Diagram of PT3001 Pharmacology MCQ Examination | Quizlet

nicotine

nAChR Agonist

tubocurarine

non-selective

hexomethonium

selective for Nn (nic nerve) over Nm(muscular)

nAChR Antagonist

muscarine

acetylcholine

both mus and nic agonist

carbachol

slightly better nic agonist

methacholine

slightly better mus agonist

mAChR Agonist

atropine

hyoscine

ipatropium

bronchodilation

mAChR Antagonist

phenylephrine

α₁ adrenoceptor Agonist

prazosin

α₁ adrenoceptor Antagonist

clonidine

alpha 2 adrenoceptor Agonist

yohimbine

alpha 2 adrenoceptor Antagonist

dobutamine

beta 1 adrenoceptor Agonist

atenolol

beta 1 adrenoceptor Antagonist

salbutamol

beta 2 adrenoceptor Agonist

butoxamine

beta 2 adrenoceptor Antagonist

Pharmacodynamics

Drug on Body

Pharmacokinetics

Body on Drug

1. Absorption

2. Distribution

3. Metabolism

4. Excretion

4 Parts of Pharmacokinetics

Formal Chemical Name

Code Name

Generic (non-proprietary) Name

Trade (proprietary) Name

Drug Naming Types

Isopropyl

Formal Chemical Name Ex.

D-135

Code Name Ex.

verapamil

no caps

Generic (non-proprietary) Name

Univer

CAPS

Trade (proprietary) Name

Diffusion

Active Transport

Pinocytosis

Like Endocytosis

3 Main Ways of Drug Membrane Transport

Lipid Diffusion

Common Route of Membrane Transport

Concentration gradient

SA of membrane

Permeability coefficient (hydrophobic is better)

Diffusion depends on...

Lipid Diffusion

Good for small hydrophobic drugs

Aqueous Diffusion

Passes between endothelial cells

Two types of diffusion

Binds with a biomolecule to form a complex

Ligand

A ligand that exists naturally within the body

Endogenous ligand

the drug is 50% ionized

Drug pH = the pH when

membranes block ions from crossing

Ion Trappin

Uncharged forms

What crosses membranes better, charged or uncharged forms?

Most drugs are weak acids or weak bases

Common pH of drugs

blood vessel endothelial cells are woven very tightly on top of each other. hydrophilic molecules can't leave!

Blood-brain barrier difference

Like endocytosis

Receptor mediated

For large proteins

Pinocytosis

Enteral

oral

Parenteral

all other routes

Enteral vs Parenteral

Convenient

Efficient

Large SA of GIT

Mixing w gut muscles

Variety of pH's in GIT

Microvili in intestine increases SA

Pros of Enteral Route

Drug can't be acid dissolved

Broken down by GIT enzymes

Cons of Enteral Route

Proportion of dosage that enters systemic circulation (100 for iv)

Bioavailability

First Pass Metabolism

When drugs get broken down the first time thru the liver. Not very effective

FPM

Inhalation

Topical

Transdermal

Buccal

Injection (iv, intramuscular, subcutaneous)

Parenteral Routes

High blood flo thru lungs

Inhalation

Local application ot body surface

Works at site of application

Topical

Slow absorption

Unlike topical, treats all over

Transdermal

Under tongue

Goes right into systemic circulation

Good for drugs with high FPM

Buccal

Bioavailability is LOW (not much reaches target)

I. V.

Most direct

Hazardous

Intramuscular

Absorption determined by bloodflow

Subcutaneous

Slow absorption

Sustained release forms

Injection

pH= pKa + log (protonated/unprotonated)

Henderson-Hasselbach Eq.

Vd= Amount drug/ Drug Concentration in Plasma

3.5 L Blood

10 L Interstitial fluid

28 L Intracellular fluid

Volume distribution

1. Blood flow

2. Ginding to proteins to help keep drug in the vascular system

Albumin (acidic drugs)

Alpha 1 (basic drugs)

Two factors that affect distribution

Hydrophilic

To extreme are drugs made more hydrophobic or philic

Drug > Derivative > Conjugate

Phase 1

Made polar by adding func groups OH NH2 etc

Phase 2

Condensation w/ hydrophilic group

Metabolism Mechanism

Oxidize wide range of chemicals

Low substrate specificity

Oxidize phase 1 reaction

Smooth ER

P450 Enzymes

Interferes with P450 enzymes

1. Competitive

Namesake

2. Direct

Suicide inactivates bind irreversibly

3. Depletion of cofactors

Metabolic Enzyme Inhibition

Age and Gender

Enzyme Inhibition

Metabolism Influenced by

Glomerular Filtration

Drugs filtered into urine

Tubular Secretion

Active transport w/ acid and base carriers

Two Routes of Kidney Excretion

Cp= C₀e^(-Kel * t)

Kel= 0.693/(half life time)

Half Life Equation

F= 1-(0.5)^(time/time taken for half life)

Fraction of new level of drug approached

D + R ⇌ DR → Response

Rate forward= k1 [D][R]

Rate reverse= k2 [DR]

[DR] = [D][R]/Ka

Receptor-Drug Interaction

Mimics endogenous ligand

Promotes

Agonist

The concentration required to get an EC50 response

Potency

The maximal effect of a drug

Efficacy

Two chemicals produce opposite effects, but acting through separate receptor systems

Physiological Antagonism

Causes drug to drop out of soln via precipitation

Chemical Antagonism

Ex. Accelerating metabolism

Pharmacokinetic Antagonism

Classical antagonism thru receptor mediation

Pharmacodynamic Antagonism

Resting state ⇌ Activated state →Response

Antagonist binds both states equally

Inverse agonist prefers resting state

Agonist prefers activated state to various degrees (partial vs. full agonist)

Two State Receptor Model

Effective dose in 50 percent of the population

ED50

Toxic does in 50 percent of the population

TD50

Between effectiveness and toxicity

Therapeutic window

1. Ion Channels

2. G-Protein Coupled Receptors

3. Kinase-linked Receptors

4. Intracellular Receptors

Types of Cell Receptors (4)

Ligand gated

Conduct small charged molecules

Alter membrane potential

Ion Channels

Capable of variety of signals due to second messengers

Steps

Ligand binds to thrombin receptor

Thrombin receptor alters g protein and GDP becomes GTP

This splits the alpha from the beta and the gamma sections of the protein

The alpha section then goes to another protein on the membrane, which can vary

This second protein then sends out a second messenger which is the cell signal

G Protein-Coupled Receptors

cAMP

cGMP

Diacylglyceral + IP3

Ca2+

Second Messengers

ARE enzymes

Extracellular ligand binding site

alpha helix crossing the membrane

Intracellular kinase

Kinase Linked Receptors

Activates receptor in the cell itself

alters gene transcription

Mediate cell response to

Steroids

Thyroid hormones

Lipids- fatty acids (PPAR) and cholesterol (LXR)

Intracellular Receptors

Bind fatty acids and fatty acid metabolites

Regulate genes that regulate lipid/carb metabolism and transport

PPARs

Sympathetic system

NA

alpha and beta adrenoceptors

fight or flight

Adrenergic system

Parasympathetic system

ACh

M and N cholinoceptors

digest and rest

Cholinergic system

reduce heart output, causes sweating, salivation and bronchiole secretion

Muscarinic agonists

tachycardia, excitatory CNS effects such as agitation and disorientation

Muscarinic antagonist effect on the heart

noradrenalne> adrenaline > isoprenaline

alpha agonist potency

isoprenaline> adrenaline> noradrenaline

beta agonist potency

Involuntary

Sympathetic, parasympathetic and enteric

Autonomic NS

AChE

Acetylecholinesterase

Turns Acetylecholine back into choline

Enzyme for ACh

Choline acetyletransferase takes choline and turns it into ACh

ACh synthesis

Nm- muscle type

Nn- nerve type

Nicotinic Receptor sub-types

M1- neural

M2- cardiac

M3- glandular

Muscarinic Receptor sub-types

muscarinic excess

nausea, vomiting, vasodilation, sweating, diarrhea

Mushroom Poisoning

Increase the response of the body to ACh because they block the breakdown of the neurotransmitter

insectisides

short/medium/long block of ser203

Short

Quaternary alcohols

Medium

Carbamyl esters (neostigmine and physostigmine

Irreversible

Pentavalent phosphorus compounds

AChE inhibitors

Receptors

AChE

Cholinergic drug targets

Receptors

Reuptake transporters

Monoamine Oxidase (MaO)

Catchecol-o-methyl transferase (COMT)

Adrenergic drug targets

excitatory effects (except in gut)

alpha adrenoceptors role

excitatory effects (except in heart)

beta adrenoceptors role

5-HT (hydroxytryptamine)

Acts via 5-HT receptors 1-5

5-HT1 agonist sumatriptan helps w migrains

5-HT2 agonist include LSD and 2c-p

Seratonin

Stored in granules in mast cells and basophils

Histamine

mimic morphine

Analgesic NOT anesthetic

Receptors μ δ κ ORL1

G protein coupling opens K+ channels causing the pain-killing effect

CNS Depressants- Opioids

Role in causing pain

Blocked by NSAIDs

Eicosanoids

Cholinergic agonist

AChE inhibitor

Encourages parasympathetic system in this way

Parasympathomimetic drug

Physostigmine

Cholinergic agonist

Activates acetylecholine receptor

Carbachol

Competitive antagonist of muscarinic cholinoceptors M1-5

Atropine

Blocks nicotinic cholinoceptors

Tubocurarine

Excites muscarinic cholinoceptors

Causing contraction

ACh role on ileum

Causes relaxation thru inhibitory β-adrenoceptors

NA role on ileum