11/23/2017

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By Live Dr - Wed Feb 11, 2:58 am

Pharmacology

potency efficacy
Refers to the amount of drug needed to produce a desired response Refers to the maximal response that can be produced by the drug
Less decisive factor More decisive factor
Competitive antagonists act by decreasing the potency of a drug, such that maximal response can still be obtained by increasing the  dose of agonist Non competitive agonist act by decreasing efficacy of a drug.

Maximal response is suppressed and insurmountable

Potency is indicated by the position of curve on the dose curve Efficacy is indicated by the upper limit of the dose response curve.

ADRENERGIC RECEPTORS

RECPTOR LOCATION AGONISTS ANTAGONISTS
Alpha 1 Postjunctional Phenylephrine Prazosin
Alpha 2 Pre and postjunctional Clonidine Yohimbine / Rauwolscine
Beta 1 Heart Dobutamine Atenolol / Metoprolol
Beta 2 Bronchi Salbutamol Butoxamine

PROSTAGLANDINS AND THEIR ACTIONS

PROSTAGLANDINS ACTIONS
PGE1 / PGI2 Vasodilation, inhibition of platelet aggregation.
PGE2 Vasodilation, bronchodilation, uterine contraction.
PGF2 α Uterine contraction, bronchoconstriction, vasoconstriction.
TXA2 Vasoconstriction, bronchoconstriction, platelet aggregation.

SEROTONIN RECEPTOR AGONISTS AND AGONISTS

5HT1A agonist Buspirone
5ht1b/1d agonist Sumatriptan
5ht2 antagonists Clozapine

Cyproheptadine

Methysergide

5ht3 antagonist Ondansetron
5ht4 agonist Cisapride

QUOTE CORNER

Don’t bother to just to be better than your contemporaries or predecessors. Try to be better than yourself.-William Faulkner.

ELEVENTH HOUR PHARMACOLOGY                                                                                                     37

USES OF PROSTAGLANDIN DRUGS

DRUG CLASS USE
PGE1 Alprostadil Causes vasodilation

Useful in erectile dysfunction

pge 1 analogue Misoprostol Gastric cytoprotection

Useful in preventing peptic ulcers caused due to nsaids.

pge2 Dinoprostone Causes contraction of uterus

Useful as abortifacient, cervical ripening

pgf2 alpha analogue Carboprost

Tromethamine

Causes uterine contraction

Abortifacient

Useful in postpartum bleeding

pgf2 alpha Latanoprost Increases outflow of aqueous humour

Used in glaucoma

pgi2 Epoprostenol Causes vasodilation

Useful in pulmonary hypertension.

MICROSOMAL ENZYME INDUCERS Drugs affected
Phenobarbitone

Rifampicin

Macrolide antibiotics

Steroids

Isoniazide

Alcohol

Griseofulvin

Antiepileptics

Omeprazole

Smoking

Phenytoin

Warfarin

Tolbutamide

Imipramine

Oral contraceptive pills

Chloramphenicol

Doxycycline

Theophylline

Drugs causing hemolysis in subjects deficient in G-6-PD are
Antimalarials- Primaquine

Sulfonamides-Cotrimoxazole

Nitrofurantoin- Nalidixic acid

Analgesic-aspirin, Phenytoin

Antiarryhthmics- Procainamide, Quinidine

Dapsone

Vit C, Vit K,

Probenecid

Furazolidone

TRIVIAL TRUTH

Opium was used widely as a painkiller during the American Civil War. As a result, over one hundred thousand soldiers had become drug addicts by the end of the war.

ELEVENTH HOUR PHARMACOLOGY                                                                                                     38

Drugs with therapeutic window
Tricyclic antidepressants

Clonidine

Glipizide

prodrug active form
Levodopa Dopamine
Enalapril Enalaprilat
Prednisone Prednisolone
Sulfasalazine 5-aminosalicylic acid
Diamorphine Morphine
Alpha methyldopa Alpha methyl norepinephrine
Drugs with high oral dose, due to high first pass metabolism
Propranolol

Alprenolol

Verapamil

Salbutamol

Nitroglycerine

Pethidine

Methyltestosterone

Amitriptyline

enzyme inhibitors

drug enzyme inhibited
Aspirin Cyclo-oxygenase
Allopurinol Xanthine oxidase
β aminopropionitrile Lysyl oxidase
Acetazolamide Carbonic anhydrase
Captopril Angiotensin convertase
5 fluorouracil Thymidine synthetase
Omeprazole Gastric H ATP ase
Pargyline MAO
Penicillin Transpeptidase
Phenelzine MAO
Sarin Cholinesterase
Statins HMG-CoA reductase
Warfarin Glutamate carboxylase

QUOTE CORNER

Intelligence is quickness to apprehend as distinct from ability, which is capacity to act wisely on the thing apprehended.-Dialogues by Alfred North Whitehead.

ELEVENTH HOUR PHARMACOLOGY                                                                                                     39

Agonist Activates a receptor to produce an effect
Inverse agonist Activates a receptor to produce an effect opposite to that of the agonist
Antagonist Prevents the action of agonist on a receptor , or subsequent response, but no effect of its own
Partial agonist Activates a receptor to produce submaximal effect but antagonizes the action of agonist.
competitive antagonist noncompetitive antagonist
Binds to the same receptor Binds to another site of receptor
Maximal response can be obtained Maximal response is suppressed
Reduces potency of the agonist Reduces efficacy of the agonist
V max is same, km increases V max is decrease, km is same.
Chemically resembles the agonist Doesn’t resemble agonist
zero order kinetics first order kinetics
Fixed amount of drug is eliminated per unit time

Rate of elimination is constant

Fixed proportion of drug is eliminated per unit time

Rate of elimination increases at higher concentration

Half life increases with dose Half life is constant
Plasma concentration against time-curve is linear Plasma concentration against time-curve is exponential

Teratogenic effects of drugs

drug effect
Methotrexte Multiple defects to fetal death
Androgens Virilisation
Progestins Virilisation of female fetus
Stibesterol Vaginal carcinoma in teenage female offspring
Steroids Cleft lip and palate, heart defects
Tetracycline Discoloured and deformed teeth
Warfarin Facial defects, growth retardation
Phenytoin Hydantoin syndrome

cleft lip and palate, microcephaly, hypoplastic phalanges

Growth and mental retardation.

Carbamazepine Neural tube defects

growth and mental retardation

Sodium valproate Neural tube defects

TRIVIAL TRUTH

Ketchup was once used as a medicine in the United States. In the 1830s it was sold as Dr. Miles’s Compound Extract of Tomato

ELEVENTH HOUR PHARMACOLOGY                                                                                                     40

Teratogenic effects of drugs CONTINUED…

drug effect
Lithium Fetal goiter, cardiac defects
Antithyroid agents Hypothyroidism
Indomethacin, Aspirin Premature closure of ductus arteriosus
Isotretinoin Craniofacial, heart and cns defects.
Trimethadione Craniofacial abnormalities

speech difficulty

growth and mental retardation

Ace inhibitors Oligohydramnios, renal anomalies, pulmonary hypoplasia
Norethisterone Virilisation of female fetus
DES Clear cell adenocarcinoma  of cervix and vagina hypoplastic T shaped uterus

In Male fetus, causes genital abnormalities

Cyclophosphamide Hypoplasia of digits, cleft palate, imperforate anus, iugr
Aminoglycosides 8th nerve damage
Sulphonamides Hyperbilirubinemia
Griseofulvin Conjoined twins.
Tobacco iugr, spontaneous abortion, abruption and preterm delivery
Cocaine Placental abruption, abortion, cranial defects, cardiac anomalies, prune belly syndrome.
Thalidomaide Phecomelia
PATHOGENIC AGENT CHEMOPROPHYLAXIS
Streptococci Penicillin
Neisseria meningitides Rifampicin / Ciprofloxacin
Clostridium perfringens Metronidazole
Clostridium tetani Penicillin
Yersinia pestis (Plague) Tetracycline / Cotrimoxazole
Bordetella pertussis  (whooping cough) Erythromycin
Mycobacterium tuberculosis Isoniazide and Rifampicin
Leptospira Doxycycline
medications contraindicated during lactation
Bromocriptine ,Cocaine

Cyclophosphamide, Cyclosporine

Doxorubicin, Lithium, Methotrexte

Phencyclidine, Phenindine, Radioactive iodine

QUOTE CORNER

Learn from yesterday, live for today, hope for tomorrow. The important thing is to not stop questioning.-Albert Einstein

ELEVENTH HOUR PHARMACOLOGY                                                                                                     41

CLASSIFICATION OF INSULINS BASED ON DURATION OF ACTION.

INSULIN TYPES DURATION (IN HOURS)
SHORT
Regular/ Simple/ Lispro

6-8

Prompt Insulin Zinc suspension (Semilente)

12-16

INTERMEDIATE

Lente / Insulin Zinc suspension.( 7 Ultra Lente + 3 Semilente)

20-24

NPH- Neutral Protamine Hagedorn / Isophane

20-24

LONG

Extended Insulin-Zinc suspension (Ultralente)

24-36

Protamine-Zinc Insulin

24-36

Glargine- (recombinant DNA from E. Coli )

24.

hypoglycemics mechanism of action
Sulphonylurea Stimulate insulin release
Biguanide Decrease hepatic gluconeogenesis,

increase glucose uptake in muscle

anorectics

Alpha glucosidase inhibitors Decrease digestion and absorption of carbohydrates
Meglinitide Stimulates insulin secretion
Insulin sensitizers Increase glucose  uptake in muscle

MECHANISM OF ACTION OF ANTIBIOTICS

Penicillin

Vancomycin

Bacitracin

Inhibit cell wall formation
Macrolides

Chloramphenicol

Tetracycline

Aminoglycosides

Inhibit protein synthesis by binding to 50 s ribosomal subunit
Sulphonamides and Trimethoprim Inhibit folic acid synthesis
Rifampicin Inhibits nucleic acid synthesis, by inhibiting DNA dependant rna polymerase
Fluoroquinolones Inhibit dna gyrase
Mupirocin Inhibits isoleucine t-rna synthetase

TRIVIAL TRUTH

Peanut butter was invented by St. Louis physician Ambrose Straub, who, concerned about the nutrition of his elderly, toothless patients, concocted a health-food product that was high in protein and easily digestible.

ELEVENTH HOUR PHARMACOLOGY                                                                                                     42

HYPOGLYCEMIC OF CHOICE

Once a day Glibenclamide
Young Glibenclamide / Glipizide
Elderly Tolbutamide, Glipizide
Potent, faster and shorter Glipizide
Renal failure Tolbutamide

Cephalosporins

generation parenteral oral
1st Cefazolin Cepahlexin, Cephradin

Cefadroxil

2nd Cefuroxime Cefaclor, Cefuroxime axetil
3rd Cefotaxim, Ceftizoxime, Ceftriaxone, Ceftazidime, Cefoperazone# Cefixime, Cefpodoxime proxetil, Cefdinir, Ceftibuten
4th Cefepime

#-Disulfiram like reaction

procaine penicillin benzathine penicillin
Short duration of action Very long duration of action
Plasma concentration is more Plasma concentration is less, so only prophylactic use
Painless injection Painful injection
Allergic phenomenon common Not common
Small dose- 0.5-1 M.U. Large dose 0.6-2.4 M.U.
Can be fortified with aqueous penicillin G Not fortified
Adverse reactions OF Rifampicin
Hepatitis

Respiratory syndrome- breathlessness

Cutaneous syndrome-flushing, pruritis, rash

Flu syndrome- chills, fever, headache,

Abdominal syndrome- nausea, vomiting, abdominal cramps

Most effective drug for specific populations of m.

tuberculosis.

Rapid growers Isoniazide
Slow growing Pyrazinamide
Spurters Rifampicin
Dormant No drug is effective

QUOTE CORNER

If it’s your limit, you can’t exceed it; If you exceed it, it’s not your limit.- Andrew Poon

ELEVENTH HOUR PHARMACOLOGY                                                                                                     43

Treatment of leprosy

Paucibacillary Multibacillary
Rifampicin-600mg monthly and Dapsone 100 mg daily

Treatment for 6 months follow up for 2 years

Rifampicin 600 mg and Clofazimine 300 mg monthly

Dapsone 100 mg and Clofazimine 50 mg daily

Treatment of 2 years , follow up for 5 years

ARV causing peripheral neuropathy Arv  not causing peripheral neuropathy
Zalcitabine, didanosine, stavudine Lamivudine, azidothymidine.
Side effects of steroids
Cushing’s habitus

Fragile skin

Osteoporosis

Peptic ulceration

Muscular weakness

Posterior subcapsular cataract

Glaucoma

Delayed wound healing

Psychiatric disturbances

ContRaindications to stEroid use
Peptic ulcer

Diabetes

Hypertension

Pregnancy

Osteoporosis

Active infections

Herpes simplex keratitis

Psychosis

Epilepsy

Chf

Renal failure.

Mechanism of action of antiepileptics

Phenytoin, Carbamazepine, Lamotrigine, Valproate Prolongation of Na+ channel inactivation
Barbiturates, benzodiazepines, Vigabatrin, Gabapentin, Valproate Facilitation of gaba mediated cl channel opening
Ethosuximide, Trimethadione, Valproate Inhibition of T type of ca++ current

TRIVIAL TRUTH

In 1900 Bayer® Aspirin became the first drug ever to be marketed in tablet form.

ELEVENTH HOUR PHARMACOLOGY                                                                                                    44

drug mechanism of action
Statins Decrease cholesterol synthesis by inhibition of rate limiting hmg-coa reductase
Bile acid sequestrants Decrease bile acid absorption, increased hepatic conversion of cholesterol to bile acids.
Fibric acid derivatives

Gemfibrozil

Increased activity of lipoprotein lipase.

Decreased release of fatty acids from adipose tissue

Nicotinic acid Decrease production of vldl. Decrease lipolysis in adipocytes.

*Nicotinic acid is the most effective drug for reducing triglyceride in genetic hypertriglyceridemia

Statin use is associated with myopathy

propylthiouracil carbimazole
Less potent More potent
Safe in pregnancy Contraindicated I pregnancy
t½  1-2 hr. t ½  6-10 hr.
No active metabolites Active metabolites
Peripheral conversion of t4 -> t3 prevented Not prevented
Useful in thyroid storm Not useful

theophylline

Dose should be increased in dose should be decreased in
Smoking

Phenytoin

Rifampicin

Phenobarbitone

Charcoal-broiled meat

Age over 60 years

chf

Pneumonia

Erythromycin

Ciprofloxacin

OC pills

Allopurinol

Drugs causing osteoporosis
Glucocorticoids

Cyclosporine

Cytotoxic drugs

Anticonvulsants

Alcohol

gnrh agonists

Heparin

Lithium

Excessive thyroxin

QUOTE CORNER

A happy life consists not in the absence, but in the mastery of hardships. –Helen keller

ELEVENTH HOUR PHARMACOLOGY                                                                                                     45

Treatment of hypercalcemia
Hydration with saline

Forced diuresis – saline+ loop diuretics

Biphosphonate

Calcitonin

Oral sodium Phosphates

High dose Glucocorticoids

Gallium nitrate

Plicamycin / Mithramycin

Dialysis

Intravenous Biphosphonate

Disodium edta

Arteriolar dilators Venodilators Mixed dilators
Hydralazine

Minoxidil

Calcium channel openers

Nitrates

Glyceryl trinitrate

Isosorbide dinitrate

Ace inhibitors

Losartan

Prazosin

Phentolamine

Nitroprusside

Chelating agents

chelating agents substances chelated
BAL (Dimercaprol) Arsenic, gold, bismuth, antimony

Lead ( with calcium-disodium EDTA)

Copper (with penicillamine)

C/I – Iron, cadmium.

Calcium-disodium EDTA Lead, zinc, cadmium, manganese, copper.
Penicillamine Copper
Desferrioxamine Iron poisoning
Deferiprone (oral) Iron overload
Contraindications to the use of morphine
Respiratory insufficiency

Hypotension and hypovolemia

Undiagnosed acute abdomen

*Flucytosine has supra-additive action with Amphotericin B

*Cholinergic crisis– Over treatment with anticholinesterases leads to persistent depolarization of muscle endplate.

TRIVIAL TRUTH

DIISOBUTYLPHENOXYETHOXYETHYLDIMETHYLBENZYLAMMONIUMCHLORIDE has appeared in the Journal of American Veterinary Medical Association. It is the chemical name of a drug they announced in the 1950s.

ELEVENTH HOUR PHARMACOLOGY                                                                                                     46

*Estrogen potency

Beta estradiol > estrone > estriol

*Sodium stibogluconate is the drug of choice for Kala azar

*Most severe ocular complication of hydroxychloroquine therapy is maculopathy, can lead to classical bull’s eye maculopathy

*Hoffmann elimination

Inactivation of the drug in the body fluids by spontaneous molecular rearrangement, without the agency of any enzyme

E.g. Atracurium.

*Monosufiram – antiscabies drug- produces Disulfiram like reaction

*Orphan drugs-

Drugs useful for rare diseases, for which there is no reasonable explanation that cost of developing and marketing will be recovered from sales of that drug.

*Hit and run drugs-

Drugs whose effect lasts much longer than the drug itself.

WHO rationale for titration of oral analgesis

Analgesic ladder

steps treatment
First step Non-opioid / + adjuvant
Second step Opioid + non opioid  /+adjuvant
Third step Opioid  / +nonopiod /  + adjuvant
Chemoprophylaxis of vivax and chloroquine sensitive falciparum malaria Chemoprophylaxis of chloroquine resistant falciparum malaria
Chloroquine 300 mg of base once weekly , started one week before exposure and continued for 4 weeks after returning Mefloquine 250 mg base once weekly.
condition drug of choice
H. simplex encephalitis Acyclovir
Neonatal herpes simplex Acyclovir
Herpes simplex keratitis Triflruidine / Vidarabine
Herpes simplex oro-labialis Pencyclovir

QUOTE CORNER

In nothing do men more nearly approach the gods than in giving health to men.- Cicero

ELEVENTH HOUR PHARMACOLOGY                                                                                                     47

*Kala azar- first line drug  is sodium stibogluconate, followed by pentamidine and amphotericin b

SEIZURES WITH DRUGS OF CHOICE

SEIZURE TYPE DRUGS OF CHOICE
Generalized tonic clonic,

Simple partial

Carbamazepine, Phenytoin
Complex partial Carbamazepine , Valproate
Absence ( petit mal ) Valproate , Ethosuximide
Myoclonic

Atonic

Valproate
Febrile seizures Diazepam (rectal)
Status epilepticus Diazepam , Clonazepam
Infantile spasm ACTH
Neonatal seizures Phenobarbitone , Phenytoin

Art

-Reverse transcriptase inhibitors

-Nucleotide RTI

AZT

Lamivudine

Abacavir

-Non nrti

Nevirapine

-Nucleotide analogue

Tenofovir

-Protease inhibitors

Indinavir

-Fusion inhibitor

Enfuviritide

trivial truth

Alexander Fleming discovered penicillin in 1928. He was researching the flu when he noticed that one of his Petri dishes had become contaminated with mould. This intruder was, killing off the Staphylococcus bug – a bug causing everything from boils to toxic shock syndrome. Eventually he identified it as the fungus Penicillium notatum, leading to the discovery of penicillin.

ELEVENTH HOUR PHARMACOLOGY                                                                                                     48

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