Med-IQ 2nd Year

Learn the basics of pharmacokinetics! ADME!💊

The ADME (Absorption, Distribution, Metabolism & Excretion) of drugs is one of the crucial concepts that you will need to understand to transition from biochemistry to pharmacology.

This concept helps you understand the various biochemical factors that affect a drug's behaviour in the human body. It helps one decide the dosage, administration and factors that one must consider before giving a drug.

I hope this video helps✨

https://youtu.be/Oi7uDTNH4EE?si=V6PCDHSG-9d3crsH

PATHOLOGY OF ISCHEMIC HEART DISEASE: https://youtu.be/Cq39-_yF6GQ?si=dX73t9I5RDnERApv

https://youtu.be/Vg6-0a7y4aE?si=yqAIU90w5TLs7hMD

Good evening,

Here's the link to the 3rd year IMD 25 (Med-IQ) resources/mcqs/notes group.

https://t.me/+0VL2Z1kyYe82YTJl

We'll be continuing the trend of posting mcqs, notes etc whenever possible. But this time we need many to participate as we all have different subjects/modules at different times.

The group has separate topics according to our section wise modules in which we can post content related to your module. So for ex. Sec A people can post in pedia, Sec B people in commed etc, Sec C in ob/gyn and Sec D in Surgery. And when module changes we can use the other already created topics and add more.

Let's help each other out like we've all been doing for the past 2 years. Feel free to share notes, tips, mcqs from your module whenever you can ❤️

Thank you 😇

And the year comes to an end...✨
Thank you for your constant support medicos!!! ❤️

Here's to being Happy, Learning every step of the way and Working together in the following year.
Let's strive to become the best version of ourselves every single day. 🔥
Wishing you all a blessed and a very Happy New Year!!! ✨❤️

Pharmacokinetics & Pharmacodynamics Basics

Pharmacokinetics - ADME of drugs
Modes of transport - active & passive
Passive transport - m/c route for drugs (simple diffusion)

Ionized drug - has charge - cannot enter cell - non absorbable
Non-ionised drug - neutral - can enter cell - absorbable

Lipophilic - lipid loving - can enter cell through lipid bilayer membrane

Polar compounds - ionic compounds - non absorbable -> easily excreted

Weak acid best absorbed in acidic medium - stomach
Weak base best absorbed in basic medium - intestine

Tx of drug poisoning - excretion of drug is hastened by alkalinization (if acidic drug poisoning) or acidification (if basic drug poisoning) of urine

Bioavailability (F) - fraction of unchanged drug that enters systemic circulation after administration and becomes available to produce action

(F) IV = 1
(F) SQ/IM = 0.75 to 1
(F) Oral = 0.05 to 1

Bioequivalence - two related drugs that have comparable bioavailability and similar times to achieve peak blood conc

Therapeutic equivalence - two similar drugs that have comparable efficacy and safety

Drug receptor interaction:

1. Agonist - primary (same site), allosteric (diff site)
2. Partial agonist - submaximal effects
3. Antagonist - syntopic (same site), allosteric (diff site), chemical (combines with agonist), functional (indirect)
4. Competitive antagonist - reversible binding
5. Non competitive antagonist - irreversible binding

ED50 - dose of drug required to produce a specified effect in 50% of the population

LD50 - dose of drug required to cause death in 50% of the population; experimental animals

Therapeutic index = LD50/ED50

Complete GI pharmacology short notes

Topics:

1. GERD
2. Peptic ulcer
3. IBD - Crohn’s, UC
4. Motility disorders

📍Endocrine
Androgens

1. Testosterone - principal secreted androgen
Leydig cells - majority
Androstenedione, dehydroepiandrosterone - weak androgens

2. 1st trimester - fetal testes
3. DHT - binds with higher affinity to androgen R compared w/testosterone

4. Testosterone —-> DHT = 5alpha reductase
Type 1 - nongenital skin, liver, bone
Type 2 - urogenital tissue in men, genital skin

5. Testosterone —-> estradiol = Aromatase

6. Ingestion of testosterone - not an effective means of replacing testosterone deficiency

7. Alkylated androgens - hepatotoxicity
8. Blood dyscrasias - Danazol

9. Androgen receptor antagonists -
Flutamide - treat hirsutism in women
Bicalutamide
Nilutamide

10. Spironolactone - weak inhibitor of aldosterone, androgen R
Gynecomastia - s/e

11. 5 alpha reductase inhibitor
Finasteride - type II
Dutasteride - both type I and II

12. PDE5 inhibitors - erectile dysfunction
Sildenafil, vardenafil
- blue green tinting of vision - inhibition of retinal PDE6
CI - patients receiving organic nitrates

📍Endocrine
Estrogen & Progesterone

1. Naturally occurring - Progesterone
2. Drosperinone - derived from spironolactone
3. Estrogen produced by - developing follicles in ovaries, corpus luteum (2nd half of menstrual cycle), placenta
Other tissues - liver, adrenal glands, breasts

4. Principal source of circulating estrogen - ovary
Main secretory product in -
- Premenopausal women - Estradiol
- Postmenopausal women - Estrone

5. Estrogen -
Control amplitude of gonadotropin pulses
Rebuilding of endometrium
Increase HDL, decrease LDL and lipoprotein A
Decrease number and activity of osteoclasts

Progesterone -
Predominant control of frequency of LH surge
Decreases firing rate of hypothalamic pulse generator
Important for maintenance of pregnancy
Suppresses menstruation and uterine contractility
Increase LDL

6. GnRH suppression - major MOA of progestin-containing contraceptives
7. Lactation begins once levels of Estrogen and progesterone decrease at parturation

8. 2 estrogen receptor genes-
ESR1 - ER alpha
ESR2 - ER beta

Er-alpha -
Most abundant in female reproductive tract
Predominant in breast cancer

Er-beta-
Prostate and ovaries
does not contain AF-1 domain

9. PR-B -
longer with additional AF-3
stimulatory activities of progesterone

PR-A -
inhibits action of PR-B

10. Estrogen
SERM - Tamoxifen, Raloxifene, Toremifene
Anti-estrogens - Clomiphene, Fulvestrant
Estrogen synthesis inhibitors -
Steroidal - Formestane, Exemestane
Non-steroidal - Anastrozole, Letrozole, Vorozole

11. Clomiphene - treatment of infertility
Fulvestrant - treatment of breast cancer

12. All oral except - Fulvestrant (IM depot)

13. early and advanced Breast cancer - Tamoxifen
Osteoporosis - Raloxifene
Tamoxifen resistant breast cancers - Fulvestrant

14. PRM-
Mifepristone -
competes with both progesterone and glucocorticoids for binding with their respective receptors
Used to terminate pregnancy w/ misoprostol

Ulipristal -
selective PR modulator, partial agonist at PRs
inhibit ovulation

15. Monophasic contraceptive - fixed amounts of P and E
21 days followed by a 7 day pill free period

16. Endometriosis
First line - combined oral contraceptives

17. Add back therapy - low dose synthetic estrogen, or a high dose progestin

18. Finasteride - inhibitor of type 2 isoenzyme of 5alpha reductase
Danazol - rarely used due to hirsuitism

Pharmacology Short Notes (Drug tabulation)

Drugs affecting renal excretory function 💧

All the best ❤️

Pharmacology
Hypnotics and Sedatives 😴😵‍💫

1. Major therapeutic use — relieve anxiety or induce sleep
2. Sedatives/Anxiolytics — among the most prescribed substances worldwide
3. Pathophysiology of anxiety —
autonomic balance, decreased GABA-ergic tone, allelic polymorphism of COMT gene, increased adenosine receptor function, increased cortisol, decreased benzodiazepine receptor function, disturbances in serotonin

4. Anxiety stimulants — Amphetamines, cocaine, TCAs, caffeine
5. Miscellaneous cause — Baclofen, cycloserine, hallucinogens, indomethacin

6. Strategy for treatment — reduce anxiety without causing drowsiness
7. Hypnotics should produce a state of sleep that resembles normal sleep

8. Hypnotics in sleep -
latency of sleep decreased (time to fall asleep)
stage 2 NREM increased
REM decreased
Slow wave sleep - decreased
Tolerance - after 1-2 weeks

9. Benzodiazepines - FAT
Short action - Triazolam
Intermediate - Alprazolam
Long - Flurazepam

10. Barbiturates -
Ultra short - Thiopental
Short - Secobarbital
Long - Phenobarbital

11. Hypnotics -- depress CNS to stage III of anesthesia

12. MOA -
Barbiturates - Activate GABA a receptor complex, increase duration of GABA R channel opening

Benzodiazepines - Increase receptor affinity for GABA, increase frequency of openings of GABA R channel.
Safer than Barbs.

13. GABA-A receptor
Cl- channel

14. Barbiturates - more potential for abuse
Benzodiazepines - most important sedative/hypnotic

15. Preferred drug for short term insomnia - Benzodiazepines
16. Diazepam, Lorazepam - used to control life threatening seizures in status epilepticus, tetanus, drug induced convulsion, febrile convulsion

17. Clonazepam - absence seizures

18. All benzodiazepines cross placenta

19. Benzodiazepines overdose treated with - Flumazenil (BDZ receptor antagonist)
Flumazenil not effective against barbiturates overdose

20. Phenobarbital is excreted unchanged

21. Phenobarbital and meprobamate - autometabolism by induction of liver enzymes

22. Barbiturates contraindication - Porphyria

23. Melatonin - circadian signalling molecule produced by pineal gland
MT1 receptor - sleep
MT2 receptor - shifts timing of circadian rhythm

Ramelteon - binds to both MT1 and MT2 - chronic and transient insomnia
Tasimelteon - blinds pts w/circadian rhythm disorder

24. Most selective anxiolytic - Buspirone
Partial agonist at 5-HT1A receptor - inhibit serotonin release presynaptically

25. Meprobamate
Bis carbamate ester - may cause gastric bezoars

26. Inhibitor of orexin 1 and 2 receptor - Suvorexant
27. Agomelatine - melatonin receptor agonist, 5HT2C receptor antagonist

COMPRE Revision - Additional Pointers

Pulmonary edema - excessive interstitial fluid in the alveoli
1. Increased hydrostatic pressure - left sided heart failure (m/c), pulmonary vein obstruction
2. Decreased oncotic pressure - hypoalbuminea, nephrotic syndrome, liver disease
3. Lymphatic obstruction
4. Direct injuries - bacterial pneumonia, liquid aspiration
5. Indirect injuries - systemic inflammatory response syndromes

Pulmonary embolism - blood clots obstructing large pulmonary arteries
1. M/c source of blood clot - deep veins of legs
2. Due to thrombophilia
3. Recurrent embolism can cause pulmonary hypertension & cor pulmonale

Mallory-Weiss tears, are most often associated with severe retching or vomiting secondary to acute alcohol intoxication. Longitudinal mucosal tears near the gastroesophageal junction.

1. Alcoholism
2. Frequent vomiting
3. Hematemesis

Gall bladder disorders

1. Biliary atresia - seen in infants within 2 months of life, presents as jaundice and progresses to cirrhosis
2. Cholelithiasis - gall stones, precipitation of cholesterol or bilirubin
3. Biliary colic - waxing & waning right upper quadrant pain
4. Acute cholecystitis - acute inflammation of gallbladder wall
5. Chronic cholecystitis - rokitansky askchoff sinus herniation of gallbladder mucosa into muscular wall
6. Gall bladder carcinoma - adenocarcinoma from glandular epithelium, gall stones major risk factor

COMPRE revision notes - PART 3

Topics:
1. Inflammation (acute vs chronic)
2. SLE
3. Tissue response to injury

COMPRE revision notes - PART 2

Topics:
1. Tumor suppressor genes
2. HIV
3. Hepatitis
4. Tumors

COMPRE revision notes - PART 1

Topics:
1. Thyroid tumors
2. Cushing’s & addisons
3. Sprue
4. Hodgkin’s lymphoma
5. Kimmelstiel Wilson disease

Genetics 2 - Pediatrics - Important points 🧬

Maple syrup urine disease - AR, defect in branched chain ketoacid dehydrogenase, accumulation of leucine, isoleucine and valine in brain, classic MSUD is most common and severe

PKU - AR, defect in phenylalanine hydroxylase or tetrahydrobiopterin metabolism, phenylalanine accumulation, seizures & mental retardation

Homocystinuria - AR, cystathionine synthase deficiency, Ectopia lentis, marfanoid habitus

Ornithine transcarbamylase deficiency - m/c inborn error of urea synthesis, X linked dominant, hyperammonemia

FAOD - fatty acid oxidation disorders - hypoglycemia, hypo ketosis, acidosis, encephalopathy etc

MCAD - medium chain acyl coa dehydrogenase deficiency - m/c FAOD

GAL - galactosemia - AR, galactose accumulation

G6PD - most common enzymopathy, destruction of RBCs, jaundice & kernicteru, normal value > 2U/g Hb, infection -> hemolysis (Hep A, B, CMV, pneumonia & typhoid fever)

Only glycogen storage disease that is X linked is Hers disease (type VI) due to liver phosphorylase deficiency. All the other GSD are AR.

Only mucopolysaccharidoses that is X linked is Hunter syndrome (type II) due to defect in iduronate sulfatase enzyme. All others are AR.

ZWS - Zellweger syndrome - PEX1 gene mutation, cerebrohepatorenal syndrome, high in VLCFA

Rhizomelic chondrodysplasia punctata - AR PEX7 gene, GNPAT gene & AGPS gene, normal VLCFA, error in plasmalogen synthesis

X lined adrenoleukodystrophy - ABCD1 gene, only in males, high VLCFA