PHARMACOLOGY
HIGH YIELD NOTES
SYMBOLS: ⊕ Agonist ⊗ Antagonist ⊖ Inhibitor # Blockade
GENERAL PHARMACOLOGY:
I. PHARMACODYNAMICS
OO Study of effects of drugs and their mechanism of action.
II. PHARMACOKINETICS
OO Study of Absorption, Distribution, Metabolism & Excretion of drugs (ADME)
III. PRO DRUGS
(Think: All Prefer Doing MD In Clinical Subjects)
OO All: ACE inhibitors except captopril & lisinopril
OO Prefer: PPIs, prednisone, proguanil
OO Doing: dipivefrine
OO M: methyl dopa, minoxidil, 6-MP
OO D: levodopa
OO In: irinotecan
OO Clinical: clopidogrel, carbimazole, cyclophosphamide
OO Subjects: sulfasaliziline, sulindac
IV. DRUGS WITH HIGH FIRST PASS METABOLISM (Think: HIT LPG)
OO Hydrocortisone
OO Isoprenaline
OO Testosterone
OO Lignocaine
OO Propranolol
OO Glycerol trinitrate
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PHARMACOLOGY
V. QUARTERNARY AMMONIUM COMPOUNDS
OO Do not cross CNS Blood brain barrier & have no CNS effects:
OO Incomplete oral absorption, hence given parenterally
OO It includes:
QQ Anticholinergics: glycopyrrolate, ipratropium, neostigmine
QQ NM blockers: d-tubocurarine, succinyl choline, heparin
QQ Non sedative antihistaminics: terfenadine, astemizole, cetirizine
VI. PLASMA PROTEIN BINDING
OO Acidic drugs bind albumin & Basic/Alkaline drugs bind α1 glycoprotein
OO Filtration 1/α PPB
OO Drugs with High PPB: (Think: PW DVT)
P: Phenytoin, Phenobarbitone, Phenylbutazone; W: Warfarin
D: Diazepam ; V: Valproate ; T: Tolbutamide
VII. THERAPEUTIC DRUG MONITORING
Continuous recording and adjustment of drug dosing according to its plasma
concentration
1. Used in drugs with low safety margins: digoxin, anticonvulsants (phenytoin),
antiarrhythmic (lignocaine), theophylline, cyclosporine, clonidine, TCA,
aminoglycosides.
2. Drugs with large individual variation: lithium, antidepressants
3. Potentially toxic drugs in renal failure: vancomycin, aminoglycosides
However, it is of no value in:
QQ Hit & run drugs eg. PPIs
QQ Drugs with irreversible action
QQ Drugs activated in body eg. levodopa
QQ Drugs whose response is easily measurable eg. antidiabetics,
antihypertensives, anticoagulants
VIII. THERAPEUTIC INDEX
TI = LD50/ ED50 ; LD: Lethal dose in 50% of population; ED: Effective dose in
50% of population
IX. BIOAVAILABILITY
OO Fraction of drug that reaches the systemic circulation in unchanged form.
OO Absorption & First pass metabolism are two important determinants
OO Bioavailability of a drug is 100% via intravenous routeQ
OO Drugs with 100% bioavailability: aromatase inhibitors, theophylline, linezolid
OO AUCQ (area under the curve) of drug concentration vs time graph signifies
extent of absorption whereas Tmax tells the rate of absorption.
X. APPARENT VOLUME OF DISTRIBUTION
OO Volume that would be required to contain the administered drug if that dose
was evenly distributed at the concentration measured in plasma.
OO Drugs with low Vd: Drugs with High PPB o Warfarin, Phenylbutazone
OO Drugs with high Vd: Drugs sequestered in body tissues o Chloroquine,
Morphine, Propranolol, Digoxin
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PHARMACOLOGY
XI. BIOTRANSFORMATION
Non synthetic/ Phase I Rxn Synthetic / Phase II Rxn
Expose functional group Used to attach conjugate to drug
Some drugs become activated All drugs become water soluble
It includes: It includes:
- Hydroxylation - Glucuronidation
- Dealkylation - Acetylation
- Hydrolysis - GSH Conjugation
- MAO - Methylation
- Dehydrogenases - Sulfation
Note: 1. Hydroxylation & dealkylation are inducible/ microsomal phase I reactions
2. All phase II reactions are non-inducible except glucuronidation
XII. CYTOCHROMES
OO Substrates of CYP3A4 (~50% of enzyme metabolism). Think: CT SCAN
QQ Cyclosporine, Calcium channel blockers
QQ Tacrolimus
QQ Statins
QQ CAT drugs (C: Cisapride; A: Astemizole; T: Terfenadine: ↑ QT interval)
QQ Amiodarone
QQ Navirs (Protease inhibitors)
OO Substrates of CYP2D6: (Think: “2D6”: 2 = beta, D = antiDepressants, 6 (read as
sing) = anti arrhythmics)
QQ Beta blockers
QQ Antidepressants: TCA, SSRIs, SNRIs
QQ Anti arrhythmics except amiodarone
OO Substrates of CYP2C9: (Think C = Clotting; 9 = P (looks like P))
QQ Clotting: warfarin
QQ Phenytoin
OO Substrates of CYP2C19:
QQ Clopidogrel
QQ PPI: prazoles
OO Substrates of CYP1A1/2:
QQ Caffeine, theophylline (methylxanthines)
QQ Paracetamol
QQ Procarcinogens carcinogens
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PHARMACOLOGY
XII. ENZYME INDUCERS & INHIBITORS
Enzyme Inducers Enzyme Inhibitors
(Think: GPRS Cell phone) (Think: VIT ACEK)
Griseofulvin Valproate
Phenytoin Isoniazid, Itraconazole
Rifampicin Acute alcoholics
Smoking Cimetidine
Carbamazepine Ciprofloxacin
Chronic alcoholic Erythromycin
Phenobarbitone Ketoconazole
XIII. CLEARANCE OF DRUGS
OO Acidic drugs are removed by Alkalinisation of urine by giving NaHCO3
o It is done in poisoning of: aspirin, barbiturates, lithium.
OO Basic drugs are removed by acidification of urine by NH4Cl/Vit C
o It is done in poisoning of: amphetamine, morphine, quinine.
XIV. DIALYSIS IN CASE OF OVERDOSAGE
Dialysis can be done in: Dialysis is not effective in:
(Think: MLA BESTI) (Think: AVOID Dialysis)
Methanol Amphetamines
Lithium Verapamil
Aspirin Opioids & OP
Barbiturates Imipramine
Ethylene glycol Digoxin
Salicylates Diazepam & BZD
Theophylline
Isoniazid
XV. KINETICS OF DRUG ELIMINATION
A] Zero order kinetics B] First order kinetics
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PHARMACOLOGY
First order kinetics Zero order kinetics
Constant fraction of drug is Constant amount of drug is
Definition
eliminated eliminated
Rate α Plasma concentration Constant
Clearance Constant 1/α Plasma concentration
t1/2 Constant α Plasma concentration
XVI. DRUGS FOLLOWING ZERO ORDER KINETICS
(Think: Zero WATT Power)
OO Warfarin
OO Alcohol/Aspirin
OO Theophylline
OO Tolbutamide
OO Phenytoin
XVII. TYPES OF INHIBITION
Km Vmax
Competitive ↑ -
Non competitive - ↓
Uncompetitive ↓ ↓
XVIII. DOSE RESPONSE CURVE
Log [Agonist] Log [Agonist]
OO Efficacy: Ability of a drug to produce maximum effect by acting on target
OO Potency: Amount of drug needed to produce a certain response
OO Mnemonic: HE LP
o More the height Efficacy
o More left Potency
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PHARMACOLOGY
XIX. AGONIST & ANTAGONISTS
Affinity Intrinsic activity
Agonist + 1
Partial Agonist + 0
Antagonist + 0
Inverse agonist + -1
XX. CLINICAL TRIALS
Phases Trial Study conducted on Notes
Microdosing Healthy human Reduce the cost & time for
0
studies volunteers drug development process
Healthy human Bio availability
I Non therapeutic
volunteers (10-100) Safety & S/E profile
Small no. of patients Therapeutic efficacy & dose
II Efficacy trial
(50-500) ranging
Therapeutic Large no. of pts RCT done to compare with
III confirmation &
(500-3000) existing treatment
comparison
Post marketing To know idiosyncratic, rare
IV General population
surveillance &long term S/E of drugs
XXI. SOME IMPORTANT FORMULAE
1. CL = Rate of elimination / Plasma concentration Renal Clearance: UV/P
2. U: Urine creatinine concentration; V: volume of urine; P: plasma creatinine
concentration
3. Rate of elimination α [Plasma concentration] order
4. T1/2 = 0.693/k
5. T1/2= 0.693 x Vd/CLVd = Volume of distribution; CL= Clearance
6. Vd= Amount of drug in body / Initial plasma concentration
7. Cpss= Dose rate/ Clearance Cpss: Steady state plasma concentration
8. Loading dose: Vd x Target plasma concentration / S x F
9. S= Salt fraction F = Bioavailability
10. Maintenance dose:
Clearance x Target plasma concentration x Dosing interval / F
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