*Pharmacology 1 (1, 2, 3) Flashcards by B -

What are the 2 compromises of pharmacology and what do they mean?

Pharmacodynamics - what a drug does to the body (biological effects and mechanisms of action)
Pharmacokinetics - what the body does to a drug (absorption, distribution, metabolism and excretion)

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What selectively of drugs result from?

chemical structure of drug

Target recognising only ligands of a precise type

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Examples of targets of drugs? (5)

enzymes, carrier molecule, ion channels, receptors, RNA/DNA

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What are receptors?

Macromolecules that mediate the biological actions of hormones and neurotransmitters

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2 types of drugs acting on receptors and meaning?

Agonists - a drug that binds to a receptor and produces a cell response
Antagonists - a drug that blocks the actions of agonists

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What is a ligand?

A molecule that binds to a receptor

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Out of affinity and efficacy, what does an agonist and antagonist posses?

Agonist = affinity and efficacy
Antagonist = affinity

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How does an agonist work?

A conformational change occurs due to the presence of an agonist molecule making it act and therefore producing a biological response

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Affinity?

Strength of association between ligands and receptor

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Dissociation rate compared to affinity

Low affinity = high dissociation rate

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What are the 2 things that determine affinity

Closer the fit

Number of bonds

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Efficacy?

Ability of agonist to provoke a cellular response

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Low efficacy?

Low ability to produce a cellular response

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Relationship between receptor occupancy and agonist concentration?

As agonist conc. increases, receptor occupancy also increases

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EC50?

Concentration of agonist which elicits a half maximal response

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Concentration (or dose) response relationship - linear plot - relationship shape

Hyperbolic

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Why is it easier to plot the concentration response relationship as the log of the agonist concentration?

It allows you to present data over a wider range of concentrations
It is easier to see the max
70% of the curve is a straight line

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What shape is the response when the concentration response relationship is plotted as a semi-logarithmic plot?

Sigmoidal

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What can a highly potent drug do?

Evoke a larger response at lower concentrations

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What are partial agonists

Drugs that bind to receptors but only have partial efficacy meaning they cannot evoke the same response as a full agonist

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Competitive antagonism?

Binding of agonist and antagonist occur at same (orthosteric) site

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Non-competitive antagonism

Agonist binds to orthosteric site and antagonist binds to allosteric site (activation cannot occur if antagonist is bound)

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Drug disposition?

The fate of drugs in the body

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Determinants of drug disposition

Adsorption
Distribution
Metabolism
Excretion

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Adsorption?

The process by which a drug enters the body from its site of administration

Distribution

The process by which the drug leaves the circulation and enters the tissues perfused by the blood (once inside the tissue, further blood-independant distribution may occur)

Metabolism

The process by which tissue enzymes (particularly in the liver-hepatic metabolism) catalyse the chemical conversion of a drug to a more polar form that is more readily excreted by the body

Excretion

The process that removes the drug from the body (principally the kidneys - renal exertion)

Aside from the liver, where does metabolism also occur?

GI tract and lungs

Aside from the kidneys, where does excretion also occur?

Breath, sweat and milk

What is elimination (sum)?

metabolism + excretion

Where does most absorption occur?

in the Small intestines (due to large SA)

Where is ethanol absorbed

The stomach

name for when unchanged drugs leave the body via the faeces?

Egestion

3 physiochemical factors controlling drug absorption

Solubility (drug must be dissolved to be absorbed) Chemical stability (some drugs are destroyed by the stomach acid or enzymes in the GI tract) Lipid to water partition coefficient (rate of diffusion increases with lipid solubility of drug)

What does ampithatic mean?

Has both polar and non polar parts (drugs must be ampithatic)

In terms of weak/ strong acids/bases, what are many drugs

Weak acids and bases existing in both the ionised and unionised forms

pH=

pH=-log10[H+]

Out of ionised and unionised forms, what readily diffuses across the lipid bilayer

Unionised forms

What does the degree of ionisation of a drug depend on?

pKa of drug and local pH

pKa?

pH @ which 50% drug is ionised and 50% is unionised

What equation can be used to determine the proportion of ionised drug?

Henderson-Hassleback

Henderson hassleback equations for acid and base

Acid: pKa - pH = log(HA/A-) Base: pKa - pH = log (BH+/B)

As pH increases, are acid drugs increasingly or decreasingly ionised?

Increasingly

What is sometimes absorbed in the stomach acid?

Weak acids

Where does most absorption occur?

Small intestines (even weak acids)

Are weak acids and weak bases or strong acids and strong bases better absorbed?

Weak acids and weak bases

Factors affecting GI absorption? (6)

GI motility (rate of stomach emptying and movement through intestine) - modified by drugs and food pH @ absorption site Blood flow to GI tract (increased by food) Way in which tablet, capsule, etc. is manufactured (can be customised to release drugs at different rates/ sites) Physiochemical interactions (e.g. rate of absorption is modified by calcium rich food) Presence of transporters in membrane of epithelial cells of GI tract

Oral Availability? Equation?

Fraction of drug that reaches the systemic circulation after oral ingestion amount in systemic circulation/ amount administered

Systemic availability? Equation?

Fraction of drug that reaches the systemic circulation after absorption amount in systemic circulation/ amount absorbed

First pass/ pre-systemic metabolism?

Drugs administered orally, once absorbed can be inactivated by enzymes in the gut wall and liver

2 categories of routes of drug administration?

ENTERAL-via GI tract | Parenteral - any route not via the GI tract

4 enteral routes of drug administration?

Oral Sublingual Buccal Rectal

4 parenteral routes of drug administration?

``` IV intramuscular subcutaneous Inhalation Topical ```

What kind of drugs are able to move freely between the compartments of the body?

Free drugs

Volume of distribution?

Apparent volume in which a drug is dissolved

Vd=

Dose/ plasma concentraiton (for a drug administered IV)

Implies that the drug is retained in the vascular compartment

Implies that the drug is restricted to extracellular fluid

Vd>15L

Indicates distribution throughout total body water (or concentration in certain tissue)

What is the drug concentration that must be achieved to achieve an effect

Minimum effective concentration

What is the concentration level that causes significant adverse affects

Maximum tolerated concentration

What is the phase between MEC and MTC

therapeutic window

Therapeutic window of safe drugs

Large

Therapeutic ratio =?

MTC/MEC

Kabs? | Kel?

Absorption rate | Elimination rate

If given IV, what is the initial concentration of drug equation?

Co = D/ Vd (C=m/V)

What factor does concentration of drug at a later time depend on (Ct)

Kel

What type of kinetics do most drugs exhibit

First order

Ct=

Ct= Coe^-Kel-t

Half life

Time taken for Ct to fall by 50%

What is t1/2 inversely related to | Equation

Kel | t1/2 = 0.69/ Kel

What is Cp shorthand for

Plasma concentration

Are Kel and half life dependant on the dose administered

What is clearance (Cl)

The volume of plasma cleared of drug per unit time (a constant relating the rate of elimination to plasma concentration)

What type of kinetics does clearance apply to?

First order

Rate of elimination =

Rate of elimination = Cl X Cp

Maintenance dose rate?

Dose per unit time required to maintain a given plasma concentration

At steady state (SS)

Rate of elimination

Cps.s.=

Cps.s. = maintenance dose rate / Cl

For drugs that exhibit first order kinetics, what is the steady state (SS) plasma concentration linearly related to

infusion rate

What is the time to reach Css determined by?

half life (NOT the infusion rate)

When is Css reached?

After approx. 5 half lives

What is bioavailability (F)

Fraction of drug administered that enters the systemic circulation?

Css(average) = (oral dose)

FXdose / Clp X dosage interval

Volume of distribution (Vd)

Volume into which a drug appears to be distributed with a concentration equal to that of plasma (relates plasma concentration (Cp) to the amount of drug in the body (Ab)

Ab = ?

Ab = Vd X Cp (C=mXV)

Loading dose (LD)?

An initial high dose of a drug given at the beginning of a course of treatment before stepping down to a lower maintenance dose

LD (for IV) =

LD (IV) = Vd X target Cp

LD (for oral) =

LD = Vd X target Cp / F

In terms of Vd and Cl, what does t1/2 =?

t1/2 = 0.693 X Vd / Cl

What happens during zero order kinetics? | Example of 2 drugs that do this?

Drugs are initially eliminated at a constant rate, rather than at a rate proportional to their concentration (straight line on graph rather than curve) Ethanol and phenytoin

When do drugs exhibit zero order kinetics?

When Cp > km of an enzyme that metabolises it