Ebse Biochem First Aid

Front 1

Vitamin A

Back 1

retinol
def: nightblindness, dry skin
xs: arthralgia, fatigue, HA, skin changes, alopecia, sore throat

found in leafy vegetables

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Vitamin B1

Back 2

Thiamine: TPP
def: BeriBeri and Wernicke-Korsakoff
Beriberi: dry: polyneuropathy and symmetrical muscle wasting; wet: dialated cardiac failure, edema;
Wenicke-Korsakoff: mammilary body destruction with alcoholics, confabulation and memory loss

use: oxidative phosphorylation of a-ketoacids and branched AA dehydrogenase; +
and a cofactor for transketolase in the HMP-shunt

Front 3

Vitamin B2

Back 3

Riboflavin: FAD, FMN
def: Cheilosis (inflammation of the lips) + Corneal vascularization

2 C's; 2 ATP from FADH

Front 4

Vitamin B3

Back 4

Niacin: NAD, NADP+
def: Pellegra: Diarrhea, Dementia, Dermatitis, beefy glossitis
causes:
a) Hartnup (decreased absorption of Trp)
b) malignant carcinoid syndrome (increased Trp metabolism)
c) decreased B6 via INH or OCP

use: made from Trp via Vit6.

3D's; 3ATP from NADH

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Vitamin B5

Back 5

Pentothenate-A
needed for CoA as component;

def: Dermatitis, enteritis, alopecia, adrenal insufficiency

Front 6

Vitamin B6

Back 6

Pyridoxine: PLP
def: convulsions, hyper-irritability (INH, OCP), peripheral neuropathy,

use: for Niacin, transaminases, heme, glycogen phosphorylase

Front 7

all vitamins wash out easily from body except

Back 7

B12 - high stores in liver for a year

and folate - also more stores in liver

Front 8

vitamin B-complex deficiencies often result in

Back 8

Diarrhea, Dermatitis, glossitis

Front 9

B12

Back 9

Cobalamin
Def: Macrocytic megaloblastic anemia, neurologic symptoms: optic neuritis, subacute combined degeneration, paresthesias; glossitis

abnormal myelin because: increased methylmalonylCoA (not turning into succinylCoA) and decreased methionine (from homocystine)

B12 is cofactor in methyltransfers (homocystine methyltransferase and methylmalonyl mutase)

large storage in liver - 1yr

get it from animal products

Schilling's test can determine what the origin of the deficiency;

if it's decreased IF (auto-immune pernicious anemia - Hashimotos thyroiditis), or malabsorption (sprue, Diphillobothrium latum, enteritis) or gastric bypass or ileal resection (from IBS)

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Vitamin K

Back 10

for Koagulation;

def: neonatal hemorrhage; increased PT, inceased PTT, normal bleeding time;

it's synthesized from gut-flora --> that's why we can get vitK def after broad spec antibiotics;

Warfarin is antagonist - II VII IX X S C

Front 11

Zinc

Back 11

def: delayed wound healing, hypogonadism, decreased adult hair, acrodermatitis enteropathica

Front 12

action of Fomepizole

Back 12

inhibits alcohol dehydrogenase --> disulfiram reaction

buildup of acetaldehyde

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alcohol dehydrogenase kinetics

Back 13

zero-order

Front 14

ethanol metabolism

Back 14

EtoH --> aldehyde --> acetic acid

via alcohol dehydrogenase and aldehyde dehydrogenase

NAD+ is limiting reagent

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ethanol hypoglycemia

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with ethanol metabolism --> NADH/NAD is increased in liver --> pyruvate is diverted to lactate and OAA is diverted to malate --> gluconeogenesis is inhibited

the altered ratio also leads to fatty change

Front 16

Kwashiorkor vs Marasmus

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K. results from a protein deficient MEAL:
Malnutrition
Edema
Anemia
Liver (fatty)
- small child with swollen belly

Marasmus:
-energy malnutrition --> muscle/tissue wasting

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cardicac conduction anomalies +
cateracts + muscle weakness + ptosis + hatchet face

Back 17

myotonic dystrophy

Classic DM1

maternal - tri-nucleotide repeat
it's expanded RNA's that affect lots of different channels

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CYP2D6 variability due to?

what happens with codeine with each of the variants?

whites have which one?

Back 18

MISSENSE mutations - decreased activity

(few: splicing/frameshift - no activity)

Copy number polymorphisms = more copies of CYP2D6 = higher activity

3 main phenotypes;

loss of function: can't convert codeine--> morphine;

slow phenotype: 1:14 in whites, rare in asia, absent in native americans

ultrafast metabolizers: can become intoxicated

Front 19

why do we have to glucuronate billirubin?

Back 19

only via UDP-glycosyltransferease can we excrete billirubin in the bile

Front 20

irinotecan for GBM - possible problems with metabolic variant in population?

Back 20

the drug is cytotoxic because it inhibit topoisomerase

UGT1A1 gene encodes a transferase that glucuonidates metabolite which is then excreted in the bile

common polymorphisms in VNTR in the TATAA box within the promoter- normal is 6 TA repeats;

there is 7TA repeat variant:
reduces the transcription of the gene and reduce the lvl of enzyme --> higher drug levls --> TOXICITY (BM supression, GI)

this is most ethnic groups world wide

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problems with giving INH?

Back 21

it's for TB; we have to give B6 with it because this causes peripheral neuropathy and BM suppression

especially the hypoacetylators: 2 recessive allels of NAT2 --> much less production of the enzyme
[most frequent in Europeans, then Africa, then only 20% of china, much less 10% in japan, 6% inuit]

there are also rapid acetylators

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problems with hydralazine? variable metabolizers

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slow acetylators will have SLE-like syndrome with butterfly rash..

this is an anti-hypertensive medication for severe hypertension.


especially the hypoacetylators: 2 recessive allels of NAT2 --> much less production of the enzyme
[most frequent in Europeans, then Africa, then only 20% of china, much less 10% in japan, 6% inuit]

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problems with procainamide? variable metabolizers

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slow acetylators will have SLE-like syndrome with butterfly rash..



especially the hypoacetylators: 2 recessive allels of NAT2 --> much less production of the enzyme
[most frequent in Europeans, then Africa, then only 20% of china, much less 10% in japan, 6% inuit]

Front 24

"Every Little Boy Must Pray":

Back 24

Vfib/Vtach drugs

Epinephrine
Lidocaine
Bretylium
Magsulfate
Procainamide


"Shock, Shock, Shock, Everybody Shock, Little Shock, Big Shock, Momma Shock, Poppa Shock":
Shock= Defibrillate
Everybody= Epinephine
Little= Lidocaine
Big= Bretylium
Momma= MgSO4
Poppa= Pocainamide

Front 25

Procainamide

Back 25

Class 1A antiarrhythmic

It blocks open sodium (Na+) channels and prolongs the cardiac action potential (outward potassium (K+) currents may be blocked). This results in slowed conduction, and ultimately the decreased rate of rise of the action potential, which may result in widening of QRS on electrocardiogram (ECG).

This drug is used for both supraventricular and ventricular arrhythmias. For example, it can be used to convert new-onset atrial fibrillation, though it is suboptimal for this purpose. It can also be used to treat Wolf-Parkinson-White syndrome by prolonging the refractory period of the accessory pathway. Typically use is secondary to lidocaine in patients who are allergic to lidocaine or dysrhythmias that are refractory to lidocaine.

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complications of malaria falciparum

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CHAPLIN:
Cerebral malaria/ Coma [which can't be cause by the other kinds of malaria]
Hypoglycemia
Anaemia
Pulmonary edema
Lactic acidosis
Infections
Necrois of renal tubules (ATN)

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Hydralazine

Back 27

The mechanism of action of hydralazine is not well known. It interferes with the action of the second messenger IP3, limiting calcium release from the sarcoplasmic reticulum of smooth muscle. This results in an arterial and arteriolar relaxation.[2]

It recently has been identified as a nitric oxide donor.[3]

Activation of hypoxia-inducible factors has been suggested as a mechanism.[4]
[edit] Clinical Use

Hydralazine is not used as a primary drug for treating hypertension because it elicits a reflex sympathetic stimulation of the heart (the baroreceptor reflex). The sympathetic stimulation may increase heart rate and cardiac output, and may cause angina pectoris or myocardial infarction.[1] Hydralazine may also increase plasma renin concentration, resulting in fluid retention. In order to prevent these undesirable side-effects, hydralazine is usually prescribed in combination with a beta-blocker (e.g., propranolol) and a diuretic.[1]

Hydralazine is used to treat severe hypertension, but again, it is not a first-line therapy for essential hypertension. However, hydralazine is the first-line therapy for hypertension in pregnancy, with methyldopa.[5]

Front 28

fast acetylators need more of what?

Back 28

hydralazine (for HTN - IP3 medicated sm muscle relax)


dapsone (leprosy/PCP)

Front 29

6-mercaptopurine for leukemia and to achieve immunosupression:

what problems with variable metabolizers?

Back 29

This is detoxified with a thiopurine methyltransferease TMPT gene

3 common missense mutations destabilize the enzyme and cause it to be rapidly degraded

the frequency of heterozygotes with these mutations are less common in caucasians (10%) than in Africa/Asia (50%)!

THe mutations are actually GOOD for tx: with less of the methyltransferease, the drug effectivity is increased for Leukemia treatment; [also increase tox if it's way too much]

Front 30

prolonged post operative paralysis from succinylcholine

Back 30

atypical allel of BCHE gene --> butyrylcholine esterase

homozygotes for this A atypical allel are 1:3300 in europe, but 10X higher in Inuit

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Lidocaine drug class

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Class Ib antiarrhythmic

Front 32

AD intolerance of halothane

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malignant hyerthermia

due to increased Ca --> muscle degradation

mutations in RYR1/CACNL

Dantrolene prevents this by inactivating the Ca release

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more likely to bleed/clot on warfarin

Back 33

Pharmacokinetic variant:
CYP2C9 deficiency
20% in whites
3.5% in blacks
<2% in asians
-- will bleed!
also a pharmacodynamic variant:
-3x increase in the amount of VKORC-1 enzyme made with the variant: B
-the variant A is more sensitive and is present in 33%whites, 89%asians, 14% africans


CYP9C9 and VKORC1 make up for >50% of variants in warfarin doses needed