Kaplan High Yield Pharm Flashcards
1
Q
What is Vmax?
A
Vmax is the maximum velocity for a given amount of enzyme
-Proportional to enzyme concentration
2
Q
What is the Michaelis constant (Km)?
A
Km is the substrate concentration required to reach half Vmax
Km = 1/affinity
3
Q
What does a high Km mean?
A
A high Km means low affinity (opposite for low Km)
4
Q
What is the equation for the intersection of the Y-axis on a Lineweaver-Burk plot?
A
Intersection of the Y-axis = 1/Vmax
5
Q
What is the equation for the intersection of the X-axis on a Lineweaver-Burk plot?
A
Intersection of the X-axis = -1/Km
6
Q
What are the characteristics of a competitive inhibitor?
A
- Resemble substrate, bind at active site
- Increasing substrate concentration can overcome inhibition
- Decrease potency
7
Q
What is the effect on Vmax and Km by a competitive inhibitor?
A
No effect on Vmax
Increases Km
8
Q
What are the characteristics of non-competitive inhibitors?
A
- Bind to allosteric site, not near active site
- Cannot be overcome with increased substrate concentration
- Decrease efficacy
9
Q
What is the effect on Vmax and Km by a non-competitive inhibitor?
A
Decreases Vmax
No effect on Km
10
Q
Do the Lineweaver-Burk plots of competitive or non-competitive inhibitors cross with the Lineweaver-Burk plot with no inhibitor?
A
The Lineweaver-Burk plot of a competitive inhibitor crosses the Lineweaver-Burk plot with no inhibitor
11
Q
What is the equation for volume of distribution (Vd)?
A
Vd = total amount of drug in body/conc. of drug in plasma
12
Q
A low Vd (4-8 L) means the drug is mostly contained in?
A
Blood
13
Q
A medium Vd (12-14L) means the drug is mostly contained in?
A
Extracellular fluid
14
Q
A high Vd (> total body water) means the drug is?
A
Distributed in all tissues, non-fluid compartments (fat)
15
Q
What is the effect of hepatic disease on the Vd of plasma protein bound drugs?
A
Decreased synthesis of plasma proteins -> Drugs diffuse into body tissues, effectively increasing the drug’s Vd
16
Q
What is the effect of renal disease on the Vd of plasma protein bound drugs?
A
Plasma proteins (and bound drugs) are excreted in the urine
17
Q
What is the equation for drug clearance?
A
Drug clearance = Rate of drug elim./plasma drug conc.
Vd x Ke
18
Q
When is renal clearance equal to GFR?
A
When there is no reabsorption, secretion, or plasma protein binding
19
Q
What 2 substances are used to estimate the GFR?
A
Inulin and creatinine
20
Q
What is the equation for the clearance of protein bound drugs (not cleared)?
A
Clearance = free fraction x GFR
21
Q
What is the half life equation?
A
T1/2 = (.7 x Vd)/clearance
22
Q
How many half lives does it take to reach steady state with continuous infusion?
A
Steady state is reached in 4-5 half lives with continuous infusion
23
Q
What is a loading dose?
A
- Large initial dose given to fill up Vd
- Can increase plasma concentration in less than 4-5 half lives
24
Q
What is the equation for loading dose?
A
LD = (Vd x Cp)/F
Cp=blood plasma conc.
F=bioavailability
25
What is a maintenance dose?
- A dose given to maintain constant blood plasma levels
| - Lowered if hepatic/renal function is impaired
26
What is the equation for maintenance dose?
MD = (Cl x Cp)/F
Cl = clearance
27
What is bioavailability (F)?
- Fraction of administered drug that reaches systemic circulation
- Some drugs fail to be absorbed, or are metabolized before reaching circulation
28
What is the bioavailability of an IV infusion?
F = 1 for IV infusion
29
What is zero order elimination?
Constant amount of drug eliminated with time
| Example: 100 mg -> 90 mg -> 80 mg...10 mg being eliminated per hr
30
What are substances that exhibit zero order elimination?
Phenytoin, aspirin, ethanol
31
What is first order elimination?
- Constant fraction of drug eliminated with time
- Most drugs follow first order kinetics
- Example: 100 mg -> 50 mg -> 25 mg...elimination of half concentration per hour
32
Explain the renal excretion of ionized and non-ionized substances
- Both ionized forms and non-ionized forms are filtered
- Only non-ionized forms are actively secreted or reabsorbed
- Ionized forms of drug are trapped in the filtrate
33
What are some examples of drugs that are weak acids?
Barbiturates, methotrexate, aspirin
34
How would you increase the elimination of a weak acid to save a patient from an overdose?
Give them base (HCO3-) -> alkalinize the urine (opposite for a weak base -> give NH4Cl)
35
What is an example of a drug that is a weak base?
Amphetamines
36
What is biotransformation?
Conversion of lipid soluble drugs into water soluble metabolites in the liver -> increases renal excretion
-Two forms of drug metabolism-phase 1 and 2
37
What is phase 1 drug metabolism?
Oxidation, reduction, and hydrolysis of drugs by cytochrome P450 enzymes
- Located in the smooth endoplasmic reticulum of the liver
- Require O2 and NADP
38
Name the drugs that are cytochrome P450 inducers (9)
| -What is the acronym?
QRBPSGGCC
- Quinidine
- Barbiturates
- Phenytoin
- St. John's Wort
- Rifampin
- Griseofulvin
- Glucocorticoids
- Carbamazepine
- Chronic alcohol use
39
Name the drugs that are cytochrome P450 inhibitors (10)
| -What is the acronym?
HIS COCK MR G
- HIV protease inhibitors
- Isoniazid (INH)
- Sulfonamides
- Cimetidine
- Omeprazole
- Chloramphenicol
- Ketoconazole
- Macrolides
- Ritonavir
- Grapefruit juice
40
What are the non-cytochrome P450 enzyme phase 1 metabolism mechanisms?
- Hydrolysis (addition of H2O to drugs to assist metabolism, esterase/amidase)
- Monoamine oxidase
- Alcohol metabolism
41
What are the endogenous amines metabolized by MAO?
Dopamine, NE, and serotonin
42
What is the exogenous amine metabolized by MAO?
Tyramine
43
What is phase 2 metabolism?
Conjugation of functional groups to a drug via transferase enzymes
- Converts polar molecules to inactive molecules -> increase renal excretion
- Mechanisms of metabolism include - acetylation, glucuronidation, sulfation, methylation, and glutathione conjugation
44
What is potency?
- Measure of how much drug is required to give desired effect
- Typically expressed as EC50 - concentration that gives 50% of max response
45
What is efficacy?
Maximal effect that a drug can produce
46
See graphs on slides 17 and 18
...
47
What is a full agonist?
With receptor saturation, drug can reach full efficacy
48
What is a partial agonist?
Acts at the same site as agonist, but lower EFFICACY
| -Can have higher or lower potency than agonist
49
What are physiologic antagonists?
Substrate that produces opposite effect of an agonist, but acts through different receptor/pathway
50
What is therapeutic index?
- Measure of drug safety
| - Higher therapeutic index indicates safer drug
51
What is the equation for therapeutic index?
TI = LD50/ED50
| -See graph on slide 20
52
Draw out the diagram on slide 22
...
53
What is a nicotinic Ach receptor (nAchr) and what are the different types?
Ligand gated Na/K channels
- Nn-autonomic
- Nm-somatic muscular (neuromuscular junction)
54
The cAMP system for GPCRs includes receptors for?
- Catecholamines beta1, beta2 (Gs), and alpha2 (Gi)
- Ach M2 (Gi)
- Glucagon (Gs)
55
The PIP2 system for GPCRs includes receptors for?
ALL are Gq
- Catecholamines alpha1
- Ach M1-M3
- Angiotensin II
- Vasopressin
56
Study the rest of slide 24 and 25
...
57
What are 3 examples of drugs that act at the cholinergic nerve terminal?
- Hemicholinium
- Botulinum toxin
- Vesamicol
58
What is the MOA of hemicholinium?
Inhibits choline uptake into nerve terminal -> decreases Ach production
59
What is the MOA of botulinum toxin?
Inhibits the release of Ach containing vesicles from the nerve terminal
60
What is the MOA of vesamicol?
Stops the conversion of acetyl CoA to Ach by inhibiting choline acetyl transferase
61
What are some examples of drugs that act at the adrenergic nerve terminal?
- Metyrosine
- Reserpine
- Cocaine, TCAs, and amphetamines
- Guanethidine
62
What is the MOA of metyrosine?
Inhibits the conversion of tyrosine to Dopa by inhibiting tyrosine hydroxylase
63
What is the MOA of reserpine?
Blocks the uptake of NE into vesicles
64
What is the dual action MOA for amphetamines?
- Directly block the reuptake of NE
| - Increase the release of NE into the synapse
65
What is the MOA of cocaine and TCAs?
Directly block the reuptake of NE
66
What is the MOA of guanethidine?
Blocks the release of NE into the synapse
67
What are examples of cholinomimetics (parasympathomimetics)?
- Bethanechol
- Carbachol
- Pilocarpine
- Methacholine
68
What is bethanechol?
- Muscarinic agonist
- Longer acting than Ach (resistant to acetylcholinesterase)
- Tx of ileus and urinary retention (Bowels and bladder)
69
What is carbachol?
- Muscarinic/nicotinic agonist
- Also resistant to acetylcholinesterase
- Applied to eye to cause contraction of ciliary muscle, relief to open angle glaucoma, also constricts pupil
70
What is pilocarpine?
- Muscarinic agonist
- Stimulates tears, sweat, saliva
- Constricts pupil and ciliary muscle
- Also used for acute glaucoma
71
What is methacholine?
- Muscarinic agonist
- Causes bronchoconstriction when inhaled
- Used for asthma challenge test
72
What are examples of anticholinesterases (indirect cholinomimetics)?
- Neostigmine
- Pyridostigmine
- Edrophonium
- Physostigmine
- Echothiophate
73
What is neostigmine?
- Quaternary amine-acts on peripheral nervous system (no entry into CNS)
- Tx of ileus, urinary retention, and myasthenia gravis
- Post-operative reversal of neuromuscular junction blockade
74
What is pyridostigmine?
- Quaternary amine-acts on peripheral nervous system (no entry into CNS)
- Treatment of myasthenia gravis
75
What is edrophonium?
- Very short acting (10-20 mins)
| - Diagnosis of myasthenia gravis
76
What is physostigmine?
- Tertiary amine (can enter CNS)
| - Tx of glaucoma, antidote for atropine toxicity
77
Echothiophate is used for the tx of?
Glaucoma
78
What are the symptoms for cholinesterase inhibitor poisoning (high systemic Ach)? What is the acronym?
DUMBBELSS
- Diarrhea
- Urination
- Miosis
- Bronchoconstriction
- Bradycardia
- Excitation (skeletal muscle and CNS)
- Lacrimation
- Salivation
- Sweating
79
What is the treatment for cholinesterase inhibitor poisoning (high systemic Ach)?
- Atropine (muscarinic antagonist)
| - Pralidoxime (2PAM) (regenerates cholinesterase)
80
What is the classic example of a muscarinic receptor antagonist?
Atropine
81
What is atropine?
- Muscarinic receptor antagonist
- Tertiary amine-can enter the CNS
- Effects-the opposite of DUMBBELSS
82
What are the clinical uses of atropine?
- Antispasmodic
- Antisecretory
- Management of AchE inhibitor OD
- Antidiarrheal
- Ophthamology (but long action)
83
What is tropicamide used for clinically?
Ophthamology (topical)
84
What is ipratropium used for clinically?
Asthma and COPD (inhalational)
| -No CNS entry, no change in mucous viscosity
85
What is scopolamine used for clinically?
Tx of motion sickness
| -causes sedation and short term memory block
86
What are benztropine and trihexyphenidyl used for?
- Lipid-soluble (CNS entry)
| - Used in parkinsonism and in acute extrapyramidal symptoms induced by antipsychotics
87
What are the direct sympathomimetics?
- Epi and NE
- Isoproterenol
- Dopamine
- Dobutamine
- Ritodrine
- Metaproterenol
- Albuterol
- Salmeterol
- Terbutaline
88
What is the function of epinephrine?
- Alpha and beta agonist (a1=a2, b1=b2)
| - Low doses selective for B1 receptors
89
What is the clinical use of epi?
- Tx for anaphylaxis, open angle glaucoma, asthma hypotension
- Prolongs the effect of local anesthesia
90
What are the adverse effects of epi?
Increased systolic blood pressure and decreased diastolic blood->Widened pulse pressure
91
What is the function of NE?
Mainly an alpha receptor agonist but has some beta receptor activity (a1=a2, b1>b2)
92
What is the clinical use of norepi?
Tx of hypotension
93
What are the adverse effects of NE?
- Splanchnic vasoconstriction (can cause bowel ischemia) and decreased renal perfusion
- Increased systolic blood pressure and diastolic blood pressure -> little/no change in pulse pressure
- Reflexive decrease in HR
94
What is isoproterenol?
- B1B2 agonist
- Tx for AV conduction block
- Decreases diastolic BP (induces a reflexive increase in HR)
95
What is dopamine?
- D1=D2 > beta > alpha
- Inotropic and chronotropic
- Treatment for shock, especially with heart failure
96
What is dobutamine?
- B1>B2 agonist
- Inotropic
- Tx of heart failure
- Used in cardiac stress test
97
What is ritodrine?
- B2 agonist
| - Reduces premature uterine contractions
98
What are the selective B2 agonists (B2>B1)?
- Metaproterenol-short-acting
- Albuterol-short-acting
- Salmeterol-long-acting
- Terbutaline
99
Name the indirect sympathomimetics
Amphetamine, ephedrine, cocaine, tyramine
100
What is amphetamine?
- Induces catecholamine release from terminals
| - Tx for narcolepsy, obesity, and ADHD
101
What is ephedrine?
- Induces catecholamine release
| - Tx for nasal congestion, urinary incontinence, and hypotension
102
What is cocaine?
- Inhibits reuptake of catecholamines
| - Causes vasoconstriction, local anesthetic
103
What is tyramine?
- Similar mechanism to amphetamines, cleared by MAO
- MAO inhibitors can cause HTN, especially with tyramine (breakdown product of tyrosine)-rich foods such as wine and cheese
104
What are the sympathoplegics?
- Clonidine
| - alpha-methyldopa
105
What is clonidine?
Agonist of central alpha2-adrenergic receptors which decrease sympathetic outflow
106
What is alpha-methyldopa?
Used to treat HTN by decreasing sympathetic tone
107
Both clonidine and alpha-methyldopa are used to tx?
HTN that is resistant to other tx
108
What are the non-selective alpha (a1 and a2) blockers?
- Phenoxybenzamine
| - Phentolamine
109
What is phenoxybenzamine?
- Non-selective and irreversible
| - Tx of pheochromocytoma, Raynaud's syndrome
110
What is important to know when giving alpha blockers for the tx of pheochromocytoma?
Give the alpha blockers before removal of pheo tumors to prevent excessive catecholamines from spilling into circulation
111
What is phentolamine?
- Non-selective and reversible
| - Tx of pheo and Raynaud's syndrome
112
What are the alpha1-selective blockers?
- Prazosin
- Terazosin
- Doxazosin
113
What are the alpha1 selective blockers used for?
- Tx of HTN, urinary retention (BPH)
| - May cause orthostatic hypotension (usually taken at bedtime)
114
Which alpha1 selective blocker is the longest acting?
Doxazosin
115
What is the alpha2-selective alpha blocker?
Mirtazapine
116
What is mirtazapine used for?
- Tx of depression
| - Can cause sedation, increased serum cholesterol, and increased appetite
117
What are the non-selective (b1 and b2) beta blockers?
- Propanolol
- Timolol
- Nadolol
- Pindolol
118
What is propanolol used for?
Migraines
119
What is timolol used for?
Glaucoma
120
What are the beta1 selective beta blockers?
- Metoprolol
- Atenolol
- Betaxolol
- Esmolol
121
Which of the beta1-selective beta blockers is very short acting?
Esmolol
122
What are the mixed alpha and beta blockers?
- Carvedilol
| - Labetalol
123
What are the partial beta-agonists?
- Pindolol
| - Acebutolol
124
When used for HTN use of beta blockers results in?
- Decreased CO
| - Decreased renin production (beta1-blockade of JG cells)
125
When used for angina use of beta blockers results in?
- Decreased HR
- Decreased inotropy
- Decreased myocardial O2 consumption
126
When used for myocardial infarction use of beta blockers results in?
decreased mortality
127
Which beta blockers are used for sinus ventricular tachycardia (SVT)?
Propanolol/esmolol -> decrease AV conduction
128
When used for HF use of beta blockers results in?
Slows the progression of CHF (decreases cardiac demand)
129
What are the side effects of beta blockers?
- Exacerbation of asthma
- Impotence
- Bradycardia
- AV blockade
- Sedation
- Decreased glucagon secretion -> Hypoglycemia in diabetics
130
What is the antidote used to treat acetaminophen toxicity?
N-acetylcysteine
131
What is the antidote for salicylate toxicity?
Sodium bicarbonate (alkalinize the urine), dialysis for severe cases
132
What is the antidote for anticholinesterases/organophosphate (insecticides) poisoning?
Atropine and pralidoxime (2-PAM)
133
What is the antidote for anticholinergics toxicity?
Physostigmine
134
What is the antidote for beta blocker toxicity?
Glucagon (to increase inotropy and chronotropy of the heart)
135
What is the antidote for digitalis toxicity?
- Anti-digitalis Fab fragments
| - Normalize serum electrolytes, especially K, then lidocaine, magnesium
136
What is the antidote for iron toxicity?
Deferoxamine
137
What are the antidotes for lead poisoning?
Ca-EDTA (chelator), dimercaprol, succimer, penicillamine
138
What is the antidote for arsenic, mercury, or gold poisoning?
Dimercaprol, succimer
139
What is the antidote for copper, arsenic, or gold poisoning?
Penicillamine
140
What is the antidote for cyanide poisoning?
Nitrite, hydroxycobalamin, thiosulfate
141
What is the antidote for methemoglobin?
Methylene blue, vitamin C
142
What is the antidote for carbon monoxide poisoning?
100% O2 (hyperbaric chamber)
143
What is the clinical presentation of methanol poisoning?
Blindness
144
What is the clinical presentation of ethylene glycol?
Nephrotoxicity -> acute renal failure
145
What is the antidote for methanol/ethylene glycol poisoning?
Ethanol, fomepizol
146
What are the antidotes for opioid overdose and what is the MOA of each?
Naloxone-Competitive antagonist
| Naltrexone-Receptor antagonist
147
What is the antidote for benzodiazepine toxicity?
Flumazenil
148
What is the antidote for TCA toxicity?
- NaHCO3 (IV alkalinization)
| - Adjunctively treat for seizure, hyperthermia, and arrhythmia
149
What is the antidote for heparin toxicity?
Protamine
150
What are the antidotes for warfarin (coumadin) toxicity?
- Vitamin K
| - Fresh frozen plasma-used for acute warfarin toxicity (restore 1972CS)
151
What is the antidote for tPA, streptokinase toxicity?
Aminocaproic acid
152
What is the antidote for theophylline?
beta-blocker
153
Atropine-like (anti-cholinergic) symptoms can be caused by what agents?
- TCAs
| - Anti-histamines
154
Dilated cardiomyopathy can be caused by what agents?
Doxorubicin, daunorubicin
155
Coronary vasospasm can be caused by what agents?
- Cocaine
| - Sumatriptan
156
Cutaneous flushing can be caused by what agents?
VANC
- Vancomycin
- Adenosine
- Niacin
- Ca channel blockers
157
The cutaenous flushing that can be caused by vancomycin is known as?
Red man syndrome
158
Torsades de pointes can be caused by what agents?
- Class III (sotalol)
- Class Ia (quinidine)
- Cisapride (removed from market d/t arrhythmias)
- Tx with Mg
159
Agranulocytosis can be caused by what agents?
- Clozapine
- Carbamazepine
- Colchicine
- Propylthiouracil
- Dapsone
- Methimazole
160
Aplastic anemia can be caused by what agents?
- Chloramphenicol
- Benzene
- NSAIDs
- Falbamate
161
Hemolytic anemia (Coombs-positive) can be caused by what agent?
Methyldopa
162
Gray baby syndrome can be caused by what agent?
Chloramphenicol
163
G6PD hemolytic anemia can be caused by what agents?
- Isoniazid (INH)
- Sulfa drugs
- Aspirin
- Ibuprofen
- Nitrofurantoin
- Primaquin
164
Megaloblastic anemia (hypersegmented neutrophils) can be caused by what agents?
- Methotrexate
- Sulfa drugs
- Phenytoin
165
Thrombosis can be caused by what agents?
Oral contraceptives (higher risk with smoking)
166
Cough can be caused by what agent?
ACE-inhibitors (use ARBs instead)
167
Pulmonary fibrosis can be caused by what agents?
- Bleomycin
- Amiodarone
- Busulfan
168
Hepatitis can be caused by what agent?
Isoniazid (INH)
169
Cholestatic hepatitis can be caused by what agents?
Macrolide abx (azithromycin, clarithromycin)
170
Hepatic necrosis can be caused by what agents?
- Halothane
- Valproate
- Acetaminophen
- Amanita phalloides (mushroom)
171
Pseudomembranous colitis (C. difficile) can be caused by what agents?
- Clindamycin
- Ampicillin
- Cephalosporins
172
Pancreatitis can be caused by what agents?
- Azathioprine
- Sulfonamides
- Valproate
- Methyldopa
- Furosemide
- Corticosteroids
173
Adrenocortical insufficiency can be caused by what agents?
- Glucocorticoid withdrawal
| - Etomidate
174
Gynecomastia can be caused by what agents?
- Spironolactone
- Digitalis
- Cimetidine
- Alcohol
- Estrogens
- Ketoconazole
175
Hot flashes can be caused by what agents?
- Tamoxifen
| - Clomiphene
176
Hypothyroidism can be caused by what agents?
- Lithium
| - Amiodarone
177
Gingival hyperplasia can be caused by what agent?
Phenytoin
178
Gout can be caused by what agents?
- Furosemide
| - Thiazides
179
Osteoporosis can be caused by what agents?
- Corticosteroids
| - Heparin
180
Photosensitivity can be caused by what agents?
- Fluoroquinolones
- Amiodarone
- Tetracyclines
- Sulfonamides
181
Rash (Stevens-Johnson syndrome) can be caused by what agents?
- Carbamazepine
- Allopurinol
- Penicillin
- Sulfa drugs
182
Lupus-like syndrome can be caused by what agents?
- Hydralazine
- INH
- Procainamide
- Phenytoin
183
Tendon rupture (achilles) can be caused by what agent?
Fluoroquinolones
184
Fanconi's syndrome can be caused by what agent?
Tetracyline (expired)
185
Interstitial nephritis can be caused by what agents?
- Methicillin
| - NSAIDs
186
Hemorrhagic cystitis can be caused by what agent?
Cyclophosphamide
187
Cinchonism can be caused by what agents?
- Quinidine
| - Quinine
188
Diabetes insipidus can be caused by what agents?
- Lithium
| - Demeclocycline
189
Seizures can be caused by what agents?
- Buproprion
- Imipenem/cilastatin
- INH
190
Parkinson-like syndrome can be caused by what agents?
- Haloperidol
- Chlorpromazine
- Reserpine
- Metoclopramide
191
Tardive dyskinesia can be caused by what agents?
Typical antipsychotics
192
Disulfiram-like reaction (acute sensitivity to alcohol) can be caused by what agents?
- Metronidazole
- Procarbazine
- Sulfonylureas
- Cephalosporins
193
Nephrotoxicity/neurotoxicity can be caused by what agents?
Polymxyins
194
Nephrotoxicity/ototoxicity can be caused by what agents?
- Aminoglycosides
- Vancomycin
- Loop diuretics
- Cisplatin
195
Review slide 58
...
196
List the sulfa drugs (any drugs that contain a sulfonamide group)
-Allergies to these drugs are common
- Sulfonamide abx
- TMP-SMX
- Acetazolamide
- Furosemide
- Thiazides
- Sulfsalazine
- Celecoxib
- Probenecid
197
What are the symptoms of a reaction to sulfa drugs?
- Pruritic rash
- Fever
- Stevens-Johnson syndrome
- Hemolytic anemia
- Thrombocytopenia
- Agranulocytosis
- Urticaria (hives)
198
Common drug suffixes-MEMORIZE
...
