Term
Name the substrate and product of the following enzymes:
- Phospholipase A2
- 5-LOX
- PGH Synthase 1/2 |
|
Definition
- Phospholipase A2: membrane phsopholipids---> AA
- 5-Lox: AA---> 5-HPETE (----> 5-HETE and LTs via other enzymes)
- PGH Synthase: AA---> PGG2---> PGH2 (---> PGs and TxA2 via other enzymes) |
|
|
Term
| List the main differences between COX-1 and 2. |
|
Definition
COX-1: constitutively expressed; house-keeping; GI mucosal integrity
COX-2: inducible (bacterial LPs, cytokines, GFs); Inflammatory response (fever and pain); NOT in platelets |
|
|
Term
| Which two PGs mediate SM mm relaxation? What induces SM mm contraction? |
|
Definition
relaxation: PGI2; PGE2 (strongly affects ductus arteriosus)
contraction: TxA2 |
|
|
Term
| Which two PGs are used to induce uterine contraction? |
|
Definition
|
|
Term
| Which two PGs mediate cytoprotective functions? |
|
Definition
| PGE2 and PGI2 (e.g. gastric acid secretion inhibition; increased mucus secretion; mucosal blood flow regulation) |
|
|
Term
| Which two factors mediate the balance of platelet aggregation? |
|
Definition
| TxA2 (promotes platelet aggregation); PGI2 (inhibits it) |
|
|
Term
| How do abnormally high (non-physiological) levels produce pain? |
|
Definition
| At site of inflammation, PGs increase sensitivity of peripheral sensory nn endings to algesic stimuli |
|
|
Term
| Explain the mechanism of PGE2-mediated PERIPHERAL pain reception. |
|
Definition
| inflammation---> COX-2---> PGE2---> binds EP-R---> opens Na+ channels---> membrane depolarized---> easier to acheive AP---> pain at lower concentrations of stimuli |
|
|
Term
| Explain the mechanism of PGE2-mediated CENTRAL pain reception. |
|
Definition
| inflammation---> cytokines---> COX-2---> PGE2---> central sensitization (similar to peripheral sensitization) |
|
|
Term
| Which cells are involved in the process of acute inflammation? Chronic inflammation? |
|
Definition
Acute: leukocytes (mostly neutrophils)
Chronic: lymphocytes; macrophages |
|
|
Term
| What endothelial components allow transmigration of leukocytes out of microcirculation to occur? |
|
Definition
| transmigration: via selectins and then integrins |
|
|
Term
What is the effect of NSAIDs on the following?
- endogenous canabinoids
- central seritonin
- NEpi-mediated analgesia |
|
Definition
- increases levels of endogenous canabinoids
- increases central seritonin
- increases alpha-2 receptor-mediated analgesic effects of NEpi |
|
|
Term
| What is the most common side effect of NSAIDs? |
|
Definition
| GI irritation---> alleviated by co-administration with proton pump inhibitor, e.g. omeprazole |
|
|
Term
|
Definition
| hyperuricemia---> deposition of monosodium urate in tissues---> inflammation |
|
|
Term
| Define myocardial ischemia. |
|
Definition
| IMBALANCE btwn O2 supply and demand in heart |
|
|
Term
| List the 3 causes of myo. ischemia and categorize them into supply ischemia and demand ischemia. |
|
Definition
supply: low coronary bld flow; hypoxia
demand: high myo. O2 demand |
|
|
Term
| List the 3 causes of myo. ischemia and categorize them into supply ischemia and demand ischemia. |
|
Definition
supply: low coronary bld flow; hypoxia
demand: high myo. O2 demand |
|
|
Term
| List the main determinants of myo O2 demand. |
|
Definition
HR
myo. contractility
wall tension (pre/afterload) |
|
|
Term
| Distinguish between myocardial stunning and myocardial hibernation. |
|
Definition
Stunning: brief period of ischemia---> PROLONGED impairment of function---> gradual return to normal
Hibernation: reduced contractility in response to ischemia to match reduced oxygen supply |
|
|
Term
| Describe the pattern of myocardial necrosis that results from prolonged, unresolved ischemia. |
|
Definition
| subendocardium-----> subepicardium; signaled by presence of cardiac cell proteins in circulation |
|
|
Term
| Define myocardial infarction. |
|
Definition
| cardiac cell death due to myocardial ischemia |
|
|
Term
List the causes of the following conditions:
- chronic stable angina
- variant angina
- unstable angina
- myocardial infarction |
|
Definition
- chronic stable: >50% atherosclerotic narrowing; during EXERTION; short lasting
- variant: coronary vasospasm; at REST (usually among smokers);
- unstable: non-occlusive coronary thrombus; LONG lasting; increasing frequency and severity at REST;
- MI: occlusive thrombus |
|
|
Term
| What ECG changes and BP changes are caused by an MI? |
|
Definition
| altered S-T segment; DECREASED SYSTOLIC |
|
|
Term
| Distinguish primary prevention and secondary prevention treatment phases for myocardial ischemia. |
|
Definition
primary: before onset of symptoms
secondary: post MI |
|
|
Term
| What is the common presentation of angina pectoris? |
|
Definition
| pressure, heaviness, squeezing |
|
|
Term
| How is time to re-stenosis prolonged? |
|
Definition
| through slow-released anti-proliferative drugs to prevent smooth mm proliferation within stent lumen + anti-platelet therapu (prevention of endothelial formation) |
|
|
Term
| Distinguish between the appropriate pt population for fibrinolytics and renal angiotensin inhibitors |
|
Definition
fibrinolytics: NOT for elderly, or HTN patients
RA inhibitors: BEST for elderly, HTN pts, and pts with hx of MI |
|
|
Term
| How is Dabigatran different from Warfarin? |
|
Definition
| Dab: requires NO monitoring; less bleeding; rapid onset of action; less drug interactions |
|
|
Term
| Which ions contribute to myocardial excitation? Relaxation? |
|
Definition
Na+: excitation
K+: relaxation |
|
|
Term
Describe the following characteristics of cardiac electrical properties:
- excitability
- automaticity
- conductivity
- refracoriness |
|
Definition
- excitability: inversely proportional to the strength of electrical impulse required to cause contraction
- automaticity: ability to SPONTANEOUSLY depolarize
- conductivity: proportional to vel. at which impulse travels through heart
- refractoriness: proportional to time required for fiber to regain ability to conduct second impulse (related to K+ conductance!) |
|
|
Term
Describe the following characteristics of cardiac electrical properties:
- excitability
- automaticity
- conductivity
- refracoriness |
|
Definition
- excitability: inversely proportional to the strength of electrical impulse required to cause contraction
- automaticity: ability to SPONTANEOUSLY depolarize
- conductivity: proportional to vel. at which impulse travels through heart
- refractoriness: proportional to time required for fiber to regain ability to conduct second impulse (related to K+ conductance!) |
|
|
Term
| Define cardiac arrhythmia. |
|
Definition
| abnormality in rate or coordination of cardiac contraction |
|
|
Term
| Distinguish between ventricular and atrial fibrillation. |
|
Definition
ventricular: acute, life-threatening
atrial: causes thrombus formation in atria---> risk of embolic stroke |
|
|
Term
| What type of arrhythmia (atrial or ventricular) presents with symptoms? |
|
Definition
| Ventricular b/c affects actual pumping action of |
|
|
Term
| Which 4 sites of origin are possible for an arrhythmia? |
|
Definition
- sinus n.
- atria
- junctional (includind AV n.)
- ventricles |
|
|
Term
| What is the common side effect of all antiarrhythmic drugs? |
|
Definition
|
|
Term
| Which two antitachyarrhythmic are most prone to cause arrhythmias? |
|
Definition
| Class 1A, 1C, and Digoxin |
|
|
Term
| Which class of antitachyarrhytmia drugs are least likely to cause arrhythmias? |
|
Definition
|
|
Term
| What is primary (essential) HT? |
|
Definition
| due to positive family history; normal urinalysis; NO CURE |
|
|
Term
|
Definition
| less common; secondary to other illness; CAN BE CURED |
|
|
Term
| What is the most significant risk factor for essential HT? |
|
Definition
|
|
Term
| What is the fundamental equation of hemodynamics? |
|
Definition
MAP = CO x TPR
(CO = SV x HR) |
|
|
Term
| What is the most recommended initial choice for HT treatment and why? |
|
Definition
| thiazide diuretic: cheap, tolerated, proven to work, and potentiates response to other anti-HT drugs |
|
|
Term
| What additional components are given alongside thiazide and loop diuretics to increase their efficacy? |
|
Definition
potassium-sparing diuretics
RAA inhibitors |
|
|
Term
| Which antiHT is unaffected by NSAIDs? |
|
Definition
|
|
Term
| What is the primary hemodynamic event in hear failure? |
|
Definition
| impaired cardiac contractility (systolic dysfunction) |
|
|
Term
| What causes diastolic dysfunction? |
|
Definition
| volume or pressure overload---> reduced diastolic compliance |
|
|
Term
| Define acute decompensation. |
|
Definition
| sudden worsening of the symptoms of heart failure |
|
|
Term
| What is more common, systolic or diastolic dysfunction? And what causes it? |
|
Definition
| systolic, via loss of myocardial contractility and ventricular dilatation---> increase in EDV and decrease in SV = lower EF ( = SV/EDV) |
|
|
Term
| Which 2 physiological responses occur minutes after myocardial failure? Weeks-months after? |
|
Definition
ventricular dilatation
neurohormonal activation
later: myocardial remodeling |
|
|
Term
| What is diastolic dysfunction? |
|
Definition
| hypertrophied, stiff ventricles OR slowed ventricular relaxation---> impaired ventricular filling---> CONSERVED EF |
|
|
Term
| What is the treatment strategy for diastolic dysfunction? |
|
Definition
| diuretics or nitrates---> vessel relaxation---> less edema; decrease preload--->reduce filling pressures----> decrease wall tension---> decrease cardiac work and O2 demand and decreased CO (which is bad because low CO is one of the problems of diastolic dysfunction) |
|
|
Term
| Distinguish between "toxicity" and "hazard." |
|
Definition
toxicity: bio. property
hazard: conditional upon use |
|
|
Term
| What is a "xenobiotic" agent? |
|
Definition
| something foreign to body |
|
|
Term
|
Definition
| metabolism to toxic metabolite |
|
|
Term
| In the treatment of acute poisonings, how soon after initial exposure should emesis be induced? |
|
Definition
|
|
Term
| Distinguish between "initiation" and "promotion." |
|
Definition
initiation: irreversible event (e.g. binding of Benzoapyrene to DNA)
promotion: allows expression of the cancer |
|
|
Term
| What is the purpose of a carcinogenicity bioassay? |
|
Definition
| to determine whether chemical has the POTENTIAL to cause cancer at ANY DOSE |
|
|
Term
| List 3 ways in which Ca2+ homeostasis can be disrupted. |
|
Definition
1. Ca2+ influx from ECF
2. Ca2+ release from intracellular stores
3. lack of efflux from dysfunctional membane pumps
---> disruption of enzymes and apoptotic DNA cleavage |
|
|
Term
| What is a teratogen? What are the effects on an early versus late embryo? |
|
Definition
chemical that harms fetus but NOT mom
early embryo: lethal effect only
late " : changes are NON-structural |
|
|
Term
What are the effects of exposure to the following teratogens?
Ethanol
Vit. A
Cocaine
Methyl Hg |
|
Definition
ethanol---> FAS
Vit. A---> heart defects
Cocaine---> GI, kidney, limb malformations
Methyl Hg---> cerebral atrophy, retardation |
|
|
Term
| What is the purpose of each of the three segments of animal reproductive toxicity testing studies? |
|
Definition
segment 1: effects on breeding---> neonatal period
segment 2: embryotoxicity, teratogenicity
segment 3: parturition, lactation, neoatal effects |
|
|
Term
| Which two populations are generally at greater risk of CO poisoning regardless of environmental factors? |
|
Definition
CAD pts (cause blood flow and O2 delivery is already compromised)
fetus (cause always on the brink of hypoxia anyway from inefficient O2 delivery from mom) |
|
|
Term
| Distinguish between pharmacogenetics and pharmacogenomics. |
|
Definition
PHMgenetics: single gene variants and variable drug effects
PHMgenomics: role of inherited and acquired genetic variation in drug response; |
|
|
Term
| What is the genetic basis of malignant hyperthermia in response to combined administration of volatile anesthetics and succinylcholine? |
|
Definition
occurs in pts with diff RYANODINE R---> INCREASED Ca2+ RELEASE FROM SR---> increased contraction---> increased heat production
Tx: Dantrolene---> spasmolytic---> blks SR Ca2+ release |
|
|
Term
| How does erythrocyte G6PD deficiency affect metabolism? |
|
Definition
| G6PD---> inability to regenerate NADPH---> inability to regenerate GSH |
|
|
Term
| What is the adverse drug risks to G6PD pts? |
|
Definition
| OXIDANT drugs---> H2O2---> soaks up available GSH---> oxidative stress and RUPTURE |
|
|
Term
| What is the relationship between INH metabolism and NAT-2? |
|
Definition
overactive NAT-2---> metabolism too rapid---> drug inefficient
inefficient NAT-2---> too little metabolism---> toxicity |
|
|
Term
| What are the consequences of alcohol consumption to those that have ALDH deficiency? |
|
Definition
| {ethanol---> acetaldehyde---> acetic acid} requires ALDH; def---> acetaldehyde accumulation---> facial flushing, tachycardia, palpitations |
|
|
Term
| What is the clinical relevance of possessing a CYP2C19 polymorphism? |
|
Definition
| poor metabolizers of omeprazpole---> HIGH CURE RATE for Helicobacter pylori infx. |
|
|
Term
| What is the clinical relevance of possessing the CYP2C19 polymorphism of CYP450? |
|
Definition
unable to metabolize codeine---> poor analgesic effect
unable to metabolize (activate) Tamoxifen---> less estrogen R blk |
|
|
Term
| What is the cause of neutropenia and bone marrow toxicity in a pt receiving 6-mercaptopurine for leukemia? |
|
Definition
| TPMT deficiency (AUTOSOMAL CODOMINANT)---> unable to catalyze drug---> drug intolerence and accumulation of THIOGAUNINE nucleotides---> toxicity |
|
|
Term
| Distinguish btwn first exposure and second exposure in T1Hyp |
|
Definition
1st: clonal expansion of B and T-cells---> IgE
2nd: mast cell degranulation
ANAPHYLAXIS; OKAY to RECHALLENGE
NMJ-blockers |
|
|
Term
|
Definition
CYTOLYTIC: Ag binds RBCs---> binds IgG/M---> T-Cyt killing
Innocent Bystander: PREFORMED Ag-Ab complex binds cell---> lysis
HIGH-DOSE Penicllins---> T2Hyp more likely---> so DOSE-DEPENDENT |
|
|
Term
|
Definition
IMMUNE COMPLEX: Ag-IgG/M complex---> deposits in tissues---> MQ and Neutrophil-mediated inflammation at site
NSAIDs |
|
|
Term
|
Definition
Delayed type:
1st: hapten (drug + macromolecule) binds protein (carrier)---> local lymph nodes on skin by DENDRITIC cells---> memory T-cell clonal expansion
2nd: activation of memory T-cells---> cytokine/chemokine/MQ-mediated inflammatory response
OKAY to RECHALLENGE
mostly at SKIN (sulfonamides - Stephen-Johnson syndrome; poison ivy; latex) |
|
|
Term
| Describe anaphylactoid reactions. |
|
Definition
NON-IgE-mediated HISTAMINE release;
DOSE-related.
OKAY to RECHALLENGE if treated with ANTI-HISTAMINES first
codeine, morphine; vancomycin (RED-NECK SYNDROME) |
|
|
Term
| Which individuals are especially at risk for anaphylactoid reactions from sulfites? |
|
Definition
| SULFITE OXIDASE Def.---> NO sulfite metabolism---> BRONCHOSPASM---> asthma |
|
|
Term
|
Definition
| forms immunogenic HAPTEN-CARRIER complexes (direct binding of MAJOR/MINOR components to macromolecules in plasma or cells)---> induces T1-4Hyp |
|
|
Term
| What is the risk of developing an allergic rxn to Cephalosporins? Given an allergy to Penicillin? |
|
Definition
| both have beta lactam ring---> likely to be allergic to Ceph; risk is > 2nd gen > 3rd gen > 4th gen (cause of increasingly diff side chains) |
|
|
Term
| Will pts who are allergic to sulfonamide antibiotics be allergic to sulfonamide non-antibiotics? |
|
Definition
| No. Side chains that cause allergy NOT present in non-antibiotics. |
|
|
Term
| Distinguish between adverse drug "event" and "reaction." |
|
Definition
"reaction": noxious, unintended response at NORMAL dose; CAUSAL link exists; from PT'S point of view
"event": injury from use---> includes ADR and OVERDOSES; from DRUG's point of view |
|
|
Term
|
Definition
MAJORITY
Dose-dependent; PREDICTABLE---> extension of PHM effects
e.g. Anti-chol.---> dry mouth |
|
|
Term
|
Definition
| NOT predictable; from long-term use and ACCUMULATION and IMMUNOLOGIC |
|
|
Term
|
Definition
|
|
Term
|
Definition
| DELAYED; NOT dose-dependent; CARCINOGENICITY; TERATOGENICITY; |
|
|
Term
| What is the role of P-Glycoprotein in drug distribution? |
|
Definition
| efflux pump located throughout body---> EXCRETORY function---> induced by RIFAMPIN; inhibited by others----> TOXICITY |
|
|
Term
| How does food affect drug absorption? |
|
Definition
slows RATE and PEAK; but NOT total amount absorbed (area under curve);
binding = BLK of absorption
or could INCREASE rate of absorption
blks P450 and P-glycoprotein (GRAPEFRUIT JUICE) |
|
|
Term
| What is the interaction between nonselective MAO inhibitors and tyramine-containing food? |
|
Definition
|
|
Term
| What is the effect of a high vit. K diet on Warfarin effects? |
|
Definition
| Antagonistic; cause acts to reduce K contribution to clotting |
|
|
Term
| What is the effect of a high salt diet on diuretics? |
|
Definition
| counteracts action of diuretic cause causes water retention! |
|
|
Term
| What is the effect of St. John's wort on drug metabolism? |
|
Definition
| activates CYP450---> INCREASED metabolism |
|
|
