Pharm 1 - Pharmacokenetics/dynamics/ANS p232-246 Flashcards
How do competitive inhibitors affect Km?
Increase Km (dec affinity)
The further to the right the x-intercept (ie, closer to zero), the greater the ___ and the lower ______.
The further to the right the x-intercept (ie, closer to zero), the greater the Km and the lower the affinity.
Which type of inhibitor will cross x-intercept of an unihibited substrate?
What does that x-intercept represent?
non competitive inhibitor
X-intercept = 1/-Km
What type of inhibitor will cross the y-intercept of an unihibited substrate? What is that y-intercept = to?
competitive inhibitor
y-intercept = 1/Vmax
Competitive (-)’r of Diazepam? What is the rec’r?
Flumazenil
GABAA- R
Competitive (-)’r vs organophosphates?
Atropine
Competitive (-)’r of xanthine oxidase?
Allopurinol
ex of competitive ACh antagonist
neuromuscular blocking drugs
Atracurium, cisatracurium, pancuronium, rocuronium, tubocurarine, vecuronium
competitive aldosterone receptor antagonists in cortical collecting tubule?
Spironolactone, Eplerenone
Competitive inhibitors of progestins at progesterone receptors?
Mifepristone, ulipristal.
Nonsteroidal competitive inhibitor at androgen receptors? use?
Flutamide; Prostate carcinoma
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How does competitive antagonists affect efficacy and potency?
dec potency; doesn’t change efficacy
How does a non competitive antagonist affect potency and efficacy?
dec potency and efficacy
How does partial agonist affect potency?
It doesn’t - it is independent of it.
How does efficacy of a partial agonist compare vs a full agonist?
It has less efficacy than a full agonist
How to calc loading dose?
(Cp × Vd) / F
Cp - plasma conc
Vd - Vol of distribution
F = bioavail
How to calc maintenance dose?
Maintenance dose =
(Cp × CL × τ )/ F
Cp = target plasma concentration at steady state
Cl = clearence τ = dosage interval (time between doses), if not administered continuousl
F = bioavail
In renal or liver disease, maintenance dose ____ and loading dose is usually ______.
In renal or liver disease, maintenance dose Dec and loading dose is usually unchanged.
Time to steady state depends primarily on _____ and is independent of ____ and _____ ________.
Time to steady state depends primarily on t1/2 and is independent of dose and dosing frequency.
How to calc t1/2?
t1/2 = (0.7 × Vd)/Cl in first-order elimination
Drugs with narrow therapeutic index?
Warfarin, Theophylline, Digoxin, Lithium, anti-epitleptics
Warning, These Drugs are lethal
Two drugs with additive effects? What does that mean?
Effect of substance A and B together is equal to the sum of their individual effects
Aspirin and acetaminophen
Give ex of a drug that has a permissive effect on another? what does that mean?
Presence of substance A is required for the full effects of substance B
Cortisol has a permissive effect on catecholamines, as it upregulates α1-receptors on arterioles, making them more sensitive to Epi/NE (leading to inc BP)
Give ex of two synergistic drugs? define.
Effect of substance A and B together is greater than the sum of their individual effects
Clopidogrel with aspirin
What is a tachyphylactic drug interaction?
Acute decrease in response to a drug after initial/repeated administration
ex/
Nitrates, niacin, phenylephrine, LSD, MDMA
In regards to drug elimination, _______ are trapped in urine and cleared quickly. ____ ______ can be reabsorbed
Ionized species are trapped in urine and cleared quickly. Neutral forms can be reabsorbed
Examples of Weak acids (4)
Weak acids
Asprin, Methotrexate, Phenobarbital, Warfarin
WAMP - you’re hit with a Weak Acid
W-arfarin
A-sprin
M-ethotrexate
P-henobarbital
If TCAs are weak bases, why do we treat TCA overdose with sodium bicarbonate (instead of maybe ammonium chloride to acidify the urine and inc elimination of the weak base)
TCA toxicity is generally treated with sodium bicarbonate to overcome the sodium channelblocking activity of TCAs, but not for accelerating drug elimination.
Examples of Weak Bases
TCAs, Amphetamines
Weak Bases = MAT DACes
(Allopurinol, Diazepam, Cocaine, Methyldopa)
What drugs would be cleared by acidifying the urine?
Acidifying urine –> inc ionization of weak bases to inc renal elimination.
What do we give to alkalinize urine?
NaHCO3, potassium citrate
What do we give to acidify urine?
Ammonium chloride, Vitamin C, Cranberry juice
Drugs with zero order kinetics?
Rate of elimination is constant regardless of Cp (ie, constant amount of drug eliminated per unit time). Cp decreases linearly with time.
high dose or toxic concentration
- Phenytoin
- Ethanol
- aspirin
Toxic dose
Salicylates, Cisplatin, Flouxetin, Omeprazole
What happens in phase I drug metabolism?
Reduction, Oxidation, Hydrolysis with cytochrome P-450 usually yield slightly polar, water-soluble metabolites (often still active).
R-OH = Phase I
What happens in phase II drug metabolism?
Conjugation (Methylation, Glucuronidation, Acetylation, Sulfation) usually yields very polar, inactive metabolites (renally excreted).
Which phase of drug metabolism do the elderly lose first?
Phase I
Patients who are slow acetylators have ___ side effects from certain drugs because of _____rate of metabolism (eg, isoniazid).
Patients who are slow acetylators have inc side effects from certain drugs because of dec rate of metabolism (eg, isoniazid).
What value of a drug curve represents efficacy?
y-intercept = Vmax
the higher the Y intercept, the higher the Vmax, the higher the efficacy
How is efficacy related to potency?
Unrelated to potency (ie, efficacious drugs can have high or low potency)
Safer drugs have higher _____ values.
Safer drugs have higher TI values.
What are drugs with lower TI values that req monitoring?
- *W**arfarin, Theophylline, Digoxin, Antiepileptic drugs, Lithium;
- *W**arning! These Drugs Are Lethal!).
Adrenal medulla is directly innervated by __________ __________ ________.
Adrenal medulla is directly innervated by preganglionic sympathetic fibers.
Sweat glands are part of the______ _____ but are innervated by _________ _______
Sweat glands are part of the sympathetic pathway but are innervated by cholinergic fibers
What is the channel assoc with nicotinic Ach receptors?
ligand gated Na/K channels
Subtypes of nicotinic Ach receptors
Two subtypes: NN (found in autonomic ganglia, adrenal medulla) and NM (found in neuromuscular junction of skeletal muscle).
Muscarinic Ach Receptors work through which receptors?
Muscarinic ACh receptors are G-protein–coupled receptors that usually act through 2nd messengers
Subtypes of Muscarinic Ach-R
5 subtypes: M1–5 found in heart, smooth muscle, brain, exocrine glands, and on sweat glands (cholinergic sympathetic).
G protein class of α1 & α2 rec’r?
α1 - Gq
α2 - Gi
Major fxn of α1-R?
Inc vascular smooth muscle contraction
Inc pupillary dilator muscle contraction (mydriasis)
Inc intestinal and bladder sphincter muscle contraction
Major fxn of α2-R?
dec sympathetic (adrenergic) outflow
dec insulin release,
dec lipolysis,
dec aqueous humor production
Inc platelet aggregation,
G protein class of β1, β2, β3 - R?
All are Gs
What g proteins are affiliated with M1-3 receptors?
M1R = Gq
M2R = Gi
M3R = Gq
Fxn of M1R
Mediates higher cognitive functions, stimulates enteric nervous system
Fxn of M2R
dec heart rate and contractility of atria
M3R fxn?
- Inc exocrine gland secretions (eg, lacrimal, sweat, salivary, gastric acid)
- Inc gut peristalsis,
- Inc bladder contraction,
- bronchoconstriction,
- Inc pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation),
- Inc insulin release,
- endothelium-mediated vasodilation
The two dopamine receptors have what g proteins as 2nd messangers?
D1R - Gs
D2R - Gi
Fxn of D1R & D2R
D1R - Relaxes renal vascular smooth muscle, activates direct pathway of striatum
D2R - Modulates transmitter release, especially in brain, inhibits indirect pathway of striatum
What g proteins are associated with histamine receptors?
H1R - Gq
H2R - Gs
Fxn of H1R & H2R
H1R
inc nasal and bronchial mucus production, vascular permeability, bronchoconstriction, pruritus, pain
H2R
inc gastric acid secretion
one - lung, two - stomach
Vasopressin receptors - what g protein?
V1R - Gq
V2R - Gs