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Pharmacology > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Km, Vmax, Michaelis-Menten kinetics

A 
Km = inverse of affinity of enzyme for substrate
Vmax = maximum velocity

Most enzyme follows hyperbolic curve (V/[S]). Cooperative kinetics - sigmoid curve

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2
Q

Lineweaker-Burk plot

A

x (1/V): y (1/[S])
Y intercept = 1/Vmax
X intercept = -1/Km

Slope = Km/Vmax

The further to the right the x-intercept, the greater the Km and the lower the affinity

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3
Q

Lineweaker-Burk and Enzyme inhibition

A

Competitive Inhibition: Right shifted X-intercept

Noncompetitive inhibition: higher y-intercept

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4
Q

Competitive vs Noncompetitive inhibitors

A 
Competitive inhibitor:
Resemble enzyme
Can be overcome
Binds to active site
No effect on Vmax (vs decreased in NC)
Increased Km (vs none in NC)
Decrease potency (vs efficacy in NC)
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5
Q

Bioavailability

A

Fraction of drug that reaches systemic circulation unchanged

IV = 100%
Oral = < 100% after incomplete absorption and first-pass metabolism
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6
Q

Volume of Distribution

A

Amount of drug in body / Plasma drug concentration

Can be altered by liver and kidney diseases (decreased protein binding, increased Vd)

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7
Q

What is the difference between low, medium, and high Vd?

A

Low Vd (4-8L): blood; large/charged molecule, plasma bound - Warfarin

Medium Vd: ECF, small hydrophilic molecule - ethanol

High Vd: All tissues - small lipophilic molecules, esp if bound to tissue protein - chloroquine

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8
Q

Half-Life (T 1/2)

A

0.7 Vd/Cl
Time needed to clear 1/2 in the body (or constant infusion)

Constant rate takes 4-5 half-lives to reach steady state

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9
Q

Clearance (Cl)

A

rate of elimination of drug / plasma drug concentration = Vd x Ke (elimination constant)

Rate of elimination to plasma concentration - may be impaired with defects in cardiac, hepatic or renal function

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10
Q

Dosage calculation for loading and maintenance dose

A

Loading dose = Cp x Vd/F
Maintenance dose = Cp x Cl/F

Cp = target drug concentration

In renal/liver diseases, maintenance dose decrease but loading dose is unchanged.

Time to steady state is dependent on half-life and is independent on dosing frequency or size

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11
Q

Zero-Order Elimination (3 drugs)

A

Constant rate regardless of Cp - capacity limited elimination

Cp decreases linearly with time

Phenytoin, Ethanol, Aspirin

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12
Q

First-Order Elimination

A

Elimination rate proportional to drug concentration (constant fraction); flow-dependent elimination

Cp decreases exponentially with time

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13
Q

Examples of weak acids and bases trapped in urine

A

Weak acids: trapped in basic environments (treat with bicarbonate)
Phenobarbital, methotrexate, aspirin
RCOOH < - > RCOO- + H+

Weak bases: trapped in acidic environment (treat with ammonium chloride)
Amphetamines
RNH3+ < - > RNH2 + H+

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14
Q

Drug metabolism: Phase I

A

Reduction, oxidation, hydrolysis with cytochrome p-450

Yield polar, water-soluble metabolisms (can still be active)

Geriatric patients lose phase I first

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15
Q

Drug metabolism: Phase II

A

Conjugation (Glucoronidation, Acetylation, Sulfation)

Yields very polar, inactive metabolites (renally excreted)

Geriatric patients have GAS (Phase II)

Slow acetylators have greater risk for side effects for some drugs (e.g. increase risk of drug-induced SLE)

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16
Q

Efficacy vs Potency

A

Efficacy: maximal effect a drug can produce
Examples: analgesic, antibiotics, antihistamines, decongestants
Partial agonists have less efficacy

Potency: amount of drug needed for given effect (dose required to produce 50% of maximal effect)
Increased affinity for receptor
Examples:
chemo, antihypertensive, antilipid drugs

17
Q

Receptor Binding Curve and Competitive Antagonist

A 
Right shift (decrease potency, no change in efficacy)
Can be overcome by increasing substrate

E.g. Diazepam + flumazenil on GABA receptor

18
Q

Receptor Binding Curve and Noncompetitive antagonist

A 
Down shift (decrease efficacy, no change in potency)
Cannot overcome by increasing substrate

E.g. NE + phenoxybenzamine on alpha-receptors

19
Q

Receptor Binding Curve and Partial agonist

A

Down shift (decrease efficacy); potency can be variable

E.g. Morphine (full agonist) + buprenorphine (partial agonist) at opioid mu receptor

20
Q

Therapeutic Index

A

Median Lethal Dose / Median Effective dose

Higher TI = safer drug
Lower TI: warfarin, digoxin, lithium, theophylline

21
Q

Therapeutic window

A

Clinical drug safety. Range of minimum effective dose to minimum toxic dose

22
Q

Pathway for Central and Peripheral Nervous System

A 
Sympathetic: ACh (Nn) -> NE (alpha/beta)
Sympathetic sweat: ACh (Nn) -> ACh (M)
Parasympathetic: ACh (Nn) -> ACh (M)
Somatic: ACh (Nm)
Adrenal: ACh (Nn) -> makes Epi, NE
23
Q

Nicotinic ACh receptors vs Muscarinic ACh receptors

A

Nicotinic ACh receptors: ligand-gated Na+/K+ channels
Nn (autonomic ganglia); Nm (neuromuscular junction)

Muscarinic ACh receptors: G-protein coupled receptors
M1-M5

24
Q

What are the G-protein linked 2nd Messengers?

A 
Sympathetic:
alpha 1 (Q), alpha 2 (I), beta 1 (S), beta 2 (S)

Parasympathetic:
M1 (Q), M2 (I), M3 (Q)

Dopamine:
D1 (S), D2 (I)

Histamine:
H1 (Q) H2 (S)

Vasopressin:
V1 (Q) V2 (S)

Gq -> phospholipase C -> increase [Ca], PKC
Gs -> increase cAMP -> PKA
Gi -> decreases cAMP -> PKA

25
Q

Sympathetic Receptors

A

Alpha 1 (Q): increase smooth muscle contraction, increase pupillary dilator muscle (mydriasis), increase intestinal/bladder sphincter muscle contraction

Alpha 2 (I): decreases sympathetic outflow, decreases insulin release, decreases lipolysis, increases platelet aggregation

Beta 1 (s): increases heart rate, contractility, renin release, lipolysis

Beta 2 (s): vasodilation, bronchodilation, increase heart rate, contractility, lipolysis, insulin release, decrease uterine tone, ciliary muscle relaxation, increase aqueous humor production

26
Q

Parasympathetic Receptors

A

M1 (Q): CNS, enteric nervous system

M2 (I): Decreases heart rate and contractility of atria

M3 (Q): increase exocrine gland secretions (lacrimal, gastric), increase gut peristalsis, increase bladder contraction, increase pupillary sphincter muscle contraction (miosis), ciliary muscle contraction, bronchoconstriction

27
Q

Dopamine Receptors

A

D1 (S): relaxes renal vascular smooth muscle

D2 (I): brain transmitter modulator

28
Q

Histamine Receptors

A

H1 (Q): increase nasal/bronchial mucus production, bronchioles constriction, pruritus, pain

H2 (S): increases gastric acid

29
Q

Vasopressin Receptors

A

V1 (Q): increases smooth muscle contraction

V2 (S): increases H2O permeability and reabsorption in collecting tubules of kidney

30
Q

Cholinergic Pathway

A

1) Acetyl-coA and Choline enters cell (Hemicholinium)
2) Choline acetyltransferase transfer Acetl-coA and Choline into vesicles (Vesamicol, Bromoacetylcholine)
3) ACh released from cell by Ca2+ influx (Botulinum)
4) ACh bind to receptors or broken down by AChE

31
Q

Noradrenergic Pathway

A

1) Tyrosine into cell
2) Tyrosine converted to Dopa (Metyrosine)
3) Dopa converted to Dopamine
4) Dopamine into vesicles (Reserpine)
5) Dopamine converted to NE in vesicles

6) NE released by Ca2+ influx
(guanethidine, bretylium; amphetamine promotes)

7) Binds to receptor or reuptake
(cocaine, TCAs, amphetamine)

32
Q

What modulates NE release from sympathetic nerve ending?

A 
NE itself (alpha2 on presynpatic autoreceptors)
ACh (M2)
Angiotensin II (AII receptors)

Pharmacology (8 decks)

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