the volume of distribution

Front 25

Relationship between dose and plasma concentration

Back 25

Directly proportional.

Front 26

What is redistribution?

Back 26

Is when a lipid-soluble drug gets temporarily stored in fat tissue before being eliminated.

Front 27

What is the significance of the redistribution rate?

Back 27

A second dose of a CNS drug redistributes to fat in lesser amount because fat is "saturated" therefore allowing more drug to enter the CNS and increasing the duration of action.

Front 28

What is biotransformation?

Back 28

Is the conversion of a drug to a more water-soluble form to be excreted. A metabolite may or may not have pharmacologic action.

Front 29

What is phase I biotransformation?

Back 29

Modification of the drug via oxidation, reduction or hydrolysis.

Front 30

What is microsomal metabolism?

Back 30

Cytochrome P450 isoenzymes in the SER require NADPH for oxidation and reduction of drugs.

Front 31

General inducers of the P450 enzymes

Back 31

Anticonvulsants (barbiturates, phenytoin, carbamazepine), antibiotics (rifampin), chronic alcohol, glucocorticoids.

Front 32

General inhibitors of the P450 enzymes

Back 32

Proton pump inhibitors (cimetidine, omeprazole), antibiotics (chloramphenicol, macrolides, ritonavir, ketoconazole), acute alcohol, grapefruit juice, isoniazid

Front 33

What is nonmicrosomal metabolism?

Back 33

Hydrolysis reactions by esterases and amidases; MAO; alcohol dehydrogenases.

Front 34

What is phase II biotransformation?

Back 34

Modification of the drug by transferases via glucoronidation, acetylation, sulfation, gluthathione conjugation.

Front 35

What are the major modes of drug elimination?

Back 35

Biotransformation to inactive metabolites, excretion via the kidney, bile ducts, lungs and sweat.

Front 36

What is the elimination half-life (t1/2)?

Back 36

t1/2 is the time to eliminate 50% of a given amount of drug.

Front 37

What is zero-order elimination rate kinetics?

Back 37

A constant amount is eliminated per unit time. Independent of plasma concentration, variable t1/2.

Front 38

What is first-order elimination rate kinetics?

Back 38

A constant percentage of the drug is eliminated per unit time. t1/2 is constant, directly porportional to plasma levels.

Front 39

Rate of elimination

Back 39

Equals to GFR + active secretion - reabsorption

Front 40

Clearance

Back 40

Equals to free fraction * GFR or 0.7 * Vd/half life

Front 41

What is steady state and when is it achieved?

Back 41

Its when the rate in = rate out. 50% of SS is achieved at 1 t1/2; 90% at 3.3 t1/2; 95% at 4-5 t1/2.

Front 42

How does rate of infusion affect steady state and plasma levels at steady state?

Back 42

It takes the same amout of time to reach steady state but if rate of infusion increases the plasma levels at steady state will increase.

Front 43

Formula: volume of distribution

Back 43

Vd = D/C0

Front 44

Formula: half life

Back 44

t1/2 = 0.7/k or t1/2 = 0.7 x Vd/Cl

Front 45

Formula: clearance

Back 45

Cl = k x Vd

Front 46

Formula: infusion rate

Back 46

k0 = Cl x Css

Front 47

Formula: loading dose

Back 47

LD = Vd x Css

Front 48

Formula: Maintenance dose

Back 48

MD = Cl x Css x t

Front 49

Relationship between half-life and elimination

Back 49

Inversely proportional

Front 50

Relationship between half-life and clearance

Back 50

Inversely proportional

Front 51

Relationship between half-life and volume of distribution

Back 51

Directly proportional.

Front 52

Relationship between clearance and volume of distribution

Back 52

Inversely proportional

Front 53

Relationship between infusion rate and clearance

Back 53

Directly proportional.

Front 54

Relationship between infusion rate and steady state concentration

Back 54

Directly proportional.

Front 55

Relationship between steady state concentration and clearance

Back 55

Inversely proportional.

Front 56

What is pharmacodynamics?

Back 56

The effects of drugs in the body and drug receptor binding.

Front 57

Affinity

Back 57

Ability of the drug to bind its receptor. The closer to the y axis, the more affinity.

Front 58

Potency

Back 58

The quanity of drug required to produce a desired effect. The closer to the y axis, the more potent.

Front 59

Efficacy

Back 59

The maximal effect an agonist can achieve at the highest practical concentration. The taller the curve, the more efficacy.

Front 60

What is meant by the "duality" of partial agonists?

Back 60

Partial agonists can compete with full agonists for its receptor, lowering the maximal response, therefore it acts as an antagonist in the presence of a full agonist.

Front 61

Effect of a competitive antagonist

Back 61

Parallel shift of the dose-response curve to the right; appears to increase potency; also increases Km; reversed by increasing agonist dose

Front 62

Effect of a noncompetitive antagonist

Back 62

Non-parallel shift to the right; appears to decrease efficacy of agonist; partially reversed by increasing agonist dose; decreases Vmax

Front 63

Physiologic antagonism

Back 63

Two agonists with opposing actions antagonize each other: vasoconstrictor Vs. vasodilator

Front 64

Chemical antagonism

Back 64

Agonist-chemical complex lowers effect of agonist

Front 65

Potentiation

Back 65

Parallel shift of the curve to the left; appears to increase potency of agonist.

Front 66

TD50

Back 66

Dose that causes toxicity in 50% of the population

Front 67

ED50

Back 67

Effective dose in 50% of the population

Front 68

Therapeutic index

Back 68

TD50/ED50; gives a measure of the relative safety of a drug

Front 69

ANS receptors and their second messenger systems

Back 69

"qiss qiq siq sqs". α1, α2, β1, β2, M1, M2, M3, D1, D2, H1, H2, V1, V2

Front 70

Substances with intracellular receptors

Back 70

Glucocorticoids, vitamin D, thyroid hormones, gonadal steroids

Front 71

Substances with ion channel receptors

Back 71

Nicotine, choline esters (ACh), ganglion blockers, skeletal muscle relaxants.

Front 72

Substances that interact with Gs receptors

Back 72

Catecholamines, dopamine, glucagon, histamine, prostacyclin. "qiss qiq siq sqs"

Front 73

Substances that interact with Gi receptors

Back 73

Epinephrine, norepinephrine, Ach, dopamine. "qiss qiq siq sqs"

Front 74

Substances that interact with Gq receptors

Back 74

Ach, norepinephrine, angiotensin II

Front 75

Phase 1 clinical testing

Back 75

Dose-response studies on small group of volunteers without disease. Includes pharmacokinetics characterization.

Front 76

Phase 2 clinical testing

Back 76

Dose-response studies on 100 patients in comparison with placebo and a positive control. Single or double blind.

Front 77

Phase 3 clinical testing

Back 77

Dose-response studies on 1000 patients in comparison to placebo and positive control. Usually double blind

Front 78

Phase 4 clinical testing

Back 78

New drug application, marketing approval and post-marketing surveillance.

Front 79

Zero-order kinetics curve

Back 79

Linear kinetics or exponential kinetics on log graph

Front 80

First-order kinetics curve

Back 80

Exponential kinetics or linear kinetics on log graph

Front 81

Dose-response curve

Back 81

Bell curve. Shows absoption phase, distribution, metabolism and elimination phases.

Front 82

Neurotransmitter of preganglionic neurons

Back 82

Acetylcholine

Front 83

Neurotransmitters of postganglionic neurons

Back 83

Acetylcholine, norepinephrine, epinephrine, dopamine

Front 84

Mechanism of miosis

Back 84

Sphincter muscle of the pupilla has M3 receptors. Muscarinic agonists causes contraction and miosis. Muscarinic antagonists cause relaxation and mydriasis with cycloplegia.

Front 85

Mechanism of mydriasis

Back 85

Dilator muscle of the pupilla has α1 receptors. α1 agonists cause contraction and mydriasis without cycloplegia. Also muscarinic blockers.

Front 86

Mechanism of accomodation

Back 86

Ciliary muscle has M3 receptors. Muscarinic agonists cause contraction and widening of the lens for close vision. Muscarinic antagonists cause cycloplegia and stretching of the lens for far vision.

Front 87

Muscarinic receptors of the eye

Back 87

Sphincter of the pupilla and cilliary muscles --> M3 --> miosis and accomodation

Front 88

Muscarinic receptors of the heart

Back 88

SA node and AV node --> M2 --> decrease heart rate, decrease conduction velocity

Front 89

Muscarinic receptors of the lungs

Back 89

Bronchioles and glands --> M3 --> bronchospasm and gland secretion

Front 90

Muscarinic receptors in the GI tract

Back 90

Stomach, intestines --> M3 --> increased motility, cramps, diarrhea; GI glands --> M1 --> gland secretion

Front 91

Muscarinic receptors of the bladder

Back 91

M3 --> contraction of detrusor, relaxation of the trigone/sphincter --> urination and urinary incontinence

Front 92

Muscarinic receptors of sphincters (GI, GU)

Back 92

M3 --> relaxation, excep LES which contracts

Front 93

Muscarinic receptors of glands

Back 93

M3 --> gland secretion --> sweat, salivation, lacrimation

Front 94

Muscarinic receptors in endothelium

Back 94

M3 --> cause vasodilation via release of NO

Front 95

Location of M3 receptros

Back 95

Eye (sphincter and cilliary), smooth muscle of bronchioles, GU and GI, glands except GI, sphicters, endothelium.

Front 96

Net effects of M3 receptor activation

Back 96

Miosis, accomodation, salivation, lacrimation, sweating, bronchoconstriction, increased GI motility, relaxation of sphincters (except LES), release of NO (indirect vasodilation).

Front 97

Net effects of M2 receptor activation

Back 97

Decreased heart rate, decreased conduction velocity of AV node.

Front 98

Net effects of M1 receptor activation

Back 98

Gland secretions of the GI tract.

Front 99

Receptors in the adrenal medulla

Back 99

Nn --> secretion of epinephrine and norepinephrine

Front 100

Receptors at the neuromuscular junction

Back 100

Nm --> muscle depolarization and contraction

Front 101

Receptors in autonomic ganglia

Back 101

Nn --> net effects depend on PANS/SANS dominance

Front 102

Muscarinic receptor mechanisms and second messenger systems

Back 102

M1, M3 --> Gq; M2 --> Gi; Nn, Nm --> Na/K channels

Front 103

Hemicholinium

Back 103

Inhibits reuptake of choline decreasing Ach synthesis (anticholinergic)

Front 104

Botulinum toxin

Back 104

Blocks release of ACh. Used in blepharospasm, strabismus, dystonia, cosmetics.

Front 105

Direct muscarinic agonists

Back 105

ACh, bethanecol, methacholine, pilocarpine

Front 106

Properties and use of acethylcholine

Back 106

Acts on muscarinic and nicotinic receptors. Strongly hydrolised by AChE. No clinical use.

Front 107

Properties and use of bethanecol

Back 107

Acts on muscarinic receptors. No AChE hydrolisis. Rx.: paralytic ileus, urinary retention

Front 108

Properties and use of methacholine

Back 108

More muscarinic than nicotinic actions. Weakly hydrolised by AChE. Used to Dx. Bronchial hyperreactivity.

Front 109

Properties and use of pilocarpine

Back 109

Acts on muscarinic receptors. Not hydrolyzed by AChE. Used for Rx. of glaucoma and xerostomia.

Front 110

Rx. of paralytic ileus

Back 110

Bethanecol, neostigmine, pyridostigmine

Front 111

Rx. of urinary retention

Back 111

Bethanecol, neostigmine, pyridostigmine

Front 112

Dx of bronchial hyperreactivity

Back 112

Methacholine

Front 113

Rx of glaucoma and xerostomia

Back 113

Pilocarpine, physostigmine

Front 114

Acetylcholinesterase inhibitors

Back 114

Edrophonium, physostigmine, neostigmine, pyridostigmine, donepezil, tacrine, organophosphates (irreversible)

Front 115

Properties and use of edrophonium

Back 115

Short acting AChE inhibitor. Dx myasthenia gravis

Front 116

Properties and use of physostigmine

Back 116

Tertiary amine AChE inhibitor. Rx glaucoma, antidote in atropine overdose

Front 117

Properties and use of neostigmine and pyridostigmine

Back 117

Cuaternary amines AChE inhibitors. Rx paralytic ileus, urinary retention, myasthenia, reversal of nondepolarizing NM blockers

Front 118

Properties and use of donepezil and tacrine

Back 118

Lipid-soluble AChE inhibitor enters CNS. Rx Alzheimer disease.

Front 119

Properties and use of organophosphates

Back 119

Lipid soluble irreversible AChE inhibitors. Rx glaucoma. Also insecticides parathion, malathion and nerve gas sarin.

Front 120

Dx and Rx of myasthenia gravis

Back 120

Edrophonium (Dx), neostigmine, pyridostigmine (Rx)

Front 121

Rx Alzheimer disease

Back 121

Donepezil, tacrine

Front 122

Signs and symptoms of organophosphate intoxication

Back 122

"Dumbbelss" Diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation, lacrimation, salivation, sweating.

Front 123

Rx of organophosphate intoxication

Back 123

Atropine + pralidoxime for regeneration of non-aged AChE.

Front 124

MOA pralidoxime

Back 124

Removes organophosphate group from AChE thus regenerating it. Aged AChE that have just a phosphate attached cannot be regenerated.

Front 125

Muscarinic blockers

Back 125

Atropine, tropicamide, ipratropium, scopolamine, benztropine

Front 126

Effects of muscarinic blockers

Back 126

Decreased salivary, bronchiolar and sweat secretions, mydriasis and cycloplegia, hyperthermia, tachychardia, sedation, urinary retention, constipation, hallucinations

Front 127

Rx of muscarinic blocker intoxication

Back 127

Physostigmine

Front 128

Uses of atropine

Back 128

Anesthesia, management of organophosphate toxicity

Front 129

Uses of propicamide

Back 129

Opthalmologic mydriasis

Front 130

Uses of ipratropium

Back 130

Inhaled in asthma and COPD. Doesn’t enter CNS.

Front 131

Uses of scopolamine

Back 131

Motion sickness, sedation, short-term memory block.

Front 132

Uses of benztropine

Back 132

Lipid-soluble, enters CNS. Used in parkinsonism and acute extrapyramidal symptoms of antipsychotics.

Front 133

Effects of ganglion blockers

Back 133

Reduce the predominant autonomic tone. PANS is dominant in heart, pupil, GI, GU and sphincters. SANS is dominant in blood vessels and sweat glands.

Front 134

Synthesis of catecholamines

Back 134

Tyrosine + tyrosine hydroxylase --> dopa + dopa decarboxylase --> dopamine + dopamine β hydroxylase --> norepinephrine + SAM + methyltransferase --> epinephrine

Front 135

MAO

Back 135

Located in outer mitochondrial membrane, degrades catecholamines by oxidative deamination. MAO-A: mainly in liver metabolizes NE, 5HT and tyramine. MAO-B mainly in brain, metabolizes DA.

Front 136

COMT

Back 136

Located in postsynaptic membrane, degrades catecholamines by methylations (requires SAM).

Front 137

Distribution of α1 receptors

Back 137

Pupil dilator muscle, arterioles of skin and viscera, veins, bladder trigone and sphincter, vas deferens, liver, kidney

Front 138

Distribution of α2 receptors

Back 138

Presynaptic terminal, platelets, pancreas

Front 139

Distribution of β1 receptors

Back 139

Heart SA node, AV node, atrial and ventricular muscle, His-Purkinje, kidney

Front 140

Distribution of β2 receptors

Back 140

All blood vessels, uterus, bronchioles, skeletal muscle, liver, pancreas

Front 141

Distribution of D1 receptors

Back 141

Renal, mesenteric, coronary vasculature

Front 142

α1 effects

Back 142

Mydriasis, increases TPR, diastolic pressure, afterload, venous return, preload, reflex bradycardia, urinary retention, ejaculation, glycogenolysis, decreases renin release

Front 143

α2 effects

Back 143

Decreases NE synthesis and release, promotes platelet aggregation, decreases insulin secretion

Front 144

β1 effects

Back 144

Increases HR, conduction velocity, contractility, CO, oxygen consumption and renin release

Front 145

β2 effects

Back 145

Vasodilation, decreases TPR, diastolic pressure and afterload, uterine relaxation, bronchodilation, increases glycogenolysis in liver and muscle, increases insulin secretion

Front 146

D1 effects

Back 146

Vasodilation of renal, mesenteric, coronary vasculatures, increases RBF, GFR

Front 147

α1 agonists

Back 147

Phenylephrine, methoxamine

Front 148

Uses of phenylephrine

Back 148

Nasal decongestant and opthalmologic mydriasis without cycloplegia

Front 149

α2 agonists

Back 149

Clonidine, methyldopa

Front 150

Uses of clonidine

Back 150

Mild to moderate hypertension

Front 151

Uses of methyldopa

Back 151

Mild to moderate hypertension

Front 152

Effects of β agonists on CV system

Back 152

β1: increase HR, CO, pulse pressure; β2: decrease TPR, BP.

Front 153

β agonists

Back 153

Isopreterenol, dobutamine

Front 154

β2 selective agonists

Back 154

Salmeterol, albuterol, terbutaline

Front 155

Uses of β2 selective agonists

Back 155

Asthma and ritodrine in premature labor

Front 156

Uses of isoproterenol

Back 156

β1=β2: used in bronchospasms, heart blocks and bradyarrhythmias. Side effects: flushing, angina, arrhythmias

Front 157

Uses of dobutamine

Back 157

β1 > β2: congestive heart failure

Front 158

Effects of norepinephrine on CV system

Back 158

Acts on α1 (increases TPR, BP), α2 and β1 (increases HR, CO, pulse pressure). Potential reflex bradycardia.

Front 159

Effects of low dose of epinephrine on CV and respiratory systems

Back 159

Acts on β1 (increases HR, SV, CO, pulse pressure), β2 (decreases TPR, BP, bronchodilation)

Front 160

Effects of medium dose epinephrine on CV and respiratory systems

Back 160

Acts on β1 (increases HR, SV, CO, pulse pressure), β2 (decreases TPR, BP, bronchodilation), α1 (increases TPR, BP)

Front 161

Effects of high dose epinephrine on CV and respiratory systems

Back 161

Acts on α1 (increases TPR, BP), β1 (increases HR, CO, pulse pressure), β2 (decreases TPR, BP, bronchodilation). Potential reflex bradycardia.

Front 162

Effect of adding α1 blocker to epinephrine

Back 162

Reverses hypertension to hypotension. Use this to differentiate from norepinephrine.

Front 163

Uses of epinephrine

Back 163

Cardiac arrest, adjunct to local anesthetic, hypotension, anaphylaxis, asthma

Front 164

Uses of norepinephrine

Back 164

Cardiac arrest, adjunct to local anesthetic, hypotension

Front 165

Indirect acting adrenergic agonists

Back 165

Releasers of catecolamines: Tyramine, amphetamines (methylphenidate), ephedrine. Reuptake inhibitors: cocaine, tricyclic antidepressants. MAO-A inhibitors interaction can cause hypertensive crisis.

Front 166

Effects of α blockers

Back 166

Decrease TPR and BP. May cause reflex tachychardia and salt/water retention.

Front 167

Uses of α blockers

Back 167

Hypertension, pheochromocytoma, BPH (selective α1 blocker)

Front 168

Nonselective α blockers

Back 168

Phentolamine (reversible), phenoxybenzamine (irreversible)

Front 169

Selective α1 blockers

Back 169

Prazosin, doxazosin, terazosin, tamsulosin

Front 170

Selective α2 blockers

Back 170

Yohimbe (used in hypotension and impotence), mirtazapine (depression)

Front 171

Effects of β1 blockers

Back 171

Decresed HR, SV, CO, renin, aqueous humor production

Front 172

Side effects of β2 blockers

Back 172

Bronchospasm in asthmatics, vasospasm, decreased glycogenolysis, gluneogenesis, increased LDLs, TGs

Front 173

Selective β1 blockers

Back 173

Acebutolol, atenolol, metroprolol

Front 174

Nonselective β blockers

Back 174

Pindolol, propranolol, timolol

Front 175

β blockers that raise blood lipids

Back 175

Atenolol (β1), metroprolol (β1), propranolol, timolol

Front 176

β blockers that cause the most sedation

Back 176

Propranolol, timolol

Front 177

β blockers with intrinsic sympathomimetic activity

Back 177

Act as partial agonists, less bradycardia, slight vasodilation, bronchodilation, minimal change in lipids: acebutolol, pindolol

Front 178

General uses of β blockers

Back 178

Angina, hypertension, post-MI

Front 179

β blockers used as antiarrhythmics

Back 179

Propranolol, acebutolol, esmolol

Front 180

Specific uses of timolol

Back 180

Glaucoma

Front 181

Specific uses of propranolol

Back 181

Migraine, thyrotoxicosis, performance anxiety, essential tremor

Front 182

Combined α1 and β blockers

Back 182

Labetalol, carvedilol. Used in CHF.

Front 183

Combined K channel and β blockers

Back 183

Sotalol. Class III antiarrhythmic.

Front 184

Phase 0 of the cardiac action potential

Back 184

Fast Na channels open causing depolarization. Class I antiarrhythmics slow or block phase 0.

Front 185

Phase 1 of the cardiac action potential

Back 185

Overshoot. Na channels inactivated, transient outward K currents.

Front 186

Phase 2 of the cardiac action potential

Back 186

Plateau phase. Slow influx of Ca and late-appearing outward K current.

Front 187

Phase 3 of the cardiac action potential

Back 187

Repolarization. Delayed rectifier K outward current. Class III antiarrhythmics slow repolarization.

Front 188

Phase 4 of the cardiac action potential

Back 188

Resting membrane potential. Maintained by the Na/K ATPase pump.

Front 189

Phase 0 of the pacemaker action potential

Back 189

Depolarization depends on Ca channels. Class IV antiarrhythmics slow or block this phase.

Front 190

Phase 3 of the pacemaker action potential

Back 190

Repolarization. Ca currents are opposed by outward delayed K currents.

Front 191

Phase 4 of the pacemaker action potential

Back 191

Spontaneous depolarization caused by Na funny current, Ca inward curents and K outward currents. Class II and IV antiarrhythmics slow this phase.

Front 192

Effective refractory period

Back 192

No stimulus can elicit a response. Lasts into phase 3 due to Na channel inactivation. K channel blockers prolong ERP.

Front 193

Relative refractory period

Back 193

Only a strong stimulus can elicit a response. Associated with arrhythmias.

Front 194

Innervation of the SA and AV nodes

Back 194

Parasympathetic via M2 receptors. Sympathetic via β1 receptors.

Front 195

What effect does sympathetic stimulation have on SA and AV nodes

Back 195

β1 activation increases cAMP, increasing upstroke velocity by increase of Ca conductance. Shortens action potential duration by increase of K conductance. Increases HR by increase of Na funny currents and increased phase 4 slope.

Front 196

What effect does parasympathetic stimulation have on SA and AV nodes

Back 196

M2 activation decreases cAMP. Decrease upstroke velocity by decreasing Ca conductance. Prolongs action potential duration by decrease of K conductance. Decreases HR by decrease of Na funny current and by increase K conductance.

Front 197

Class 1A antiarrhythmics

Back 197

Quinidine, procainamide

Front 198

1A antiarrhythmics MOA

Back 198

Block fast Na channels in the open state (decreases excitability and phase 0 slope) increasing APD and ERP. Block K channels which prolongs repolarization (decrease phase 3 slope).

Front 199

Quinidine pharmacokinetics

Back 199

Orally effective weak base enhanced absorption and toxicity by antacids. In atrial fibrilation needs intitial digitalization.

Front 200

Quinidine pharmacodynamics

Back 200

Class 1A effects plus muscarinic receptor blockade (increase HR and AV conduction); vasodilation via alpha block with reflex tachychardia.

Front 201

Quinidine adverse effects

Back 201

Cinchonism (GI, tinnitus, ocular dysfunction, CNS excitation), hypotension, QRS and QT prolongation associated with syncope torsades

Front 202

Quinidine drug interactions

Back 202

Hyperkalemia enhances effects and vice versa. Displaces digoxin from tissue binding sites, enhancing toxicity.

Front 203

Procainamide pharmacokinetics

Back 203

Phase 2 acetylation by N-acetyltransferase to N-acetylprocainamide (NAPA) active metabolite. Subject to genotypic variation/slow acetylators/drug-induced lupus.

Front 204

Procainamide adverse effects

Back 204

SLE-like syndrome (30%) in slow acetylators. Thrombocytopenia, agranulocytosis, torsades.

Front 205

Class 1B antiarrhythmics

Back 205

Lidocaine, mexiletine, tocainide

Front 206

Class 1B antiarrhythmics MOA

Back 206

Block fast Na channels in the inactive state, preferentially in hypoxic tissues results in increased threshold for excitation and less excitability of hypoxic heart muscle. Block of slow Na window currents with decreased APD (decreased phase 2 of AP). Increases dyastole and time for recovery (leads to asystolia)

Front 207

Uses and side effects of lidocaine

Back 207

Post MI, open heart surgery, digoxin toxicity. Seizures, least cardiotoxic antiarrhythmic. IV because of first-pass metabolism.

Front 208

Class 1C antiarrhythmics MOA

Back 208

Block fast Na channels specially in His-Purkinje fibers without altering the APD (decreases phase 0 slope at the expense of shortening phase 2 duration)

Front 209

Flecainide

Back 209

Class 1C antiarrhythmic. Limited use because of proarrhythmogenic effects. Increased risk of sudden death post-MI.

Front 210

Effects of class 1A antiarrhythmics on action potential

Back 210

Decrease slope of phase 0; increase APD and ERP.

Front 211

Effects of class 1B antiarrhythmics on action potential

Back 211

Decrease length of phase 2 (plateau) with no change in phase 0 or 3 which decreases APD.

Front 212

Effects of class 1C antiarrhythmics on action potential

Back 212

Decrease slope of phase 0 and decrease length of phase 2 which cancels out effect on APD.

Front 213

Class II antiarrhythmics MOA

Back 213

Block β1 receptors in the heart decreasing cAMP; Decrease upstroke velocity by decreasing Ca conductance (decreased phase 4). Prolongs action potential duration by decrease of K conductance (decreased phase 3 slope). Decreases HR by decrease of Na funny current and by increase K/ACh conductance (decreased phase 4)

Front 214

Class II antiarrhythmics

Back 214

Propranolol (nonselective), acebutolol, esmolol (β1 selective)

Front 215

Uses of class II antiarrhythmics

Back 215

Prophylaxis post MI, supraventricular tachyarrhythmias

Front 216

Properties of propranolol

Back 216

Nonselective β blocker, no sympathicomimetic activity, produces sedation and increases blood lipids.

Front 217

Properties of acebutolol

Back 217

Selective β1 blocker with intrinsic sympathicomimetic activity, no sedation, no increase in blood lipids.

Front 218

Class III antiarrhythmics MOA

Back 218

Decreased delayed rectifier K currents which slows phase 3 and increases APD and ERP.

Front 219

Class III antiarrhythmics

Back 219

Amiodarone, sotalol (combined K channel and β1 blocker)

Front 220

Amiodarone pharmacokinetics

Back 220

t1/2 > 80 days, large Vd.

Front 221

Amiodarone pharmacodynamics

Back 221

Blocks K channels in many tissues. Mimics class I, II and IV antiarrhythmics. Increases APD and ERP.

Front 222

Amiodarone side effects

Back 222

Large Vd affects many tissues: pulmonary fibrosis, blue pigmentation of skin, phototoxicity, corneal deposits, hepatic necrosis, thyroid dysfunction.

Front 223

Sotalol MOA

Back 223

Blocks K channels decreasing phase 3 of AP (increases APD); blocks β1 which decreases phase 4 and phase 3 slopes in pacemaker cells (which decreases HR and conduction)

Front 224

Class IV antiarrhythmics MOA

Back 224

Block slow Ca channels in pacemaker cells which decreases phase 4 and 0 slopes, which decreases HR.

Front 225

Class IV antiarrhythmics

Back 225

Verapamil, diltiazem

Front 226

Uses of verapamil

Back 226

Supraventricular tachyarhythmias

Front 227

Verapamil side effects

Back 227

Constipation, dizziness, flushing, hypotension, AV block

Front 228

Verapamil drug interactions

Back 228

Additive AV block with β-blockers and digoxin; displaces digoxin from tissue-binding sites.

Front 229

Properties of adenosine

Back 229

Activates adenosine receptors coupled to Gi, decreasing cAMP, decreasing SA and AV node activity. Used for paroxysmal supraventricular tachyarrhythmias. t1/2 < 10 seconds. Side effects: flushing, sedation, dyspnea. Antagonized by theophylline.

Front 230

Drugs that cause torsades

Back 230

Class IA (quinidine) and III (sotalol) antiarrhythmics, antipsychotics (ziprasidone), tricylic antidepressants.

Front 231

Drugs that displace digoxin

Back 231

Verapamil, quinidine

Front 232

Drugs that cause drug-induced lupus

Back 232

Hydralazine > procainamide > isoniazid (slow acetylators)

Front 233

Effects of hyperkalemia on heart

Back 233

Decreases K efflux reducing repolarization. Membrane is depolarized. Can cause heart stop on systole. Peaked T waves.

Front 234

Effects of hypokalemia on heart

Back 234

Increases K conductance and hyperpolarization. Heart stops of dyastole.

Front 235

What is the strategy to treat hypertension

Back 235

Decrease TPR (α2 agonists, α1 blockers), decrease CO (β-blockers), decrease body fluids (diuretics), vasodilation (hydralazine, nitirites, ACEIs, ARBs).

Front 236

α2 agonists

Back 236

Clonidine, methyldopa

Front 237

Uses and side effects of clonidine

Back 237

Uses: Mild to moderate hypertension, opiate withdrawal; Side effects: CNS depression, edema.

Front 238

Uses and side effects of methyldopa

Back 238

Uses: mild to moderate hypertension, hypertension management in pregnancy; Side effects: positive Coombs test, CNS depression, edema.

Front 239

Reserpine MOA and side effects

Back 239

Destroys catecolamine vesicles leading to decrease in CNS and peripheral levels. Side effects: depression, edema.

Front 240

Guanethidine MOA and side effects

Back 240

Accumulates into nerve endings by reuptake, binds catecolamine vesicles and inhibits release of NE; Side effects: diarrhea, edema. Tricyclics block reuptake and actions of guanethidine

Front 241

α1 blockers

Back 241

Prazosin, doxazosin, terazosin

Front 242

α1 blockers MOA

Back 242

Decrease arteriolar and venous resistance. Decrease prostate and urinary sphincter tone.

Front 243

α1 blockers side effects

Back 243

First dose syncope, orthostatic hypotension, urinary incontincence

Front 244

β-blockers cautions in use

Back 244

Asthma, vasospastic disorders (atherosclerosis, Raynauds), diabetics (hypoglycemia normally induces tachychardia which is perceived by patient, but β-blockers prevent tachychardia warning signs).

Front 245

Properties of hydralazine

Back 245

Direct vasodilator as nitric oxide donor. Decreases TPR. Use in moderate to severe hypertension. Side effects: Drug-induced lupus in slow acetylators, edema, reflex tachychardia.

Front 246

Drugs metabolized by acetylation

Back 246

Hydralazine > procainamide > isoniazid (slow acetylators)

Front 247

Nitroprusside

Back 247

Nitric oxide donor vasodilates arterioles and venules. Used for hypertensive emergencies. Releases cyanide thus coadminister thiosulfate to form nontoxic thiocyanate. In case of cyanide poisoning give nitrites.

Front 248

Direct vasodilators

Back 248

Hydralazine (NO), nitroprusside (NO), minoxidil (opens K channels --> hyperpolarization --> vasodilation)

Front 249

Minoxidil

Back 249

Opens K channels in smooth muscle --> hyperpolarization --> vasodilation. Use in severe hypertension and alopecia. Side effects: hypertrichosis, edema, reflex tachychardia.

Front 250

Diazoxide

Back 250

Opens K channels in smooth muscle --> hyperpolarization --> vasodilation. Use in hypertensive emergencies. Side effects: hyperglycemia (decreases insulin release)

Front 251

Arteriolar vasodilators

Back 251

Ca channel blockers (nifedipine), hydralazine, K channel openers (minoxidil)

Front 252

Venular vasodilation

Back 252

Nitrates (nitroprusside)

Front 253

Orthostatic hypotension

Back 253

Due to venular dilation not arteriolar. Usually from α1 blockers.

Front 254

Calcium channel blockers MOA

Back 254

Block L-type Ca channels in heart and blood vessels smooth muscle --> decrease intracellular Ca --> decreased CO and TPR.

Front 255

Calcium channel blockers

Back 255

Verapamil, diltiazem, nifedipines and derivatives.

Front 256

Uses of calcium channel blockers

Back 256

Hypertension, angina, antiarrhythmics (verapamil, diltiazem)

Front 257

Side effects of calcium channel blockers

Back 257

Reflex tachychardia (nifedipine and derivatives), gingival hyperplasia (nifedipine and derivatives), constipation (verapamil)

Front 258

ACE inhibitors MOA

Back 258

Block formation of angiotensin II --> no AT-1 receptor stimulation --> decreased aldosterone secretion and vasodilation; also prevent bradykinin degradation by ACE (dry cough). Captopril and other -prils

Front 259

Angiotensin receptor blockers MOA

Back 259

Block angiotensin receptors --> decreased aldosterone secretion and vasodilation. Losartan and other -sartans

Front 260

Uses of ACEIs and ARBs

Back 260

Mild to moderate hypertension, protective of diabetic neprhopathy, CHF

Front 261

ACEIs side effects

Back 261

Dry cough (no degradation of bradykinin), hyperkalemia (no aldosterone), acute renal failure in renal artery stenosis (angiotensin maintains RBF), angioedema, rash

Front 262

ARBs side effects

Back 262

Hyperkalemia (no aldosterone), acute renal failure in renal artery stenosis (angiotensin maintains RBF), angioedema

Front 263

Treatment strategy for heart failure

Back 263

Decrease preload (diuretics, ACEIs, ARBs, venodilators), decrease afterload (ACEIs, ARBs, arteriodilators), increase contractility (digoxin, beta agonists), decrease cardiac remodeling (ACEIs, ARBs, spironolactone)

Front 264

What drugs are beneficial in CHF and why?

Back 264

ACEIs, ARBs and spironolactone prevent cardiac remodeling

Front 265

Digoxin MOA

Back 265

Inhibits cardiac Na/K ATPase --> increase intracellular Na --> decrease Na/Ca exchange --> increase intracellular Ca --> increase Ca release on sarcoplasmic reticulum --> increase contractile force. It also inhibits neuronal Na/K ATPase which increases vagal and sympathetic stimulation.

Front 266

Digoxin pharmacokinetics

Back 266

Long t1/2 needs loading dose; renal clearance; large Vd and displacement by verapamil and quinidine

Front 267

Uses of digoxin

Back 267

CHF and supraventricular tachychardias except Wolff-Parkinson-White syndrome

Front 268

Wolff-Parkinson-White syndrome

Back 268

Prexcitation of the ventricles due to accesory conduction bundle of Kent. Block accessory path with class IA or III antiarrhythmics, avoid β-blockers, CCBs and adenosine

Front 269

Digoxin side effects

Back 269

Anorexia, nausea, ECG changes, disorientation, visual halos, cardiac arrhythmias

Front 270

Digoxin toxicity

Back 270

Can cause cardiac arrhythmias. Use Fab antibodies against digoxin and class IB antiarrhythmics.

Front 271

Digoxin drug interactions

Back 271

Quinidine, verapamil displace digoxin; sympathicomimetics; diuretics

Front 272

Phosphodiesterase inhibitors MOA

Back 272

Inamrinone, milrinone. Phosphodiesterase normally converts cAMP into AMP, inhibitors increase cAMP and inotropy in heart and relax smooth muscle cells which leads to decreased TPR

Front 273

Antianginal drugs

Back 273

Nitroglycerin, isosorbide, CCBs (nifedipine), β-blockers and carvedilol

Front 274

Nitrates MOA

Back 274

Pro drugs of nitric oxide; NO activates smooth muscle guanylyl cyclase --> increase cGMP --> relaxation --> venodilation --> decrease preload --> decrease cardiac work and oxygen requirements

Front 275

Nitroglycerin side effects

Back 275

flushing, headache, orthostatic hypotension, reflex tachychardia, methhemoglobinemia.

Front 276

Nitroglycerin interactions

Back 276

Cardiovascular toxicity with sildenafil

Front 277

Sildenafil MOA

Back 277

Inhibits PDE5 in blood vessels of corpora cavernosa --> increase cGMP --> vasodilation --> erection

Front 278

Uses and side effects of manitol

Back 278

Decreases IOP in glaucoma, decreases intracerebral pressure in cerebral edema. Side effects: hypovolemia

Front 279

Carbonic anhydrase inhibitors drugs

Back 279

Acetazolamide, dorzolamide

Front 280

Azetazolamide MOA

Back 280

Decreases H+ formation in PCT --> decrease Na/H+ antiport --> increases Na and HCO3 in lumen --> diuresis

Front 281

Uses of azetazolamide and CA inhibitors

Back 281

Glaucoma, acute moutain sickness (acidosis stimulates ventilation), metabolic alkalosis

Front 282

Azetazolamide and CA inhibitors side effects

Back 282

Bicarbonaturia/acidosis, hypokalemia (increases Na load dowstream), hyperchloremia, paresthesia, renal stones (alkalinizes urine), sulfa hypersensitivity

Front 283

Loop diuretic drugs

Back 283

Ethacrynic acid, furosemide

Front 284

Loop diuretics MOA

Back 284

Inhibit Na/K/2Cl cotransporter --> decrease intracell K+ --> decrease positive potential --> decrease reabsorption of Ca, Mg --> increased diuresis

Front 285

Uses of loop diuretics

Back 285

Acute pulmonary edema, CHF, hypertension, refractory edema, acute renal failure, anion overdose, hypercalcemia

Front 286

Loop diuretic side effects

Back 286

Sulfonamide hypersensitivity (except ethacrynic acid), hypokalemia, alkalosis, hypocalcemia, hypomagnasemia, hyperuricemia, ototoxicity (ethacrynic acid > furosemide)

Front 287

Loop diuretics drug interactions

Back 287

Enhanced ototoxicity with aminoglycosides; decrease clearance of lithium, increase digoxin toxicity

Front 288

Thiazide drugs

Back 288

Hydrochlorothiazide, indapamide

Front 289

Thiazides MOA

Back 289

Inhibit Na/Cl transporter in DCT --> increases Na and Cl in the lumen --> increase diuresis

Front 290

Uses of thiazides

Back 290

Hypertension, CHF, nephrolithiasis (calcium stones), nephrogenic diabetes insipidus

Front 291

Thiazides side effects

Back 291

Sulfonamide hypersensitivity, hypokalemia, alkalosis, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia

Front 292

Thiazide drug interactions

Back 292

Increase digoxin toxicity, avoid in diabetics

Front 293

K+ sparing agents

Back 293

Spironolactone, eplerenone, amiloride, triamterene

Front 294

MOA spironolactone

Back 294

Aldosterone receptor antagonist --> no sodium reabsorption --> no K+ secretion

Front 295

Uses of spironolactone

Back 295

Hyperaldosteronism, adjunct to K+ wasting diuretics, hirsutism, CHF

Front 296

Spironolactone side effects

Back 296

Hyperkalemia, acidosis, antiandrogenic (except eplerenone)

Front 297

MOA amiloride/triamterene

Back 297

Blocks Na+ channels in principal cells of collecting ducts --> decreased Na+ reabsorption and K+ secretion

Front 298

Uses of K+ sparing agents

Back 298

Adjunct to K+ wasting diuretics, lithium-induced nephrogenic diabetes insipidus (amiloride)

Front 299

Side effects of K+ sparing agents

Back 299

Hyperkalemia, acidosis, antiandrogenic (except epleronone)

Front 300

Electrolytes excreted by acetazolamide

Back 300

Na, K, HCO3

Front 301

Electrolytes excreted by loop diuretics

Back 301

Na, K, Ca, Mg, Cl

Front 302

Electrolytes excreted by thiazides

Back 302

Na, K, Cl; Ca is reabsorbed

Front 303

Electrolytes excreted by K+ sparing agents

Back 303

Na; K is not secreted

Front 304

Statins MOA

Back 304

Inhibition of HMG-CoA-Reductase --> decreased cholesterol --> increased LDL receptor expression --> decresed LDLs

Front 305

Statins side effects

Back 305

Myalgia, myopathy, rhabdomyolysis due to decrease in farnesyl ppi

Front 306

Statins drug interactions

Back 306

Gemfribozil increases rhabdomyolysis; P450 inhibitors enhance toxicity

Front 307

Bile acid sequestrant drugs

Back 307

Cholestyramine, colestipol

Front 308

MOA of bile acid sequestrants

Back 308

Decreased enterohepatic circulation --> increased new bile salts in liver --> decreased liver cholesterol --> increased LDL receptor expression --> decreased blood LDL

Front 309

Side effects of bile acid sequestrants

Back 309

Increased VLDL and triglycerides; gastrointestinal disturbances; malabsorption of lipid-soluble vitamins

Front 310

Drug interactions of bile acid sequestrants

Back 310

Interact with orally administered drugs

Front 311

Contraindications of bile acid sequestrants

Back 311

Hypertriglyceridemia

Front 312

Niacin MOA

Back 312

Inhibits VLDL synthesis --> decreased plasma VLDL --> decreases LDL --> increases HDL

Front 313

Niacin side effects

Back 313

Flushing, pruritus, rashes, hepatotoxicity

Front 314

Gemfibozil MOA

Back 314

Activates lipoprotein lipase --> decreases VLDL and IDL --> decreases LDL --> increases HDL

Front 315

Uses of gemfibrozil

Back 315

Hypertriglyceridemia

Front 316

Ezetimibe MOA

Back 316

Prevents intestinal reabsorption of cholesterol --> decreased LDL

Front 317

Which antihyperlipidemic: increased cholesterol

Back 317

Cholestyramine, colestipol, ezetimibe

Front 318

Which antihyperlipidemic: increased triglycerides

Back 318

Gemfibrozil

Front 319

Which antihyperlipidemic: increased cholesterol and triglycerides

Back 319

Statins, niacin, ezetimibe

Front 320

Properties of benzodiazepines

Back 320

Bind to gamma subunit of GABAa complex to increase frequency of Cl- channel opening; no GABAmimetic activity; BZ1 mediates sedation; BZ2 mediates antianxiety and impairment of cognitive functions

Front 321

Benzodiazepine drugs

Back 321

Alprazolam, diazepam, lorazepam, midazolam, temazepam, oxazepam

Front 322

Uses of alprazolam

Back 322

Anxiety, phobias, panic attacks

Front 323

Uses of diazepam

Back 323

Anxiety, preop sedation, muscle relaxation, withdrawal states

Front 324

Uses of lorazepam

Back 324

Anxiety, preop sedation, status epilepticus

Front 325

Uses of midazolam

Back 325

Preop sedation and anesthesia, anterograde amnesia

Front 326

Uses of temazepam

Back 326

Sleep disorders

Front 327

Uses of oxazepam

Back 327

Sleep disorder and anxiety

Front 328

Pharmacokinetics of benzodiazepines

Back 328

Liver metabolized to active compounds except oxazepam, temazepam, lorazepam; t1/2: diazepam > lorazepam > alprazolam > temazepam > oxazepam > midazolam

Front 329

Uses of barbiturates

Back 329

Phenobarbital for seizures; thiopental for induction of anesthesia

Front 330

Properties of barbiturates

Back 330

Prolong GABA activity; increase duration of Cl- channel opening; GABAmimetic activity at high doses; bind to beta subunit of GABA(a) complex; inhibit complex I of ETC, induces P450

Front 331

Pharmacokinetics of barbiturates

Back 331

General inducers of P450; contraindicated in porphyrias

Front 332

Withdrawal signs of benzodiazepines

Back 332

Rebound insomnia, anxiety, seizures

Front 333

Withdrawal signs of barbiturates and ethanol

Back 333

Anxiety, agitation, life threatening seizures

Front 334

Drug interactions of GABA drugs

Back 334

Life threatening respiratory depression if used with other CNS depressants (antihistaminics, opiates, beta blockers); Barbiturates induce metabolism of lipid-soluble drugs (oral contraceptives, carbamazepine, phenytoin, warfarin)

Front 335

Flumazenil

Back 335

Benzodiazepine receptor antagonist. Used as antidote for benzodiazepine overdose.

Front 336

Zolpidem

Back 336

BZ1 receptor agonist used in sleep disorders. No cognitive impairment (no BZ2 actions), overdose reversed by flumazenil, less tolerance and abuse liability

Front 337

Buspirone

Back 337

No effect on GABA, 5-HT1a partial agonist, used for generalized anxiety, nonsedative, 1-2 weeks for effects

Front 338

Effects of alcohols

Back 338

GABA mimetic activity causes CNS depression; metabolic acidosis; fetal alcohol syndrome

Front 339

Metabolism of ethylene glycol

Back 339

Ethylene glycol + alcohol DH --> glycoaldehyde + aldehyde DH --> glycolic acid --> oxalic acid

Front 340

Effects of ethylene glycol

Back 340

CNS depression, severe metabolic acidosis, nephrotoxicity

Front 341

Metabolism of methanol

Back 341

Methanol + alcohol DH --> formaldehyde + aldehyde DH --> formic acid

Front 342

Effects of methanol

Back 342

Respiratory failure, severe anion gap metabolic acidosis, ocular damage

Front 343

Treatment of alcohol overdose

Back 343

Fomepizole (alcohol DH inhibitor) and hemodialisis

Front 344

Metabolism of ethanol

Back 344

Ethanol + alcohol DH --> acetaldehyde + NADH + acetaldehyde DH --> acetic acid + NADH

Front 345

Effects of ethanol

Back 345

CNS depression, metabolic acidosis, acetaldehyde toxicity

Front 346

Acetaldehyde toxicity

Back 346

Nausea, vomit, headache, hypotension, inactivates folate, decreases availability of thiamine

Front 347

Drugs that cause disulfram-like effects

Back 347

Disulfram-like effects = acetaldehyde toxicity. Disulfram inhibits acetaldehyde DH. Metronidazole, cefamandole, cefoperazone, cefotetan, chlorpropamide

Front 348

Anticonvulsant drugs

Back 348

Phenytoin, carbamazepine, benzodiazepines, barbiturates, lamotrigine, topiramate, felbamate, ethosuximide, valproic acid

Front 349

Drugs used for partial seizures

Back 349

Valproic acid, phenytoin, carbamazepine

Front 350

Drugs used for general tonic-clonic seizures

Back 350

Valproic acid, phenytoin, carbamazepine

Front 351

Drugs used for absence seizures

Back 351

Ethosuximide

Front 352

Drugs used for status epilepticus

Back 352

Lorazepam, diazepam, phenytoin

Front 353

Phenytoin MOA

Back 353

Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation

Front 354

Pharmacokinetics of phenytoin

Back 354

Variable absorption, nonlinear kinetics at low doses, zero-order kinetics at high doses, inducer of P450

Front 355

Phenytoin side effects

Back 355

CNS depression, gingival hyperplasia, hirsutism, osteomalacia (decreases vitamin D), megaloblastic anemia (decreases folate), aplastic anemia, teratogenic (cleft lip and palate).

Front 356

Carbamazepine MOA

Back 356

Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation

Front 357

Pharmacokinetics of carbamazepine

Back 357

Induces P450

Front 358

Carbamazepine side effects

Back 358

CNS depression, osteomalacia, megaloblastic anemia, aplastic anemia, exfoliative dermatitis, increases ADH secretion (dilutional hyponatremia), teratogenic (cleft lip and palate, spina bifida)

Front 359

Valproic acid MOA

Back 359

Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation; Inhibits GABA transaminase; Blocks presynaptic Ca+ channels

Front 360

Uses of valproic acid

Back 360

Seizures, bipolar mania, migraines

Front 361

Pharmacokinetics of valproic acid

Back 361

Inhibits P450

Front 362

Valproic acid side effects

Back 362

Hepatotoxic metabolite, thrombocytopenia, pancreatitis, alopecia, spina bifida

Front 363

Ethosuxamide MOA

Back 363

Blocks presynaptic T-type Ca+ channels in thalamic neurons

Front 364

Lamotrigine MOA

Back 364

Blocks Na+ channels and glutamate receptors. Side effect: Steven-Johnson

Front 365

Inhaled anesthetic drugs

Back 365

Nitrous oxide, halothane

Front 366

Properties of halothane

Back 366

High potency (0.8% MAC), high blood-gas ratio (2.3), sensitizes heart to catecholamines

Front 367

Side effects of halothane

Back 367

Malignant hyperthermia, hepatitis, cardiac arrhythmias

Front 368

What is MAC?

Back 368

Minimal alveolar concentration is the amount of anesthetic at which 50% of patients don't respond to surgical stimulus. Analogous to ED50, measures potency, the more lipid soluble the lower the MAC, lower in elderly

Front 369

What is the blood-gas ratio?

Back 369

Measure of the onset of recovery. The more soluble in the blood the slower the anesthesia and recovery.

Front 370

Intravenous anesthetic drugs

Back 370

Midazolam, thiopental, propofol, fentanyl, ketamine

Front 371

General anesthesia protocol

Back 371

Includes sedation and anterograde amnesia (midazolam), induction (propofol), analgesia (fentanyl), muscle relaxant for intubation (succinylcholine) and may or may not include atropine in case of CV depression due to propofol

Front 372

Naloxone

Back 372

Antidote for opiods

Front 373

Neostigmine

Back 373

AChE inhibitor reverses non-depolarizing muscle relaxants

Front 374

What are the ester local anesthetics?

Back 374

Procaine, cocaine, benzocaine. Metabolized by plasma esterases. All have only one "i"

Front 375

What are the amide local anesthetics?

Back 375

Lidocaine, bupivacaine, mepivacaine. Metabolized by liver amidases. All have two "i".

Front 376

MOA of local anesthetics

Back 376

Nonionized form crosses axonal membrane --> ionized form blocks inactivated Na+ channel --> prevent propagation of action potentials

Front 377

Side effects of local anesthetics

Back 377

Neurotoxicity, cardiovascular toxicity, allergies. Use alpha-1 agonists to prevent absorption.

Front 378

Skeletal muscle relaxants MOA

Back 378

Nicotinic antagonists (competitive, nondepolarizing); Nicotinic agonists (noncompetitive, depolarizing)

Front 379

Non-depolarizing muscle relaxant drugs

Back 379

Atracurium, mivacurium, tubocurarine

Front 380

Non-depolarizing muscle relaxant properties

Back 380

Nicotinic antagonists, reversible with AChE inhibitors, progressive paralysis, no effects on heart or CNS

Front 381

Properties of succinylcholine

Back 381

Depolarizing muscle relaxant, nicotinic agonist; Phase I: depolarization, fasciculation, flaccid paralysis; Phase II: desensitization. Caution in atypical pseudocholineeterase, hyperkalemia, malignant hyperthermia

Front 382

Malignant hyperthermia

Back 382

Succinylcholine side effect in genetically susceptible people. Muscle rigidity, hyperthermia, hypertension, acidosis, hyperkalemia. Rx.: dantrolene

Front 383

Opiod analgesic drugs

Back 383

Morphine, meperidine, methadone, codeine, fentanyl

Front 384

Contraindications of opiod analgesics

Back 384

Head injuries, pulmonary dysfunction, hepatic or renal dysfunction, adrenal or thyroid deficiencies, pregnancy

Front 385

Effects of morphine

Back 385

Analgesia, sedation, respiratory depression (decreased response to PCO2), miosis, cough supression, nausea, vomiting

Front 386

Pharmacokinetics of morphine

Back 386

Phase 2 metabolism by glucoronidation. Caution in renal dysfunction as morphine-6-glucoronide is highly active

Front 387

Opiod toxicity

Back 387

Pinpoint pupils, repiratory depression and coma. Rx. Naloxone

Front 388

Meperidine

Back 388

Opiod without miosis or spasms. Metabolized via P450 to normeperidine which can cause seizures

Front 389

Methadone

Back 389

Used for opiate withdrawal in addicts

Front 390

Codeine

Back 390

Cough suppressant, analgesia, use in combination with NSAIDs

Front 391

Symptoms of opiod withdrawal

Back 391

Yawning, lacrimation, rhinorrea, salivation, anxiety, muscle spasms and CNS-originating pain. Rx.: methadone

Front 392

Drugs used in Parkinson disease

Back 392

Levodopa, tolcapone, selegiline, bromocriptine, benztropine, amantadine

Front 393

Levodopa

Back 393

Crosses CNS barrier. Converted to dopamine in CNS and periphery, so use tolcapone, carbidopa and selegiline

Front 394

Tolcapone

Back 394

Inhibits COMT which blocks levodopa conversion to methyldopa which has no pharm actions

Front 395

Carbidopa

Back 395

Inhibits conversion of levodopa to dopamine in peripheral tissues, increasing CNS availability

Front 396

Selegiline

Back 396

MAOb selective inhibitor, adjunt to levodopa to decrease dopamine metabolism in CNS

Front 397

Bromocriptine

Back 397

Dopamine-receptor agonist used in hyperprolactinemia, acromegaly

Front 398

Benztropine

Back 398

Muscarinic blocker used to decrease Ach activity in Parkinson. Decreases tremor and rigidity but not bradykinesia

Front 399

Atypical antipsychotics

Back 399

Clozapine, olanzapine, risperidone, aripiprazole, quetiapine, ziprasidone, paliperidone

Front 400

Atypical antipsychotic MOA

Back 400

Inhibition of dopamine and 5HT2 receptors

Front 401

Side effects of antipsychotic drugs

Back 401

Extrapyramidal symptoms, akathisia, tardive dyskinesia, dysphoria, endocrine dysfunction, weight gain, hypotension, muscarinic blockade tachychardia

Front 402

Specific side effects of thioridazine

Back 402

Torsades, retinal deposits

Front 403

Typical antipsychotics

Back 403

Chlorpromazine, thioridazine, fluphenazine, haloperidol

Front 404

Specific side effects of haloperidol

Back 404

Neuroleptic malignant syndrome, tardive diskynesia

Front 405

Specific side effects of clozapine

Back 405

Agranylocytosis, seizures, salivation

Front 406

MAO inhibitor drugs

Back 406

phenelzine, tranylcypromine

Front 407

Drug interaction of MAO inhibitors

Back 407

Tyramine, TCAs, alpha-1 agonists, levodopa: increase NE --> hypertensive crisis; Serotonin syndrome with SSRI, TCA, meperidine --> sweating, rigidity, myoclonus, hyperthermia

Front 408

Tricyclic antidepressant drugs

Back 408

Amitriptyline, imipramine, clomipramine

Front 409

TCAs MOA

Back 409

Nonspecific blockade of 5HT and NE reuptake

Front 410

Side effects of TCAs

Back 410

Muscarinic blockade, alpha blockade, serotonin syndrome, hypertensive crisis

Front 411

SSRI drugs

Back 411

Fluoxetine, sertraline, paroxetine, citalopram

Front 412

Side effects of SSRI

Back 412

Anxiety, agitation, bruxism, sexual dysfunction, weight loss, serotonin syndrome

Front 413

Serotonin syndrome

Back 413

Sweating, rigidity, myoclonus, hyperthermia. Interaction between MAOi, TCAs, SSRIs, meperidine, dextromethorphan

Front 414

Drug-induced hypertensive crisis

Back 414

Due to interaction between MAOi, TCAs, alpha-1 agonists

Front 415

Venlafaxine

Back 415

Selective reuptake inhibitor of NE and 5HT. Can cause hypertensive crisis and serotonin syndrome

Front 416

Bupropion

Back 416

Dopamine reuptake blocker. Used in smoking cessation

Front 417

Lithium MOA

Back 417

Prevents recycling of inositol (decreases PIP2), decreases cAMP

Front 418

Lithium side effects

Back 418

Narrow therapeutic index requires monitoring, tremor, hypothyroidism (decreases TSH effects and inhibits 5'-deiodinase), nephrogenic diabetes insipidus (manage with amiloride), teratogenic

Front 419

Methylphenidate

Back 419

inhibits reuptake of DA and NE. Side effects: agitation, restlessness, insomnia, CV toxicity. Treats ADHD.

Front 420

Atomoxetine

Back 420

Selective NE reuptake inhibitor. Treats ADHD.

Front 421

MOA of penicillins

Back 421

Bind PBPs to inhibit transpeptidation reactions in peptidoglycan cross-linking --> inhibit cell wall synthesis

Front 422

Mechanism of resistance to penicillin

Back 422

Beta-lactamases (staphylococci); structural change in PBPs (MRSA); change in porin structure (pseudomonas)

Front 423

Narrow spectrum penicillins

Back 423

Penicillin G and V. Strep, pneumococci, menigococci, treponema

Front 424

Very narrow spectrum penicillins

Back 424

Nafcillin, methcillin, oxacillin. Staph. If MRSA use vancomycin.

Front 425

Broad spectrum penicillins

Back 425

Ampicillin, amoxicillin. Gram+ cocci (except staph), Listeria, H. influenzae, E. coli., Borrelia and H. pylory: amoxi

Front 426

Extended spectrum penicillins

Back 426

Ticarcillin, piperacillin, azlocillin. Increased activity against gram- plus anti-pseudomonal

Front 427

Beta-lactamase inhibitors

Back 427

Clavulanic acid, sulbactam. Use in combination with broad and extended spectrum penicillins

Front 428

Pharmacokinetics of penicillins

Back 428

Most are eliminated via active tubular secretion. Nafcillin and oxacillin are eliminated in bile. Ampicillin undergoes enterohepatic circulation but is excreted by the kidney. Benzathine penicillin G repository form (t1/2: 2 weeks)

Front 429

Side effects of penicillins

Back 429

Hypersensitivity (5-7%). Urticarial skin rash to anaphylaxis. Interstitial nephritis (methicillin).

Front 430

First generation cephalosporins

Back 430

Cefazolin, cephalexin. Gram+ cocci (not MRSA), E. coli, Klebsiella pneumoniae, some proteus. Surgical prophylaxis

Front 431

Second generation cephalosporins

Back 431

Cefotetan, cefaclor, cefuroxime. Increased gram- coverage, including some anaerobes

Front 432

Third generation cephalosporins

Back 432

Ceftriaxone (IM), cefotaxime (IV), cefdinir, cefixime (oral). Gram+ and gram- cocci plus gram- rods. Enter CNS. Use in meningitis, sepsis

Front 433

Fourth generation cephalosporins

Back 433

Cefepime (IV). Enter CNS, resistant to betalactamases

Front 434

Pharmacokinetics of cephalosporins

Back 434

Active tubular secretion blocked by probenecid. Cefoperazone and ceftriaxone largely eliminated in bile.

Front 435

Side effects of cephalosporins

Back 435

Hypersensitivity (2%), rashes, fever, positive Coombs test, disulfram-like effect

Front 436

Drugs to use in case of penicillin/cephalosporin allergy

Back 436

Macrolides for gram+, aztreonam for gram- rods

Front 437

Imipenem and meropenem

Back 437

Resistant to betalactamases. Active against gram+ cocci, gram- rods and anaerobes. Use in life-threatening infections. Used IV. Imipenem is given with cilastatin to inhibit rapid renal metabolism by dehydropeptidase. Side effect: seizures

Front 438

Aztreonam

Back 438

Resistant to betalactamases. Used IV against gram- rods. No cross-allergenicity with penicillins or cephalosporins

Front 439

Vancomycin MOA

Back 439

Binds D-Ala-D-Ala pentapeptide to inhibit elongation of peptidoglycan chains. Does not bind PBPs.

Front 440

Uses of vancomycin

Back 440

MRSA, enterococci, C. difficile (backup drug)

Front 441

Resistance to vancomycin

Back 441

Terminal D-ala is replaced with D-lactate in muramyl pentapeptide

Front 442

Pharmacokinetics of vancomycin

Back 442

Used IV and orally (not absorbed) in colitis. Enters most tissues but not CNS. Eliminated by renal filtration. Long t1/2

Front 443

Side effects of vancomycin

Back 443

"Red man syndrome" (histamine release); permanent ototoxicity; nephrotoxicity

Front 444

Antibiotics that act on 30S ribosomal subunit

Back 444

Aminoglycosides, tetracyclines. "buy AT 30, CCEL at 50".

Front 445

Antibiotics that act on 50S ribosomal subunit

Back 445

Chloranphenicol, clindamycin, erythromycin (macrolides), linezolid. "buy AT 30, CCEL at 50"

Front 446

Antibiotics that inhibit formation of initiation complex

Back 446

Aminoglycosides (30S), linezolid (50S)

Front 447

Antibiotics that block attachment of aminoacyl-tRNA to A site

Back 447

Tetracyclines (30S), dalfopristin (50S)

Front 448

Antibiotics that inhibit peptidyltransferase (peptide bond formation)

Back 448

Chloranphenicol (50S)

Front 449

Antibiotics that inhibit translocation

Back 449

Macrolides (50S), clindamycin (50S)

Front 450

Mecanisms of resistance to macrolides and clindamycin

Back 450

Methyltransferases alter drug binding site on the 50S ribosome; active transport out of cell

Front 451

Mechanism of resistance to tetracyclines

Back 451

Tetracycline pumps transport drug out of the cell

Front 452

Mechanism of resistance to aminoglycosides

Back 452

Conjugation enzymes

Front 453

Mechanism of resistance to sulfonamides

Back 453

Change in target enzyme decreases drug sensitivity; formation of PABA; use of exogenous folic acid

Front 454

Mechanism of resistance to fluoroquinolones

Back 454

Change in target enzyme decreases drug sensitivity; pumps transport drugs out of the cell

Front 455

Mechanism of resistance to chloranphenicol

Back 455

Formation of inactivating acetyltransferases

Front 456

Pharmacokinetics of aminoglycosides

Back 456

Polar compounds not absorbed orally or widly distributed. Renal elimination. Modify in renal dysfunction

Front 457

Aminoglycoside drugs

Back 457

Gentamicin, tobramycin, amikacin: gram- aerobic rods; Streptomycin: TB, plague and tularemia; neomycin

Front 458

Side effects of aminoglycosides

Back 458

Nephrotoxicity (6-7%), ototoxicity enhanced by loop diuretics.

Front 459

Tetracycline drugs

Back 459

Tetracycline, doxycycline, minocycline, demeclocycline

Front 460

Uses of tetracyclines

Back 460

Chlamydia, mycoplasma, H. pylory, Rickettsia, Borrelia, Brucella, Vibrio

Front 461

Phamacokinetics of tetracyclines

Back 461

Metabolized by kidney (most), and liver (doxycycline). Decrease absorption of divalent cations by chelation.

Front 462

Side effects of tetracyclines

Back 462

Tooth enamel dysplasia, decreased bone growth (avoid in children), phototoxicity, contraindicated in pregnancy

Front 463

Drugs that cause phototoxicity

Back 463

amiodarone, tetracyclines, sulfonamides, quinolones

Front 464

Drugs that are nephrotoxic

Back 464

Vancomycin, aminoglycosides, amphotericin B, cisplatin, cyclosporine

Front 465

Drugs that are ototoxic

Back 465

Aminoglycosides, loop diuretics

Front 466

Pharmacokinetics of chloranphenicol

Back 466

Orally effective, enters CNS, metabolized by hepatic glucoronidation, inhibits P450

Front 467

Side effects of chloranphenicol

Back 467

Dose-dependant bone-marrow suppression, "gray baby" in neonates (decreased glucoronosyl transferase)

Front 468

Macrolide drugs

Back 468

Erythromycin, azithromycin, clarithromycin

Front 469

Uses of Erythromycin

Back 469

Gram+ cocci, atypicals (chlamydia, mycoplasma, ureaplasma), legionella, campylobacter

Front 470

Uses of azithromycin

Back 470

Gram+ cocci, atypicals (chlamydia, mycoplasma, ureaplasma), legionella, campylobacter, more activity in respiratory infections

Front 471

Pharmacokinetics of macrolides

Back 471

Erythromycin and clarithromycin: metabolized by liver, excreted in bile, inhibit P450, not safe in pregnancy. Azithromycin: excreted by kidney, doesn't inhibit P450, safer in pregnancy

Front 472

Side effects of macrolides

Back 472

Stimulate motilin receptors and cause GI distress, reversible deafness, cholestasis, jaundice

Front 473

Drugs to avoid in pregnancy

Back 473

Aminoglycosides, erythromycin, clarithromycin, fluoroquinolones, sulfonamides, tetracyclines

Front 474

Uses of clindamycin

Back 474

Gram+ cocci, anaerobes, toxoplasmosis. Use in gram+ osteomyelitis. Can cause pseudomembranous colitis

Front 475

Linezolid

Back 475

VRSA, VRE, drug-resistant pneumococci. Side effect: bone marrow suppression (platelets)

Front 476

Streptogramin drugs

Back 476

Quinupristin-dalfopristin

Front 477

MOA of streptogramins

Back 477

Bind 50S ribosomal subunit

Front 478

Uses of streptogramins

Back 478

Vancomycin resistant staph (VRSA), vancomycin resistant enterococci (VRE), drug-resistant gram+ cocci

Front 479

Inhibitors of nucleic acid synthesis drugs

Back 479

5-MP, 6-FU, hydroxyurea, methotrexate, sulfonamides, trimethoprim, pyrimethamine

Front 480

MOA of sulfonamides

Back 480

Inhibits dihydropteroate synthetase which inhibits folic acid synthesis

Front 481

MOA of trimethoprim

Back 481

Inhibits dihydrofolate reductase which inhibits folic acid synthesis

Front 482

Uses of trimethoprim-sulfamethoxazole

Back 482

DOC in Nocardiosis; mycobacteria; gram+ cocci, E. coli, Salmonella, Shigella, H. influenzae, P. carinii, toxoplasma

Front 483

Pharmacokinetics of sulfonamides

Back 483

Hepatically acetylated; renally excreted metabolites cause crystalluria; high protein binding

Front 484

Side effects of sulfonamides

Back 484

Hypersensitivity, Steven Johnson, phototoxicity, GI distress, hemolysis in G6PDH deficiency

Front 485

Side effects of trimethoprim

Back 485

Bone marrow suppression, enterocolitis

Front 486

Quinolone drugs

Back 486

Norfloxacin, ciprofloxacin, ofloxacin, levofloxacin

Front 487

MOA of quinolones

Back 487

Bactericidal. Inhibit topoisomerase II (DNA gyrase).

Front 488

Uses of quinolones

Back 488

UTIs resistant to cotrimoxazole, PID (chlamydia, gonococcus), skin and bone infections by gram-, diarrhea to shigella, salmonella, E. coli, campylobacter

Front 489

Pharmacokinetics of quinolones

Back 489

Iron and Ca+ limit their absorption, eliminated by kidney active secretion (inhibited by probenecid)

Front 490

Side effects of quinolones

Back 490

GI distress, phototoxicity, rashes, tendonitis, increases QT interval, contraindicated in pregnancy and children

Front 491

Regimens used in H. pylori infections and ulcers

Back 491

BMT: bismuth, metronidazole, tetracyclines or clarithromycin, amoxicillin, omeprazole

Front 492

Uses of metronidazole

Back 492

Giardia, trichomonas, entamoeba, gram- anaerobics, clostridium (DOC pseudomembranous colitis)

Front 493

MOA and resistance to isoniazid

Back 493

Inhibits mycolic acid synthesis; prodrug requires conversion by catalase; resistance: deletions if katG gene encodes catalase needed for activation; deletions in inhA gene encodes acyl carrier protein, the target

Front 494

Side effects of isoniazid

Back 494

Age-dependant hepatitis, peripheral neuritis (use B6), sideroblastic anemia (use B6), hemolysis in G6PDH deficiency, drug-induced lupus in slow acetylators

Front 495

MOA and resistance to rifampin

Back 495

Inhibits DNA-dependant RNA polymerase; resistance via change in enzyme

Front 496

Side effects of rifampin

Back 496

Hepatitis, induction of P450, red-orange metabolites

Front 497

MOA of ethambutol

Back 497

Inhibits synthesis of cell wall component arabingalactan

Front 498

Side effects of ethambutol

Back 498

Dose-dependant retrobulbar neuritis --> decreases visual acuity and red-green discrimination

Front 499

Side effects of streptomycin

Back 499

Deafness, vestibular dysfunction, nephrotoxicity

Front 500

Polyene drugs

Back 500

Amp B, nystatin

Front 501

MOA of polyenes

Back 501

Formation of artificial pores in the ergosterol membranes disrupts membrane permeability

Front 502

Uses of amphotericin B

Back 502

Severe infections by Aspergillus, Candida, Cryptococcus, Histoplasma, Mucor, Sporothrix

Front 503

Uses of nystatin

Back 503

Topical localized infections; too toxic for systemic use

Front 504

Pharmacokinetics of amphotericin B

Back 504

Given by slow IV infusion, does not enter CNS, slow t1/2 > 2 weeks, hepatic metabolism and renal elimination

Front 505

Side effects of amphotericin B

Back 505

Infusion-related: fever chills, muscle rigor, hypotension alleviated by NSAIDs, antihistamines, meperidine, steroids. Dose-dependant: nephrotoxicity, decreased GFR, tubular acidosis, anemia

Front 506

Azole drugs

Back 506

Ketoconazole, fluconazole, itraconazole, clotrimazole

Front 507

MOA of azoles

Back 507

Fungicidal by inhibiting 14-alpha-demethylase which converts lanosterol to ergosterol

Front 508

Uses of ketoconazole

Back 508

DOC for Paracoccidioides; backup for Blastomyces, Histoplasma; Oral use in mucocutaneous candidiasis or dermatophytoses

Front 509

Uses of fluconazole

Back 509

DOC for esophageal and invasive candidiasis and coccidioidomycoses. Prophylaxis and suppression of cryptococcal meningitis

Front 510

Uses of itraconazole

Back 510

DOC in blastomycoses and sporotrichoses

Front 511

Uses of clotrimazole

Back 511

Used topically for candidal and dermatophytic infections

Front 512

Pharmacokinetics of ketoconazole

Back 512

Orally effective; absorption decreased by antacids; metabolized by liver enzymes; inhibits P450

Front 513

Pharmacokinetics of itraconazole

Back 513

Orally effective; absorption increased by food; metabolized by liver enzymes; inhibits P450

Front 514

Pharmacokinetics of fluconazole

Back 514

Orally effective; enters CSF; eliminated in the urine in unchanged form

Front 515

Side effects of azoles

Back 515

Decreased synthesis of cortisol and testosterone --> decreased libido, gynecomastia, menstrual irregularities; Increased liver function tests and rare hepatotoxicity

Front 516

Drugs that block viral penetration and uncoating

Back 516

Amantadine, enfurvitide

Front 517

Drugs that inhibit viral DNA polymerases

Back 517

Acyclovir, foscarnet, ganciclovir

Front 518

Drugs that inhibit viral RNA polymerases

Back 518

Foscarnet, ribavirin

Front 519

Drugs that inhibit viral reverse transcriptase

Back 519

Zidovudine, didanosine, zalcitabine, lamivudine, stavudine, nevirapine, delavirdine, efavirenz

Front 520

Drugs that inhibt viral aspartate protease

Back 520

Indinavir, ritonavir, saquinavir, nelfinavir

Front 521

Drugs that inhibit viral neuraminidase

Back 521

Zanamivir, oseltamivir

Front 522

Drugs used to treat herpes

Back 522

Acyclovir, ganciclovir, foscarnet

Front 523

Acyclovir

Back 523

Activated by viral thymidine kinase, inhibitor and chain terminator of DNA polymerase. Use for HSV ans VZV. Side effects: crystalluria, neurotoxicity

Front 524

Ganciclovir

Back 524

Activated by viral thymidine kinase, inhibitor and chain terminator of DNA polymerase. Use for HSV, VZV, CMV, AIDS retinitis and transplant patients. Side effects: hematotoxicity, crystalluria, rash

Front 525

Foscarnet

Back 525

Inhibits viral DNA and RNA polymerases. Use for HSV, VZV, CMV, AIDS retinitis, transplant patients. Side effects: nephrotoxic acute tubular necrosis, hypocalcemia (tremors, seizures)

Front 526

Zidovudine (ZDV, AZT)

Back 526

Converted to triphosphate that inhibits reverse transcriptase and causes chain termination. Resistance by mutations of RT gene.

Front 527

Drug interaction of zidovudine (ZDV, AZT)

Back 527

Increase levels of ZDV: azoles, cimetidine, indomethacin, probenecid, TMP-SMX. Decrease levels of ZDV: rifampin

Front 528

Side effects of ZDV

Back 528

Neutropenia, anemia, granulocytopenia, headache, myalgias, neuropathy, lactic acidosis

Front 529

MOA enfuvirtide

Back 529

Binds gp41 and inhibits fusion of HIV-1 to CD4 cells

Front 530

Needle stick HIV prophylaxis

Back 530

ZDV + 3TC + indinavir

Front 531

Pregnancy HIV prophylaxis

Back 531

ZDV trimester 2 and 3 plus 6 weeks to neonate reduces vertical transmission by 80%. Or ZDV intrapartum reduces transmission by 50-60%

Front 532

Amantadine

Back 532

Blocks attachment, penetration and uncoating of Influenza A. May decrease flu symptoms. Side effects: nervousness, insomnia, atropine-like effects

Front 533

Uses of interferons

Back 533

Antiviral: HBV, HCV; antiumor: Kaposi, CML, multiple myeloma, renal CA; Immunoregulatory: mutiple sclerosis

Front 534

Effects of H1 receptor activation

Back 534

Increased capillary dilation and permeability (hypotension, edema), bronchoconstriction, activation of nociceptive receptors (pain, pruritus)

Front 535

Effects of H2 receptor activation

Back 535

Increased gastric acid secretion (ulcers), positive inotropism

Front 536

H1 antagonist drugs

Back 536

Diphenhydramine, promethazine, chlorpheniramine, meclizine, hydroxyzine, loratadine, fexofenadine

Front 537

Uses of H1 antagonists

Back 537

Hay fever, rhinitis, urticaria, motion sickness and vertigo (meclizine), nausea in pregnancy

Front 538

Adverse effects of H1 antagonists

Back 538

M block and sedation, GI distress, allergic reactions.

Front 539

Substances that increase proton pump activity

Back 539

ACh, gastrin, histamine (H2 receptors)

Front 540

H2 antagonist drugs

Back 540

Cimetidine, ranitidine

Front 541

MOA of H2 antagonists

Back 541

Indirectly decrease proton pump activity (histamine increases proton pump activity)

Front 542

Uses of H2 antagonists

Back 542

Peptic ulcer disease, GERD, Zollinger-Ellison

Front 543

Side effects of H2 antagonists

Back 543

GI distress, dizziness, sommnolence; Cimetidine: inhibits P450 --> increases effects of quinidie, phenytoin, TCAs, warfarin; also decreases androgens --> gynecomastia

Front 544

Omeprazole

Back 544

Direct, irreversible proton pump inhibitor. Uses: PUD, GERD, Zollinger-Ellison, H. pylori. Side effects: decreases bioavailability of weak acids (fluoroquinolones, ketoconazole), inhibits P450

Front 545

Misoprostol

Back 545

PGE1 analog, increases mucus and bicarbonate, decreases HCL secretion. Use: NSAID-induced ulcers.

Front 546

Sulcralfate

Back 546

Polymerizes in stomach to coat ulcers. Increases healing and decreases ulcer recurrence.

Front 547

Drugs that require acid stomach pH to be absorbed

Back 547

Azoles, fluoroquinolones, warfarin

Front 548

Drugs used as antiemetics

Back 548

5HT3 antagonists (ondansetron), DA antagonists (metoclopramide), H1 blockers (diphenhydramine, meclizine), muscarinic blockers (scopolamine)

Front 549

Metabolism of serotonin

Back 549

5HT is metabolized by MAOa to 5-hydroxyinolacetic acid (marker for carcinoid)

Front 550

Buspirone

Back 550

Partial 5HT1a agonist used for generalized anxiety disorder

Front 551

Sumatriptan

Back 551

5HT1d agonist in cerebral vessels, used for migraine

Front 552

Olanzapine

Back 552

Atypical antipsychotic, 5HT2A and D2 receptor antagonist, decreases psychosis. Side effects: weight gain, tardive diskinesia, metabolic syndrome

Front 553

Cyproheptadine

Back 553

5HT2 antagonist used in carcinoid

Front 554

Ondansetron

Back 554

5HT3 antagonist, used as antiemetic in chemotherapy, radiation and post-op. 5HT3 receptors are found in area postrema

Front 555

Ergonovine

Back 555

Uterine muscle contraction after placental delivery

Front 556

Ergotamine

Back 556

Partial 5HT2 and alpha agonist causes vasoconstriction to decrease pulsation in migraine acute attack. Side effect is vasoconstriction (prinzmetal)

Front 557

Prophylaxis of migraine headaches

Back 557

Propranolol, verapamil, amitriptyline, valproic acid

Front 558

PGE2

Back 558

Vasodilation in kidneys, increases renal blood flow, increases gastric mucosal blood flow (mucoprotection), activates osteoclasts, fever, pain, maintains ductus arteriosus

Front 559

Prostacyclin (PGI2)

Back 559

Vasodilation and inhibits platelet aggregation

Front 560

COX1

Back 560

Constitutive enzyme synthesizes GI PGs and TxA2

Front 561

COX2

Back 561

Inducible enzyme synthesizes PGs involved in inflammation, fever and pain.

Front 562

Zileuton

Back 562

Lipoxygenase inhibtor used in asthma

Front 563

Zafirlukast and -lukasts

Back 563

Leukotriene receptor antagonist used in asthma

Front 564

MOA of aspirin

Back 564

Nonselective, irreversible COX inhibitor via acetylation of serine near active site

Front 565

Actions of aspirin

Back 565

Low dose: antiplatelet aggregation (post-MI); moderate dose: analgesia, antipiresis, hyperuricemia; High dose: antiinflammatory, uricosuria

Front 566

Effects of aspirin on acid-base and electrolytes

Back 566

Antiinflammatory doses: uncoupling of ETC --> increases respiration --> decreased pCO2 --> resp. alkalosis --> renal compensation via HCO3 excretion --> compensated respiratory alkalosis. Toxic doses: inhibits respiratory center --> decreases respiration --> resp. acidosis plus ETC uncoupling --> metabolic acidosis, decreases ATP, hyperthermia, hypokalemia

Front 567

Side effects of aspirin

Back 567

Gastritis, ulcers, bleeding, tinnitus, vertigo, decreased hearing, bronchoconstriction, hypersensitivity (asthma, nasal polyps, rhinitis), Reye syndrome, increased bleeding time, renal dysfunction at high doses

Front 568

Aspirin overdose management

Back 568

Gastric lavage, alkalinization of urine (zero-order kinetics at toxic doses)

Front 569

Celecoxib

Back 569

Selective COX-2 inhibitor. Antiinflammatory. Increases PT when used with warfarin, prothrombotic. Cross hypersensitivity with sulfonamides. Potential cardiotoxicity resulted in withdrawal of rofecoxib.

Front 570

Acetaminophen

Back 570

Inhibits COX in CNS only. No antiplatelet activity, not implicated in Reye syndrome, no effects on uric acid, no bronchoconstriction. Metabolized via P450. Hepatotoxic due to reactive metabolite N-acetylbenzoquinonemine, which is inactivated by GSH. Upon GSH depletion, metabolite damages hepatocytes, nausea, vomiting, abdominal pain, centrilobular necrosis. Inducers of P450 enhance toxicity. Management of hepatotoxicity: N-acetylcysteine.

Front 571

Hydroxychloroquine

Back 571

Used for rheumatoid arthritis. Stabilizes lysosomes and decreases chemotaxis. Side effects: GI distress, visual dysfunction, hemolysis in G6PDH deficiency

Front 572

Methotrexate

Back 572

Used for rheumatoid arthritis. Cytotoxic to lymphocytes. Side effects: hematotoxicity, mucositis, crystalluria

Front 573

Sulfasalazine

Back 573

Used for rheumatoid arthritis. Decreases B cell function, possibly inhibits COX. Side effects: GI distress, rash, hemolysis in G6PDH deficiency, drug-induced lupus

Front 574

Glucocorticoids

Back 574

Used in rheumatoid arthritis. Decrease LTs and platelet activating factor (PAF). Side effects: ACTH suppression, Cushingoid state, osteoporosis, GI distress, glaucoma

Front 575

Gold salts

Back 575

Used in rheumatoid arthritis. Decreases lysosomal and macrophage functions. Side effects: dermatitis, hematotoxicity, nephrotoxicity

Front 576

Penicillamine

Back 576

Used in rheumatoid arthritis. Suppresses T cells and circulating rheumatoid factor. Side effects: proteinuria, hematotoxicity, autoimmune disease.

Front 577

Etanercept

Back 577

Used in rheumatoid arthritis. Binds TNF. Side effects: hypersensitivity, injection site reactions, infections

Front 578

Infliximab

Back 578

Used in rheumatoid arthritis. Monoclonal antibody to TNF. Side effects: infusion reactions, infections

Front 579

Anakinra

Back 579

Used in rheumatoid arthritis. IL-1 receptor antagonist. Side effects: infections, injection site reactions

Front 580

Colchicine

Back 580

Used in acute gout. Binds tubulin --> decreases microtubular polymerization ; decreases LTB4 and leukocyte/granulocyte migration. Side effects: diarrhea, GI pain, hematuria, myelosuppression, neuropathy

Front 581

Allopurinol

Back 581

Prodrug converted by xanthine osidase into alloxanthine which inhibits the enzyme --> decreases purine metabolism --> decreases uric acid. Side effects: GI distress, neuropathy, rash, vasculitis, stones.

Front 582

Probenecid

Back 582

Inhibits tubular reabsorption of urate. Interactions: inhibits secretion of acidic drugs (cephalosporins, fluoroquinolones). Side effects: GI distress, rash, nephrotic syndrome, crystallization

Front 583

Glucocorticoid drugs

Back 583

Cortisol, prednisone, triamcinolone, betamethasone, dexamethasone

Front 584

MOA of glucocorticoids

Back 584

Inhibits leukocyte migration, phagocytosis and capillary permeability, decreases PGs, LTs, expression of COX2, PAF and interleukins

Front 585

Uses of glucocorticoids

Back 585

Antiinflammatory and immunosuppressive

Front 586

Side effects of glucocorticoids

Back 586

Suppression of ACTH --> cortical atrophy, shock if abruptly withdrawn, cushingoid syndrome, hyperglycemia (increased gluconeogenesis), osteoporosis with vertebral fractures, gastric acid secretion (ulcers), Na+ and H2O retention with edema and hypertension, hypokalemic alkalosis, hypocalcemia, inhibits bone growth in children, decreases wound healing (infections), increased sorbitol (glaucoma, cataracts), mental dysfunction.

Front 587

Role of beta agonists in asthma

Back 587

Slective β2 agonists: Relief of acute bronchoconstriction (albuterol, metaproterenol, terbutaline) and prophylaxis of nightime attacks (salmeterol). Side effects include anxiety, tremors and CV toxicity

Front 588

Ipratropium

Back 588

Muscarinic blocker causes bronchodilation in acute asthma. Safer than β1 agonists in patients with cardiovascular disease. DOC in bronchospasm induced by β-blockers.

Front 589

Theophylline

Back 589

Inhibits phosphodiesterase --> increases cAMP --> bronchodilation. Also antagonizes adenosine (bronchoconstrictor). Narrow therapeutic index. Side effects: nausea, diarrhea, increases HR, arrhythmias. Increased toxicity with erythromycin, cimetidine and fluoroquinolones.

Front 590

Role of glucocorticoids in asthma

Back 590

Decreases reactivity by decreasing PGs, LTs and Ils; May cause oropharyngeal candidiasis and retarded bone growth with chronic use; low doses prevent desensitization of β receptors.

Front 591

Zafirlukast, mentelukast

Back 591

LTD4 antagonists with slow onset. Used prophylactically for antigen, exercise or drug-induced asthma.

Front 592

Zileuton

Back 592

Selective inhibitor of lypoxygenases --> decreased ILs. Rapid onset, adjunct to steroids.

Front 593

first generation sulfonylureas

Back 593

tolbutamide, chlorpropamide; block K+ channels of β cells --> depolarization --> ↑Ca+ --> release of insulin

Front 594

second generation sulfonylureas

Back 594

glipizide, glyburide, glimepiride; block K+ channels of β cells --> depolarization --> ↑Ca+ --> release of insulin

Front 595

side effects of sulfonylureas

Back 595

hypoglycemia, weight gain, sulfa allergy, hypoglycemia with cimetidine (fisrt generation), disulfram-like (first generation)

Front 596

hypoglycemia

Back 596

paresthesia, lethargy, confusion, sweats, tremors, tachychardia, coma, seizures

Front 597

metformin

Back 597

↓ gluconeogenesis; can be used in patients with no islet function; side effect: lactic acidosis

Front 598

glitazones

Back 598

↑ target cell sensitivity to glucose via PPARs; side effects: weight gain, edema, hepatotoxicity, CV toxicity

Front 599

α-glucosidase inhibitors

Back 599

acarbose, miglitol; no hypoglycemia; inhibit brush border α-glucosidase; side effects: GI disturbance

Front 600

xenatide

Back 600

GLP-1 receptor full agonist --> augments insulin secretion; hypoglycemia when used with sulfonylureas

Front 601

orlistat

Back 601

inhibits pancreatic lipases; used in obesity; side effects: steatorrhea, fat malabsorption

Front 602

sibutramine

Back 602

serotonin/norepinephrine reuptake inhibitor; obesity management; side effects: tachychardia

Front 603

propylthiouracil/methimazole

Back 603

inhibits organification and coupling; side effects: agranulocytosis, aplastic anemia, skin rash

Front 604

anastrozole

Back 604

aromatase inhibitor --> ↓ estrogen synthesis; use: estrogen-dependant postmenopausal breast cancer

Front 605

clomiphene

Back 605

↓ feedback inhibition --> ↑FHS/LH --> ↑ovulation; fertility drugs; adverse effects: multiple births

Front 606

tamoxifen/raloxifene

Back 606

estrogen receptor agonist in bone; estrogen receptor antagonist in breast; partial agonist in endometrium

Front 607

progestins/estrogens/oral contraceptives

Back 607

medroxyprogesterone, norethindrone, desogestrel, estrogens; ↑progesterone --> ↓LH/FSH; side effects: ↑LDL ↓HDL, glucose intolerance, androgenic, antiestrogenic

Front 608

mifepristone

Back 608

progesterone antagonist --> abortifacient

Front 609

methyltestosterone

Back 609

ilicit in athletics, used in male hypogonadism; side effects: premature closure of epiphysis, jaundice, aggression

Front 610

flutamide

Back 610

androgen receptor blocker; used in prostate cancer

Front 611

leuprolide

Back 611

GnRH analog; prostate cancer

Front 612

finasteride

Back 612

5-α-reductase inhibitor --> ↓dihydrotestosterone; BPH, baldness; teratogenic

Front 613

biphosphonates

Back 613

use in Paget, osteoporosis; alendronate, etidronate, pamidronate

Front 614

energy source of RBC

Back 614

anaerobic glycolysis --> lactate (90%) and HMP shunt (10%)

Front 615

antithrombin III

Back 615

activated by heparin; inactivates thrombin, IXa, Xa, XIa

Front 616

tPA

Back 616

tissue plasminogen activator; fibrinolytic; generates plasmin from plasminogen; ↑PT and ↑PTT

Front 617

protein C

Back 617

inactivates factors Va and VIIIa --> anticoagulation

Front 618

factor V leiden

Back 618

mutation causes resistance to activated protein C --> hypercoagulable state

Front 619

warm agglutinin

Back 619

IgG; AIHA seen in SLE, CLL and methyldopa; "Warm weather is GGGreat, Cold ice cream MMM"

Front 620

cold agglutinin

Back 620

IgM; AIHA seen in mycoplasma or infectious mononucleosis infections; "Warm weather is GGGreat, Cold ice cream MMM"

Front 621

heparin

Back 621

activates antithrombin III; measure PTT; use: PE, DVT, AMI, DIC; side effects: bleeding, heparin-induced thrombocytopenia, hypersensitivity

Front 622

protamine sulfate

Back 622

rapid reversal of heparinization; binds negatively-charged heparin

Front 623

antithrombin III

Back 623

serine protease inhibitor binds to activated clotting factors (IXa, Xa, XIa) to inactivate them

Front 624

warfarin antidote

Back 624

vitamin K

Front 625

warfarin

Back 625

epoxide reductase inhibitor decreases vitamin K-dependant factors; slow onset; check PT; SE: skin necrosis; metabolized by P450

Front 626

warfarin-induced skin necrosis

Back 626

protein C and VIIa have the shortest half-lives --> transient inactivation of protein C and extrinsic pathway while intrinsic path is still active and unopposed due to longer half-lives of factors --> hypercoagulable state --> thrombosis

Front 627

platelet activators

Back 627

TxA2, ADP, 5HT --> ↑expression of GpIIb/IIIa receptors

Front 628

platelet deactivators

Back 628

prostacyclin, cAMP, clopidogrel, gpIIb/IIIa blockers (abciximab)

Front 629

clopidogrel

Back 629

blocks platelet ADP receptors --> ↓platelet activation; SE neutropenia

Front 630

abciximab

Back 630

gpIIb/IIIa antagonist --> ↓platelet aggregation

Front 631

methotrexate

Back 631

inhibits dihydrofolate reductase --> ↓dTMP --> ↓DNA synthesis; uses: leukemias, lymphomas, abortion, ectopic pregnancy, rheumatoid arthritis, psoriasis

Front 632

5-FU MOA

Back 632

inhibits thymidylate synthase --> ↓dTMP --> ↓DNA synthesis; uses: colon cancer and solid tumors, basal cell carcinoma

Front 633

6-MP

Back 633

activated by HGPRTase --> blocks purine synthesis; uses: leukemias, lymphomas (except CLL or Hodgkin); metabolized by xanthine oxidase (↑toxicity with allopurinol); hepatotoxic

Front 634

cytarabine (ara-C)

Back 634

DNA polymerase inhibitor; use: AML

Front 635

cyclophosphamide

Back 635

alkylating agent ---> attacks guanine N7 --> denatures DNA; uses: non-Hodgkin lymphoma, ovarian and breast cancer, neuroblastoma

Front 636

cisplatin

Back 636

alkylating agent cross-links DNA strands; uses testicular, bladder, ovary and lung carcinomas; nephrotoxic

Front 637

doxorubicin

Back 637

intercalates DNA inhibits topoisomerase II; uses: Hodgkin's, myelomas, solid tumors; dilated cardiomyopathy

Front 638

actinomycin D (dactinomycin)

Back 638

intercalates DNA inhibits topoisomerase; uses: Wilm's tumor, Ewing's sarcoma. Rhabdomyosarcoma

Front 639

bleomycin

Back 639

formation of free radicals cause breaks in DNA strands; uses: testicular cancer, lymphomas; pulmonary fibrosis is side effect

Front 640

hydroxyurea

Back 640

inhibits ribonucleotidde reductase --> decreases DNA synthesis; uses: melanoma, CML, sickle cell disease

Front 641

tamoxifen

Back 641

estrogen receptor antagonist in breast, agonist in bone; use: breast cancer

Front 642

vincristine

Back 642

bind tubulin during M phase blocking polymerization of microtubules and formation of mitotic spindle; uses: lymphoma, Wilm's tumor, choriocarcinoma; neurotoxic

Front 643

cyclosporine

Back 643

binds cyclophillin --> ↓calcineurin --> ↓IL-2, IL-3, IFN-gamma; use in organ transplants

Front 644

tacrolimus

Back 644

inhibits calcineurin --> ↓IL-2, IL-3, IFN-gamma; use in organ transplants

Front 645

infliximab

Back 645

monoclonal Ig against TNF; use in rheumatoid arthritis and Crohn's

Front 646

trastuzumab

Back 646

erb-B2 antagonist; use in breast cancer

Front 647

dacliximab

Back 647

blocks IL-2 receptors; use in kidney transplants

Front 648

etanercept

Back 648

Recombinant TNF receptor binds TNF; uses: rheumatoid arthritis, psoriasis, ankylosing spondylitis

Front 649

first generation H1 blockers

Back 649

reversible; diphenhydramine, chlorpheniramine; uses: allergy, motion sickness, sleep aid; SE: sedation, antimuscarinic and anti-alpha adrenergic effect

Front 650

2nd generation H1 blockers

Back 650

loratadine, fexofenadine, desloratadine, cetirizine; use: allergy; less sedation

Front 651

salmeterol

Back 651

beta2 agonist; long-acting; tremor and arrhythmias

Front 652

albuterol

Back 652

beta2 agonist; use in acute asthma attack

Front 653

theophylline

Back 653

inhibits phosphodiesterase and increases cAMP --> bronchodilation; cardiotoxic, neurotoxic, narrow therapeutic index; metabolized by P450

Front 654

ipratropium

Back 654

antimuscarinic used in asthma and COPD

Front 655

cromolyn

Back 655

stabilizes mast cell membrane; not effective in acute asthma attack just prophylaxis

Front 656

zileuton

Back 656

5-lipoxygenase inhibitor --> decreases leukotrienes

Front 657

lukasts

Back 657

leukotriene receptor antagonists; aspirin-induced asthma

Front 658

guainfenesin

Back 658

expectorant; doesn’t suppress cough reflex

Front 659

colchicine

Back 659

use in acute gout; depolymerizes tubulin microtubules, prevents leukocyte chemotaxis and degranulation; SE: GI disturbances

Front 660

probenecid

Back 660

use in chronic gout; inhibits reabsorption of uric acid in PCT

Front 661

allopurinol

Back 661

use in chronic gout and leukemia; inhibits xanthine oxidase and decreases uric acid.