PHARMA101: PHARMACOKINETICS ②

Lecture-2: Pharmacokinetics(absorption) has been covered in the last article. If you have not read that I would suggest you go for it Here➚. Welcome again to Pharma101 to boost your USMLE preparation and education for all initiatives.

PHARMACOKINETICS- DISTRIBUTION

The distribution of drugs is the movement of drugs from the systemic blood circulation to the organs. It depends upon:

1. Lipid Solubility: Drug distribution ∝ Lipid Solubility. The drug has to cross the lipid membrane to enter the cells.
2. Protein Binding Capacity: Drug distribution is inversely proportional to the drug’s protein binding. If the drug isn't able to get free from the protein then how can it exit blood vessels? Albumin binds acidic drugs and ⍺₁ acid Glycoprotein for Basic Drugs.
3. Displacement interaction: Let’s say 🅰️ and 🅱️ drugs are albumin binding. If one of the drugs among them is having more protein binding capacity then one drug will bind to albumin. The other one will be forced to displace. This may lead to the toxicity of the drug which is displaced.
4. Action Duration- ∝ Protein Binding Capacity of the drug. If it will bind the plasma protein for a longer duration then it will be excreted late. So, it can act for a longer time.

Q. Why do we need to ⬇se drug in the nephrotic syndrome?
Hint: ⬇sed amount of albumin

DRUG TOXICITY

It is the presence of a dose greater than the maximum dose in the plasma. There are some methods by which we can treat drug toxicity.

1. Antidote- Antidote is always preferred to be given in any toxicity. Sometimes, antidotes aren’t available. We can do dialysis in those cases.
2. Dialysis- Used for drugs having low water distribution (drug will be present in plasma) and low plasma protein binding (because plasma proteins aren’t filtered in dialysis).

Drug's Toxicity in which Dialysis is performed-
Methanol, Lithium, and Aspirin {MLA}
Drug's Toxicity in which Dialysis is contraindicated-
A- Amphetamine
V- Verapamil
O- Opioids
I- Imipramine (TCA-Tricyclic Antidepressants)
D- Digoxin
Dialysis- Diazepam (BZD)

Barriers and Drugs

Drugs that can cross various barriers e.g., the Blood-Brain Barrier have more distribution. Any drug can cause vomiting and nausea as any drug can stimulate the CTZ centre in the brain. The CTZ zone is a circumventricular organ means the Blood-Brain Barrier is absent over it. So, any drug can cause vomiting except antiemetic drugs which are designed to prevent vomiting and nausea.

Most drugs can cause the blood-placental barrier except insulin and heparin. If they cause damage to the development of the baby then they are called teratogenic drugs. Thalidomide is the classical example which was responsible for causing phocomelia or sea limbs in newborns.

VOLUME OF DISTRIBUTION

It represents the apparent volume into which the drug is distributed to provide the same concentration as it currently is in blood plasma.

Volume of Distribution formula

Loading and Maintenance Dose

Loading Dose is the amount of drug required just to start the action of the drug. It depends upon the Volume of Distribution and Target Plasma Concentration.

Loading Dose=
Volume of Distribution ❌ Target Plasma Concentration

The maintenance dose is a drug required to continue drug action. It should depend upon the rate of excretion of the drug.

Maintenance Dose=
Clearance ❌ Target Plasma Concentration

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