Pharmacology Flashcards
What is the K, Vmax, of Micehalis-menton kinetics?
Km is inversely related to the affinity of the enzyme for its substrate
Vmax: directly proportional to the enzyme concentration
What type of enzyme reaction do most medication follow?
Hyperbolic curve
Some enzyme reactions exhibit sigmoid
Which type of inhibitor can be overcome by increasing the substrate concentration?
1) Only reversible competitive inhibitors (irreversible compeitive and non competitive cannot)
What is the effect of Km depending on the type of inhibitor?
Competitive inhibitor reverible (Increased)
Comp. non revers. unchanged
Non. comp: unchanged
Effect on Vmax?
Comp In (rev.) unchanged Comp in (irr) decreased Non. irr decreased
What is bioavilability of IV dose?
F= 100
What is the bioavailability of PO dose?
Less then 100% due to incomplete absorbtion and first pass metabolism
What is the volume distribution?
Amount of drug in the body relative to its plasma concentration
What can affect the volume of distribution?
Altered by liver or kidney disease
How to calculate the volume of distribution?
Vd= Amount of drug in the body/plasma drug concentration
what are characteristics of low volume of distribution?
Compartment: blood (drug: large charged molebules) with plasma protein bound
What are characteristic of medium distribution?
ECF
Small, hydrophilic molecules
What are characteristics of high distribution?
All tissues including fat
Small, lipophilic molecules, especially bound by tissue protein.
How to determine the clearance ?
CL = rate of elimination of the drug/plasma drug concentration = Vd X Ke
What is the half time?
Time required for the body to 1/2 elimination
T1/2 = ).693 X Vd/ CL
What is meant by the different number of half times?
1 half life: 50%
2 half life: 25%
3 half life: 12.5%
4 half life: 6.25%
How to calculate a loading dose?
Cp X Vd / F
Cp=target plasma concentration at steady state
Vd is volume distribution
F = bioavilability
How to calculate the maintenece dose?
Maintence dose=Cp X Cl X t/F
Cp (target plasma steady state)
T= dosage interval (if not administered continuousely
What happens to the loading dose if have liver or kidney disease?
The loading dose is usually unchanged, but the maintence dose is decreased
What determines the time to the steady state?
The T1/2 is independent of dose, and of dosing frequency
What is an additive drug interaction, and what is an example?
effect of substance A and B is equal to sum of their individual effects (ASA and acetaminophen)
What is a permissive effect of drugs?
Presence of substance A needed to get full effect of B (cortisol on catecholamine effect)
what is a synergistic effect of drugs?
Effect of substance A and B is greater then the sum of individual effects
What is tachyphylactic drug interaction?
Acute decrease in response to the drug after initial administration
MDMA and LSD
What is zero order drug?
Constant amount of drug eliminated regardless of unit of time (graph is a straight line)
What are examples of drugs that are zero order?
Phenytoin
Ethanol
ASA
What is first order elimination?
Rate of elimination is directly proportional to the concentration of the drug (graph is a curved line)
How does urine pH affect the drug elimination?
Ionized species are trapped in urine and eliminated quickly
Neutral forms can be reabsorbed
How do weak acids work?
Examples of weak acids?
1) Trapped in basic environment (treat with bicarbonate)
2) Examples: phenobarbitol methrotrexate, ASA
How do weak bases work?
How to treat overdose?
What are some examples?
1) Trapped in acideic environment (treat overdose with ammonia chloride)
2) Amphetamines and TCA’s
What are the two phases of drug metabolism?
Phase 1: Reduction, oxidation, hydrolysis with cytochrome p-450 (Geriatric patients lose phase 1 first)
Phase 2: conjugation (methylation, acetylation) usually yeilds very polar inactive metabolits that are renally excreted
What is the efficacy of a drug?
Maximal effect a drug can produce
Represented by the y value (V max)
Partial agnosits have less efficiency then full agonist
What is the potency of a drug?
1) Amount of drug needed for a given effect
2) Rpresented by the EC 50
What happens whe the EC 50 has a left shift?
A left shift will increase the potency
Will decrease the amount of drug needed for a given effect
what happens when agonist is placed with competitive antagonist? What is the effect?
1) Shifts the curve to the right
2) Decrease the potency
3) Can be overcome by increasing the concentration of the agonist substrate
Ex. Diazepm with flumazenil (competitive on GABA receptor)
What happens when agonist with non-competitive antagonist?
1) Shifts curve down (decrease efficiency)
2) Cannot be overcome by increasing the agonist substrate concentration
3) example: Norepi and alpha receptor
What happens when partial agonist is places with agonist?
1) Acts at the same site as full agonist
2) Lower maximal effect (decrease of efficiency)
3) Potency is independent variable
Ex Morphine vs burenorphine
How is the safety of drug measured?
TD 50/ ED50
TD 50 (median toxic dose) ED 50 (median effective dose)
What is therapeutic window?
Dosage range that can safetly and effectvely be used to treat the disease
What is the TI of a safer drug?
Usually have a higher TI
What is the TI of a more dangerous drug?
What needs to be done with less safe drugs?
1) More dangerous drug will have lower TI
2) Will need more monitoring
3) Examples include: digoxin, lithium, theophylline
What is the difference between the parasympathetic and sympathetic system?
Parasympathetic: controls rest and digest and hemostatic
Sympathetic: In charge of the fight or flight response
Where does the parasympathetic vs sympathetic system originate?
Para: spinal cord and medulla
Sympathetic: Spinal cord, thoracic and lumber spine
How does the trajectory of the nerves para vs sympa?
Para are long neurons (slow pathways)
Symp are short neurons (fast pathways)
What are effects of para and sympa (cardio, lungs, muscles, glycogen, urinary?
Para: decrease heart rate, bronchial constrict, muscles relax, no effect on glycogen, increase urinary output
Sympa: Increase contraction and heart rate, bronchials releax, muscle contract, glycogen to glucose, decrease urinary output
What are the types of ach receptors, and where are they found?
Nictonic: Na-K+ ligated Nn (found in autonomic ganglia/adrenal medulla)
Nm (found in neuromuscular junction of muscle)
Muscarinic: G-coupled receptors (act through second messengers) there are 5 types (Smooth muscle, brain, exocrne, sweat glands)
What are the two types of alpha receptos, and their functions?
1) Alpha 1: increase smooth muscle contraction,pupil dilates, increase the intestinal and bladder sphincter
2) Alpha 2: Decrease sympathetic outflow, decrease insulin release, decrease lipolysis increase platelet aggregation
What are the Beta receptors and their functions?
Beta 1: Increase heart rate, contractility, and renin, and lipolysis
Beta 2: Vasodilation, bronchodilation, increase lipolysis, increase insulin release
Beta 3: Increase lipolysis, increase thermogenesis
What are the parasympathetic M receptors?
1) M1: CNS, enteric nervous system
2) M2: decrease heart rate, and contractility of the atria
3) M3: Increase exocrine gland secretion, increase gut peristalsis, increase bladder contraction, bronchoconstriction
What are the dopamine receptors?
1) D1: relaxes the renal vascular smooth muscle
2) D2: Modulates transmitter release in the brain
What are the histamine receptors?
1) H1: increase the nasal and bronchial mucus production
2) H2: increased gastric acid secretion
What are the receptors of vasopressin?
1) V1: increase smooth muscle contraction
2) V2: increased H2O permeability and reabsorption in the collecting tubules
How does botulism work (postsynaptic membrane)?
Blocks the release of the ACH from the presynaptic membrane
How does amphetamine and ephedrine work?
increase the NE
How does cocaine, TCA, and amphetamine work?
Decrease the reuptake of NE by the presynaptic membrande
How does ingestion of tyramine and MAO inhibitors cause hypertensive crisis?
Wine, cheese cause more tryamine, and diaplaces NE, releases more active presynaptic neurotransmittos, increase diffusion of neurotransmittors into the synaptic cleft, leads to increase stimulation, and HTN
Name 4 cholinomimetic agents, and their applications?
1) Bethanechol: Activates bowl and bladder (for postoperative ileus, and neurogenic urinary retention)
2) Carbachol (copy of acetylcholine: constrics the pupil, and relieves intraocular pressure in open angle glaucoma)
3) Methacoline: (stimulates muscarinic receptors) Challenge test for asthma
4) Pilocarpine contracts the ciliary muscle of the eye :stimulates the production of sweat, tears, and saliva (Sjogren)
What are the medications used to treat Alzehimers?
1) Donepezil
2) Galantamine
3) Rivastigmine
What is edrophonium used for?
1) Increase Ach
2) Diagnosis for mysanthia gravis
3) Mysanthia gravis now diagnosed by anti-acetycholine test
What is neostigmine used for?
1) Increased ACH
2) For neurogenic ileus and urinary retntion
3) For mysanthia gravis
4) For reversal of neuromuscular junction blockade/
What is physostigmine used for?
1) Increases ACH
2) used to fixed atropine overdose
3) Used when have anticholinergic toxicity (crosses blood, brain barrier)
What does pyridostigmine used for?
1) Increase ACH
2) Increases muscle strength
3) Used for mysanthia gravis
How are cholinesterase inhibitor poisoning treated?
1) Usually due to organophosphates ( components of insecticides)
2) Treat with atropine
What are signs of cholinesterase inhibitor poisoning?
1) Diarrhea
2) Bronchospasm
3) Sweating
4) Salivation
5) Urination
6) Miosis
What is atropine, homatropine, tropicamide used for?
1) Eye
2) Produce mydriasis and cycloplegia
What is Benztropine used for?
1) Parkinsons disease
2) Acute dystonia
what are glycopyrrolate used for?
GI and resp
To reduce the airway secretions
Oral: drooling or peptic ulcer
What is hyoscyamine and dicyclomine used for?
GI
Antispasmodics for irritable bowel syndrome
What is ipratropium and tiotropium used for?
COPD and asthma
What is oxybutin, solifernacine, and tolterodine used for?
Bladderspasms
Urge of urinary incontinence
Overactive bladder
What is scopalamine used for?
1) CNS
2) Motion sickness
What are the actions of atropine?
1) Incease pupil dilations
2) Decrease secretions
3) Decrease gastric acid
4) Decrease motility
Sideeffecects: Hot as a hare Dry as a bone Red as a beet Blind as a bat Mad as a hatter
Actions and applications of Benztropine?
Parkinson disease
Acute dystonia
Actions of glycopyrrolate?
GI and respiratory
Reduce airway secretions
Drooling, peptic ulcer
Actions of Hyoscyamine and dicyclomine>
Anti-sposmodics for irritable bowel
Actions of Ipratropium and tiotropium?
Respiratory
COPD and asthma
Actions of oxybutynin and solifenacin?
Reduce bladder spasm and urge urinary continence
Actions of scopolamine?
Motion sickness
Receptors of albuterol and salmeterol?
B2 more then B1
Albuterol for acute asthma or COPD
