Basic pharm Flashcards
Michaelis Menten graph and key variables
Velocity vs. substrate, MM = hyperbolic curve
Km = inversely related to enzyme’s affinity for substrate, is equal to [substrate] at 50% Vmax) ie as affinity increases, [substrate] needed to reach 50% decreases!
Vmax = directly proportional to enzyme concentration
Lineweaver-Burk plot and intercept meanings
1/V vs. 1/S
used to show relationships of inhibitors
y-intercept = 1/Vmax (therefore, incr. y-intercept = decr. Vmax) x-intercept = 1/Km (therefore, closer to 0 = incr. Km = decr. affinity)
Inhibitors and their effects on Vmax and Km
Competitive, reversible: no change on Vmax, incr. Km
leads to decr. potency of a drug
Comp., irreversible: decr. Vmax, no change on Km
leads to decr. efficacy of a drug
Noncompetitive: decr. Vmax, no change on Km
leads to decr. efficacy
Volume of distribution
give formula for Vd
- for protein-bound drugs, this volume can be affected by liver or renal disease (decr. protein binding = incr. volume)
- Vd = amount of drug in body / plasma drug concentration
Clearance of a drug
give formula
volume of plasma cleared of drug per unit time. IT’S A VOLUME!
CL = rate of elimination / plasma drug concentration = Vd x Ke (elim constant)
Half-life
4-5 half-lives to reach steady state
3.3 half-lives to reach 90% steady state
Dosage calculations
Loading dose, maintenance dose
Loading dose = Cp x Vd / F
Maintenance = Cp x CL x r / F
F = bioavailability (100 for IV dose) Cp = target plasma concentration r = dosage interval (time)
Zero-order elimination
constant rate of elimination (no effect of target plasma conc.), therefore linear decrease in conc. with time
aka. capacity dependent
Ex: phenytoin, ethanol, aspirin
First-order elimination
rate of elimination is proportional to drug concentration, therefore exponential decrease in conc. with time
aka. flow dependent
Weak acid overdose
ex. phenobarbital, methotrexate, ASPIRIN
Get trapped in basic environment (when they are ionized), therefore treat with bicarbonate
Weak base overdose
ex. amphetamines
Trapped in acidic environment, therefore treat with ammonium chloride
Drug metabolism Phase 1 (modification)
Reduction, oxidation, hydrolysis with cytochrome p450
Yields slightly polar, still-active metabolites
Lost first in old people
Drug metabolism Phase 2 (conjugation)
Glucoronidation, Acetylation, Sulfation
Yields very polar, inactive metabolites (renally excreted)
Definition of efficacy
maximal effect a drug can produce
represented by Vmax
partial agonists < full agonists
Definition of potency
amount of drug needed for a given effect
represented by EC50 (effective concentration)
Competitive antagonist effects
Decreased potency
Overcome by increasing concentration of agonist substrate
Noncompetitive antagonist
Decreased efficacy
Partial agonist
Lowers the maximal effect of the full agonist
Note: potency is an independent variable, though generally, a partial agonist is designed to have a higher potency
Therapeutic index
TD50/ED50 = median toxic dose/median effective dose
Safe drugs have higher TI values (means there is more wiggle room between the efficacious dose and possibly going up to the toxic dose)
Nicotinic Ach receptors
Ligand-gated Na/K channels
Muscarinic Ach receptors
G-protein coupled receptors that act through 2nd messengers
What is special about the sweat glands and adrenal medulla vs. all other autonomic nervous systems organs?
They are innervated by the SYMPATHETIC nervous system, but are innervated by CHOLINERGIC (sweat glands have muscarinic receptors, but adrenal medulla has nicotinic)
Give the G-protein class for the appropriate sympathetic receptor
Alpha1
Alpha2
Beta1
Beta2
Alpha1: Gq (IP3)
Alpha2: Gi (decr. cAMP)
Beta1: Gs (incr. cAMP)
Beta2: Gs (incr. cAMP)
Describe the major functions of the sympathetic receptors
Alpha1
Alpha2
Beta1
Beta2
Alpha1: vascular smooth muscle contraction, sphincter contraction, pupillary dilator
Alpha2: decr. symp. outflow
Beta1: incr. heart rate, contractility, incr. renin release
Beta2: vasodilation, bronchodilation, tocolysis
Give the G protein class for the parasympathetic receptors
M1: Gq
M2: Gi
M3: Gq
Gq = h1, a1, V1, M1, M3
Describe the major functions of the parasympathetic receptors
M1: CNS, enteric nervous system
M2: decr. heart rate and contractility of atria
M3: incr. exocrine secretions, incr. peristalsis, bladder contraction, close pupil
Describe the general roles of dopamine in the body
D1: relaxes renal vascular smooth muscle
D2: modulates transmitter release
Describe the general roles of histamine in the body
H1: mucus production, allergic response
H2: gastric acid production
Gq pathway
Receptor –> phospholipase C
- ) —> DAG —> protein kinase C
- ) —> IP3 —> incr. in [Ca] (smooth muscle contraction)
Gs pathway
Gi opposes this from happening
adenylyl cyclase –> (ATP to cAMP) –> protein kinase A
- -> heart [Ca] incr. - -> smooth muscle relaxation
Notable cholinergic drugs and specific mechanisms
Botulinum: block Ach-granule release AChE inhibitor (-stigmines, donepezil): block breakdown of choline in the synaptic cleft
Notable noradrenergic drugs and specific mechanisms
Reserpine: block transport of dopamine into granule (for converstion to NE)
Amphetamine/ephedrine: promote NE release into cleft
Cocaine/TCAs/amphetamine: inhibition of NE re-uptake
Direct cholinergic memetics
bethanecol: activates bowel/bladder smooth muscle
pilocarpine: stimulate sweat/tears/saliva, glaucoma
Indirect Ach agonists, anticholinesterase inhibitors
All increase Ach!
donepezil: Alzheimer
edrophonium: test for MG
neostigmine: urinary retention, MG
“phys”ostigmine: “phyxes” atropine overdose (note: crosses CNS barrier)
py”rid”ostigmine: gets “rid” of MG
Indirect Ach agonist (AChEi) poisoning
Aka Organophosphates
tx: atropine! (ACh antag)
DUMBBELSS:
diarrhea, urination, miosis, brochospasm, bradycardia, excitation of muscle, lacrimation, sweating, salivation
Muscarinic antagonists (block Ach)
aka anticholinergics
atropine: mydriasis (dilation)
benztropine: parkinson dz (park my benz), dystonia
glycopyrrolate: reduce airway secretions
ipratropium: COPD, asthma
oxybutynin: reduce bladder spasms, overactive bladder
scopolamine: motion sickness
Atropine toxicity
Hot, Dry, Red, Blind, Mad
can cause…
- acute angle glaucoma due to mydriasis
- urinary retention w/ prostatic hyperplasia
- hyperthermia in infants
Fish toxins
Pufferfish: tetrodotoxin (binds fast voltage-gated Na, prevent depol)
Reef fish: ciguatoxin (opens Na channels, causing depol)
Dark-meat fish: histamine build-up (aka scombroid)
Lipid-lowering therapies
HMG-CoA reductase inhibitors Bile acid resins (cholestyramine) Ezetimibe Fibrates Niacin
Gastric acid suppresion therapy
histamine inhibitors (octreotide, ECL cell)
H2 receptor blockers (ranitidine, parietal cell)
PPIs
mucus layer enhancers (misoprostol, bismuth)
antacids
Heparin vs. warfarin
heparin = large, acts in blood, acute onset, PTT, no placenta crossing
warfarin = small, acts in liver, long onset, PT/INR, can be teratogenic
Cancer chemotherapeutics and the cell cycle
Mitosis: microtubule inhibitors (taxols, vinca alkaloids)
G1/G0 inhibs: carmustine, cisplatin
S phase: antimetabolites (azathioprine/6-MP, 5-FU, hydroxyurea, MTX)
G2 inhib: bleomycin
Inflammatory mediators
LTB4 - neutrophil chemotaxis
PGI2 - inhibits plt. aggregation (Plt Gathering Inhibitor)
Steroids basically block synthesis of arachidonic acid
Glaucoma treatment
goal: decr. intraocular pressure (decr. aqueous humor)
decr. aq humor synthesis: alpha agonists (via vasoconstriction) epinephrine, b-blockers timolol, acetazolomide
incr. aq humor outflow (opening of meshwork): direct/indirect cholinergic agonist (use pilocarpine in emergencies), prostaglandin
Opioid analgesics mechanism
open K channels, close Ca channels –> decr. synaptic transmission
mu = morphine delta = enkephalin kappa = dynorphin
Anesthetics
decr. blood solubility = rapid induction and recovery
incr. lipid solubility = incr. potency 1/MAC
eg. NO. incr. blood/lipid solubility = slow induction, high potency
halothane: high lipid/blood solubility = high potency, slow induction
Malignant hyperthermia
Caused by inhaled anesthetics and succinylcholine
often defect in the sarcoplasmic reticulum ryanodine receptor
tx: dantrolene (inhibits Ca flux through ryanodine receptor)
Local anesthetics
Esters vs. amides
variables for rate of analgesia
block activated Na channels by binding to receptors on inner portion of channel (most effective in rapidly firing neurons)
Esters = procaine, cocaine Amides = 2 I's in the name (eg. lidocaine, bupivicaine)
infected tissue requires more anesthetic
small diameter/myelinated fibers affected before large diameter/unmyelinated fibers (size matters more than myelination)
lose pain, then temp, then touch
Parkinson’s drugs
BALSA: increase dopamine and decrease cholinergics
Bromocriptine Amantadine Levodopa Selegiline Antimuscarinics
Diuretics: order of location of action
PCT: acetazolomide Thin descending limb: mannitol Thick ascending limb: loop diuretics DCT: thiazides Collecting tubule: K sparing diuretics Medullary CT: ADH antagnonists
Electrolyte changes with diuretics
acidemia: CA inhibs, K sparing
alkalemia: loops, thiazides (volume contraction alkalosis, K loss)
urine Ca incr. w/ loop (decr. paracellular reabsorption!)
urine Ca decr. w/ thiazides (enhanced Ca reabsorption in DCT)
Centrally acting reproductive drugs
Clomiphene - activates GnRH
GnRH antagonists
GnRH agonists
Location of female reproductive drugs
OCPs - ovary
Danazol - cytochrome p450c17 (synthesis of androstenedione/testosterone)
Anastrozole - block aromatase
SERMs - block estrogen reception in sensitive cells
Location of male reproductive drugs
Spironolactone - block synthesis of testosterone
Finasteride - 5a-reductase
Flutamide - blocks androgen-receptor complex
Asthma treatment basics
Exposure –> antigen and IgE complex on mast cells –> mediators (leukotrienes, histamine) –> 1.) bronchoconstriction 2.) inflammation
Steroids block release of mediators
Early response tx: B-agonists, theophylline, muscarinic antagonists
Late response tx: steroids, anti-leukotrienes
