TO RECALL 1 Flashcards
1
Q
Drug:
AMIODARONE
A
- drug for cardiac arrythmias
- has multiple receptors (i.e. nuclear thyroid hormone receptor) - contributes to its toxicity
2
Q
Drug:
SOTALOL
A
- Beta-blocker
- used as an anti-arrythmic
- Given as a racemic mixture where both L- and D- enantiomers are equipotent K+ channel blockers BUT L- as the more potent Beta-adrenergic antagonist
Example for The Specificity of Drug Responses
3
Q
Drug:
Nitrovasodilators
A
- treats angina where NO-dependent elevation of cGMP in vascular smooth muscle produces vasodilation
- chronic administaration results in complete tolerance (Tachyphylaxis)
4
Q
Drug:
VARENICLINE
A
- used for smoking cessation therapy
- partial agonist of nicotinic receptors
5
Q
Drug:
SIDENAFIL, TADALAFIL, VARDENAFIL
A
- phosphodiesterase (PDE) 5 inhibitors
- in vasculature
- SIDENAFIL - treatment for erectile dysfunction
- co-administration with nitrovasodilators can cause catastrophic vasodilation & severe hypotension
6
Q
Drug:
WARFARIN
A
- oral anticoagulant
- has a narrow margin between therapeutic inhibiton of clot formation and bleeding complications
- Antibiotics (decrease vit. K absorption) & NSAIDS (i.e. Aspirin that inhibits platelet aggregation) will enhance effect of warfarin - AT RISK FOR BLEEDING
7
Q
Drug:
ALPHA-METHYL TYROSINE
A
- inhibits synthesis of norepinephrine
8
Q
Drug:
COCAINE
A
- BLOCKS Norepinephrine uptake
9
Q
Drug:
AMPHETAMINE
A
- promotes NE release
- similar effect to cocaine
10
Q
Drug:
SELEGILINE
A
- inhibits NE breakdown by MAO (Monoamine Oxidase)
11
Q
Drug:
FUROSEMIDE, CHLOROTHIAZIDE, AMILORIDE
A
- Diuretics
- affects ion pumps & transporters to increase movement of Na+ into the urine
12
Q
Drug:
OMEPRAZOLE
A
- Proton pump inhibitor (H+-K+ ATPase)
13
Q
Drug:
TERBUTALINE
A
- Beta 2 adrenergic agonist
- used for broncodilation in asthma
14
Q
Drug:
Sulfonylureas & Meglitinides
A
- oral hypoglycemic drug (lowers blood sugar)
- activate Beta cells to increase insulin release in pancreas
- used in treatment of type II diabetes mellitus
Sulfonylureas - target ATP-sensitive potassium channels
Meglitinides - target sulfonylurea receptor 1 (SUR1)
15
Q
Drug:
LIDOCAINE & TETRACAINE
A
- Local anesthetics
- block voltage-gated Na+ channels in pain neurons to inhibit depolarization
16
Q
Drug:
NIFEDIPINE, DILTIAZEM, VERAPAMIL
A
- Ca+ channel antagonist/blockers
- blocks muscle contraction in blood vessels leading to vasodilation
17
Q
Drug:
ROCURONIUM
A
- competitive antagonist of acetylcholine
- Muscle Relaxant
18
Q
Drug:
NESIRITIDE
A
- Synthetic BNP agonist
- used in treatment of acute decompensated heart failure
19
Q
Drug:
SACUBITRIL
A
- neprilysin inhibitor
- blocks ANP & BNP breakdown
- treats decompensated heart failure
20
Q
Drug:
ATROPINE
A
- blocks acetylcholine (parasympathetic ligand)
21
Q
Drug:
DOBUTAMINE
A
- Beta 1 receptor agonist
- increase strength of heart contractions
22
Q
Drug:
TETRABENZINE
A
- Symptomatic treatment for your Huntington disease - Antichorea (chorea: movement disorder)
- inhibits (SLC18A2) VMAT2: Vesicular monoamine transporter - function to store amines (i.e. Dopamine)
23
Q
Drug:
CANAGLIFLOZIN, DAPAGLIFLOZIN, EMPAGLIFLOZIN
A
- Inhibits SLC5 family transporters SGLT1 & SGLT2 (Na+-glucose transporters)
- treatment for diabetes
- reduces renal reabsorption of glucose, leading to glucose elimination
at the proximal convoluted tubules
24
Q
Drug:
LESINURAD
A
- Treatment for gout
- targets (SLC22A12) URAT1 (Uric Acid Transporter 1) to inhibit uric acid reabsorption in the kidney
at the proximal convoluted tubules
25
# Drug:
IVACAFTOR
* used in treatment for cystic fibrosis
* a potentiator that increases the probability that the mutant chloride channel (CFTR-G551D) remains open
26
# Drug:
PARAVASTATIN
* HMG-CoA reductase Inhibitor
* used to reduce amount of 'bad cholesterol'
* functions through uptake by SLC OATP1B1 in liver
* when it does not enter the liver, an adverse response is *skeletal muscle myopathy*
27
# Drug:
LOPERAMIDE
* Peripheral opioid
* for diarrhea
* Do not mix with Quinidine (potent Pgp inhibitor)
28
# Drug:
QUINIDINE
* anti-arrythmia
* Potent Pgp inhibitor
29
# Transporter:
Pgp or MDR1
P-glycoprotein or Multidrug Resistance Protein 1
* works to eliminate drugs via powerful efflux mechanisms
* usually for protection (common in BBB) but pathogenic when present in tumor cells
30
# Drug:
SSRI - Selective Serotonin **Reuptake** inhibitor
* anti-depressants
* targets SERT (Serotonin Transporter) or SLC 6A4
31
# Drug:
TIAGABINE
* anti-epileptic drug
* inhibits GABA reuptake by interacting with GAT1 (GABA transporter in the brain) to prolong GABA in the synaptic cleft
32
# Drug:
FEXOFENADINE
* antihistamine drug: H1 receptor **antagonist**
## Footnote
Uptake: in liver by OATP1B1 and OATP1B3
Excretion: in bile by MRPT2 and BSEP
33
# Drug:
BOSENTAN
* an endothelin antagonist
* treatment for pulmonary arterial hypertension
* *Cyclosporine, rifampicin, sidenafil* inhibits its uptake
## Footnote
Uptake: OATP1B1 and OATP1B3
Metabolized by: CYPC9 and CYP3A4
34
# Drug:
RIFAMPICIN
* treats tuberculosis infection
35
# Drug:
ACETAMINOPHEN
* non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain
* aka Paracetamol
36
# Drug:
VALPROIC ACID
* anticonvulsant (or anti-epileptic)
37
# Poisoning-Antidote: *What is the antidote for?*
Acetaminophen
N-Acetylcysteine
38
# Poisoning-Antidote: *What is the antidote for?*
Organophosphorus and carbamate
(in pesticides)
Atropine Sulfate
39
# Poisoning-Antidote: *What is the antidote for?*
Iron
Deferoxamine
40
# Poisoning-Antidote: *What is the antidote for?*
Lead
* EDTA
* CaNa2
41
# Poisoning-Antidote: *What is the antidote for?*
Methanol, ethylene glycol
* ethanol
* fomepizole
42
# Poisoning-Antidote: *What is the antidote for?*
Cyanide
* Thiosulfate
* sodium
* Hydroxocobalamine
* hydrochloride
43
# Poisoning-Antidote: *What is the antidote for?*
Carbon monoxide
Oxygen
44
# Poisoning-Antidote: *What is the antidote for?*
Opioids
Naloxone hydrochloride
45
# Poisoning-Antidote: *What is the antidote for?*
Coumarin, indanedione
Vitamin K (phytonadione)
46
Isoniazid is metabolized by what enzyme? What are the enzyme’s gene variations?
N-acetyl transferase 2 (NAT2)
NAT2 gene can result to 3 variations of acetylators : (1) fast acetylator, (2) intermediate acetylator, (3) slow acetylator
*slow acetylators are associated with hepatotoxicity*
47
# Drug
Primaquine
Anti malaria drug
First pharmacogenetics discovery where primaquine induces hemolysis in patients with G6PD deficiency leading to anemia
48
# Drug
Thiopental
Anesthetic - very lipophilic
49
2 most important phase 2 reactions and why
* glucuronidation - most dominant phase in adults
* sulfation - only phase 2 reactions in neonates
50
Major enzyme family for Phase 1 metabolism - what is the most common enzyme from that family
CYP 450 - CYP3A4
51
# Drug
Anastrozole
Drug to treat estrogen dependent tumors
It inhibits CYP19/aromatase which functions to produce estrogen from testosterone (metabolizes testosterone and androstenedione)
52
Most polymorphic CYP450 enzyme - be conservative with associated drugs
CYP2D6
53
Drugs metabolized by FMO3
* nicotine
* ranitidine & cimetidine (H2 antagonists/blockers)
* clozapine (antipsychotics)
* itopride (antiemeptics)
54
# Drug
Carbamazepine
Anti epileptic drug
Metabolized by microsomal EHs to dihydrodiol for inactivation
*Valnoctamide (tranquilizer) and Valproate (anticonvulsant) inhibits mEH which leads to carbamazepine toxicity
55
sEH - soluble Epoxide hydrolase
Epoxides of arachidonic acid and docosahexaenoic acid reduce inflammation, hypertension, and pain but are normally degraded quickly by sEH to vicinal diols that are generally less biologically active
sEH inhibitors reduce both inflammatory and neuropathic pain and synergize with nonsteroidal anti-inflammatory drugs
56
# Drug
IRINOTECAN
Cancer chemotherapeutic agent
Metabolized by intracellular **carboxylesterases**
57
What drug is more pharmacologically active than the parent after phase 2 metabolism
Morphine (glucuronide conjugate)
Minoxidil ( sulfate conjugate)
58
Only phase 2 reaction that occurs in the ER (like phase 1) instead of the cytosol (normal for phase 2)
Glucuronidation
59
Crigler-Najjar Syndroe
Defect in UGT enzyme (glucuronidation)
Type 1 - complete lack
Type 2 - deficiency
60
Gilbert Syndrome
Mutation in the UGT1A1 gene
Indications:
- predisposed to adverse drug reactions
- reduced capacity to metabolize drugs by UGT1A1
61
*Sulfation as Phase 2 metabolism reaction*
Sulfotransferase (SULT) more abundant in intestine than liver
SULT1B1
*SULT1A1 is most important in the liver*
62
*Sulfation as Phase 2 metabolism reaction*
SULT enzyme in human fetal tissues
SULT1C1
63
*Sulfation as Phase 2 metabolism reaction*
SULT in skin that catalyzes cholesterol
SULT2B1b
64
NAPQI (N-acetyl-p-benzoquinone imine)
Toxic metabolite of acetaminophen; neutralized through conjugation with GSH (reduced form of glutathione)
65
Phase 2 reaction that protects cellular macromolecules from damage against reactive electrophiles
Glutathione Conjugation/ Glucuronidation
GSTs catalyze the transfer of glutathione to reactive electrophile
*Over expression of GSTs is related to resistance to apoptosis and reduced efficacy of chemotherapy - inhibition of GSTs is used to modulate drug resistance by sensitizing tumors to anticancer drugs*
66
# Drug
Isoniazid
Antibiotic (common for TB)
67
# Drug
Dextromethorphan
Cough suppressant
68
Enzyme Induction vs. Enzyme Inhibition
*Drug A is the inducer of enzyme; Drug B is the one being
metabolized by the enzyme. Drug B will be metabolized faster and it becomes less effective if it is coadministered with Drug A*
