Basics of Pharmacology

definition of a drug

a substance that changes a biological system by interacting with it

definition of medicine

a substance/mixture of substances used in restoring/preserving health

can be natural

regulated by medicines act (1968)

when does a drug become a medicine

when used to restore/preserve heath

BNF

British National Formulary

used to provide sound up-to-date information about the use of medicines

how many medicines are in BNF

over 1700

how to learn drugs

biochemical effect

physiological effect

the clinical effect of the pathology

targets of drug action

Regulatory proteins

RECI

Receptors

Enzymes

Carriers/Transporters

Ion Channels

How do drugs work

Bind to targets (RECI), changing function of physiological systems they regulate

What happens when a drug targets a Receptor

binds causing downstream change e.g. enzyme cascade, leading to physiological effect

what happens when drug targets ion channel?

binds to stop or increase ion flow

what happens when drug target a carrier/transporters?

binds to distrupt movement of other molecules

what happens when drug targets an enzyme?

modifies cell signalling causing a direct change of function

Inhibition- direct + rapid

Induction- gene effect+ delayed

what can drugs do at their targets?

activate

partially activate

block/inactivate/inhibit

functional effects of drugs

Biochemical

Cellular

Physiological

Structural

biochemical definition

chemical processes and substances which occur within living organisms

cellular definiton

relating to/consisting of living cells

physiological definition

relating to normal functions of living organisms and their parts.

structural definition

the composition and arrangement of the component parts of an organism or a device

temporal effects of drugs

Drug + target:

RAPID physiological response or Altered Gene expression

Physiological Response ⇌ Altered gene expression is SLOW

Altered Gene expression ⇌ Delayed Responses is SLOW (causes altered protein expression)

How do drugs interact with Receptors?

Exogenous ligands compete with Endogenous ligands causing downstream change, leading to a physiological effect

e.g. Beta blockers (e.g. bisoprolol) are adrenaline antagonists with high affinity for β₁-adrenergic receptors in heart. Binding causes heart to beat slower and weaker.

Affinity

How avidly a ligand binds to a receptor

Efficacy

Magnitude of the effect once a ligand is bound

Ligands

molecules that bind to receptors and cause changes in cell signalling and hence cell behaviour or structure.

Agonists

Bind, activating receptor

Antagonists

Bind, inhibiting activation by preventing endogenous ligand binding

Receptors

protein molecules which recognise endogenous signals e.g. hormones, neurotransmitters, inflammatory mediators.

response- series of downstream reactions, causing physiological effect

Enzymes

biological catalysts

basis for intracellular signalling cascades

drug effects: inhibition- direct+rapid; induction- gene effect+delayed

How do drugs interact with enzymes?

Inhibition- direct + rapid

Induction- gene effect+ delayed

e.g. statins are HMG CoA reductase analogues, binding to HMG-CoA competitively inhibiting HMG-CoA reductase binding, hence prevent conversion of HMG-CoA into mevalonate- slowing cholesterol production in the liver

Channel

Protein forming Lipid Bilayer pore

allows passive diffusion down concentration gradient for specific ions/molecules

e.g. Amlodipine binds to L-type calcium channels, stabilising channel in closed/inactive state, reducing influx of Ca²⁺ which inhibits release from SR and binding to myofilaments, reducing cardiac contractility, lowering blood pressure and reducing heart rate.

Exchanger (Antiporter)

moves two different ions across lipid bilayer in opposite directions. one down conc gradient and one up.

Co-transporter (Symporter)

moves two different ions/molecules across lipid bilayer in same direction.

One moves down conc gradient, and one up.

e.g. furosemide inhibits the Na⁺/K⁺/2Cl⁻ co-transporter, leading to increased urine production by blocking ion reabsorption at LoH in the kidneys.

specificity

the receptors ability to respond to a single ligand

effective drugs have high specifity, binding to other targets- side effects

Pharmodynamics

What the drug does to the body

effects of drug in body and mechanism of action

bioavailability

pharmacokinetics

what the body does to the drug

ADME

Absorption

Distribution

Metabolism

Excretion

ADME

pharmacokinetics- what the body does to the drug

Absorption- depends on administration route. passive/facilitated diffusion, active transport, endocytosis. IV/PO. plasma drug conc

Distribution- drug nature lipo-/hydro- phillic. blood flow- brain vs skin. capillary permeability e.g. high in liver, low in brain. plasma+ tissue binding- e.g. albumin systemic availability lower

Metabolism- Liver. Phase I- Oxidation, hydrolysis or reduction by cytochrome P450s. Phase II if still lipophillic- glutathione conjugation, acetylation, sulfation, glucuronidation. makes drug more readily excretable.

Excretion- Renal (adjust if creatinine eGFR low), Bile (adjust dosage if LFT low)

A in ADME

Absorption

depends on route of administration

passive diffusion (most common) - down conc gradient

facilitated diffusion- requires specific membrane molecules

active transport- not conc dependent. uses transporters

endocytosis- rare, larger molecules

IV/PO

Plasma drug conc

Bioavailability

fraction of administered dose that reaches systemic circulation

determined by drug properties and route of administration

AUC PO/ AUC IV

D in ADME

Distribution

NBCPT

Nature of drug- lipo-/hydro- phillic

blood flow- brain vs skin

capillary permeability- e.g. high in liver, low in brain

plasma+ tissue binding- e.g. albumin systemic availability low

M in ADME

Metabolism

makes drug more readily excretable

Liver

Phase I- oxidation, hydrolysis, reduction - by cytochrome P450s

Phase II if metabolites still lipophillic- gluthione conjugation, acetylation, sulfation, glucuronidation

Phase I of Metabolism

by cytochrome P450s

oxidation, hydrolysis, reduction

if still lipophillic goes to Phase II

Phase II of metabolism

if metabolism still lipophillic after Phase I by cytochrome P450s (oxidation , reduction, hydrolysis)

glutathione conjugation, acetylation, sulfation, glucuronidaton

E in ADME

Excretion

Renal (reconsider if creatinine/ eGFR low)

Bile (adjust dosage if LFT low)

Medicine classes

PoM- prescription only- from pharmacist with Rx from approved practitioner

Pharmacy only- purchased under supervision of a registered pharmacist

GSL- general sales list- can be bought from any outlet without Rx or pharmacist supervision

PoM

prescription only medicines

only from pharmacists with Rx from approved practitioner

pharmacy only medicine

bought under supervision of registered pharmacist

GSL medicines

General sales list

can be bought without Rx or pharmacist supervision

Medicines are regulated by

Medicines act (1968)

defines where which medicines can be obtained and where

components of Medicines in healthcare

PDAM

Prescribing

Dispensing

Administration

Monitoring

Prescribing

A Rx from a suitably-qualitied healthcare professional that authorises dispensing/administration of a medicine for a pt

Rx definition

a written order from a suitably-qualified healthcare professional (within scope of practice) that authorises the dispensing/administration of a medicine for a ppt

Dispensing

to make up + distribute medicines- especially on Rx

Primarily by pharmacists, also dispensing doctors + nurses

1. receive +validate Rx

2. understand + interpret

3. prepare + label

4. final check

5. record action

6. issue medicine with clear instructions + advice to pt

dispensing process

1. receive +validate Rx

2. understand + interpret

3. prepare + label

4. final check

5. record action

6. issue medicine with clear instructions + advice to pt

drug administration

giving a therapeutic agents to a pt e.g. by infusion, inhalation, injection, paste, suppository or tablet

primarily pts + carers. organisations- determined by local policy- self administration, appropriately trained + competent staff-mostly nurses, some doctors (emergency) and other practitioners

Check, Give, Record, Monitor

What to check when administering a drug

Identify pt

Rx

Consent

Allergies/ADR

identify meds + expiry date

storage compliance

not already given

give, record, monitor

What to check when monitoring a patients drugs

SEA, symptoms (hx), signs (exam), investigations

Safety- side effects (hx), exam, any side effect markers deteriorated)

Efficacy- feeling better (hx), improved signs, disease markers improved?

acceptability- Can they manage to take it?

interactions

How to check safety in drug monitoring

SIDE EFFECTS

any side effects in hx?

any signs of emerging side effects?

any side effect markers deteriorated?

how to check efficacy in drug monitoring

do they feel better?

have signs of disease improved?

have diseases markers improved?

how to check acceptability in drug monitoring

Can they manage to take the medicine?

Drug monitoring treatment regimen

Pt Tx goals/concerns

Best medication? - start additional drugs/ increase dose

anything to remove? stop/reduce dose- reduce harm/ treatment burden

How to make a therapeutic decision

Work out what is wrong- Presenting complaint, DDx

Identify right treatment- treat before if in emergency

start Tx + monitor

review + repeat

Pattern recognition- Hx, exam, inv, summarise, dx/ddx

How to work out what is wrong when making a therapeutic decision

p/c

DDx

Aims of treatment

Prioritised

Save life

relieve sxs

treat underlying disease cure for short term, control for long term

improve px- delay diseases progression, prolong survival

manage drug side effects

Social prescribing

lifestyle- diet, exercise, weight management. alcohol, smoking, illict drugs

MH- TThxm support+ counselling

social- housing, loneliness, isolation, family issues

medicines

interventions

surgery

Adverse drug reaction

unintended response in a patient resulting from medical intervention

prescribing should

Firstly do no harm

reduce mortality+ morbidity

basic duties of prescribing

Dukes and Seartz

restrictive use

careful choice

consultation and consent

Rx + recording

explanation

supervision

termination

conformity

drug use process

establish need- appropriate indication, address problems therapeutically, not prescribing is an option

select drug + regimen- factors- safety, tolerance, efficacy +price, pt factors, formulary alternative, risk:benefit

provide drug- dispensing, blister back etc

drug administration- appropriate devices + techniques

monitor- effectiveness/AEs, determine to maintain/modify/discontinue

counsel+closure- management plan to optimise care, identify ideas, concerns, expectations, establish responsibilities, safety net

Pt factors to consider when prescribing

coexisting disease- hepatic renal metabolism+excretion, cardiac/cancer side effects+ vulnerability, drug interactions, check BNF for dosage

pregnancy- malformation- T1 follic acid effects, T3

allergies

key steps in prescribing

STEP

safety

tolerability

efficacy - pt trust

Price

drug absorption methods

Oral

buccal

rectal

transdermal

nasal

lungs

intramuscular

subcutaneous

intravenous

intrathecal

oral absorption

enters bloodstream from digestive system

easy for pt compliance +administration

tablets, liquid

variable absorption, first-pass effect

buccal absorption

cheek

direct absorption into bloodstream through mucous membranes

rapid onset

avoiding liver metabolism

e.g. nitroglycerin for angina, buprenorphine for pain/opioid dependence

rectal absorption

when oral not possible- vomiting/ unconscious

localised effects in rectum

e.g. diazepam for seizures, acetaminophen

transdermal absorption

topical

continuous release- steady levels in blood, avoid frequent dosing

e.g. nicotine patch for smoking cessation

nasal absorption

rapid absorption through nasal mucosa

quick relief, emergencies

e.g. fluticasone for allergies, naloxone for opioid overdose

Lung absorption

inhalation

directly targets respiratory system for quick relief of symptoms w minimal systemic side effects

e.g. salbutamol for asthma

intramuscular absorption

relatively fast into bloodstream from muscle tissue

useful for larger volumes/ medications that irritate veins

e.g. epinephrine for anaphylaxis, vaccines

subcutaneous absorption

under skin

slower, sustained release into bloodstream

consistent levels over time

e.g. insulin for diabetes, heparin for thrombosis

Intravenous absorption

vein

direct into bloodstream, immediate effect + precise dosage control

ideal for emergency/ rapid action

e.g. morphine, antibiotics like ceftriaxone

intrathecal absorption

spinal canal

targets CNS directly by delivery into CSF- high local conc + reducing systemic side effects

e.g. morphine, methotrexate for certain cancers

Consider when prescribing to older people

reduced absorption- increased gastric motility

decreased intestinal/hepatic/renal blood flows (decreased renal clearance of digoxin and aminoglycosides)

reduced clotting factor synthesis -increased NSAID toxicity

anti-cholinergic, opiates, TCAD, antihistamines- constipation

anti-cholinergics- constipation, confusion

hypnotics, Beta blockers- confusion

fat soluble drugs- (increased sensitivity to benzodiazepine)

reduced hepatic clearance (increased level of benzodiazepine)

Stop Smoking advice

Ask status

Advice value of stopping

Assess intrest

Assist treatment options

Arrange follow up and monitor

Drugs

monitoring books of drugs

Steroid- Blue card

Warfarin- Orange book

Methotrexate/ Lithium- purple

Drugs with narrow therapeutic index

lithium

digoxin

theophylline

gentamicin

phenytoin

warfarin

drugs that require regular monitoring

morphine

insulin

neoplasia- chemo

digoxin

theophylline

hypoglycaemic agents- SU

epileptic treatments

gentamicin

anticoagulants- warfarin

anti-psychotics- lithium