Intro Pharm/Receptors/Admin

Disease, pregnancy

A drug is any agent used in treatment or prevention of __ and or __

Generic Name

Name of drug that is the same between companies

• Ex: Ibuprofen, acetaminophen

Trade Name

Advil, motrin, others– brand name

Pharmacokinetics

What the body does to the drug

Absorption, distribution, metabolism, elimination

ADME of pharmacokinetics

Pharmacodynamics

What the drug does to the body (i.e. efficacy, toxicity)

Stimulation, depression

• norepinephrine effect on heart rate =

• barbiturates’ effect on CNS =

Replacement, cytotoxic action

• working insulin given for tx diabetes =

• carboplatin for infected/cancer cell DNA damage =

Ligand-Gated Ion Channels

Activate in response to changes in the membrane potential OR ion concentration

Direct-ligand-activated ion channels

Activate in response to changes ion concentration (specific to Ca2+, K+, or Na+)

Benzodiazepines

Drug binds to GABAa receptor to enhance Cl- channels in brain allosterically

(ligand ion channel interaction)

Acetylcholine

Drug activates nicotinic receptor to open Na+ channel

(ligand ion channel interaction)

Voltage-Gated ion channels

Activate in response to membrane depolarization

Lidocaine

Drug acts as voltage-gated Na+ channel inhibitor, reduce pain

G Protein-Coupled Receptors

Activated via protein phosphorylations in sequence // GTP activated proteins

Adenyl cyclase, cAMP, PKA

Gs/Gi = Activation/inactivation of __ __ (enzyme)

• Converts ATP to ___ → Activates/inactivates ___ (enzyme) for further phosphorylations

Beta 1, beta 2, M2, alpha 2, opioids (Rs)

2 examples of Gs…

3 examples of Gi…

*Hint: QIQ QISS

M1, M3, alpha 1 (Rs)

Gq Rs

*Hint: QIQ QISS

phospholipase C, IP3, DAG, Ca2+, contraction, PKC

Gq = Activation of ___ (enzyme)

• PIP2 becomes → __ and __, from PLC activity

  • IP3 stimulates release of __ from sarcoplasmic reticulum

    • Net: Smooth muscle __

  • DAG then activates __ (enzyme)

Enzyme-linked Receptors (Intrinsic enzymes)

Activated via protein and receptor phosphorylation from kinases

Intrinsic Enzymes

Enzymatic domain is integral part of transmembrane receptor protein for phosphorylation

Growth factors, insulin

Examples of intrinsic enzyme Rs include:

epidermal __ __, __ Rs, and other RTKs

Extrinsic Enzymes

Enzyme is separate protein that associates/links with transmembrane receptor and phosphorylates

Cytokine, JAK-STAT

Examples of extrinsic enzyme Rs include:

__ Rs stimulating __-__ pathways (non-RTK)

Specific Receptors Class

Regulator proteins with endogenous ligands (i.e. glutamate Rs)

Intracellular Receptors

Activated via protein phosphorylation and later translocate to nucleus via diffusion → control gene expression

Steroid, thyroid

Intracellular Rs

• In cytosol - __ hormone Rs

• In nucleus - __ hormone Rs

First-Pass Effect

Metabolism of drug occurring during its first pass through liver immediately following absorption from GI tract

Oral, less, first-pass effect

Amount of active drug entering __ (route) systemic circulation after GI admin is __ (more/less), by amount of the __ __ __, than that after another route of admin

Oral, sublingual, rectal

3 types of Enteral Administration

PO advantages

• Most used route of admin, convenient

• Safe drug recall, inexpensive

• Self-administration

PO disadvantages

• Absorption is slow and highly variable between patients

• Absorption also affected by pH in GI tract, presence of food/enzymes/bacteria, other drugs

• Oral bioavailability less than 100% due to first-pass metabolism

Sublingual

Drug placed under the tongue then drug absorbed directly in bloodstream via small veins

Sublingual advantages

• Rapid absorption directly into systemic circulation via mouth

• NO first-pass effect

Sublingual disadvantages

• Erratic absorption leads to unpredictable effects

• Useful only for small doses

• Requires prolonged contact with mucosa, inconvenient

intravenous, intramuscular, subcutaneous (IV, IM, SC)

3 routes of parenteral administration

IV advantages

• Large fluid volumes possible

• Avoids first-pass effect (100% bioavailability)

• Rapid onset and subsequent control of drug concen.

IV disadvantages

• Higher cost compared to oral, difficult to admin, irreversible

• Possible infections, hematoma

• Unsuitable for non-aqueous solutions, drug must be soluble

IM advantages

• Fairly rapid and complete absorption of water soluble drugs

• Allows injection of depot preparations, larger volume than SC

• Avoids first-pass effect

• Patients can self-admin

IM disadvantages

• Painful, inconvenient

• Possible hematoma/bleeding

Subcutaneous

Needle inserted into fatty tissue layer beneath skin, then reaches capillaries to bloodstream via lymphatics

SC advantages

• Slower absorption than IM since blood flow is less in fatty tissue

• Used for many protein drugs (insulin)

• Avoids first-pass effect

• Patients can self-admin

SC disadvantages

• Discomfort, inconvenient

• Possible tissue irritation/injury

Intradermal

Commonly used for penicillin allergy and PPD tests

Cutaneous (topical), Percutaneous (transdermal), Inhalation, Nasal, Vaginal, Eye drops

Local routes of administration - (6)

IM, 90

Subcutaneous, 45

Intradermal, 10-15

90

Degree angle for insulin pen delivered subQ

Drug Absorption

Transfer of a drug from site of administration to bloodstream and to site of action

Drug permeation, passive diffusion

Via __ __: In order to reach site of action, drugs have to pass through several biological membranes

• Most important mechanism for permeation is __ __ of most drugs

Lipid, unionized, protein

• __-soluble or __ (ionized/unionized) drugs most easily diffuse across membranes

• __ Therapeutics - are injected as they are too large to cross membranes and would degraded by enzymes/acid in GI tract if oral admin

Ionization, water, excreted

Drug __ refers to drug molecule carrying an electric charge that is __ soluble and __ (absorbed/excreted)

Acidic, absorbed, acidic, basic, basic

Rules of AAA or BB for absorption

• __ drugs are best __ from __ environments

• __ drugs are absorbed best in __ environments

Acids, basic, bases, acidic, urine pH, ionized

Rules of AB or BA for excretion

• Weak __ are usually excreted faster in __ urine (AB)

• Weak __ are usually excreted faster in __ urine (BA)

• Goal is to accelerate excretion of drug and adjust the __ __

• Thus make certain most of drug is __ (ionized/unionized) state → drug gets “trapped” in urine

Bioavailability (F)

Fraction of administered dose of drug reaching systemic circulation in unchanged form

IV, lesser

F of ___ = 1, All other routes: F is __ (greater/lesser) than 1

IV, IM, SC, oral

Absorption Speed ~ __ > __ > __ > __

*Think first pass

Time course curve

Measured via drug plasma levels across different times points following routes of admin

AUC oral / AUC IV

When IM and IV doses are equal in time course curve:

F (bioavailability) = ___ / ___