Pharm Flashcards
(313 cards)
1
Q
What is an inert binding site
A
Binding site that doesn’t change function when a drug binds
2
Q
Describe a covalent bond drug receptor interaction
A
Irreversible; drug removal requires new synthesis of a receptor or enzymatic removal of the drug
3
Q
List the bonds in order of strongest to weakest
A
Ionic (btw positive and negative), hydrogen (btw net positive charge of hydrogen and negative charge of electronegative atom), hydrophobic (hydrophobic regions of drug and receptor), van der waals
4
Q
How do you plot a dose response curve
A
Dose on x axis and drug effect on y axis (makes a hyperbolic curve)
5
Q
What kind of curve do you get when you plot a concentration-effect curve (logarithm of drug vs response)
A
Sigmoidal
6
Q
What is Emax
A
Maximal effect produced by a drug
7
Q
What is ED50
A
Effective dose: dose of a drug that produces 50% of its maximal effect
8
Q
What is a graded dose response curve
A
Answers: “how much?”
9
Q
What does a quintal response require
A
Pre-defined response
10
Q
What are the types of quantal dose responses
A
Non-cumulative: # or % of ppl responding to a certain dose and only at that dose
Cumulative: # or % of ppl responding to a certain dose and at all doses lower than that dose
11
Q
What is the therapeutic index
A
TD50/ED50 = TI; higher the TI, safer the drug
12
Q
What is the therapeutic window
A
Range of doses of a drug in a bodily system that provides for safe and effective therapy
13
Q
What is the parameter that describes affinity
A
Kd = drug concentration at which 50% of the drug receptor binding sites are occupied by the drug; unit used is molar concentration; lower Kd = higher affinity
14
Q
What is the intrinsic activity of a drug
A
Ability of the drug to change a receptor function and produce a physiological response upon binding; agonists have intrinsic activity
15
Q
What is a full agonist
A
Fully activate receptors, produce maximal pharm effect when all receptors occupied, maximal intrinsic activity
16
Q
What is a partial agonist
A
Partially activate the receptor, produce sub-maximal pharm effect when all receptors occupied, intrinsic efficacy varies but is always submaximal
17
Q
What is an inverse agonist
A
Decrease receptor signaling, decrease response at receptors, intrinsic activity is present and related to inhibition of receptor function
18
Q
What is pharmacologic antagonism (receptor)
A
Action at the same receptor as endogenous ligands or agonist drugs
19
Q
What is chemical antagonism
A
When the chemical antagonist makes other drug unavailable
20
Q
What is physiologic antagonism
A
Occurs btw endogenous pathways and regulated by different receptors
21
Q
What is the difference between a competitive and non-competitive antagonist
A
Competitive: can be displaced from receptor by other drugs
Non-competitive: inactivation not surmountable; two types: irreversible (occluded agonist site via covalent bonds) and allosteric (binds to site other than agonist site)
22
Q
Describe what competitive antagonism does to the dose response curve
A
Increases EC50 but does not change E max
23
Q
Describe what non competitive antagonism does to the dose response curve
A
Decrease Emax but EC50 does not change
24
Q
What is drug potency
A
Amount of drug required to produce specific pharm effect; higher affinity drugs are more potent, lower ED50, more potent the drug, determines drug dose used clinically
25
What is drug efficacy
Describes max pharm effect that drug can produce; represented by Emax; greater Emax = more efficacious drug; related to total number of receptors available to bind the drug; determines clinical effectiveness
26
What do TF regulate the recruitment of
RNA polymerase
27
What do TF bind to
Response element
28
What are the GPCR ligands
Biogenic amines, peptides/proteins, amino acids, lipids, nucleotides
29
What are the classes of GPCRs
Gs: activates adenylyl cyclase and Src tyrosine kinase
Gi: inhibits adenylyl cyclase but activates Src tyrosine kinase
Gq: activates phospholipase C
30
What are the GPCR ligands
Biogenic amines, peptides/proteins, amino acids, lipids, nucleotides
31
What is different about insulin and IGF RTK
They contain 2 polypeptide chains
32
What are examples of JAK STAT receptors
Growth hormone, erythropoietin, leptin, interferons, interleukins 2-10 and 15
33
What is unique about the effects of nuclear receptor drugs
Effects can last even after agonist concentration has been reduced to zero
34
Describe the mechanism of hormone receptor activation
In unbound state, heat shock protein 90 is bound to receptor; binding of hormone dissociates the heat shock protein and converts to active configuration
35
What drugs inhibit Na+ voltage gated channels
Local anesthetics, antiarrythmia drugs, epilepsy drugs
36
What is the difference between the actions of excitatory and inhibitory NT in terms of channels they open
Excitatory open cation channels, inhibitory open anion channels
37
What are GABA-A receptors a target for
Inhalation anesthesia, IV anesthesia, ethanol, and anxiety benzodiazepines
38
What is pharmacogenomics
Different response based on different genetics
39
How are individuals defined in terms of their metabolizing ability
0=PM
.5=IM
1-2=EM
>2=UM
40
Which CYP2D6 alleles are nonfunctional
3-6; 10,14,71 have reduced function, and 1-2 are fully functional
41
What is the active metabolite of codeine
Morphine
42
How is codeine converted to morphine
CYP2D6
43
What does CYP2C19 metabolize
Acidic drugs (PPI, antidepressants, antiepileptics and antipltls
44
Which CYP2C19 alleles are nonfunctional
2 and 3; 1 is fully functional; 17 is increased function (but cannot make up for non functioning; therefore heterozygous will be IM; seen in Europeans )
45
What is dihydropyrimidine DH
Elimination for chemo agents; 2A is nonfunctional; ie: fluorouracil (must be IV)
46
What is uridine 5 diphosphoglucoronysyl transferase an example of
Phase II enzyme; 28/28 allele = Gilbert syndrome ; can cause unconjugated bilirubin buildup
47
What is the strategy for eliminating compounds
Converting to more polar and water soluble derivatives (easier to excrete in urine)
48
What are the consequences of bio transformation
- inactivation (aspirin ->acetic acid+salicylate)
- active compound -> active compound (diazepam->oxazepam)
- activation (L-dopa->dopamine)
49
What is an example of a first pass effect that limits the bioavailability
Morphine
50
What happens during the phase I reactions vs phase II reactions
Phase I: makes it inactive (oxidation, reduction, hydrolysis); catabolic; products can be more reactive and toxic
Phase II: makes it more water soluble and increases molecular weight (anabolic)
51
What is unique about the metabolism of isoniazid
Phase II Reaction first
52
What carries out phase I reactions
Mixed function oxidases or monooxygenases (CYP, flavin containing monooxygenase (FMO), epoxide hydrolases)
53
Where are phase I enzymes located
Lipophilic ER membrane of liver
54
What are examples of phase II enzymes
UGT, GST, NAT (n acetyltransferase), TPMT (thiopurine methyltransferase), SULT (sulfotransferase)
55
What are some enzyme inducers in drug metabolism
Phenobarbital, chronic ethanol, aromatic hydrocarbons (benzopyrene - smoke), rifampin, St. John’s wort, carbamazepine, phenytoin
56
What is glucose 6 phosphate DH deficiency
Can’t produce NADPH and therefore cant reduce glutathione from its oxidized form; cells can’t be protected from oxidative damage -> hemolytic anemia in presence of oxidants
57
What causes malignant hyperthermia
Inhalation of succinylcholine activates ryanodine receptor -> increased calcium leading to muscle contraction and formation of heat -> rhabdomyollysis
58
What is the acute toxicity test
Determine the no effect dose and the lethal dose in two species and via 2 routes
59
What is the subacute toxicity effect
Three doses, 2 species
60
What is the chronic toxicity test
Rodent and non rodent species for > 6 months; requires when drug intended to be used for long duration
61
What is the carcinogenic potential
Two years on two species
62
What is the no effect dose
Maximum dose and which a toxic effect is not seen
63
What is a surrogate endpoint
Ex: tumor size instead of survival
64
What was the outcome in the Vytorin vs simvastatin study
Vytorin had greater reduction of LDL but no overall reduction of CV events
65
What is dobutamine
B agonist that activates GPCR; used as a model for desensitization via GRK
66
What do SH2 and 3 bind to, respectively
2: tyrosine kinases
3: proline rich
67
What is SOS
Encodes Guanine nucleotide exchange factor; activates Ras
68
What are targeted anti cancer drugs to RTK signaling
Abs to GF receptors or GFs; multikinase inhibitors
69
What kind of receptor does mineralcorticoid aldosterone have
Nuclear
70
What is spironolactone
Aldosterone antagonist; suppresses expression of ENaC and Na/K pump, decreases reabsorption reduces BP and alleviates heart failure
71
What is verapamil?
Calcium channel blocker used to treat atrial and supraventricular arrhythmia, angina pectoris, HTN; adverse affect: constipation (relaxes gut mm)
72
What are the effects of digoxin
Vomiting and diarrhea (increases contractility of smooth m), disorientation, confusion, visual disturbances (increases vagal activity)
73
What is etoposide
Topoisomerase inhibitor -> activates p53 (because causes DNA damage)
74
What are the different types of antagonism
Pharmacological: action at the same receptor as endogenous ligand or agonist drug; receptor* antagonist
Chemical: when a chemical antagonist makes the other drug unavailable
Physiologic: endogenous pathways regulated by different receptors
75
When are calculations for pharmokinetics used
On drugs with narrow therapeutic index and concentration dependent efficacy and toxicity
76
What are the passive routes of absorption of drugs
- Filtration: through pores or channels; determined by osmotic and hydrostatic pressure
- Diffusion: through cell membranes determined by concentration gradient***most common
77
What do the names of weak bases/acidic drugs end in
Bases: chloride, acetate, hydrochloride, sulfate
Acids: sodium, potassium
78
What are the features of ionized compounds
Lower lipid solubility (more water soluble); do not cross membrane
79
What are the features of unionized compounds
Higher lipid solubility (not water soluble) cross bilateral
80
What does the ionization status depend on
PKa of med and pH of membrane
81
The lower the pka the ______ the acid
Stronger
82
What are the characteristics of active absorption
Saturable (competitive inhibition by other drugs), move against gradient
-Facilitated diffusion is dfft because only one that doesn’t require energy and doesn’t move against a gradient
83
What does alpha represent
Unbound fraction of a drug; small alpha equal small unbound portion
84
Are drugs with high alphas more or less effected by drug-drug interaction
Less; not as much bound so don’t have to compete
85
How do you calculate a drug-drug interaction in terms of bound vs unbound proportion
Percentage drug displacement x bound, add that to free; take that value - original free/original free x 100
86
What are some inhibitors of P450
Fluoxetine, omeprazole, cimetidine, isoniazid, ketoconazole
87
What are the process of renal elimination
- passive glomerular filtration: blood flow dependent
- passive tubular diffusion: proximal or distal tubules; ionization and concentration status dependent
- active tubular secretion: acids/bases secreted
88
What is the rate elimination of first order kinetic drugs
Proportional to plasma concentration
89
What are the kinetic properties of zero order drugs
Saturable; rate of elimination NOT proportional to concentration in plasma; amount of drug removed is same over time; percentage of total amount does not stay the same over time
90
What is Tmax
Onset of activity
91
What is Cmax
Maximum drug concentration
92
What is MTC
Maximum therapeutic concentration
93
Between what two values does the therapeutic window reside
Maximal therapeutic concentration and minimum effective concentration
94
What does F=1 mean
100% absorbed
95
How do you calculate bioavailability
AUCoral/AUCiv x 100
96
What are the 3 things that determine the amount of a drug absorbed
Dose, bioavailability, salt factor
97
What do you have to do to Vd before putting it in an equation
Multiply by body weight in kg
98
What is the formula for ideal body weight for males and females
Female: 45 kg + (2.3 kg x heigh in inches - 60 inches))
Male: 50 kg + (2.3 kg x height - 60)
99
What is clearance
Volume of blood per unit of time that is cleared of the drug
100
What is tau
Dosing interval in hours (ie: q8h, tau=8)
101
What is the tau for continuous infusion
1
102
What is Kel
Elimination rate constant; fraction of drug removed per unit time
103
What is the equation for amount of drug absorbed
S x F x Dose
104
What is the equation for dose of different dosage form
Amount absorbed from current form/S x F of new form
105
What is the equation for concentration in plasma
(S x F x Dose)/ Vd
106
What is the equation for loading dose
(Vd)(Cp)/SxF
107
What is the equation for supplemental loading dose
(Vd)(Cp desired - Cp initial)/ SxF
108
What is the equation for clearance
(S)(F)(dose/tau)/Cp
109
What is the equation for maintenance dose
(Cl)(Cp)(tau)/(S)(F)
110
What is the equation for elimination rate. Constant
Cl/Vd OR (ln Cpt1 - ln Cpt2)/(t2-t1)
111
What is the equation for half life
.693/Kel
112
What is the equation for creatinine clearance
[(140-age) x IBW / (72 x Scr)
| *multiply by .85 if patient is female
113
What are choline esters
Acetylcholine, carbachol, Bethune howl; poor absorption; less active when given PO; hydrolyzed by cholinesterase but at diff rates (acetylcholine most rapid); MOA: agonist on cholinergic receptors
114
What are alkaloids
Ex: muscadine, nicotine, pilocarpine; uncharged tertiary amines; well absorbed through most sites; muscadine is highly toxic when ingested and can enter brain; excreted by kidneys (acidification of urine excelerates clearance); MOA: agonist on cholinergic receptors
115
What are the muscarinic receptor types
```
M1: on nerves; Gq
M2: heart, nerves, smooth m; Gi (activates K channels)
M3: glands, smooth m, endothelium; Gq
M4: CNS; Gi
M5: CNS; Gq
```
116
How do muscarinic agonists cause smooth m relaxation around bv
Causes them to release EDRF -> increases cGMP
117
What is the effect of small doses of Ach versus large doses
Small: vasodilation and reflex increased heart rate
Large: bradycardia and hypotension
118
What mAChR is required for direct activation of smooth m contraction
M3
119
What cholinergic receptors are seen in difft parts of the CNS
Brain -> mAChRs
| SC -> nAChRs
120
What are excitatory vs inhibitory mAChRs involved in the CNS
Excitatory: increased cognitive function and seizures
Inhibitory: tremors, hypothermia, analgesia
121
What do different doses of nAChRs cause in the brain
Moderate -> alertness, high -> tremor, emesis, respiratory stimulation; lethal -> convulsions and coma (insectiside)
122
What are the effects of stimulation of nAChR on the PNS
CV: sympathomimetic (HTN)
| GI/GU: parasympathomimetic
123
what are the uses for direct acting cholinergic agonists
Glaucoma (contracts culinary body which facilitates outflow of aqueous humor and reduces pressure), accommodative esotropia (misalignment of eyes), GI/GU tract disorders (bethanechol; used for stony of bowel, mega colon, urinary retention, esophageal reflux (increases tone), *must be certain no obstruction before use*, piocarpine and cevimeline increase salivary secretion (sjogren)
124
What are the toxic effects of muscarinic stimulants
- Overdose of pilocarpine and choline esters -> NVD, urgency, salivation, sweating, vasodilation, bronchial constriction); blocked by atropine
- mushrooms of genus inocybe contain alkaloids -> muscarinic poisoning
* contraindications = asthma, hyperthyroidism, coronary insufficiency, acid-peptic dz
125
What are the toxic effects of nicotinic stimulants
-Acute: CNS stimulation (convulsions->coma->resp arrest), skeletal m depolarization -> blockade -> resp paralysis, HTN, cardiac arrhythmia
Treat with atropine and diazepam; blockade is not responsive to pharm treatment
-Chronic: increased risk of vascular dz and peptic ulcers
126
What is Ach used for
Intraocular use during surgery; not given systemically
127
What is methacholine used for
Inhaled for bronchial airway hyperactivity who don’t have asthma; rarely used
128
What is bethanechol used for
Urinary retention and heartburn; selective mAChR agonist; can produce UTI if sphincter fails to relax
129
What is carbachol used for
Nonspecific cholinergic agonist used to treat glaucoma or to produce miosis during surgery
130
What is cevimeline used for
Oral; treats dry mouth in sjogren
131
What is pilocarpine used for
Xerostomia in sjogren or head and neck CA; miosis, glaucoma (topical); pure mAChR agonist
132
What is varenicline used for
Smoking cessation; partial agonist binds to nicotinic receptors in brain; releases dopamine to reduce craving; eliminated in urine as unchanged drug nausea, changes in behavior, agitation, depression, suicide
133
What are the indirect acting cholinergic agonists
Cholinesterase inhibitors
- alcohol
- carbamic acid esters
- organophosphates
134
What is the difference between binding of alcohols/carbamic acid esters and organophosphates to AChE
Organophosphates bind covalently and irreversibly; opposite for alcohols and carbamic acid
135
What is special about the negative side effects of organophophates
Lipid soluble and therefore CNS toxic
136
What is the only organophosphate that doesn’t have effects on CNS
Echothiophate
137
What is irontecan
Topoisomerase I inhibitor prodrug; chemo combined with 5 FU; metabolized into SN-38; UGT1A polymorphisms at increased risk for toxicity (b/c breaks down SN-38 which is highly toxic)
138
What is thiopurine s methyltransferase
Phase II enzyme; deactivates thiopurine drugs; ex; azathiorprine (prodrug of 6-MP), 6-MP and G-Tg;
139
What are the classifications of G6PD deficiencies
I most severe, V no deficiency (enhanced activity); III is hemolysis with stressors
140
How is glucose-6PDH deficiency inherited
X linked
141
What is rasburicase
Urate oxidase enzyme used for chemo; produces hydrogen peroxide during metabolism; don’t give to G6PDH deficiency
142
What population is most at risk for G6PDH
African
143
What is the OATP1B1 transporter
Organic anion transporter; encoded by SLCO1B1; located on absolute real side of hepatocytes and up takes acidic drugs (statins, methotrexate and bilirubin); most common variant increases systemic exposure of simvastatin -> lower dose to reduce this problem
144
What is the breast cancer resistance protein
BCRP (encoded by ABCG2); efflux transporter in ABC family; decreased function found in Asians -> associated with changes in response to xanthine oxidase inhibitor (allopurinol) and rose a statin
145
Which drugs are associated with hypersensitivity reactions
Methotrexate, NSAIDs, sulfonamides, abx, steroids, Anti-epileptic; hypersensitivity attributed to HLA polymorphisms
146
What is abacavir
Nucleoside reverse transcriptase inhibitor used in HIV; causes Steven Johnson syndrome in people with HLAB 57:01 polymorphisms (more common in European); abacavir is a prodrug -> activated to arborvitae triphosophate; hypersensitivity reaction may involve CD8 cells (HLA B 57:01 presents it to CD8 cells)
147
What is flucloxacillin
Causes hypersensitivity reaction that causes liver toxicity; polymorphism in HLAB 57:01
148
What polymorphism is associated with ximelagatran induced liver injury
HLA DRB1 07:01
149
What are genetic variants in IFNL3 (IL-28B) associated with
Predicts success of HCV treatment response to iFN alpha and ribavirin
150
What is CYP2C9
Phase I metabolized acting on acidic drugs (warfarin, phenytoin, and NSAIDs)
151
What is the target of warfarin
Inactivates VKORC1; polymorphism can cause increased sensitivity to warfarin
152
What is an example of a prodrug
Chlorazepate
153
What is the important part about pharmacotherapeutics
Evidence based
154
What is pharmaceutical equivalence
- same active ingredients
- same dosage form/route of administration
- same strength/concentration of active ingredient
- meet same standards for quality/purity
155
What are pharmaceutical alternatives
Same active drug, but different salt/complexes or different dosage forms or strengths
156
What does bioequivalence mean
Similar rate and extent of absorption (80%-125%)
157
What is therapeutic equivalence
Must be pharmaceuticals equivalent and bio equivalent; also expected to have the same clinical effect and safety profile
158
What are the equivalency ratings
A: equivalent
B: not equivalent
159
What are the classifications of legend drugs
* drugs that needs a script
- Non-scheduled/non-controlled: NO abuse potential (ex: furosemide, cephalexin, amoxicillin, propranolol)
- scheduled/controlled: Based on abuse potential; ie: morphine, codeine, amphetamine, diazepam; CI agents have no FDA approved indications; CV = not as abusive (lower number, higher risk of addiction)
160
How many mcg are in a mg
1000
161
What is mEq
Milliequivalent
162
How many pounds is one kg
2.2
163
How many tsps are in one tbsp
3; tsp is 5 ml; tbsp is 15 ml
164
How many ml is in one ounce
30 ml; 2 tbsps, 6 tsps
165
How many ounces is in one cup
8
166
How many cc are in one liter
1000
167
How many pints are in a quart
2
168
How many ounces is in one pint
16 oz
169
How many ml is one quart
946
170
How many ml is one pint
473
171
How many liters is in a gallon
3.79
172
What does qhs stand for
Every night at bed time
173
What does ac mean
Before meals; pc is after meals
174
What are the abbreviations used for administration in eyes
Od: right eye
Os: left eye
Ou: both eyes
175
What are the abbreviations for administration of drugs in ears
Ad: right ear
As: left ear
Au: both ears
176
What are the quarternary and charged AChE inhibitors
Neostigmine, pryidostigmine, edrophonium, echothiophate, ambenonium; not soluble in lipids = poor absorption; IV administration; no CNS distribution; duration of effect determined by stability of inhibitor:enzyme complex NOT by metabolism
177
What are the tertiary uncharged AChE inhibitors
Well absorbed from all sites, distributes in CNS, more toxic than quaternary; physostigmine, donepezil, tacrine, rivastigmine, galantamine
178
How do alcohols bind to AChE
Reversibly; short lived therefore short duration of action as AChE inhibitor
179
How do carbamic acid esters act as AChE inhibitors
Hydrolyze to analogue of ACh; second step forms covalent bond btw enzyme and carbamic acid group of inhibitor; * requires 30 min-6 hrs to hydrolyze
180
How do organophosphates act as AChE inhibitors
Phosphorus-enzyme bind highly stable and hydrolysis at a slow rate; undergoes aging (breaking of oxygen-P bond of inhibitor which further strengthens the bond)
181
Where do quaternary AChE inhibitors mainly work
NMJ
182
Which AChE inhibitors are most commonly used to reverse paralysis during surgery
Neostigmine and edrophonium
183
Which drugs are used to treat Alzheimer’s
Donepezil, rivastigmine, galantamine, physostigmine
184
What are the side effects of anti cholinergic drugs
Cutaneous vasodilation, anhydrotic hyperthermia, nonreactive mydriasis, delirium, hallucinations, etc
185
What is given to reverse anticholinergic toxicity
Phsyostigmine
186
What happens if you give AChE inhibitors and systemic corticosteroids to someone with myasthenia Travis
Enhances muscle weakness
187
How do you treat AChE inhibitor poisoning
Atropine and cholinesterase regenerator (pralidoxime) -> can regenerate enzyme by removal of phosphorous group from the active site
188
What is pyridostigmine
Prophylaxis treatment for AChE inhibitor poisoning
189
What are the tertiary amines vs quaternary amines of anticholinergic drugs
Tertiary: atropine, tropicamide, benztropine; used for effects on eye and CNS
Quaternary: charged - exert effects in periphery; ipratropium, glycopyrrolate
190
Is atropine selective
No
191
What are the side effects of scopolamine
Drowsiness
192
What is cycloplegia
Inability to accomodate(results from anti muscarinic agents)
193
Which muscarinic receptor is found on the bladder
M3; targeted for overactive bladder; ex: trospium, oxybutynin, darifenacin, solifenacin, tolterodine (last 3 have fewer side efffects)
194
What is atropine contraindicated in
Glaucoma and men with BPH
195
What is pirenzepine
Selective for M1; inhibits gastric secretion - treats ulcers
196
What is mecamylamine
Tertiary amine that blocks ganglion
197
What do ganglionic blockers do
Enhance sympathetic tone; cause sedation, cycloplegia, decreased BP, inhibited motility of GI, urinary retention
198
What are the GPCRs associated with each of the dopamine receptors
D1 and D5: Gs; all others GI
199
Where are alpha 1 receptors located
Vascular smooth m, pupillary dilator m, prostate, and heart (increases force of contraction)
200
Where are alpha 2 receptors located
Postsynaptic CNS neurons, platelets, adrenergic and cholinergic nerve terminals (inhibits transmitter release), vascular smooth m, fat cells (inhibits lipolysis)
201
Where are B1 receptors located
Heart and juxtaglomerular cells
202
Where are beta 2 receptors located
Lungs, uterine, vascular smooth m (Relaxation), skeletal m(potassium uptake), liver (activates GNG and glycogenolysis)
203
Where are beta 3 receptors located
Bladder (Relaxes detrusor) and fat cells (activates lipolysis)
204
Where are D1 vs D2 receptors located
D1: smooth m (dilates renal arteries)
D2: nerve endings (modulates transmitter release)
205
What are the indirect acting adrenomimetics
Cocaine, phenelzine (MAOI), amphetamines, ephedrine
206
What are the alpha agonists
Clonidine (alpha 2) and phenylephrine (alpha 1)
207
What are the mixed alpha and beta agonists
Norepinephrine (more alpha than beta) and epi (alpha=beta)
208
What are the beta agonists
Dobutamine (beta 1), isoproterenol (both), terbutaline (beta 2), albuterol (beta 2)
209
What are the dopamine agonists
Dopamine and fenoldopam
210
What are the effects of epi on the heart
Increased contraction (positive inotropic effect), increase HR, increases conduction velocity
211
What are the effects of epi on vascular tone
Increase sytosolic BP, but decrease diastolic BP and PVR, MAP unchanged
212
What are the effects of epi on the respiratory system
Relaxes bronchial muscle, decreases secretion via alpha 1
213
What are the effects of epi on skeletal m
Muscle tremor (beta2), increases K+ uptake (B2); elevates blood glucose (B2), increases FFA and increases renin release
214
What are the effects of norepi
Cardiac stimulant but reduces heart rate; vasoconstrictor; no beta 2 effects; increases BP (baroreceptor reflex)
215
What does phenylephrine do
Mydriasis and decongestant, vasoconstriction, decreased HR
216
What is the effect of clonidine
Decreases symp outflow, reduces BP, bradycardia, locally -> vasoconstriction b/c causes release of NE from presynaptic neurons (its an alpha 2 agonist)
217
What does isoproterenol do
Positive inotropic and chronotropic affect (B1), vasodilator, decreases BP (B2), and causes bronchodilation
218
What does dobutamine do
B1 with alpha 1 activity; potent inotropic action
219
What do terbutaline and albuterol do
Both B2; bronchodilation and relaxation of uterus
220
What is the effect of dopamine
D1: vasodilation (high density in renal, cerebral, mesenteric, and coronary aa); D2 suppresses NE release; B1 activation at higher doses, alpha agonist at even higher doses
221
What is ephedrine
Releasing agent and direct adrenergic agonist
222
What are characteristics of indirect adrenergic agonists
More lipophilic and cross BBB
223
What is tyramine
Indirect acting adrenergic agonist; product of tyrosine metabolism from cheese and meets; releases NE from presynaptic terminals if IV administration; metabolized by MAO (can cause increased BP in patients taking MAO inhibitors)
224
What adrenergic agonists would you use in hypotensive emergencies
NE and phenyephrine
225
What adrenergic agonist would you use for chronic hypotension
Ephedrine
226
What adrenergic agonists would you used to treat cardiogenic shock (due to MI)
Dopamine; dobutamine
227
What adrenergic agonists would you use for heart failure
Acute: dobutamine
| Severe with decreased renal perfusion: dopamine
228
What adrenergic agonists would you use for complete AV block and cardiac arrest
Epi and isoproterenol
229
What adrenergic agonist do you use for narcolepsy
Amphetamines and methylphenidate
230
What adrenergic agonists inhibit appetite
Phentermine, ephedrine, amphetamines
231
What do you use to treat anaphylaxis
Epi
232
What adrenergic agonist do you use to treat glaucoma
Alpha 2 selective agonist; apraclonidine, brimonidine
233
What are adverse effects of adrenergic agonists
Elevated BP, worsening heart failure, tachycardia, insomnia, convulsions and hemorrhagic stroke (cocaine)
234
What are the indirect acting anti adrenergic drugs
Metyrosine (inhibits tyrosine hydroxylase so cant make dopamine), guanethidine (prevents storage and depletes NE)
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What are the non selective alpha antagonists
Phentolamine and phenoxybenzamine
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What are the alpha 1 selective antagonists
Prazosin, terazosin, tamsulosin, doxazosin, alfuzosin, silodosin
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What is the difference between phentolamine and phenoxybenzamine
Phentolamine: reversible competitive antagonist; shorter acting
Phenoxybenzamine: non-competitive irreversible alpha antagonist; longer acting
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What do alpha antagonists do
Decrease BP, reflex tachycardia, relax prostate and bladder; relaxation of pupillary dilator m
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When would you use alpha antagonists
- Pheochromocytoma: treat with phentolamine or phenoxybenzamine
- HTN: -osin
- ED: phentolamine and vasodilator papaverine
- BPH: tamsulosin, silodosin
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What are the adverse effects of alpha antagonists
Seen more with alpha 2; postural hypotension (ant of alpha 1 on venous sm); tachycardia, retention of fluid and salt, impaired ejaculation, nasal stuffiness
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What are the mixed adrenergic blockers
Labetalol and carvedilol (beta and alpha1 antagonist)
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What are the non selective beta blockers
Propranolol, pindolol, nadolol, penbutolol
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What are the beta 1 blockers
Metoprolol, betaxolol, acebutolol, atenolol
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What are the partial agonists of beta receptors
Acebutolol, labetalol, penbutolol, pindolol
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What are the inverse agonists of beta receptors
Carvedilol and metoprolol
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What are beta blockers with ISA
Intrinsic sympathomimetic activity; they are partial agonists at beta receptors; block symp effect but have submaximal effects of their own (blunted symp); use for less risk of inducing bradycardia, increases VLDL/HDL
247
What are the effects of beta blockers
Negative inotropic, negative chronotropic, initial rise in PVR but with chronic use decrease in PVR; inhibits renin release, increases airway resistance, reduces production of aqueous humor, inhibits lipolysis
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Which beta blockers are used after an MI
Timolol, propranolol, metoprolol
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Which beta blockers are given for heart failure
Metoprolol, bisoprolol, carvedilol *contraindicated in acute CHF
250
What beta blockers are used to treat glaucoma
Timolol and betaxolol NOT propranolol
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Which beta blocker is used to treat hyperthyroidism
Propranolol
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What should you switch to if the beta blocker administered causes a hypoglycemic episode
Seen more in patients with T1DM; Beta 1 selective (also switch to this if it causes HTN or increases airway resistance)
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What does s.l. Stand for
Sublingually
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What does s.q. Stand for
Subcutaneously
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What does p.r. Stand for
Per rectum
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What does NGT and OGT stand for
NGT: nasogastric tube and oro-gastric tube
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What does ut.dict. Stand for
As directed
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What does t.r.a stand for
To run at
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What does k.v.o stand for
Keep vein open
260
What does NS stand for
Normal saline *.9% NaCl
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How many phases of clinical trials need to be conducted in order to be approved by the FDA
I-III
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What is a lead compound
Chemical compound that has pharmacological or biological activity and who’s chemical structure is used as a starting point for chemical modification in order to improve efficacy, potency, or selectivity
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What happens after identification of a lead compound
Drug is screened and studied in vitro and in vivo leading candidate then undergoes preclinical and toxicity testing before human evaluation
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What is the purpose to in vitro studies
Esablishes the drugs target and effects; tested in cellular system that best represents the disease state the therapy is tarteting
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When can the lead compound be submitted for approval to test in human
If the pharmacological properties are safe and adequate and if the compound produces the expected result
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What is the no effect dose
Max dose at which a specified toxic effect is not seen
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What is a crossover design
Patients receiving each therapy in sequence (serve as own controls)
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What is phase 0 of clinical trial
Study subpharmacological doses of drug; low cost
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What is phase I of clinical trials
First stage of drug testing in humans; determines whether humans and animals show significantly different responses; 25-50 ppl; if drug induces toxicity, sick volunteers are used; generally not blind; absorption, half life and metabolism are studied; usually in patient
270
What is phase II of clinical trials
100-200 patients that have the target disease to determine efficacy; typically single blind; include placebo, established drug for positive control and investigational agent; efficacy, dosing, and toxicity are reported; often in clinical centers; drug failure typically occurs here
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What is phase III of clinical trials
Conducted after preliminary studies; further establishes drug safety and efficacy by including 300-3000 patients with the target disease; crossover and double blind techniques used; carried out in similar settings to how the drug will be used; most expensive
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What is phase IV of clinical trials
After approval to marker the new drug; new drugs with side effects that occur with incidence of 1 in 1,000, this is essential; no fixed duration
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What kind of xenobiotics can be excreted by the kidneys
Polar and small compounds
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What is biotransformation
Chemical modification of lipophilic, unionized or large compounds to terminate their actions
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What is an example of biotransformation that activates a compound
L-dopa to dopamine
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What is an example of a drug that undergoes extensive first pass biotransformation
Morphine *need to give IV
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Can phase II Reactions proceed phase I
Yes
278
Describe the features of phase I Reactions
Catabolic; converts to more polar metabolite by adding or removing functional group; oxidation, reduction, hydrolysis, hydroxylation, epoxidation, dealkylation, deamination, desulfurization, dechlorination; Carried out by mixed function oxidases (MFOs) or monooxygenases (located in ER membrane of liver)
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Describe the features of phase II reactions
Anabolic; occurs at faster rate
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How does CYP450 work
Uses O2, H+ derived from NADPH to carry out oxidation
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What does a defect in pseudocholinesterase cause
Metabolize succinylcholine slower than normal
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What is slower acetylator phenotype
Have decrease in N-acetyltransferase which causes isoniazid, hydralazine, caffeine and other amines to be metabolized at slower rates leading to toxicity (hepatitis)
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What are cyp inducers
Phenytoin (Anti convulsants), ethanol, armonatic hydrocarbons benzopyrene (Tobacco smoke), rifampin, phenobarbital (anesthesia)
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What does grapefruit juice inhibit
CYP3A4
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What is the effect of administering allopurinol with mercaptopurine
Allopurinol will inhibit metabolism of mercaptopurine which extends its action (enhances toxic effect)
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What are the changes related to aging that affect pharmacokinetics
Body water, lean body mass, body fat, serum albumin, kidney weight, hepatic blood flow
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What drugs are flow-limited
Rate of elimination depends on rate of blood flow; therefore will be affected with cardiac dz; examples are morphine, lidocaine, beta blockers, verapamil
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The wider the therapeutic window the _________ the drug
Safer
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How are GPCR responses desensitized
GRK phosphorylates the GPCR and arrestin binds to it; cannot bind ligand
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What does a small alpha mean
Small unbound portion of drug
291
What is the impact of an inducer on pro drugs
Faster onset but a shorter duration
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How is the rate of elimination related to the blood concentration in a first order drug
Rate of elimination is proportional to the amount of drug in the blood; fraction lost doesn’t change (ie: lose 50% every time)
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What would be the difference between an IV push and IV drip
IV push has sharp increase in drug concentration, drip does not because controlled
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What units is the Vd in
L/kg
295
What is clearance measured in
L/hr
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For a first order drug, what happens to the steady state if you double the dose you give your patient
The steady state will double
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What is potency
The amount of drug required to produce an effect *ED50; determines clinical dose
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What is efficacy
Maximum effect
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What is the relationship between clearance and half life
Inversely proportional
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What does G6PD do
Converts NADP to NADPH which then reduces glutathione; if deficient do not give antimalarial, aspirin, nitrofurantoin, NSAIDs, quinidine, or sulfa drugs
301
Does norepi have effects on beta 2
No
302
What are the effects of clonidine
When given IV: vasoconstriction b/c occurs post synaptically
| Orally: vasodilation and Bradycardia (decrease release of NE)
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What are the side effects of AChE inhibitor poisoning
Salivation, lacrimation, urination, defecation, GI pain and gas, emesis
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How do you treat organophosphate poisoning
Atropine and pralidoxime (pulls organophosphate out of AChE - used for nicotinic effects)
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What is glycopyrrolate
MAChR antagonist; used after surgery to reverse paralysis
306
What is oxybutynin used for
Urinary disorders
307
What are ipatropium and tiotropium used for
COPD; inhaled *charged
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What is varenicline used for
Smoking cessation; partial agonist to nAChR
309
What effect do anti-histamines have on the cholinergic system
MAChR antagonist
310
Can physostigmine cross the BBB
Yes
311
What cholinergic drug is used for Parkinson’s
Benzotropine
312
What two drugs make up lomotil
Diphenoxylate (opiate) and atropine
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If you don’t have dobutamine, what combination of drugs can you give for a similar affect
NE and phentolamine
