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Pharmacology 7301 Exam 1

Terms in this set (213)

Acetylcholine (Receptor Type(s))

Ligand-Gated Ion Channel
G-Protein Coupled Receptor

Epinephrine (Receptor Type(s))

G-Protein Coupled Receptor

Insulin (Receptor Type(s))

Transmembrane Enzymes

Thyroxine (Receptor Type(s))

Intracellular/Nuclear Receptor

Cortisol (Receptor Type(s))

Intracellular/Nuclear Receptor

Aspirin (acetylsalicylic acid) (Receptor Type(s))

Intracellular Enzyme

γ-aminobutyric aicd (GABA) (Receptor Type(s))

Ligand-Gated Ion Channel
G-Protein Coupled Receptor

Glutamate (Receptor Type(s))

Ligand-Gated Ion Channel
G-Protein Coupled Receptor

Histamine (Receptor Type(s))

G-Protein Coupled Receptor

Dopamine (Receptor Type(s))

G-Protein Coupled Receptor

Acetylcholine (Receptor Name(s))

Nicotine acetylcholine receptors
Muscarinic 1 acetylcholine receptors
Muscarinic 2 acetylcholine receptors

Epinephrine (Receptor Name(s))

Alpha 1 adrenergic receptors
Alpha 2 adrenergic receptors
Beta adrenergic receptors

Insulin (Receptor Name(s))

Receptor Tyrosine Kinase

Thyroxine (Receptor Name(s))

Thyroid hormone receptor

Cortisol (Receptor Name(s))

Glucocorticoid receptor

Aspirin (acetylsalicylic acid) (Receptor Name(s))

Cyclooxygenase 1 and 2

γ-aminobutyric aicd (GABA) (Receptor Name(s))

GABA type A Receptors
GABA type B Receptors

Glutamate (Receptor Name(s))

Amino-hydroxy-Methyl-isoxazole-Propionic Acid (AMPA) receptor
N-Methyl-D-Aspartate (NMDA) receptor
Matabotropic Glutamate Receptors

Histamine (Receptor Name(s))

Histamine (H1) receptors
Histamine (H2) receptors

Dopamine (Receptor Name(s))

Dopamine (D1) receptors
Dopamine (D2) receptors

Please select the appropriate receptor type that mediates the therapeutic effect of Aspirin (acetylsalicylic acid).
A. Voltage-Gated Sodium Channel
B. Ligand-Gated Ion Channel
C. G-protein coupled receptor
D. Receptor Tyrosine Kinase
E. Intracellular enzymes

E. Intracellular enzymes

Please select the appropriate receptor type that mediates the therapeutic effect of Lidocaine.
A. Voltage-Gated Sodium Channel
B. Ligand-Gated Ion Channel
C. G-protein coupled receptor
D. Receptor Tyrosine Kinase
E. Intracellular enzymes

A. Voltage-Gated Sodium Channel

Please select the appropriate receptor type that mediates the therapeutic effect of Nicotine.
A. Voltage-Gated Sodium Channel
B. Ligand-Gated Ion Channel
C. G-protein coupled receptor
D. Receptor Tyrosine Kinase
E. Intracellular enzymes

B. Ligand-Gated Ion Channel

Please select the appropriate receptor type that mediates the therapeutic effect of Morphine.
A. Voltage-Gated Sodium Channel
B. Ligand-Gated Ion Channel
C. G-protein coupled receptor
D. Receptor Tyrosine Kinase
E. Intracellular enzyme

C. G-protein coupled receptor

Voltage-Gated Ion Channels Example:

Voltage-Gated Sodium Channels

Voltage-Gated Ion Channels Example:

Voltage-Gated Calcium Channels

Ligand-Gated Ion Channels Example:

Nicotinic Acetylcholine Receptors (nAChRs)

Ligand-Gated Ion Channels Example:

y-aminobutyric acid Type A Receptors (GABA-A R)

Ligand-Gated Ion Channels Example:

N-methyl-D-aspartate receptor (NMDA R)

G Protein-Coupled Receptors G as Example:

Beta (β1, β2, β3) Adrenergic Receptors

G Protein-Coupled Receptors G as Example:

Histamine (H2) Receptor

G Protein-Coupled Receptors G as Example:

Adenosine (A2) Receptor

G Protein-Coupled Receptors G ai Example:

Alpha 2 (α2A, α2B, α2C) Adrenergic Receptors

G Protein-Coupled Receptors G ai Example:

Dopamine (D2) Receptor

G Protein-Coupled Receptors G ai Example:

Mu (u) Opioid Receptors

G Protein-Coupled Receptors G aq/11 Example:

Alpha 1 (α1A, α1B, α1D) Adrenergic Receptors

G Protein-Coupled Receptors G aq/11 Example:

Histamine (H1) Receptor

G Protein-Coupled Receptors G aq/11 Example:

Serotonin (5-HT2) Receptor

Intracellular/Extracellular Enzymes

Cyclooxygenases (COX-1 & COX-2)

Intracellular/Extracellular Enzymes

Carbonic Anhydrase (CA)

Intracellular/Extracellular Enzymes

Acetylcholinesterase (AChE)

Intracellular/Extracellular Enzymes

Angiotensin-Converting Enzyme (ACE)

Intracellular/Extracellular Enzymes

Vitamin K epoxide reductase (VKOR)

Nuclear Receptors Transcription Factors:

Proteins localized in the cytoplasmic/nuclear compartments. Responsible for initiation and regulation of gene expression.

Nuclear Receptors Example:

receptors mediate the effect of steroids and thyroid hormone

Transmembrane proteins

extracellular ligand binding is linked to intracellular (cytoplasmic) enzymatic activity

Transmembrane Enzymes

Transduce signals regulating cell growth, differentiation, survival, and migration.

Receptor Tyrosine Kinases

autophosphorylation/phosphorylate tyrosine residues on intracellular (cytoplasmic) proteins/kinases

Receptor Tyrosine Kinases Example:

Receptor Serine/Threonine Kinases

phosphorylate serine and threonine residues on intracellular (cytoplasmic) proteins/kinases

Receptor Serine/Threonine Kinases Example:

transforming growth factor-beta (TGF-β)

Agonists, Antagonists, Modulators

Ligand-receptor (Bound)

Total receptors =

At equilibrium:

[L][R]Kon = [LR]Koff

Equilibrium dissociation constant

Kd = Koff/Kon = [L][R]/[LR]

Types of antagonists

Receptor and nonreceptor

Types of Nonreceptor Antagonists

chemical and physiological

Types of receptor antagonists binding sites

active and allosteric

a pharmacologic antagonist that can be overcome by increasing the concentration of agonist

Competitive antagonists

binds to an allosteric (non-agonist) site on the receptor to prevent activation of the receptor.

Non-competitive antagonists

produce loss of feeling and affect a local area only

Local anesthetics

Local anesthetics mechanism of action

Block Voltage-Gated Sodium Channel

Inhibit Sensory (e.g. pain), motor and autonomic pathways

Local Anesthetics

is the basic structural & functional unit of Peripheral Nerves

First pain, sharp localized pain

second pain; dull, diffused pain

General order of functional block:

Pain > Temperature > Touch > Proprioception > Skeletal muscle tone > Involuntary

pain ≈≡≈ motor

Voltage-Gated Sodium Channel (VGSC) Depolarization Process:

Fast process (~1 ms)

Voltage-Gated Sodium Channel (VGSC) Recovery Process:

Local anesthetics bind preferentially to _________?

open and inactivated state of VGSC

slowly/normally firing neurons

Tonic inhibition

Long intervals between action potential

Tonic inhibition

Drug dissociate completely between signals

Tonic inhibition

Rapidly firing neurons

Phasic inhibition

Short intervals between action potential

Phasic inhibition

LAs do NOT dissociate completely between signals

Phasic inhibition

Amine group of LA

weak base (pKa 8-10)

Henderson-Hasselbalch equation

pKa = pH - log [base] / [conjugated Acid]

main determinant of lipophilicity (hydrophobicity)

Procaine partition coefficient

Procaine duration

Mepivacaine pKa

Mepivacaine partition coefficient

Mepivacaine duration

Bupivacaine pKa

Bupivacaine partition coefficient

Bupivacaine duration

Tetracaine partition coefficient

Tetracaine duration

LAs binding sites in the VGSC contains ____________ amino acids residues

Local Anesthetics attack from the __________

Procaine potency

Tetracaine potency

Mepivacaine potency

metabolized in the blood by esterase

Ester-linked LAs

metabolized by CYP in the liver, lung and kidney

Amide-linked LAs

Slower metabolism of Amide-linked LAs in patients with ______________

the more potent drugs with greater lipid solubility will result in _______ systemic absorption and peak plasma concentration

with Benzocaine and o-toluidine (metabolite of prilocaine)

Methemoglobinemia

Local Anesthetics CNS toxicity

Dose dependent symptoms

Local Anesthetics CNS toxicity Progressive may lead to _________.

Local Anesthetics CNS to Depression may lead to death from ____________ failure.

A larger LA dose is required for _________ toxicity than CNS toxicity

At low doses; some LAs act as ____________

Extremely rare; almost exclusively with ester-linked LA.

Hypersensitivity for Local Anesthetics

Hypersensitivity Local Anesthetic example:

procaine: metabolized to p-amino benzoic acid (PABA)

Skeletal muscle relaxants:

Neuromuscular Blockers, Spasmolytics, Dantrolene

Spasmolytic agent, act within skeletal muscles

Used to treat malignant hyperthermia

During surgical procedures and in ICU

Neuromuscular Blockers

To produce muscle paralysis

Neuromuscular Blockers

To facilitate intubation, optimize surgical conditions

Neuromuscular Blockers

To reduce spasticity in a variety of conditions

Centrally acting muscle relaxants

Non-depolarizing NMJ blockers are __________________.

Competitive Antagonists

Non-depolarizing NMJ blockers bind at the ________ binding site.

Non-depolarizing NMJ blockers have no __________ activity... no channel opening

Non-depolarizing NMJ blockers cause muscle __________ then paralysis

Depolarizing NMJ blockers are:

Partial agonists

Depolarizing NMJ blockers bind at the ______ binding site

Depolarizing NMJ blockers have __________ activity... open channel...Depolarize

Depolarizing NMJ blockers are not metabolized by _______

Depolarizing NMJ blockers cause __________ muscle fasciculation then paralysis

All NMJ blockers have at least one __________ amine group

ALL NMJ blockers are highly polar compounds and ______________.

inactive orally

____________ undergo spontaneous breakdown to Laudanosine which crosses the BBB and can cause seizures

Cisatracurium, vecuronium, rocuronium side effects:

have minimal CV side effects

Tubocurarine and mivacurium side effects:

systemic histamine release

Tubocurarine at higher doses side effects:

ganglionic blockers

Rapid hydrolysis by pseudocholinesterase

Succinylcholine

Only small % of the IV dose reach the NMJ

Succinylcholine

Extremely short duration (5-10 min)

Succinylcholine

Non-depolarizing muscle relaxant

No effect on autonomic ganglia

No effect on Cardiac M receptors

Release Histamine

The most commonly used muscle relaxant

All the clinical advantages of atracurium with less SE

Less likely to release Histamine

Hepatic metabolism and spontaneous breakdown

_____________ potentiate the action of GABA in the CNS

Benzodiazepines

can be used in almost any muscle spasm

produce sedation at the doses required to reduce muscle tone

Have been used as spasmolytic.

Agonist of GABA-B receptors

Baclofen (p-chlorophenyl-GABA)

Postsynaptic hyperpolarization, increasing K+ conductance

Baclofen (p-chlorophenyl-GABA)

Presynaptic inhibition (reduce Ca+ influx) and reduce the release of excitatory NT in the brain and spinal cord

Baclofen (p-chlorophenyl-GABA)

is effective in reducing spasticity

reduce pain in patients with spasticity

Less sedation and does not reduce overall muscle strength

Rapidly and completely absorbed after oral administration

Side effects of ___________ include drowsiness, but patients become tolerant with chronic use

α2-adrenoceptor agonists effects

Reduces spasticity at doses that cause minimal CV effect

Presynaptic and postsynaptic inhibition in the spinal cord

same efficacy as diazepam and baclofen

side effects of _________ are drowsiness (take at night), hypotension, dizziness, dry mouth, hepatotoxicity

Also effective for management of chronic migraine

General central depressant effect, no precise MoA yet

Inhibits interneuronal activity/synaptic transmission in the spinal cord and descending reticular formation

Has rapid onset, 2-4 hours duration of effect

FDA approved for short period (up to 2-3 weeks only)

Metabolized to Meprobamate (anxiolytic/sedative)

Side effects of ____________ are Sedation, drowsiness, dizziness, headache, seizure, with overdose/other drugs, abuse, dependence, and withdrawal.

Similar or better than diazepam against muscle spasm, local pain, limitation of motion.

Cyclobenzaprine

No precise MoA yet! acts mainly at brain stem centers, has no direct effect on muscles, or NMJ.

Cyclobenzaprine

Inhibits tonic somatic motor activity (both α and γ)

Cyclobenzaprine

Structurally related to TCA: potentiates norepinephrine effect, has anticholinergic effects and sedative effect.

Cyclobenzaprine

Oral bioavailability <60%, extensively metabolized (FPE), AUC/Cmax doubled in patient with hepatic impairment.

Cyclobenzaprine

Side effects of ___________ are severity/frequency are comparable to Diazepam, More dry mouth than diazepam, Less dizziness than diazepam

Cyclobenzaprine

General CNS depressant, sedative, muscle relaxant

No precise MoA yet

Has no direct effect on muscles, NMJ, or motor nerve fiber

Metabolized to inactive metabolite then excreted. Clearance reduced in patient with renal or hepatic impairment.

Side effects of __________ are sedation, dizziness, drowsiness, muscular incoordination, amnesia, confusion, blurred vision, headache seizures, fever, anaphylactic reaction, hypersensitivity reactions, bradycardia, flushing, hypotension, syncope, dyspepsia, jaundice, nausea and vomiting

Use in the treatment of Malignant-hyperthermia

Malignant-hyperthermia

Rare heritable disorder, Mutations in Ryanodine Receptors (RyR1) channels

Symptoms triggered by Volatile anesthetics, NMJ blockers

Prolonged release of Ca2+ via RyR1 channel

Massive muscle contraction

Lactic acid production and increased body temperature

Side effects of ___________ are generalized muscle weakness, sedation

It is the study of how drugs are Absorbed, Distributed, Metabolized, and Excreted from the body.

Pharmacokinetics

What the body does to the drug

Pharmacokinetics

It is the study of relationship between the drug concentration and the site of action.

Pharmacodynamics

What the drug does to the body

Pharmacodynamics

Routes of Drug Administration (from increasing drug absorption)

Inhalation, Intravenous, Sublingual, Rectal, Intramuscular, Subcutaneous Oral, Transdermal

this is equal to total mass of drug administered

AUC of IV is 100%

the actual amount of drug that gets into plasma = mass of drug after absorption

Bioavailability (F) (route) =

AUC (route) / AUC (IV)

Once the drug has gained access to the blood stream it gets ___________ to other tissue that initially had no drug.

Direction of distribution

Plasma (blood) --> tissue

[Concentration] =

Mass of drug (initial)/volume

Mass(absorbed) =

Mass(administered) X F

___________ always happens from Blood (plasma) to rest of the body or extravascular space

_______ mainly detoxify the drugs: This means if drug is in its active form, _______ deactivates drug or to less active form.

It is also called as Pre-systemic metabolism

First Pass Metabolism

Metabolism of drug during its passage from the site of absorption into systemic circulation.

First Pass Metabolism

It is also called as non-synthetic or functionalization reaction.

Phase 1 of Metabolism

Metabolite become active or inactive by introducing or crosslinking with groups (-OH, -NH2,-SH)

Phase 1 of Metabolism

is the time taken for its plasma concentration to be reduced to half of its original concentration

Plasma half-life (t1/2) of a drug

Half-life is depends on what two things:

1) Clearance (2) Volume of distribution

rate of change is independent of concentration

Zero Order Kinetics

rate of change is proportion to plasma concentration; a constant fraction of the drug will be eliminated (or absorbed) per unit time

First Order Kinetics

To determine t1/2, choose any two concentration values from y-axis that are exactly one-half of each other and corresponding time value from x-axis.

Graphical Method

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