converted Flashcards
(500 cards)
1
Q
What is pharmacokinetics?
A
Deals with what the body does to the drug: absorption, distribution, sites of action, tissue storage, metabolism and excretion.
2
Q
What factors are involved in drug permeation/absorption?
A
Solubility, concentration gradient, surface area, vascularity, ionization.
3
Q
In what form can drugs cross cell membranes?
A
Non-ionized form (lipid soluble).
4
Q
In what form are drugs excreted?
A
Ionized form (water soluble) are better renally excreted
5
Q
What factors affect renal clearance of drugs?
A
The drug must be in free form, ionized or nonionized. Only nonionized drug can be actively secreted or reabsorbed.
6
Q
What effect does acidification of urine have on drugs?
A
Increases ionized fraction of weak bases and increases their renal elimination. NH4Cl, vitamin C, cranberry juice.
7
Q
What effect does alkalinization of urine have on drugs?
A
Increases ionized fraction of weak acids and increases their renal elimination. NaHCO3, acetazolamide.
8
Q
Urine alkalinization agents
A
NaHCO3, acetazolamide
9
Q
Urine acidification agents
A
NH4Cl, vitamin C, cranberry juice
10
Q
What is Cmax?
A
Maximal drug level obtained with the dose
11
Q
What is Tmax?
A
Time at which Cmax occurs
12
Q
What is the lag time?
A
Time from administration to appearance in blood
13
Q
What is onset of activity?
A
Time from administration to blood level reaching minimal effective concentraion
14
Q
What is duration of action?
A
Time that the plasma concentration remains above minimial effective concentration
15
Q
What is time to peak?
A
Time from administration to Cmax.
16
Q
What is bioavailability?
A
Is the fraction of a dose that reaches the systemic circulation after 1st pass metabolism
17
Q
What is the first-pass effect?
A
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.
18
Q
What is bioequivalence and what factors are involved?
A
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.
19
Q
How are rate of absorption, Tmax and Cmax related?
A
The faster the rate of absorption the smaller Tmax and larger Cmax. Tmax and Cmax are rate dependant.
20
Q
What is distribution?
A
Is the process by which a drug reaches the target tissues from systemic circulation.
21
Q
What factors affect distribution of a drug?
A
Protein-binding capacity and competition between drugs for protein-binding sites, barriers such as placenta or brain.
22
Q
What is volume of distribution?
A
Correlates dose given with the plasma level at time X. Vd=Dose/C0. C0=[plasma] at zero time.
23
Q
What is the significance of the volume of distribution?
A
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.
24
Q
Relationship between plasma concentration and volume of distribution
A
Inversely proportional. The higher the plasma concetration, the lower the volume of distribution
25
Relationship between dose and plasma concentration
Directly proportional.
26
What is redistribution?
Is when a lipid-soluble drug gets temporarily stored in fat tissue before being eliminated.
27
What is the significance of the redistribution rate?
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."
28
What is biotransformation?
Is the conversion of a drug to a more water-soluble form to be excreted. A metabolite may or may not have pharmacologic action.
29
What is phase I biotransformation?
Modification of the drug via oxidation, reduction or hydrolysis.
30
What is microsomal metabolism?
Cytochrome P450 isoenzymes in the SER require NADPH for oxidation and reduction of drugs.
31
General inducers of the P450 enzymes
Anticonvulsants (barbiturates, phenytoin, carbamazepine), antibiotics (rifampin), chronic alcohol, glucocorticoids.
32
General inhibitors of the P450 enzymes
Proton pump inhibitors (cimetidine, omeprazole), antibiotics (chloramphenicol, macrolides, ritonavir, ketoconazole), acute alcohol, grapefruit juice, isoniazid
33
What is nonmicrosomal metabolism?
Hydrolysis reactions by esterases and amidases; MAO; alcohol dehydrogenases.
34
What is phase II biotransformation?
Modification of the drug by transferases via glucoronidation, acetylation, sulfation, gluthathione conjugation.
35
What are the major modes of drug elimination?
Biotransformation to inactive metabolites, excretion via the kidney, bile ducts, lungs and sweat.
36
What is the elimination half-life (t1/2)?
t1/2 is the time to eliminate 50% of a given amount of drug.
37
What is zero-order elimination rate kinetics?
A constant amount is eliminated per unit time. Independent of plasma concentration, variable t1/2.
38
What is first-order elimination rate kinetics?
A constant percentage of the drug is eliminated per unit time. t1/2 is constant, directly porportional to plasma levels.
39
Rate of elimination
Equals to GFR + active secretion - reabsorption
40
Clearance
Equals to free fraction * GFR or 0.7 * Vd/half life
41
What is steady state and when is it achieved?
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.
42
How does rate of infusion affect steady state and plasma levels at steady state?
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.
43
Formula: volume of distribution
Vd = D/C0
44
Formula: half life
t1/2 = 0.7/k or t1/2 = 0.7 x Vd/Cl
45
Formula: clearance
Cl = k x Vd
46
Formula: infusion rate
k0 = Cl x Css
47
Formula: loading dose
LD = Vd x Css
48
Formula: Maintenance dose
MD = Cl x Css x t
49
Relationship between half-life and elimination
Inversely proportional
50
Relationship between half-life and clearance
Inversely proportional
51
Relationship between half-life and volume of distribution
Directly proportional.
52
Relationship between clearance and volume of distribution
Inversely proportional
53
Relationship between infusion rate and clearance
Directly proportional.
54
Relationship between infusion rate and steady state concentration
Directly proportional.
55
Relationship between steady state concentration and clearance
Inversely proportional.
56
What is pharmacodynamics?
The effects of drugs in the body and drug receptor binding.
57
Affinity
Ability of the drug to bind its receptor. The closer to the y axis, the more affinity.
58
Potency
The quanity of drug required to produce a desired effect. The closer to the y axis, the more potent.
59
Efficacy
The maximal effect an agonist can achieve at the highest practical concentration. The taller the curve, the more efficacy.
60
What is meant by the duality" of partial agonists?"
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.
61
Effect of a competitive antagonist
Parallel shift of the dose-response curve to the right; appears to increase potency; also increases Km; reversed by increasing agonist dose
62
Effect of a noncompetitive antagonist
Non-parallel shift to the right; appears to decrease efficacy of agonist; partially reversed by increasing agonist dose; decreases Vmax
63
Physiologic antagonism
Two agonists with opposing actions antagonize each other: vasoconstrictor Vs. vasodilator
64
Chemical antagonism
Agonist-chemical complex lowers effect of agonist
65
Potentiation
Parallel shift of the curve to the left; appears to increase potency of agonist.
66
TD50
Dose that causes toxicity in 50% of the population
67
ED50
Effective dose in 50% of the population
68
Therapeutic index
TD50/ED50; gives a measure of the relative safety of a drug
69
ANS receptors and their second messenger systems
qiss qiq siq sqs". ?1, ?2, ?1, ?2, M1, M2, M3, D1, D2, H1, H2, V1, V2"
70
Substances with intracellular receptors
Glucocorticoids, vitamin D, thyroid hormones, gonadal steroids
71
Substances with ion channel receptors
Nicotine, choline esters (ACh), ganglion blockers, skeletal muscle relaxants.
72
Substances that interact with Gs receptors
Catecholamines, dopamine, glucagon, histamine, prostacyclin. qiss qiq siq sqs
73
Substances that interact with Gi receptors
Epinephrine, norepinephrine, Ach, dopamine. qiss qiq siq sqs""
74
Substances that interact with Gq receptors
Ach, norepinephrine, angiotensin II
75
Phase 1 clinical testing
Dose-response studies on small group of volunteers without disease. Includes pharmacokinetics characterization.
76
Phase 2 clinical testing
Dose-response studies on 100 patients in comparison with placebo and a positive control. Single or double blind.
77
Phase 3 clinical testing
Dose-response studies on 1000 patients in comparison to placebo and positive control. Usually double blind
78
Phase 4 clinical testing
New drug application, marketing approval and post-marketing surveillance.
79
Zero-order kinetics curve
Linear kinetics or exponential kinetics on log graph
80
First-order kinetics curve
Exponential kinetics or linear kinetics on log graph
81
Dose-response curve
Bell curve. Shows absoption phase, distribution, metabolism and elimination phases.
82
Neurotransmitter of preganglionic neurons
Acetylcholine
83
Neurotransmitters of postganglionic neurons
Acetylcholine, norepinephrine, epinephrine, dopamine
84
Mechanism of miosis
Sphincter muscle of the pupilla has M3 receptors. Muscarinic agonists causes contraction and miosis. Muscarinic antagonists cause relaxation and mydriasis with cycloplegia.
85
Mechanism of mydriasis
Dilator muscle of the pupilla has ?1 receptors. ?1 agonists cause contraction and mydriasis without cycloplegia. Also muscarinic blockers.
86
Mechanism of accomodation
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.
87
Muscarinic receptors of the eye
Sphincter of the pupilla and cilliary muscles --> M3 --> miosis and accomodation
88
Muscarinic receptors of the heart
SA node and AV node --> M2 --> decrease heart rate, decrease conduction velocity
89
Muscarinic receptors of the lungs
Bronchioles and glands --> M3 --> bronchospasm and gland secretion
90
Muscarinic receptors in the GI tract
Stomach, intestines --> M3 --> increased motility, cramps, diarrhea; GI glands --> M1 --> gland secretion
91
Muscarinic receptors of the bladder
M3 --> contraction of detrusor, relaxation of the trigone/sphincter --> urination and urinary incontinence
92
Muscarinic receptors of sphincters (GI, GU)
M3 --> relaxation, excep LES which contracts
93
Muscarinic receptors of glands
M3 --> gland secretion --> sweat, salivation, lacrimation
94
Muscarinic receptors in endothelium
M3 --> cause vasodilation via release of NO
95
Location of M3 receptros
Eye (sphincter and cilliary), smooth muscle of bronchioles, GU and GI, glands except GI, sphicters, endothelium.
96
Net effects of M3 receptor activation
Miosis, accomodation, salivation, lacrimation, sweating, bronchoconstriction, increased GI motility, relaxation of sphincters (except LES), release of NO (indirect vasodilation).
97
Net effects of M2 receptor activation
Decreased heart rate, decreased conduction velocity of AV node.
98
Net effects of M1 receptor activation
Gland secretions of the GI tract.
99
Receptors in the adrenal medulla
Nn --> secretion of epinephrine and norepinephrine
100
Receptors at the neuromuscular junction
Nm --> muscle depolarization and contraction
101
Receptors in autonomic ganglia
Nn --> net effects depend on PANS/SANS dominance
102
Muscarinic receptor mechanisms and second messenger systems
M1, M3 --> Gq; M2 --> Gi; Nn, Nm --> Na/K channels
103
Hemicholinium
Inhibits reuptake of choline decreasing Ach synthesis (anticholinergic)
104
Botulinum toxin
Blocks release of ACh. Used in blepharospasm, strabismus, dystonia, cosmetics.
105
Direct muscarinic agonists
ACh, bethanecol, methacholine, pilocarpine
106
Properties and use of acethylcholine
Acts on muscarinic and nicotinic receptors. Strongly hydrolised by AChE. No clinical use.
107
Properties and use of bethanecol
Acts on muscarinic receptors. No AChE hydrolisis. Rx.: paralytic ileus, urinary retention
108
Properties and use of methacholine
More muscarinic than nicotinic actions. Weakly hydrolised by AChE. Used to Dx. Bronchial hyperreactivity.
109
Properties and use of pilocarpine
Acts on muscarinic receptors. Not hydrolyzed by AChE. Used for Rx. of glaucoma and xerostomia.
110
Rx. of paralytic ileus
Bethanecol, neostigmine, pyridostigmine
111
Rx. of urinary retention
Bethanecol, neostigmine, pyridostigmine
112
Dx of bronchial hyperreactivity
Methacholine
113
Rx of glaucoma and xerostomia
Pilocarpine, physostigmine
114
Acetylcholinesterase inhibitors
Edrophonium, physostigmine, neostigmine, pyridostigmine, donepezil, tacrine, organophosphates (irreversible)
115
Properties and use of edrophonium
Short acting AChE inhibitor. Dx myasthenia gravis
116
Properties and use of physostigmine
Tertiary amine AChE inhibitor. Rx glaucoma, antidote in atropine overdose
117
Properties and use of neostigmine and pyridostigmine
Cuaternary amines AChE inhibitors. Rx paralytic ileus, urinary retention, myasthenia, reversal of nondepolarizing NM blockers
118
Properties and use of donepezil and tacrine
Lipid-soluble AChE inhibitor enters CNS. Rx Alzheimer disease.
119
Properties and use of organophosphates
Lipid soluble irreversible AChE inhibitors. Rx glaucoma. Also insecticides parathion, malathion and nerve gas sarin.
120
Dx and Rx of myasthenia gravis
Edrophonium (Dx), neostigmine, pyridostigmine (Rx)
121
Rx Alzheimer disease
Donepezil, tacrine
122
Signs and symptoms of organophosphate intoxication
Dumbbelss" Diarrhea, urination, miosis, bradycardia, bronchoconstriction, excitation, lacrimation, salivation, sweating."
123
Rx of organophosphate intoxication
Atropine + pralidoxime for regeneration of non-aged AChE.
124
MOA pralidoxime
Removes organophosphate group from AChE thus regenerating it. Aged AChE that have just a phosphate attached cannot be regenerated.
125
Muscarinic blockers
Atropine, tropicamide, ipratropium, scopolamine, benztropine
126
Effects of muscarinic blockers
Decreased salivary, bronchiolar and sweat secretions, mydriasis and cycloplegia, hyperthermia, tachychardia, sedation, urinary retention, constipation, hallucinations
127
Rx of muscarinic blocker intoxication
Physostigmine
128
Uses of atropine
Anesthesia, management of organophosphate toxicity
129
Uses of propicamide
Opthalmologic mydriasis
130
Uses of ipratropium
Inhaled in asthma and COPD. Doesnt enter CNS.
131
Uses of scopolamine
Motion sickness, sedation, short-term memory block.
132
Uses of benztropine
Lipid-soluble, enters CNS. Used in parkinsonism and acute extrapyramidal symptoms of antipsychotics.
133
Effects of ganglion blockers
Reduce the predominant autonomic tone. PANS is dominant in heart, pupil, GI, GU and sphincters. SANS is dominant in blood vessels and sweat glands.
134
Synthesis of catecholamines
Tyrosine + tyrosine hydroxylase --> dopa + dopa decarboxylase --> dopamine + dopamine ? hydroxylase --> norepinephrine + SAM + methyltransferase --> epinephrine
135
MAO
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.
136
COMT
Located in postsynaptic membrane, degrades catecholamines by methylations (requires SAM).
137
Distribution of alpha 1 receptors
Pupil dilator muscle, arterioles of skin and viscera, veins, bladder trigone and sphincter, vas deferens, liver, kidney
138
Distribution of alpha 2 receptors
Presynaptic terminal, platelets, pancreas
139
Distribution of Beta 1 receptors
Heart SA node, AV node, atrial and ventricular muscle, His-Purkinje, kidney
140
Distribution of Beta 2 receptors
All blood vessels, uterus, bronchioles, skeletal muscle, liver, pancreas
141
Distribution of D1 receptors
Renal, mesenteric, coronary vasculature
142
alpha 1 effects
Mydriasis, increases TPR, diastolic pressure, afterload, venous return, preload, reflex bradycardia, urinary retention, ejaculation, glycogenolysis, decreases renin release
143
alpha 2 effects
Decreases NE synthesis and release, promotes platelet aggregation, decreases insulin secretion
144
beta 1 effects
Increases HR, conduction velocity, contractility, CO, oxygen consumption and renin release
145
beta 2 effects
Vasodilation, decreases TPR, diastolic pressure and afterload, uterine relaxation, bronchodilation, increases glycogenolysis in liver and muscle, increases insulin secretion
146
D1 effects
Vasodilation of renal, mesenteric, coronary vasculatures, increases RBF, GFR
147
alpha 1 agonists
Phenylephrine, methoxamine
148
Uses of phenylephrine
Nasal decongestant and opthalmologic mydriasis without cycloplegia
149
alpha 2 agonists
Clonidine, methyldopa
150
Uses of clonidine
Mild to moderate hypertension
151
Uses of methyldopa
Mild to moderate hypertension
152
Effects of beta agonists on CV system
b1: increase HR, CO, pulse pressure; b2: decrease TPR, BP.
153
beta agonists
Isopreterenol, dobutamine
154
beta2 selective agonists
Salmeterol, albuterol, terbutaline
155
Uses of beta 2 selective agonists
Asthma and ritodrine in premature labor
156
Uses of isoproterenol
b1=b2: used in bronchospasms, heart blocks and bradyarrhythmias. Side effects: flushing, angina, arrhythmias
157
Uses of dobutamine
b1 > b2: congestive heart failure
158
Effects of norepinephrine on CV system
Acts on a1 (increases TPR, BP), a2 and b1 (increases HR, CO, pulse pressure). Potential reflex bradycardia.
159
Effects of low dose of epinephrine on CV and respiratory systems
Acts on b1 (increases HR, SV, CO, pulse pressure), b2 (decreases TPR, BP, bronchodilation)
160
Effects of medium dose epinephrine on CV and respiratory systems
Acts on b1 (increases HR, SV, CO, pulse pressure), b2 (decreases TPR, BP, bronchodilation), a1 (increases TPR, BP)
161
Effects of high dose epinephrine on CV and respiratory systems
Acts on a1 (increases TPR, BP), b1 (increases HR, CO, pulse pressure), b2 (decreases TPR, BP, bronchodilation). Potential reflex bradycardia.
162
Effect of adding a1 blocker to epinephrine
Reverses hypertension to hypotension. Use this to differentiate from norepinephrine.
163
Uses of epinephrine
Cardiac arrest, adjunct to local anesthetic, hypotension, anaphylaxis, asthma
164
Uses of norepinephrine
Cardiac arrest, adjunct to local anesthetic, hypotension
165
Indirect acting adrenergic agonists
Releasers of catecolamines: Tyramine, amphetamines (methylphenidate), ephedrine. Reuptake inhibitors: cocaine, tricyclic antidepressants. MAO-A inhibitors interaction can cause hypertensive crisis.
166
Effects of alpha blockers
Decrease TPR and BP. May cause reflex tachychardia and salt/water retention.
167
Uses of alpha blockers
Hypertension, pheochromocytoma, BPH (selective ?1 blocker)
168
Nonselective alpha blockers
Phentolamine (reversible), phenoxybenzamine (irreversible)
169
Selective alpha 1 blockers
Prazosin, doxazosin, terazosin, tamsulosin
170
Selective alpha 2 blockers
Yohimbe (used in hypotension and impotence), mirtazapine (depression)
171
Effects of beta 1 blockers
Decresed HR, SV, CO, renin, aqueous humor production
172
Side effects of beta 2 blockers
Bronchospasm in asthmatics, vasospasm, decreased glycogenolysis, gluneogenesis, increased LDLs, TGs
173
Selective beta 1 blockers
Acebutolol, atenolol, metroprolol
174
Nonselective beta blockers
Pindolol, propranolol, timolol
175
beta blockers that raise blood lipids
Atenolol (beta 1), metroprolol (beta 1), propranolol, timolol
176
beta blockers that cause the most sedation
Propranolol, timolol
177
beta blockers with intrinsic sympathomimetic activity
Act as partial agonists, less bradycardia, slight vasodilation, bronchodilation, minimal change in lipids: acebutolol, pindolol
178
General uses of beta blockers
Angina, hypertension, post-MI
179
beta blockers used as antiarrhythmics
Propranolol, acebutolol, esmolol
180
Specific uses of timolol
Glaucoma
181
Specific uses of propranolol
Migraine, thyrotoxicosis, performance anxiety, essential tremor
182
Combined alpha 1 and beta blockers
Labetalol, carvedilol. Used in CHF.
183
Combined K channel and beta blockers
Sotalol. Class III antiarrhythmic.
184
Phase 0 of the cardiac action potential
Fast Na channels open causing depolarization. Class I antiarrhythmics slow or block phase 0.
185
Phase 1 of the cardiac action potential
Overshoot. Na channels inactivated, transient outward K currents.
186
Phase 2 of the cardiac action potential
Plateau phase. Slow influx of Ca and late-appearing outward K current.
187
Phase 3 of the cardiac action potential
Repolarization. Delayed rectifier K outward current. Class III antiarrhythmics slow repolarization.
188
Phase 4 of the cardiac action potential
Resting membrane potential. Maintained by the Na/K ATPase pump.
189
Phase 0 of the pacemaker action potential
Depolarization depends on Ca channels. Class IV antiarrhythmics slow or block this phase.
190
Phase 3 of the pacemaker action potential
Repolarization. Ca currents are opposed by outward delayed K currents.
191
Phase 4 of the pacemaker action potential
Spontaneous depolarization caused by Na funny current, Ca inward curents and K outward currents. Class II and IV antiarrhythmics slow this phase.
192
Effective refractory period
No stimulus can elicit a response. Lasts into phase 3 due to Na channel inactivation. K channel blockers prolong ERP.
193
Relative refractory period
Only a strong stimulus can elicit a response. Associated with arrhythmias.
194
Innervation of the SA and AV nodes
Parasympathetic via M2 receptors. Sympathetic via ?1 receptors.
195
What effect does sympathetic stimulation have on SA and AV nodes
?1 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.
196
What effect does parasympathetic stimulation have on SA and AV nodes
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.
197
Class 1A antiarrhythmics
Quinidine, procainamide
198
1A antiarrhythmics MOA
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).
199
Quinidine pharmacokinetics
Orally effective weak base enhanced absorption and toxicity by antacids. In atrial fibrilation needs intitial digitalization.
200
Quinidine pharmacodynamics
Class 1A effects plus muscarinic receptor blockade (increase HR and AV conduction); vasodilation via alpha block with reflex tachychardia.
201
Quinidine adverse effects
Cinchonism (GI, tinnitus, ocular dysfunction, CNS excitation), hypotension, QRS and QT prolongation associated with syncope torsades
202
Quinidine drug interactions
Hyperkalemia enhances effects and vice versa. Displaces digoxin from tissue binding sites, enhancing toxicity.
203
Procainamide pharmacokinetics
Phase 2 acetylation by N-acetyltransferase to N-acetylprocainamide (NAPA) active metabolite. Subject to genotypic variation/slow acetylators/drug-induced lupus.
204
Procainamide adverse effects
SLE-like syndrome (30%) in slow acetylators. Thrombocytopenia, agranulocytosis, torsades.
205
Class 1B antiarrhythmics
Lidocaine, mexiletine, tocainide
206
Class 1B antiarrhythmics MOA
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)
207
Uses and side effects of lidocaine
Post MI, open heart surgery, digoxin toxicity. Seizures, least cardiotoxic antiarrhythmic. IV because of first-pass metabolism.
208
Class 1C antiarrhythmics MOA
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)
209
Flecainide
Class 1C antiarrhythmic. Limited use because of proarrhythmogenic effects. Increased risk of sudden death post-MI.
210
Effects of class 1A antiarrhythmics on action potential
Decrease slope of phase 0; increase APD and ERP.
211
Effects of class 1B antiarrhythmics on action potential
Decrease length of phase 2 (plateau) with no change in phase 0 or 3 which decreases APD.
212
Effects of class 1C antiarrhythmics on action potential
Decrease slope of phase 0 and decrease length of phase 2 which cancels out effect on APD.
213
Class II antiarrhythmics MOA
Block ?1 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)
214
Class II antiarrhythmics
Propranolol (nonselective), acebutolol, esmolol (beta 1 selective)
215
Uses of class II antiarrhythmics
Prophylaxis post MI, supraventricular tachyarrhythmias
216
Properties of propranolol
Nonselective beta blocker, no sympathicomimetic activity, produces sedation and increases blood lipids.
217
Properties of acebutolol
Selective beta 1 blocker with intrinsic sympathicomimetic activity, no sedation, no increase in blood lipids.
218
Class III antiarrhythmics MOA
Decreased delayed rectifier K currents which slows phase 3 and increases APD and ERP.
219
Class III antiarrhythmics
Amiodarone, sotalol (combined K channel and ?1 blocker)
220
Amiodarone pharmacokinetics
t1/2 > 80 days, large Vd.
221
Amiodarone pharmacodynamics
Blocks K channels in many tissues. Mimics class I, II and IV antiarrhythmics. Increases APD and ERP.
222
Amiodarone side effects
Large Vd affects many tissues: pulmonary fibrosis, blue pigmentation of skin, phototoxicity, corneal deposits, hepatic necrosis, thyroid dysfunction.
223
Sotalol MOA
Blocks K channels decreasing phase 3 of AP (increases APD); blocks beta 1 which decreases phase 4 and phase 3 slopes in pacemaker cells (which decreases HR and conduction)
224
Class IV antiarrhythmics MOA
Block slow Ca channels in pacemaker cells which decreases phase 4 and 0 slopes, which decreases HR.
225
Class IV antiarrhythmics
Verapamil, diltiazem
226
Uses of verapamil
Supraventricular tachyarhythmias
227
Verapamil side effects
Constipation, dizziness, flushing, hypotension, AV block
228
Verapamil drug interactions
Additive AV block with beta -blockers and digoxin; displaces digoxin from tissue-binding sites.
229
Properties of adenosine
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.
230
Drugs that cause torsades
Class IA (quinidine) and III (sotalol) antiarrhythmics, antipsychotics (ziprasidone), tricylic antidepressants.
231
Drugs that displace digoxin
Verapamil, quinidine
232
Drugs that cause drug-induced lupus
Hydralazine > procainamide > isoniazid (slow acetylators)
233
Effects of hyperkalemia on heart
Decreases K efflux reducing repolarization. Membrane is depolarized. Can cause heart stop on systole. Peaked T waves.
234
Effects of hypokalemia on heart
Increases K conductance and hyperpolarization. Heart stops of dyastole.
235
What is the strategy to treat hypertension
Decrease TPR (alpha 2 agonists, alpha 1 blockers), decrease CO (beta -blockers), decrease body fluids (diuretics), vasodilation (hydralazine, nitirites, ACEIs, ARBs).
236
alpha 2 agonists
Clonidine, methyldopa
237
Uses and side effects of clonidine
Uses: Mild to moderate hypertension, opiate withdrawal; Side effects: CNS depression, edema.
238
Uses and side effects of methyldopa
Uses: mild to moderate hypertension, hypertension management in pregnancy; Side effects: positive Coombs test, CNS depression, edema.
239
Reserpine MOA and side effects
Destroys catecolamine vesicles leading to decrease in CNS and peripheral levels. Side effects: depression, edema.
240
Guanethidine MOA and side effects
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
241
alpha 1 blockers
Prazosin, doxazosin, terazosin
242
alpha 1 blockers MOA
Decrease arteriolar and venous resistance. Decrease prostate and urinary sphincter tone.
243
alpha 1 blockers side effects
First dose syncope, orthostatic hypotension, urinary incontincence
244
Beta-blockers cautions in use
Asthma, vasospastic disorders (atherosclerosis, Raynauds), diabetics (hypoglycemia normally induces tachychardia which is perceived by patient, but ?-blockers prevent tachychardia warning signs).
245
Properties of hydralazine
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.
246
Drugs metabolized by acetylation
Hydralazine > procainamide > isoniazid (slow acetylators)
247
Nitroprusside
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.
248
Direct vasodilators
Hydralazine (NO), nitroprusside (NO), minoxidil (opens K channels --> hyperpolarization --> vasodilation)
249
Minoxidil
Opens K channels in smooth muscle --> hyperpolarization --> vasodilation. Use in severe hypertension and alopecia. Side effects: hypertrichosis, edema, reflex tachychardia.
250
Diazoxide
Opens K channels in smooth muscle --> hyperpolarization --> vasodilation. Use in hypertensive emergencies. Side effects: hyperglycemia (decreases insulin release)
251
Arteriolar vasodilators
Ca channel blockers (nifedipine), hydralazine, K channel openers (minoxidil)
252
Venular vasodilation
Nitrates (nitroprusside)
253
Orthostatic hypotension
Due to venular dilation not arteriolar. Usually from ?1 blockers.
254
Calcium channel blockers MOA
Block L-type Ca channels in heart and blood vessels smooth muscle --> decrease intracellular Ca --> decreased CO and TPR.
255
Calcium channel blockers
Verapamil, diltiazem, nifedipines and derivatives.
256
Uses of calcium channel blockers
Hypertension, angina, antiarrhythmics (verapamil, diltiazem)
257
Side effects of calcium channel blockers
Reflex tachychardia (nifedipine and derivatives), gingival hyperplasia (nifedipine and derivatives), constipation (verapamil)
258
ACE inhibitors MOA
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
259
Angiotensin receptor blockers MOA
Block angiotensin receptors --> decreased aldosterone secretion and vasodilation. Losartan and other -sartans
260
Uses of ACEIs and ARBs
Mild to moderate hypertension, protective of diabetic neprhopathy, CHF
261
ACEIs side effects
Dry cough (no degradation of bradykinin), hyperkalemia (no aldosterone), acute renal failure in renal artery stenosis (angiotensin maintains RBF), angioedema, rash
262
ARBs side effects
Hyperkalemia (no aldosterone), acute renal failure in renal artery stenosis (angiotensin maintains RBF), angioedema
263
Treatment strategy for heart failure
Decrease preload (diuretics, ACEIs, ARBs, venodilators), decrease afterload (ACEIs, ARBs, arteriodilators), increase contractility (digoxin, beta agonists), decrease cardiac remodeling (ACEIs, ARBs, spironolactone)
264
What drugs are beneficial in CHF and why?
ACEIs, ARBs and spironolactone prevent cardiac remodeling
265
Digoxin MOA
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.
266
Digoxin pharmacokinetics
Long t1/2 needs loading dose; renal clearance; large Vd and displacement by verapamil and quinidine
267
Uses of digoxin
CHF and supraventricular tachychardias except Wolff-Parkinson-White syndrome
268
Wolff-Parkinson-White syndrome
Prexcitation of the ventricles due to accesory conduction bundle of Kent. Block accessory path with class IA or III antiarrhythmics, avoid ?-blockers, CCBs and adenosine
269
Digoxin side effects
Anorexia, nausea, ECG changes, disorientation, visual halos, cardiac arrhythmias
270
Digoxin toxicity
Can cause cardiac arrhythmias. Use Fab antibodies against digoxin and class IB antiarrhythmics.
271
Digoxin drug interactions
Quinidine, verapamil displace digoxin; sympathicomimetics; diuretics
272
Phosphodiesterase inhibitors MOA
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
273
Antianginal drugs
Nitroglycerin, isosorbide, CCBs (nifedipine), ?-blockers and carvedilol
274
Nitrates MOA
Pro drugs of nitric oxide; NO activates smooth muscle guanylyl cyclase --> increase cGMP --> relaxation --> venodilation --> decrease preload --> decrease cardiac work and oxygen requirements
275
Nitroglycerin side effects
flushing, headache, orthostatic hypotension, reflex tachychardia, methhemoglobinemia.
276
Nitroglycerin interactions
Cardiovascular toxicity with sildenafil
277
Sildenafil MOA
Inhibits PDE5 in blood vessels of corpora cavernosa --> increase cGMP --> vasodilation --> erection
278
Uses and side effects of manitol
Decreases IOP in glaucoma, decreases intracerebral pressure in cerebral edema. Side effects: hypovolemia
279
Carbonic anhydrase inhibitors drugs
Acetazolamide, dorzolamide
280
Azetazolamide MOA
Decreases H+ formation in PCT --> decrease Na/H+ antiport --> increases Na and HCO3 in lumen --> diuresis
281
Uses of azetazolamide and CA inhibitors
Glaucoma, acute moutain sickness (acidosis stimulates ventilation), metabolic alkalosis
282
Azetazolamide and CA inhibitors side effects
Bicarbonaturia/acidosis, hypokalemia (increases Na load dowstream), hyperchloremia, paresthesia, renal stones (alkalinizes urine), sulfa hypersensitivity
283
Loop diuretic drugs
Ethacrynic acid, furosemide
284
Loop diuretics MOA
Inhibit Na/K/2Cl cotransporter --> decrease intracell K+ --> decrease positive potential --> decrease reabsorption of Ca, Mg --> increased diuresis
285
Uses of loop diuretics
Acute pulmonary edema, CHF, hypertension, refractory edema, acute renal failure, anion overdose, hypercalcemia
286
Loop diuretic side effects
Sulfonamide hypersensitivity (except ethacrynic acid), hypokalemia, alkalosis, hypocalcemia, hypomagnasemia, hyperuricemia, ototoxicity (ethacrynic acid > furosemide)
287
Loop diuretics drug interactions
Enhanced ototoxicity with aminoglycosides; decrease clearance of lithium, increase digoxin toxicity
288
Thiazide drugs
Hydrochlorothiazide, indapamide
289
Thiazides MOA
Inhibit Na/Cl transporter in DCT --> increases Na and Cl in the lumen --> increase diuresis
290
Uses of thiazides
Hypertension, CHF, nephrolithiasis (calcium stones), nephrogenic diabetes insipidus
291
Thiazides side effects
Sulfonamide hypersensitivity, hypokalemia, alkalosis, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia
292
Thiazide drug interactions
Increase digoxin toxicity, avoid in diabetics
293
K+ sparing agents
Spironolactone, eplerenone, amiloride, triamterene
294
MOA spironolactone
Aldosterone receptor antagonist --> no sodium reabsorption --> no K+ secretion
295
Uses of spironolactone
Hyperaldosteronism, adjunct to K+ wasting diuretics, hirsutism, CHF
296
Spironolactone side effects
Hyperkalemia, acidosis, antiandrogenic (except eplerenone)
297
MOA amiloride/triamterene
Blocks Na+ channels in principal cells of collecting ducts --> decreased Na+ reabsorption and K+ secretion
298
Uses of K+ sparing agents
Adjunct to K+ wasting diuretics, lithium-induced nephrogenic diabetes insipidus (amiloride)
299
Side effects of K+ sparing agents
Hyperkalemia, acidosis, antiandrogenic (except epleronone)
300
Electrolytes excreted by acetazolamide
Na, K, HCO3
301
Electrolytes excreted by loop diuretics
Na, K, Ca, Mg, Cl
302
Electrolytes excreted by thiazides
Na, K, Cl; Ca is reabsorbed
303
Electrolytes excreted by K+ sparing agents
Na; K is not secreted
304
Statins MOA
Inhibition of HMG-CoA-Reductase --> decreased cholesterol --> increased LDL receptor expression --> decresed LDLs
305
Statins side effects
Myalgia, myopathy, rhabdomyolysis due to decrease in farnesyl ppi
306
Statins drug interactions
Gemfribozil increases rhabdomyolysis; P450 inhibitors enhance toxicity
307
Bile acid sequestrant drugs
Cholestyramine, colestipol
308
MOA of bile acid sequestrants
Decreased enterohepatic circulation --> increased new bile salts in liver --> decreased liver cholesterol --> increased LDL receptor expression --> decreased blood LDL
309
Side effects of bile acid sequestrants
Increased VLDL and triglycerides; gastrointestinal disturbances; malabsorption of lipid-soluble vitamins
310
Drug interactions of bile acid sequestrants
Interact with orally administered drugs
311
Contraindications of bile acid sequestrants
Hypertriglyceridemia
312
Niacin MOA
Inhibits VLDL synthesis --> decreased plasma VLDL --> decreases LDL --> increases HDL
313
Niacin side effects
Flushing, pruritus, rashes, hepatotoxicity
314
Gemfibozil MOA
Activates lipoprotein lipase --> decreases VLDL and IDL --> decreases LDL --> increases HDL
315
Uses of gemfibrozil
Hypertriglyceridemia
316
Ezetimibe MOA
Prevents intestinal reabsorption of cholesterol --> decreased LDL
317
Which antihyperlipidemic: increased cholesterol
Cholestyramine, colestipol, ezetimibe
318
Which antihyperlipidemic: increased triglycerides
Gemfibrozil
319
Which antihyperlipidemic: increased cholesterol and triglycerides
Statins, niacin, ezetimibe
320
Properties of benzodiazepines
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
321
Benzodiazepine drugs
Alprazolam, diazepam, lorazepam, midazolam, temazepam, oxazepam
322
Uses of alprazolam
Anxiety, phobias, panic attacks
323
Uses of diazepam
Anxiety, preop sedation, muscle relaxation, withdrawal states
324
Uses of lorazepam
Anxiety, preop sedation, status epilepticus
325
Uses of midazolam
Preop sedation and anesthesia, anterograde amnesia
326
Uses of temazepam
Sleep disorders
327
Uses of oxazepam
Sleep disorder and anxiety
328
Pharmacokinetics of benzodiazepines
Liver metabolized to active compounds except oxazepam, temazepam, lorazepam; t1/2: diazepam > lorazepam > alprazolam > temazepam > oxazepam > midazolam
329
Uses of barbiturates
Phenobarbital for seizures; thiopental for induction of anesthesia
330
Properties of barbiturates
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
331
Pharmacokinetics of barbiturates
General inducers of P450; contraindicated in porphyrias
332
Withdrawal signs of benzodiazepines
Rebound insomnia, anxiety, seizures
333
Withdrawal signs of barbiturates and ethanol
Anxiety, agitation, life threatening seizures
334
Drug interactions of GABA drugs
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)
335
Flumazenil
Benzodiazepine receptor antagonist. Used as antidote for benzodiazepine overdose.
336
Zolpidem
BZ1 receptor agonist used in sleep disorders. No cognitive impairment (no BZ2 actions), overdose reversed by flumazenil, less tolerance and abuse liability
337
Buspirone
No effect on GABA, 5-HT1a partial agonist, used for generalized anxiety, nonsedative, 1-2 weeks for effects
338
Effects of alcohols
GABA mimetic activity causes CNS depression; metabolic acidosis; fetal alcohol syndrome
339
Metabolism of ethylene glycol
Ethylene glycol + alcohol DH --> glycoaldehyde + aldehyde DH --> glycolic acid --> oxalic acid
340
Effects of ethylene glycol
CNS depression, severe metabolic acidosis, nephrotoxicity
341
Metabolism of methanol
Methanol + alcohol DH --> formaldehyde + aldehyde DH --> formic acid
342
Effects of methanol
Respiratory failure, severe anion gap metabolic acidosis, ocular damage
343
Treatment of alcohol overdose
Fomepizole (alcohol DH inhibitor) and hemodialisis
344
Metabolism of ethanol
Ethanol + alcohol DH --> acetaldehyde + NADH + acetaldehyde DH --> acetic acid + NADH
345
Effects of ethanol
CNS depression, metabolic acidosis, acetaldehyde toxicity
346
Acetaldehyde toxicity
Nausea, vomit, headache, hypotension, inactivates folate, decreases availability of thiamine
347
Drugs that cause disulfram-like effects
Disulfram-like effects = acetaldehyde toxicity. Disulfram inhibits acetaldehyde DH. Metronidazole, cefamandole, cefoperazone, cefotetan, chlorpropamide
348
Anticonvulsant drugs
Phenytoin, carbamazepine, benzodiazepines, barbiturates, lamotrigine, topiramate, felbamate, ethosuximide, valproic acid
349
Drugs used for partial seizures
Valproic acid, phenytoin, carbamazepine
350
Drugs used for general tonic-clonic seizures
Valproic acid, phenytoin, carbamazepine
351
Drugs used for absence seizures
Ethosuximide
352
Drugs used for status epilepticus
Lorazepam, diazepam, phenytoin
353
Phenytoin MOA
Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation
354
Pharmacokinetics of phenytoin
Variable absorption, nonlinear kinetics at low doses, zero-order kinetics at high doses, inducer of P450
355
Phenytoin side effects
CNS depression, gingival hyperplasia, hirsutism, osteomalacia (decreases vitamin D), megaloblastic anemia (decreases folate), aplastic anemia, teratogenic (cleft lip and palate).
356
Carbamazepine MOA
Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation
357
Pharmacokinetics of carbamazepine
Induces P450
358
Carbamazepine side effects
CNS depression, osteomalacia, megaloblastic anemia, aplastic anemia, exfoliative dermatitis, increases ADH secretion (dilutional hyponatremia), teratogenic (cleft lip and palate, spina bifida)
359
Valproic acid MOA
Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation; Inhibits GABA transaminase; Blocks presynaptic Ca+ channels
360
Uses of valproic acid
Seizures, bipolar mania, migraines
361
Pharmacokinetics of valproic acid
Inhibits P450
362
Valproic acid side effects
Hepatotoxic metabolite, thrombocytopenia, pancreatitis, alopecia, spina bifida
363
Ethosuxamide MOA
Blocks presynaptic T-type Ca+ channels in thalamic neurons
364
Lamotrigine MOA
Blocks Na+ channels and glutamate receptors. Side effect: Steven-Johnson
365
Inhaled anesthetic drugs
Nitrous oxide, halothane
366
Properties of halothane
High potency (0.8% MAC), high blood-gas ratio (2.3), sensitizes heart to catecholamines
367
Side effects of halothane
Malignant hyperthermia, hepatitis, cardiac arrhythmias
368
What is MAC?
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
369
What is the blood-gas ratio?
Measure of the onset of recovery. The more soluble in the blood the slower the anesthesia and recovery.
370
Intravenous anesthetic drugs
Midazolam, thiopental, propofol, fentanyl, ketamine
371
General anesthesia protocol
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
372
Naloxone
Antidote for opiods
373
Neostigmine
AChE inhibitor reverses non-depolarizing muscle relaxants
374
What are the ester local anesthetics?
Procaine, cocaine, benzocaine. Metabolized by plasma esterases. All have only one i""
375
What are the amide local anesthetics?
Lidocaine, bupivacaine, mepivacaine. Metabolized by liver amidases. All have two i"."
376
MOA of local anesthetics
Nonionized form crosses axonal membrane --> ionized form blocks inactivated Na+ channel --> prevent propagation of action potentials
377
Side effects of local anesthetics
Neurotoxicity, cardiovascular toxicity, allergies. Use alpha-1 agonists to prevent absorption.
378
Skeletal muscle relaxants MOA
Nicotinic antagonists (competitive, nondepolarizing); Nicotinic agonists (noncompetitive, depolarizing)
379
Non-depolarizing muscle relaxant drugs
Atracurium, mivacurium, tubocurarine
380
Non-depolarizing muscle relaxant properties
Nicotinic antagonists, reversible with AChE inhibitors, progressive paralysis, no effects on heart or CNS
381
Properties of succinylcholine
Depolarizing muscle relaxant, nicotinic agonist; Phase I: depolarization, fasciculation, flaccid paralysis; Phase II: desensitization. Caution in atypical pseudocholineeterase, hyperkalemia, malignant hyperthermia
382
Malignant hyperthermia
Succinylcholine side effect in genetically susceptible people. Muscle rigidity, hyperthermia, hypertension, acidosis, hyperkalemia. Rx.: dantrolene
383
Opiod analgesic drugs
Morphine, meperidine, methadone, codeine, fentanyl
384
Contraindications of opiod analgesics
Head injuries, pulmonary dysfunction, hepatic or renal dysfunction, adrenal or thyroid deficiencies, pregnancy
385
Effects of morphine
Analgesia, sedation, respiratory depression (decreased response to PCO2), miosis, cough supression, nausea, vomiting
386
Pharmacokinetics of morphine
Phase 2 metabolism by glucoronidation. Caution in renal dysfunction as morphine-6-glucoronide is highly active
387
Opiod toxicity
Pinpoint pupils, repiratory depression and coma. Rx. Naloxone
388
Meperidine
Opiod without miosis or spasms. Metabolized via P450 to normeperidine which can cause seizures
389
Methadone
Used for opiate withdrawal in addicts
390
Codeine
Cough suppressant, analgesia, use in combination with NSAIDs
391
Symptoms of opiod withdrawal
Yawning, lacrimation, rhinorrea, salivation, anxiety, muscle spasms and CNS-originating pain. Rx.: methadone
392
Drugs used in Parkinson disease
Levodopa, tolcapone, selegiline, bromocriptine, benztropine, amantadine
393
Levodopa
Crosses CNS barrier. Converted to dopamine in CNS and periphery, so use tolcapone, carbidopa and selegiline
394
Tolcapone
Inhibits COMT which blocks levodopa conversion to methyldopa which has no pharm actions
395
Carbidopa
Inhibits conversion of levodopa to dopamine in peripheral tissues, increasing CNS availability
396
Selegiline
MAOb selective inhibitor, adjunt to levodopa to decrease dopamine metabolism in CNS
397
Bromocriptine
Dopamine-receptor agonist used in hyperprolactinemia, acromegaly
398
Benztropine
Muscarinic blocker used to decrease Ach activity in Parkinson. Decreases tremor and rigidity but not bradykinesia
399
Atypical antipsychotics
Clozapine, olanzapine, risperidone, aripiprazole, quetiapine, ziprasidone, paliperidone
400
Atypical antipsychotic MOA
Inhibition of dopamine and 5HT2 receptors
401
Side effects of antipsychotic drugs
Extrapyramidal symptoms, akathisia, tardive dyskinesia, dysphoria, endocrine dysfunction, weight gain, hypotension, muscarinic blockade tachychardia
402
Specific side effects of thioridazine
Torsades, retinal deposits
403
Typical antipsychotics
Chlorpromazine, thioridazine, fluphenazine, haloperidol
404
Specific side effects of haloperidol
Neuroleptic malignant syndrome, tardive diskynesia
405
Specific side effects of clozapine
Agranylocytosis, seizures, salivation
406
MAO inhibitor drugs
phenelzine, tranylcypromine
407
Drug interaction of MAO inhibitors
Tyramine, TCAs, alpha-1 agonists, levodopa: increase NE --> hypertensive crisis; Serotonin syndrome with SSRI, TCA, meperidine --> sweating, rigidity, myoclonus, hyperthermia
408
Tricyclic antidepressant drugs
Amitriptyline, imipramine, clomipramine
409
TCAs MOA
Nonspecific blockade of 5HT and NE reuptake
410
Side effects of TCAs
Muscarinic blockade, alpha blockade, serotonin syndrome, hypertensive crisis
411
SSRI drugs
Fluoxetine, sertraline, paroxetine, citalopram
412
Side effects of SSRI
Anxiety, agitation, bruxism, sexual dysfunction, weight loss, serotonin syndrome
413
Serotonin syndrome
Sweating, rigidity, myoclonus, hyperthermia. Interaction between MAOi, TCAs, SSRIs, meperidine, dextromethorphan
414
Drug-induced hypertensive crisis
Due to interaction between MAOi, TCAs, alpha-1 agonists
415
Venlafaxine
Selective reuptake inhibitor of NE and 5HT. Can cause hypertensive crisis and serotonin syndrome
416
Bupropion
Dopamine reuptake blocker. Used in smoking cessation
417
Lithium MOA
Prevents recycling of inositol (decreases PIP2), decreases cAMP
418
Lithium side effects
Narrow therapeutic index requires monitoring, tremor, hypothyroidism (decreases TSH effects and inhibits 5'-deiodinase), nephrogenic diabetes insipidus (manage with amiloride), teratogenic
419
Methylphenidate
inhibits reuptake of DA and NE. Side effects: agitation, restlessness, insomnia, CV toxicity. Treats ADHD.
420
Atomoxetine
Selective NE reuptake inhibitor. Treats ADHD.
421
MOA of penicillins
Bind PBPs to inhibit transpeptidation reactions in peptidoglycan cross-linking --> inhibit cell wall synthesis
422
Mechanism of resistance to penicillin
Beta-lactamases (staphylococci); structural change in PBPs (MRSA); change in porin structure (pseudomonas)
423
Narrow spectrum penicillins
Penicillin G and V. Strep, pneumococci, menigococci, treponema
424
Very narrow spectrum penicillins
Nafcillin, methcillin, oxacillin. Staph. If MRSA use vancomycin.
425
Broad spectrum penicillins
Ampicillin, amoxicillin. Gram+ cocci (except staph), Listeria, H. influenzae, E. coli., Borrelia and H. pylory: amoxi
426
Extended spectrum penicillins
Ticarcillin, piperacillin, azlocillin. Increased activity against gram- plus anti-pseudomonal
427
Beta-lactamase inhibitors
Clavulanic acid, sulbactam. Use in combination with broad and extended spectrum penicillins
428
Pharmacokinetics of penicillins
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)
429
Side effects of penicillins
Hypersensitivity (5-7%). Urticarial skin rash to anaphylaxis. Interstitial nephritis (methicillin).
430
First generation cephalosporins
Cefazolin, cephalexin. Gram+ cocci (not MRSA), E. coli, Klebsiella pneumoniae, some proteus. Surgical prophylaxis
431
Second generation cephalosporins
Cefotetan, cefaclor, cefuroxime. Increased gram- coverage, including some anaerobes
432
Third generation cephalosporins
Ceftriaxone (IM), cefotaxime (IV), cefdinir, cefixime (oral). Gram+ and gram- cocci plus gram- rods. Enter CNS. Use in meningitis, sepsis
433
Fourth generation cephalosporins
Cefepime (IV). Enter CNS, resistant to betalactamases
434
Pharmacokinetics of cephalosporins
Active tubular secretion blocked by probenecid. Cefoperazone and ceftriaxone largely eliminated in bile.
435
Side effects of cephalosporins
Hypersensitivity (2%), rashes, fever, positive Coombs test, disulfram-like effect
436
Drugs to use in case of penicillin/cephalosporin allergy
Macrolides for gram+, aztreonam for gram- rods
437
Imipenem and meropenem
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
438
Aztreonam
Resistant to betalactamases. Used IV against gram- rods. No cross-allergenicity with penicillins or cephalosporins
439
Vancomycin MOA
Binds D-Ala-D-Ala pentapeptide to inhibit elongation of peptidoglycan chains. Does not bind PBPs.
440
Uses of vancomycin
MRSA, enterococci, C. difficile (backup drug)
441
Resistance to vancomycin
Terminal D-ala is replaced with D-lactate in muramyl pentapeptide
442
Pharmacokinetics of vancomycin
Used IV and orally (not absorbed) in colitis. Enters most tissues but not CNS. Eliminated by renal filtration. Long t1/2
443
Side effects of vancomycin
Red man syndrome" (histamine release); permanent ototoxicity; nephrotoxicity"
444
Antibiotics that act on 30S ribosomal subunit
Aminoglycosides, tetracyclines. buy AT 30, CCEL at 50"."
445
Antibiotics that act on 50S ribosomal subunit
Chloranphenicol, clindamycin, erythromycin (macrolides), linezolid. buy AT 30, CCEL at 50""
446
Antibiotics that inhibit formation of initiation complex
Aminoglycosides (30S), linezolid (50S)
447
Antibiotics that block attachment of aminoacyl-tRNA to A site
Tetracyclines (30S), dalfopristin (50S)
448
Antibiotics that inhibit peptidyltransferase (peptide bond formation)
Chloranphenicol (50S)
449
Antibiotics that inhibit translocation
Macrolides (50S), clindamycin (50S)
450
Mecanisms of resistance to macrolides and clindamycin
Methyltransferases alter drug binding site on the 50S ribosome; active transport out of cell
451
Mechanism of resistance to tetracyclines
Tetracycline pumps transport drug out of the cell
452
Mechanism of resistance to aminoglycosides
Conjugation enzymes
453
Mechanism of resistance to sulfonamides
Change in target enzyme decreases drug sensitivity; formation of PABA; use of exogenous folic acid
454
Mechanism of resistance to fluoroquinolones
Change in target enzyme decreases drug sensitivity; pumps transport drugs out of the cell
455
Mechanism of resistance to chloranphenicol
Formation of inactivating acetyltransferases
456
Pharmacokinetics of aminoglycosides
Polar compounds not absorbed orally or widly distributed. Renal elimination. Modify in renal dysfunction
457
Aminoglycoside drugs
Gentamicin, tobramycin, amikacin: gram- aerobic rods; Streptomycin: TB, plague and tularemia; neomycin
458
Side effects of aminoglycosides
Nephrotoxicity (6-7%), ototoxicity enhanced by loop diuretics.
459
Tetracycline drugs
Tetracycline, doxycycline, minocycline, demeclocycline
460
Uses of tetracyclines
Chlamydia, mycoplasma, H. pylory, Rickettsia, Borrelia, Brucella, Vibrio
461
Phamacokinetics of tetracyclines
Metabolized by kidney (most), and liver (doxycycline). Decrease absorption of divalent cations by chelation.
462
Side effects of tetracyclines
Tooth enamel dysplasia, decreased bone growth (avoid in children), phototoxicity, contraindicated in pregnancy
463
Drugs that cause phototoxicity
amiodarone, tetracyclines, sulfonamides, quinolones
464
Drugs that are nephrotoxic
Vancomycin, aminoglycosides, amphotericin B, cisplatin, cyclosporine
465
Drugs that are ototoxic
Aminoglycosides, loop diuretics
466
Pharmacokinetics of chloranphenicol
Orally effective, enters CNS, metabolized by hepatic glucoronidation, inhibits P450
467
Side effects of chloranphenicol
Dose-dependant bone-marrow suppression, gray baby" in neonates (decreased glucoronosyl transferase)"
468
Macrolide drugs
Erythromycin, azithromycin, clarithromycin
469
Uses of Erythromycin
Gram+ cocci, atypicals (chlamydia, mycoplasma, ureaplasma), legionella, campylobacter
470
Uses of azithromycin
Gram+ cocci, atypicals (chlamydia, mycoplasma, ureaplasma), legionella, campylobacter, more activity in respiratory infections
471
Pharmacokinetics of macrolides
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
472
Side effects of macrolides
Stimulate motilin receptors and cause GI distress, reversible deafness, cholestasis, jaundice
473
Drugs to avoid in pregnancy
Aminoglycosides, erythromycin, clarithromycin, fluoroquinolones, sulfonamides, tetracyclines
474
Uses of clindamycin
Gram+ cocci, anaerobes, toxoplasmosis. Use in gram+ osteomyelitis. Can cause pseudomembranous colitis
475
Linezolid
VRSA, VRE, drug-resistant pneumococci. Side effect: bone marrow suppression (platelets)
476
Streptogramin drugs
Quinupristin-dalfopristin
477
MOA of streptogramins
Bind 50S ribosomal subunit
478
Uses of streptogramins
Vancomycin resistant staph (VRSA), vancomycin resistant enterococci (VRE), drug-resistant gram+ cocci
479
Inhibitors of nucleic acid synthesis drugs
5-MP, 6-FU, hydroxyurea, methotrexate, sulfonamides, trimethoprim, pyrimethamine
480
MOA of sulfonamides
Inhibits dihydropteroate synthetase which inhibits folic acid synthesis
481
MOA of trimethoprim
Inhibits dihydrofolate reductase which inhibits folic acid synthesis
482
Uses of trimethoprim-sulfamethoxazole
DOC in Nocardiosis; mycobacteria; gram+ cocci, E. coli, Salmonella, Shigella, H. influenzae, P. carinii, toxoplasma
483
Pharmacokinetics of sulfonamides
Hepatically acetylated; renally excreted metabolites cause crystalluria; high protein binding
484
Side effects of sulfonamides
Hypersensitivity, Steven Johnson, phototoxicity, GI distress, hemolysis in G6PDH deficiency
485
Side effects of trimethoprim
Bone marrow suppression, enterocolitis
486
Quinolone drugs
Norfloxacin, ciprofloxacin, ofloxacin, levofloxacin
487
MOA of quinolones
Bactericidal. Inhibit topoisomerase II (DNA gyrase).
488
Uses of quinolones
UTIs resistant to cotrimoxazole, PID (chlamydia, gonococcus), skin and bone infections by gram-, diarrhea to shigella, salmonella, E. coli, campylobacter
489
Pharmacokinetics of quinolones
Iron and Ca+ limit their absorption, eliminated by kidney active secretion (inhibited by probenecid)
490
Side effects of quinolones
GI distress, phototoxicity, rashes, tendonitis, increases QT interval, contraindicated in pregnancy and children
491
Regimens used in H. pylori infections and ulcers
BMT: bismuth, metronidazole, tetracyclines or clarithromycin, amoxicillin, omeprazole
492
Uses of metronidazole
Giardia, trichomonas, entamoeba, gram- anaerobics, clostridium (DOC pseudomembranous colitis)
493
MOA and resistance to isoniazid
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
494
Side effects of isoniazid
Age-dependant hepatitis, peripheral neuritis (use B6), sideroblastic anemia (use B6), hemolysis in G6PDH deficiency, drug-induced lupus in slow acetylators
495
MOA and resistance to rifampin
Inhibits DNA-dependant RNA polymerase; resistance via change in enzyme
496
Side effects of rifampin
Hepatitis, induction of P450, red-orange metabolites
497
MOA of ethambutol
Inhibits synthesis of cell wall component arabingalactan
498
Side effects of ethambutol
Dose-dependant retrobulbar neuritis --> decreases visual acuity and red-green discrimination
499
Side effects of streptomycin
Deafness, vestibular dysfunction, nephrotoxicity
500
Polyene drugs
Amp B, nystatin
