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concentration at 1/2 Vmax

reflects the affinity of the enzyme for its substrate.

The smaller the Km, the greater the affinity

The maximum rate (velocity) of a reaction

Occurs when all enzymes are saturated with substrate - thus reactions are occurring at a max rate

Vmax is directly proportional to the enzyme concentration

Vd = amount of drug in body/plasma drug concentration

Thus HIGH Vd distribute into all tissues and are small, lipophilic molecules

Lov Vd (4-8 L) distribute in blood and are large or charged molecules.

CL = rate of elimination of drug/plasma drug concentration

or CL = Vd x Ke

t1/2 = 0.7Vd/CL

It takes 4-5 half lives to reach steady state.

Loading Dose = Cp x Vd/F

Cp = target plasma concentration
F= Bioavailability (100% when IV)

UNAFFECTED by liver/kidney disease unlike maintenance dose

Maintenance Dose = CP x CL/F

Cp = target plasma calculation

DECREASES with liver/kidney disease - because clearance is decreased.

Efficacy - maximal effect a drug can produce

Potency - amount of drug needed for a given effect

Gq --> Phospholipase C --> Increased DAG and IP3 --> Increase PKC and Ca

-Increased vascular smooth muscle contraction
-Increased pupillary Dilator Muscle Contraction (mydriasis)
-Increased Intestinal and Bladder sphincter muscle contraction

Gq --> Phospholipase C --> Increased DAG and IP3 --> Increase PKC and Ca

CNS and enteric nervous system

Gq --> Phospholipase C --> Increased DAG and IP3 --> Increase PKC and Ca

GI Endothelium
Increased Bladder Contraction
Bronchoconstriction
Increased Pupillary sphincter muscle contraction (miosis)
Ciliary muscle contraction (accomodation)

Histamine
Gq --> Phospholipase C --> Increased DAG and IP3 --> Increase PKC and Ca

-increased nasal and bronchial mucus production
-contraction of bronchioles
Pruritis and Pain

Gq --> Phospholipase C --> Increased DAG and IP3 --> Increase PKC and Ca

Increased vascular smooth muscle contraction

HAVe 1 M&M

H1 a1 V1
M1 M3

Gi --> decreased Adenylyl Cyclase --> Decrease cAMP --> decreased PKA --> decreased Ca2+

-Decreased sympathetic outflow
-Decreased Insulin Release

Gi --> decreased Adenylyl Cyclase --> Decrease cAMP --> decreased PKA --> decreased Ca2+

-Decreased HEART rate
-Decreased contractility of Atria

Gi --> decreased Adenylyl Cyclase --> Decrease cAMP --> decreased PKA --> decreased Ca2+

Modulates transmitter release, especially in the BRAIN

Gs --> increased Adenylyl cyclase --> increased cAMP --> increased PKA --> increased Ca2+ (in heart)
-decreases MLCK in smooth muscle

-Increased Heart rate, contractility, RENIN release and lipolysis

Gs --> increased Adenylyl cyclase --> increased cAMP --> increased PKA --> increased Ca2+ (in heart)
-decreases MLCK in smooth muscle

Vasodilation
-Bronchodilation
-Increased INSULIN release
Increased HR, Contractility, Lipolysis as well.

Gs --> increased Adenylyl cyclase --> increased cAMP --> increased PKA --> increased Ca2+ (in heart)
-decreases MLCK in smooth muscle

Relaxes renal vascular smooth muscle

Gs --> increased Adenylyl cyclase --> increased cAMP --> increased PKA --> increased Ca2+ (in heart)
-decreases MLCK in smooth muscle

Increases gastric acid secretion

Gs --> increased Adenylyl cyclase --> increased cAMP --> increased PKA --> increased Ca2+ (in heart)
-decreases MLCK in smooth muscle

Increases H2O permeability and reabsorption in collecting tubules of kidney
-ie increased AQP expression

V2 is found in 2 kidneys

Desmopressin acts on V2

MAD 2's

M2 a2 and D2 are all Gi ane the only Gi

ACE inhibitors
ARBs
B-Blockers
Spironolactone = aldosterone antagonist

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Tyrosine Kinase associated with CML

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Transcription factor associated with Burkitt's lymphoma

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Anti-apoptotic molecule associated with lymphomas

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Tyrosine kinase associated with breast, ovarian, and gastric cancer

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

GTPase associated with colon carcinoma

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Transcription factor associated with lung tumors

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Transcription factor associated with Neuroblastoma

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Tyrosine kinase associated with MEN type II
(menin is associated with MEN I)

Oncogene - Gain of Function --> Cancer
-only 1 allele needs to be damaged

Cytokine receptor associated with GIST (Gastrointestinal stromal tumor)

Tumor Suppressor - LOF --> cancer
-both alleles must be lost for expression of disease

gene product blocks G1-->S phase of cell cycle

results in Retinoblastoma and OSTEOSARCOMA

Tumor Suppressor - LOF --> cancer
-both alleles must be lost for
expression of disease

blocks G1-->S phase of cell cycle (like Rb)

assoc with most human cancers, Li Fraumeni

Tumor Suppressor - LOF --> cancer
-both alleles must be lost for expression of disease

DNA REPAIR PROTEIN

assoc with breast/ovarian cancer

Tumor Suppressor - LOF --> cancer
-both alleles must be lost for expression of disease

DNA REPAIR PROTEIN

Associated with just breast, not ovarian cancer

Tumor Suppressor - LOF --> cancer
-both alleles must be lost for expression of disease

associated with Melanoma

Tumor Suppressor - LOF --> cancer
-both alleles must be lost for expression of disease

on 5q

Associated with Colorectal cancer (FAP)

C=UV/P

V=urine flow rate

Freely Filtered, Neither Secreted nor Absorbed

C inulin estimates GFR as does C creatinine

Freely Filtered, Actively Secreted

C PAH estimates RPF

RBF = RPF/1-Hct

RPF is estimated by clearance of PAH

FF= GFR/RPF

or C inulin/C PAH