KAPS Exam Miles PDF - Biopharmaceutics and Pharmacokinetics

2022 E D I T I O N 01 KAPS EXAM MILES KNOWLEDGE ASSESSMENT OF PHARMACEUTICAL SCIENCES www.academic...

2022 E D I T I O N 01 KAPS EXAM MILES KNOWLEDGE ASSESSMENT OF PHARMACEUTICAL SCIENCES www.academically.ai [email protected] +61 406 525 564 3/20 Bailey St,Westmead- 2145,Sydney, Australia.  Quick revision handouts for KAPS:  Dear students, these handouts will help you quickly revise the topics discussed in our lectures before examination. They shall not replace the lectures as lectures involve detailed explanation with all important points highlighted for KAPS preparation. In order to clear KAPS ACADEMICALLY strongly recommends you re-listen to lectures again and prepare notes and practice multiple choice questions for KAPS examination. w w w. www academically.ai [email protected] Page 1  Revision Hand out 5 Biopharmaceutics and Pharmacokinetics Pharmacokinetics:  Pharmaco means drug  Kinetics means motion  What our body does to the drug  How drug concentration changes as it moves through the different compartments of our body Pharmacodynamics: Pharmaco means drug Dynamics means power How the drug exerts its power of effect on our body How powerful is the drug, (how potent is it, its efficacy is a parameter of pharmacodynamics) Here we deal with drug-receptor interactions Things to remember:  Many drugs are weak acids or weak bases  A drug tends to pass through the membranes if it is uncharged  Uncharged (lipophilic, unionised, non-polar drugs) are more lipid soluble than the charged drugs  Uncharged drugs are absorbed well  Charged drugs are eliminated well w w w. www academically.ai [email protected] Page 2   Weak acids donate hydrogens and become charged HA ←→ H++A-  Weak bases accept hydrogens and become charged B+H+←→ BH+ First pass metabolism:  Orally administered drugs are absorbed from the gastrointestinal (GI) tract.  The blood from the GI tract then travels through the liver, the great chemical plant in the body.  Many drugs that undergo liver metabolism will be extensively metabolized during this passage from the GI tract to the body.  This effect of liver metabolism is called the first-pass effect. Topical: This refers to external application of the drug to the surface for localized action. Drugs can be efficiently delivered to the localized lesions on skin, oropharyngeal/ nasal mucosa, eyes, ear canal, anal canal or vagina in the form of lotion, ointment, cream, powder, rinse, paints, drops, spray and lozenges. w w w. www academically.ai [email protected] Page 3  Drugs like salbutamol, which is inhaled to show the action on bronchi is also an example for topical. Absorption is rapid, few systemic side effects Gives localized effect Deeper tissue: Intra-articular injection of corticosteroids is also an example of locally acting drug. Systemic Routes of Administration: Oral:  Both solid dosage forms and liquid dosage forms can be given orally.  Safest route of administration  Main limitations of oral route include:  Action of drugs is slower and thus not suitable for emergencies.  Unpalatable (bad taste) drugs (chloramphenicol) are difficult to administer  May cause nausea and vomiting.  Limited absorption of some of the drugs  Food may affect the absorption of drugs  Drugs like aminoglycosides (amikacin/gentamycin) cannot be administered orally as they get easily ionized in gastric pH, once ionized the drug molecules cannot get absorbed into systemic circulation.  Drugs like penicillin G, insulin gets rapidly hydrolyzed in the gastric fluid, hence they can't be administered orally.  Patient’s compliance is necessary Sublingual: Only lipid soluble and non-irritating drugs can be so administered. Absorption is relatively rapid; action can be produced in minutes. First-pass metabolism can be avoided by this route. Bypasses destruction by stomach acid. **limited to drugs that can be taken in small doses** w w w. www academically.ai [email protected] Page 4  Example: nitroglycerine Rectal: Certain irritant and unpleasant drugs can be put into rectum as suppositories or retention enema for systemic effect. First-pass metabolism can be avoided to some extend (only the drug which gets absorbed in the internal hemorrhoidal vein will reach the liver) (partially bypasses the first pass metabolism.) Example: rectal diazepam, paracetamol suppositories. Cutaneous/transdermal patch: Only lipid soluble drugs can be applied over the skin for slow and prolonged systemic absorption. Drug is subjected to little first pass effect Application site allergies can occur. Limited to drugs that can be take only in small doses. Examples: Transdermal patches of GTN, fentanyl, nicotine and estradiol. Inhalation: Certain are inhaled drugs show systemic action. Example: inhaled general anesthetics. Parenteral: Conventionally, Parenteral refers to administration by injection which takes the drug directly into the tissue fluid or blood without having to cross the enteral mucosa Advantages of parenteral route:  Drug action is faster and surer  Gastric irritation and vomiting are not provoked.  Parenteral routes can be employed even in unconscious, uncooperative or vomiting patient.  There are no chances of interference by food or digestive juices.  Liver is bypassed (first pass metabolism is bypassed). w w w. www academically.ai [email protected] Page 5  Subcutaneous: The drug is deposited in the loose subcutaneous tissue which is richly supplied by nerves (irritant drugs cannot be injected) but is less vascular. Suitable for slow-release drugs. *As it is less vascular, absorption is slower when compared to intramuscular route. (Many times, this question was asked in entrance/licencing exams). Only small volumes can be injected through this route. Example: insulin injection If the drug is irritating pain/necrosis may occur. Route of absorption is very slow when compared to intramuscular. Intramuscular: The drug is injected in one of the large skeletal muscles—deltoid, triceps, gluteus etc. Muscle is less richly supplied with sensory nerves (mild irritants can be injected) and is more vascular As it is more vascular, the rate of drug absorption through this route will be faster compared to subcutaneous tissue. Depot preparations (oily solutions, aqueous suspensions) can be injected by this route. w w w. www academically.ai [email protected] Page 6  Intravenous: The drug is injected as a bolus or infused slowly over hours in one of the veins. As drugs get diluted with blood, therefore, even highly irritant drugs can be injected. (Remember: only mild irritants can be injected through intramuscular. To avoid confusion just remember that the only route of administration for irritant drugs is i.v) Only aqueous solutions (not suspensions, because drug particles can cause embolism) are to be injected intravenously and there are no depot (sustained release) preparations for this route. The bioavailability through this route is 100%. (as first pass metabolism is bypassed). PHARMACOKINETICS  Absorption  Distribution  Metabolism  Excretion Absorption: The movement of drug from the site of administration to systemic circulation. Factors influencing the rate of absorption: Chemical characteristics of the drug The route of administration PH of the medium Blood flow to the absorption site, ***more blood flow more absorption. ( intestines receive more blood flow compared to the stomach. Total surface area increases absorption increases. Contact time of absorption surface, (presence of food dilutes the drug and slows gastric emptying hindering the absorption. w w w. www academically.ai [email protected] Page 7 w w w. www academically.ai [email protected] Page 8  Distribution: Distribution is dispersion of drug throughout the body From vascular space to extravascular space…(REVERSIBLY leaves the blood stream and enters the interstitium (extracellular fluid) and tissues. Drugs can get into the fat, muscle. w w w. www academically.ai [email protected] Page 9  Note:- All the other drugs apart from the above drugs are basic in nature********* w w w. www academically.ai [email protected] Page 10  Excretion of Drugs: Acidic drugs are ionized more in alkaline urine. Once ionized, they do not back diffuse in the kidney tubules and are excreted faster. That’s why in case of salicylate or barbiturate poisoning, physicians will administer sodium bicarbonate to make the urine alkaline. If the urine is alkaline the molecules get ionized and excreted out. Accordingly, basic drugs are excreted faster if urine is acidified. In acidic urine the basic drug molecules get ionized and excreted out. However, acidification of urine is not clinically used. In case of poisoning with basic drugs they use some antidotes or hemodialysis rather than acidifying the urine. Bioequivalence: Oral formulations of a drug from different manufacturers or different batches from the same manufacturer may have the same amount of the drug (chemically equivalent) but may not yield the same blood levels—biologically inequivalent. Two preparations of a drug are considered bioequivalent when the rate and extent of bioavailability of the active drug from them is not significantly different under suitable test conditions. w w w. www academically.ai [email protected] Page 11 w w w. www academically.ai [email protected] Page 12 w w w. www academically.ai [email protected] Page 13 w w w. www academically.ai [email protected] Page 14 w w w. www academically.ai [email protected] Page 15 w w w. www academically.ai [email protected] Page 16  Elimination: Renal elimination of drugs involves three physiological processes:  Glomerular filtration, : Free drug flows out of the body and into the urine-to-be as part of the glomerular filtrate. The size of the molecule is the only limiting factor at this step.  proximal tubular secretion, : Some drugs are actively secreted into the proximal tubule.  distal tubular reabsorption. Uncharged drugs may diff use out of the kidney and escape elimination. Manipulating the pH of the urine may alter this process by changing the ionization of the weak acids and bases. However, for a drug to be excreted, it needs to be charged so that it is trapped in the urine and can’t cross the membrane to sneak back into the body. This process is called ion-trapping. w w w. www academically.ai [email protected] Page 17 w w w. www academically.ai [email protected] Page 18 w w w. www academically.ai [email protected] Page 19 w w w. www academically.ai [email protected] Page 20 w w w. www academically.ai [email protected] Page 21 w w w. www academically.ai [email protected] Page 22 w w w. www academically.ai [email protected] Page 23 w w w. www academically.ai [email protected] Page 24  PRACTICE IS THE KEY TO SUCCESS WISHES YOU ALL THE BEST FOR YOUR KAPS EXAM www.academically.ai [email protected] +61 406 525 564 3/20 Bailey St,Westmead- 2145,Sydney, Australia.