Flashcards in FA - Pharmacology I Deck (108):
Vmax is DIRECTLY PROPORTIONAL to ...?
The ENZYME CONCENTRATION.
Most enzymatic reactions follow a ... curve.
HYPERBOLIC curve (Michaelis-Menten kinetics).
Enzymatic reactions that exhibit a sigmoid curve usually indicate ...?
Cooperative kinetics (eg Hb).
Lineweaver-Burk plot - Up the y intercept means ...?
DECREASE IN Vmax.
Lineweaver-Burk plot - The further to the right the x-intercept (ie closer to zero), what is the effect to the Km?
The GREATER the Km = The LOWER the affinity.
Lineweaver-Burk plot - Reversible competitive inhibitors cross each other competitively, whereas NON competetitive inhibitors ...?
REVERSIBLE Competitive inhibitors - Resemble substrate?
IRREVERSIBLE competitive inhibitors - Resemble substrate?
NON competitive inhibitors - Resemble substrate?
REVERSIBLE competitive inhibitors - Overcome by incr. [S]?
IRREVERSIBLE competitive inhibitors - Overcome by [S]?
NON competitive inhibitors - Overcome by [S]?
REVERSIBLE competitive inhibitors - Bind active site?
IRREVERSIBLE competitive inhibitors - Bind active site?
NON competitive inhibitors - Bind active site?
REVERSIBLE competitive inhibitors - Effect on Vmax?
IRREVERSIBLE competitive inhibitors - Effect on Vmax?
NON competitive inhibitors - Effect on Vmax?
REVERSIBLE competitive inhibitors - Effect on Km?
IRREVERSIBLE competitive inhibitors - Effect on Km?
NON competitive inhibitors - Effect on Km?
REVERSIBLE competitive inhibitors - Pharmacodynamics?
IRREVERSIBLE competitive inhibitors - Pharmacodynamics?
NON competitive inhibitors - Pharmacodynamics?
Fraction of administered drug reaching systemic circulation UNCHANGED.
For an IV dose, F= ...?
Orally, F= ...?
Volume of distribution (Vd):
THEORETICAL volume occupied by the total amount of drug in the body relative to its plasma concentration.
Apparent Vd of plasma protein-bound drugs can be altered by ...?
LIVER + KIDNEY disease.
--> Decreased protein binding --> INCREASED Vd.
Low Vd - Compartment:
BLOOD - Large/charged molecules + Plasma protein bound.
Medium Vd - Compartment:
ECF - Small hydrophilic molecules.
High Vd - Compartment:
All tissues including fat - Small lipophilic molecules, especially if bound to tissue protein.
The volume of plasma cleared of drug per unit time.
Clearance may be impaired with defects in:
3. Renal function.
Number of t1/2 and % remaining:
1 --> 50%.
2 --> 25%.
3 --> 12.5%.
4 --> 6.25%.
In renal/liver disease, what happens in loading dose and maintenance dose?
LOADING DOSE --> Usually unchanged.
MAINTENANCE DOSE --> DECREASED.
Types of drug interactions - Additive:
Effect of substance A and B together is equal to the sum of their individual effects.
Example of additive interaction:
ASPIRIN + ACETAMINOPHEN.
Types of drug interactions - Permissive:
Presence of substance A is required for the full effects of substance B.
Example of permissive interaction:
CORTISOL + CATECHOLAMINES responsiveness.
Types of drug interactions - Synergistic:
Effect of substance A and B together is greater than the sum of their individual effects.
Example of synergistic interaction:
CLOPIDOGREL + ASPIRIN.
Types of drug interactions - Tachyphylactic:
Acute decrease in response to a drug after initial/repeated administration.
Example of tachyphylactic interaction:
MDMA + LSD.
3 weak acids:
2 weak bases:
Treat OD of weak acids with?
Treat OD of weak bases with:
Drug metabolism - Geriatric patients lose phase I or phase II first?
1. Maximal effect a drug can produce.
2. Represented by Vmax.
Efficacy related to potency?
UNRELATED to potency - Efficacious drugs can have high or low potency.
Partial agonists have ... efficacy than full agonists.
The amount of drug needed for a given effect.
--> EC50 (Effective concentration).
Potency related to efficacy?
UNRELATED to efficacy - Potent drugs can have high or low efficacy.
Agonist + Competitive antagonist - Effect:
1. RIGHT shift (decr. potency).
2. No change in efficacy.
3. Can be OVERCOME by increasing the concentration of agonist substrate.
Agonist + Competitive antagonist - Example:
Diazepam + Flumazenil on GABA receptor.
Agonist + NON competitive antagonist - Effect:
1. DOWN shift (decreased efficacy).
2. Cannot be overcome by increased substrate concentration.
Agonist + Non competitive antagonist - Example:
NE (agonist) + Phenoxybenzamine (non competitive antagonist) on alpha receptors.
Agonist + Partial agonist (alone) - Effect:
Acts at same site as full agonist, but with lower maximal effect (decr. efficacy).
--> Potency is an independent variable.
Agonist + Partial agonist - Example:
Morphine (full agonist) + Buprenorphine (partial agonist) at opioid μ receptors.
Therapeutic index - LD50 often replaces ...?
TD50 in ANIMAL STUDIES.
The adrenal medulla + Sweat glands are part of the SNS BUT are innervated by ...?
1. Nicotinic: Subtypes NN and NM.
2. Muscarinic: Subtypes M1-M5.
Nicotinic ACh receptors are:
Ligand-gated Na/K channels.
ACh receptors - NN are found in ...?
Autonomic ganglia + Adrenal medulla.
ACh receptors - Nm are found in ...?
Alpha-1 - G-protein?
Alpha-1 - Major functions:
1. Incr. vascular smooth muscle contraction.
2. Incr. pupillary dilator muscle contraction = MYDRIASIS.
3. Incr. intestinal + bladder sphincter muscle contraction.
Alpha-2 - G-protein?
Alpha-2 - Major functions:
1. Decr. sympathetic (adrenergic) outflow.
2. Decr. insulin release.
3. Decr. lipolysis.
4. Decr. aqueous humor production.
5. Incr. platelet aggregation.
Beta-1 - Major functions:
1. Incr. HR.
2. Incr. contractility.
3. Incr. renin release.
4. Incr. lipolysis.
Beta-2 - Major functions:
3. Incr. lipolysis.
4. Incr. insulin release.
5. Decr. uterine tone = TOCOLYSIS.
6. Ciliary muscle relaxation.
7. Incr. aqueous humor production.
Beta-3 - Major functions:
1. Incr. lipolysis.
2. Incr. thermogenesis in skeletal muscle.
M1 - G protein?
M1 - Major functions:
2. Enteric nervous system.
M2 - G protein?
M2 - Major functions:
1. Decr. HR.
2. Decr. contractility of ATRIA.
M3 - G protein?
M3 - Major functions:
1. Incr. exocrine gland secretons = Lacrimal, sweat, salivary, gastric.
2. Incr. gut peristalsis.
3. Incr. bladder contraction.
4. Incr. bronchoconstriction.
5. Incr. pupillary sphincter muscle contraction = MIOSIS.
6. Ciliary muscle contraction = ACCOMMODATION.
D1 - G protein?
D2 - G protein?
D1 - Major functions:
Relaxes renal vascular smooth muscle.
D2 - Major functions:
Modulates transmitter release, especially in brain.
H1 - G protein?
H1 - Major functions:
1. Incr. nasal and bronchial mucus production.
2. Incr. vascular permeability.
3. Contraction of bronchioles.
H2 - G protein?
H2 - Major functions:
Incr. gastric acid secretion.
V1 - G protein?
V1 - Major function:
Incr. vascular smooth muscle contraction.
V2 - G protein?
V2 - Major functions:
Incr. H2O permeability + Reabsorption in CCT of kidneys.
Release of NE from a SNS nerve ending is modulated by ...?
NE itself, acting on PRESYNAPTIC alpha-2-AUTORECEPTORS.
What is the mechanism of amphetamines?
1. Use the NE transporter (NET) to enter the PRESYNAPTIC terminal, where they utilize the vesicular monoamine transporter (VMAT) to enter the neurosecretory vesicles.
2. This DISPLACES NE from the vesicles.
3. Once NE reaches a concentration threshold within the presynaptic terminal, the action of NET is REVERSED, and NE is EXPELLED into the synaptic cleft.
Tyramine - Normally degraded by ...?
Excess tyramine enters ...?
PRESYNAPTIC vesicles and DISPLACES other neurotransmitters (eg NE) --> Incr. presynaptic neurotransmitters --> Incr. diffusion of neurotransmitters into synaptic cleft --> Incr. SNS stimulation.
Tyramine classically results in ...?
Bethanechol - Action:
Activates Bowel + Bladder smooth muscle.
Bethanechol is AChE sensitive or resistant?
Bethanechol - Applications:
1. Post-op ileus.
2. Neurogenic ileus.
3. Urinary retention.
Carbachol - Action:
Carbon copy of ACh.
Carbachol - Applications:
1. Constricts pupil.
2. Relieves IOP in open-angle glaucoma.
Methacholine - Action:
Stimulates muscarinic (M3) receptors in airway when INHALED.
Methacholine - Application:
Challenge test for diagnosis of asthma.
Pilocarpine - Action:
1. Contracts ciliary muscle of eye (open-angle glaucoma).
2. Constracts pupillary sphincter (closed-angle glaucoma).
Pilocarpine is sensitive or resistant to AChE?
Pilocarpine - Applications:
1. Potent stimulator of sweat + tears + saliva.
2. OPEN + CLOSED-ANGLE GLAUCOMA.
3. Xerostomia (Sjogren).