Pharmacology - First Aid Flashcards
Km is inversely related to…
the affinity of the enzyme for its substrate.
Vmax is directly proportional to…
the enzyme concentration.
Most enzymatic reactions follow…
a hyperbolic curve (follow Michaelis-Menten kinetics); however, enzymatic reactions that exhibit a sigmoid curve usually indicate cooperative kinetics (ex. hemoglobin).
On a Lineweaver-Burk plot, increased y-intercept means…
decreased Vmax.
On a Lineweaver-Burk plot, the further to the right the x-intercept…
the greater the Km and the lower the affinity.
Slope of a Lineweaver Burk-plot =
Km/Vmax
x-intercept of Lineweaver-Burk plot =
1/-Km
y-intercept of Lineweaver-Burk plot =
1/Vmax
On a Lineweaver-Burk plot, competitive inhibitors…
cross each other competitively, whereas noncompetitive inhibitors do not.
Inhibitors that resemble substrate
Competitive (both reversible and irreversible)
Inhibitor that is overcome by increased substrate
reversible, competitive inhibitors
Competitors that bind the active site
competitive, both reversible and irreversible
Effect of competitors on Vmax
Competitive reversible: unchanged Competitive irreversible: decreased Noncompetitive: decreased
Effect of competitiors on Km
Competitive reversible: increased Competitive irreversible: unchanged Noncompetitive: unchanged
Pharmacodynamics of competitors
Competitive reversible: decreased potency Competitive irreversible: decreased efficacy Noncompetitive: decreased efficacy
Pharmacokinetics
the effects of the body on the drug (absorption, distribution, metabolism, excretion)
Pharmacodynamics
the effects of the drug on the body (receptor binding, drug efficacy/potency, toxicity)
Bioavailability (F) is the…
fraction of administered drug that reaches the systemic circulation unchanged.
For an IV dose, F =
100%. Orally, F typically is <100% due to incomplete absorption and first-pass metabolism.
The volume of distribution (Vd) is the…
theoretical volume occupied by teh total absorbed drug amount at the plasma concentration.
The apparent volume of distribution of plasma protein boudn drugs can be altered by…
liver and kidney disease becasue decreased protein binding will increase Vd.
Vd =
(amount of drug in the body)/(plasma drug concentration)
Vd is usually low if the drug is in the…
blood. Drug types include large, charged molecules that are plasma protein bound.
Vd is medium if the drug is in the…
ECF. Drug types include small hydrophilic molecules.
Vd is large if the drug is in…
all tissues including fat. Drug types include small lipophilic molecules, especially if bound to tissue protein.
Half-life (t1/2) is the…
time required to change the amoun tof drug in the body by 1/2 during elimination (or constant infusion).
To reach steady state, a drug infused at a constant rate takes…
4-5 half lives.
t1/2 =
(.693 x Vd)/CL
Clearance (CL) is the…
volume of plasma cleared of drug per unit time. It may be impaired by defects in cardiac, hepatic or renal function.
CL =
(rate of elimination of drug)/(plasma drug concentration) = Vd x Ke
Loading dose =
(Cp x Vd)/F
Maintenance dose =
(Cp x CL x tau)/F
In renal or liver disease, maintenance dose…
decreases and loading dose is usually unchanged.
Time to steady state primarily depends on…
t1/2 and is independent of dose and dosing frequency.
Zero order elimination is when…
the rate of elimination is constant regardless of Cp. (capacity-limited elimination) (it is a constant AMOUNT of drug eliminated per unit time)
In zero order elimination, with time, Cp decreases…
linearly.
Examples of drugs with zero order elimination
Phenytoin Ethanol Aspirin
First order elimination is…
when the rate of elimination is directly proportional to the drug concentration. (flow-dependent elimination) (a constant FRACTION of drug is eliminated per unit time)
In first order elimination, with time, Cp decreases…
exponentially.
Ionized drug species are…
trapped in the urine and cleared quickly. Netural forms can be reabsorbed.
Examples of weak acids
Phenobarbital, Methotrexate, aspirin (overdose should be treated with bicarbonate)
Weak acids become..
trapped in basic environments.
Example of weak base
Amphetamines (overdose should be treated with ammonium chloride)
Weak bases become…
trapped in acidic environments.
Phase I of drug metabolism includes…
reduction, oxidations, hydrolysis with cytochrome P-450 usually yields slightly plar, water-soluble metabolites (often still active).
Geriatric patients lose…
phase I first.
Phase II of drug metabolism includes…
conjugation (glucuronidation, acetylation, and sulfation) which usually yields very polar, inactive metabolites that are renally excreted.
Patients who are slow acetylators have…
greater side effects from certain drugs due to decreased rate of metabolism.
Efficacy is the..
maximal effect a drug can produce.
High-efficacy drug classes are…
analgesics, antibiotics, antihistamines and decongestants.
Potency is the…
amount of drug needed for a given effect. Increased potency has increased affinity for receptors.
High potency drug classes include…
chemo, antihypertensives, and lipid-lowering drugs.
Therapeutic index is a measure of…
drug safety. Safer drugs have higher TI values.
Examples of drugs with lower TI values include…
digoxin, lithium, theophylline and warfarin.
TI =
(TD50)/(ED50) = (median toxic dose)/(median effective dose)
The therapeutic window is the…
measure of clinical drug effectivenes for a pt.
The adrenal medulla and sweat glands are part of…
the sympathetic nervous system but are innervated by cholinergic fibers.
Botulinum toxin prevents release of…
NT at all cholinergic terminals.
Nicotinic ACh receptors are…
ligand gated Na+/K+ channels.
Subtypes of nicotinic receptors are…
N(N) - found in autonomic ganglia N(M) - found in NMJ
Muscarinic ACh receptors are…
G-protein coupled receptors that usually act through 2nd messengers. 5 subtypes (M1, M2, M3, M4 and M5).
alpha1 receptor G-protein class
q
alpha2 receptor G-protein class
i
beta1 and beta2 receptor G-protein class
s
alpha1 receptor major functions (3)
- increase vascular smooth muscle contraction 2. increase pupillary dilator muscle contraction 9mydriasis) 3. increase intestinal and bladder sphincter muscle contraction
alpha2 receptor major functions (4)
- decrease sympathetic outflow 2. decrease insulin release 3. decrease lipolysis 4. increase platelet aggregation
beta1 receptor major functions (4)
- increase hr 2. increase contractility 3. increase renin release 4. increase lipolysis
beta2 receptor major functions (9)
- vasodilation 2. bronchodilation 3. increase hr 4. increase contractility 5. increase lipolysis 6. increase insulin release 7. decrese uterine tone 8. ciliary muscle relaxation 9. increase aqueous humor production
Sympathetic receptors
alpha1 alpha2 beta1 beta2
Parasympathetic receptors
M1 M2 M3
M1 and M3 G-protein class
q
M2 G-protein class
i
M1 receptor major functions
CNS, enteric nervous system
M2 receptor major functions
decrease hr and contractility of atria
M3 receptor major functions (6)
- increase exocrine gland secretions 2. increase gut peristalsis 3. increase bladder contraction 4. bronchoconstriction 5. increase pupillary sphincter muscle contraction (miosis) 6. ciliary muscle contraction (accommodation)
D1 receptor G-protein class
s
D2 receptor G-protein class
i
D1 receptor major function
relaxes renal vascular smooth muscle
D2 receptor major function
modulates transmitter releases, especially in the brain
H1 receptor G-protein class
q
H2 receptor G-protein class
s
H1 receptor major functions (5)
- increased nasal and bronchial mucus production 2. increased vascular permeability 3. contraction of bronchiles 4. pruritis 5. pain
H2 receptor major functions
increase gastric acid secretion
V1 (vasopressin) G-protein class
q
V2 (Vasopressin) G-protein class
s
V1 receptor major function
increase vascular smooth muscle contraction
V2 receptor major function
increase H2O permeability and reabsorption in the collecting tubules of the kidney
Gq proteins interact with…
phospholipase C
Gs and Gi interact with..
adenylyl cyclase
Release of NE from a sympathetic nerve ending is modulated by…
NE itself, acting on presynaptic alpha2 autoreceptors, AngII and other substances.
Direct ACh agonists (4)
- Bethanechol 2. Carbachol 3. Pilocarpine 4. Methacholine
Bethanechol action
activate bowel and bladder smooth muscle; resistant to AChE
Use of Bethanechol
postoperative ileus, neurogenic ileus and urinary retention
Carbachol action
carbon copy of acetylcholine
Use of Carbachol
-glaucoma -pupillary constriction -relief of intraocular pressure
Pilocarpine action
contracts ciliary muscle of eye, pupillary sphincter; resistant to AChE
Use of Pilocarpine
-potent stimulator of tears, sweat and saliva -open and closed angle glaucoma
Methacholine Action
stimulates muscarinic receptors in the airway when inhaled
Methacholine use
challenge test for asthma diagnosis
Indirect agonists of ACh (anticholinesterases) (5ish)
- Neostigmine 2. Pyridostigmine 3. Physostigmine 4. Donepezil, Rivastigmine, Galantamine 5. Edrophonium (they all increase endogenous ACh)
Use of Neostigmine
-postoperative and neurogenic ileus and urinary retention, myasthenia gravis, reversal of NMJ blockade
Use of Pyridostigmine
myasthenia gravis (long acting) (does not penetrate CNS)
Use of Donepezil, Rivastigmine, Galantamine
Alzheimer’s
Use of Edrophonium
Dx of myastenia gravis (historically) *Myasthenia gravis now diagnosed by anti-AChR Ab
With all cholinomimetic agents, watch for..
exacerbation of COPD, asthma, and peptic ulcers.
Cholinesterase inhibitor poisoning is often due to..
organophosphates such as parathion that irreversibly inhibit AChE. Organophosphates are components of incesticides so this poisoning is usually seen in farmers.
Cholinesterase inhibitor poisoning causes…
diarrhea, urination, miosis, bronchospasm, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating and salivation.